The study of the protein complement of the genome, or proteome, represents an important new avenue for drug discovery. Proteomics research aims to quantify and characterize all of the expressed proteins in a biological system, and to determine the effect of various perturbations of the system on the expressed proteins. (omitted)

Over the last 5 years or so, there has been a significant increase in the molecular characterization of transport proteins in animals and man. This has led to a better understanding of the importance of such transport proteins in the disposition of endogenous compounds, drugs and other xenobiotics in many organs such as the intestine, liver, kidney and brain. (omitted)

Recent technological innovations in the drug discovery process such as combinatorial synthesis and high throughput screening have led to the identification of an increasingly large number of compounds at the hits-to-leads stage. Therefore, rapid and precise pharmacokinetic/metabolic screening is essential to enhance the tractability of selected leads and to minimize the risk of failure in the later stages of drug development. (omitted)

Traditionally, kinetics of brain influx of drugs has been evaluated by a number of experimental techniques. Brain uptake index and in situ brain perfusion study have been used for the determination of the kinetics; However, these methods generally focus on the accuracy of the uptake rate into the brain rather than the speed of the determination. In addition, application of radiolabelled substrates (e.g., $_{14}$C-labelled sucrose) further impedes the wide spread acceptance of these techniques for the application of high throughput screening system. (omitted)

The brain is unique as target for drug delivery because it is an organ with the greatest blood supply, which receives about 20% of the cardiac output in humans and is highly restricted by a tight vascular barrier, the blood-brain barrier (BBB). Since the BBB forms the interface between blood and brain, the biology of the BBB plays a role in multiple disciplines other than pharmacology, physiology, pathology and neurosciences. (omitted)

With the recent development of combinatorial chemistry, recombinant biotechnology and rational drug design, millions of compounds are being produced in the laboratories of pharmaceutical companies. These new drug candidates are evaluated their efficacy and toxicity through in vivo animal model studies which is very important in drug development. From these studies, very successful drug candidates are selected. (omitted)

Drug targeting to the central nervous system (CNS) is the limiting factor in CNS drug development because most of drug do not cross the brain capillary endothelial wall, which forms the blood-brain barrier (BBB) in vivo. One strategy for drug targeting to the brain is to use endogenous BBB transport systems. (omitted)

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (SIP) are bioactive lysophospholipids (LPs) that act as mediators in various cellular processes, such as cell growth, differentiation, survival, motility, and cytoskeletal reorganization (1,2). LPA and S1P are both abundant in serum and are produced by activated platelets and other cell types. (omitted)

The completion of the draft sequence of the human genome has provided us with a partial list of known and putative human genes, the total number of which is estimated between 30, 000 and 45, 000 (1, 2). These genes provide many potential targets for drugs, some of which may be useful in stopping the growth of cancers. The development of gene-targeting anticancer drugs could be greatly facilitated by the ability to narrow down the list of human genes to those that are necessary for the growth of tumor cells. (omitted)

Signal transduction refers to the processes by which cells perceive the environment and/or internal status. In many physiological responses, cellular signals are activated by the transducers attached to the cell surface plasma membrane in response to chemical modulators. Advances in information technology are required in the pharmaceutical sciences to screen and explore the potential therapeutic agents. (omitted)

In 'Nature', Dixon et al. reported the first cloned mammalian G-protein coupled receptor sequence (1). The DNA sequence from a hamster encodes the $\beta$$_2$-aderenergic receptor. In the same year, 1986, Kubo et al. published the muscarinic acetylcholine receptor sequence (M$_1$) from a rat in the same journal (2). Both groups purified the receptor proteins and identified the DNA sequences (1, 2). (omitted)

Legumes are important agricultural and commercial crops characterized by root nodules formed as a result of the symbiotic relationship with nitrogen-fixing rhizobia. Due to the economic significance the chemistry of some of these species has been well recognized. Soybeans and processed soy products, which contain isoflavonoids and saponins, are of wide interest for their multifacted biological effects. (omitted)

Lonicera japonica Thunb. is a twining shrub that has been used as an antidote and to treat urinary disorders, fever and headache. It has been known as an anti-inflammatory agent in Korea from ancient times and is used widely for treating upper-respiratory tract infections, diabetes mellitus and rheumatoid arthritis. In the previous research, we isolated several flavonoid derivatives from the EtOAc soluble fraction. (omitted)

The diverse, widespread, and exceedingly numerous family of natural products constructed from five carbon building-units and so comprising compounds with $C_{5}$, $C_{10}$, $C_{15}$, $C_{20}$, ${\cdots}$, $C_{40}$ skeletons (together with a few higher members) are synoymously termed terpenes or terpenoids. Among the terpene classes, the triterpenes ($C_{30}$ skeletones) form the largest group and are widely distributed in the plant kingdom, either in the free state or as esters or glycosides, although a few important members found in the animal kingdom such as squalene and a number of tetracyclic component including lanosterol. (omitted)

The fruiting body of Ganoderma lucidum (Polyporaceae) is one of the valuable crude drugs, which has been used clinically in Korea, China, and Japan for a long time as a tonic and sedative, and for the treatment of hepatopathy, chronic hepatitis, nephritis, gastric ulcer, hypertension, arthritis, neurasthenia, insomnia, asthma, and poisoning and chronic bronchitis. Nowadays, this mushroom is used for leukopenia and paid much attention as a home remedy. (omitted)

Saponins are glycosidic compounds present in many edible and inedible plants. Structurally, they are composed of a lipid-soluble aglycone consisting of either a sterol or, more commonly, a triterpenoid and water-soluble sugar residues differing in type and amount of sugars ［1］. Because of their amphiphilic nature, they are highly surface-active. Their biological activity is closely related to the chemical structures that determine the polarity, hydrophobicith and acidity of compounds ［1］. (omitted)

Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis are encapsulated bacteria which encounter the respiratory mucosa and cause nasopharyngeal carriage that may lead to mild mucosal infections or severe invasive disease. (omitted)

Despite various efforts on improving vaccines and antivirals, influenza epidemics continue to afflict many people, causing widespread morbidity and mortality in the young and the elderly. Since the discovery of the unusual 'cap-stealing'mechanism of transcription, significant advances were made on molecular aspects of influenza gene regulation. This provides new insights for developing new antiviral compounds. Reverse genetic technologies have also been advanced for generating recombinant chimeric viruses suitable for designing live vaccine. (omitted)

Bacterial infection is a very complex process in which both pathogenic microorganisms and host cells play crucial roles, and it is the outcome of interactions between the two participants. To elucidate the bacterial pathogenesis mechanisms, therefore, it is essential to understand the cellular and systemic responses of the host as well as the virulence factors of the pathogen. Infection of a host by pathogenic bacteria causes drastic changes in the physiology of host cells, leading to activation of a program of various gene expression. (omitted)

Salmonella typhi Ty21a is an attenuated strain of S. typhimurium and used for oral typhoid vaccine. In an attempt to increase the stability of Ty21a manufacturing typhoid vaccine, the stability of freeze-dried Ty21a including additives at various temperature conditions was studied. In order to investigate the freeze-drying rate of Ty21a according to various absorbance, Ty21a was lyophilized by using 8% sucrose as a stabilizer. (omitted)

A series of modified oligonucleotides containing a phosphorothioate (P=S) backbone and a six-membered azasugar (6-AZS) as a sugar substitute in a nucleotide were synthesized and tested for their ability to inhibit the human immunodeficiency virus type I(HIV-l) in vitro without the aid of any transfecting agents. While P=S oligonucleotides with natural nucleotides had little anti-HIV-l activity, the six-membered azasugar nucleotide (6-AZN)-containing P=S oligonucleotides (AZPSONs) potently inhibited the HIV-l/SHIV replication and syncytium formation (ECso = 0.02-0.2 /lM) without cytotoxicity up to 100 /lM. DBM-2198, the most effective in anti-HIV-l activity among the AZPSONs, consists of random sequence and five 6¬AZNs evenly distributed in 18 nucleotides. DBM-2198 showed strong antiviral activity against, not only laboratory strains, but also primary isolates and even drug-resistant strains of HIV-I. DBM-2198 was much more effective than ddI or ddC in its anti-HIV-l activity in vitro. Particularly noteworthy is that the anti-HIV-l activity of DBM-2198 was better than that of AZT with respect to its long-lasting efficacy after a single treatment. Nevertheless, the antiviral activity of the AZPSONs was very specific to HIV-I. Poliovirus, or even simian immunodeficiency virus (SIV), was not inhibited by the AZPSONs. Taken together, our results strongly suggest that AZPSON can be used as a safe and effective AIDS-therapeutic drug against a broad spectrum of HIV -1 strains.

Field of enantioseparations represents one of the actual topics of chemistry. Significant, in some cases dramatic differences in a desired activity as well as in toxic properties of enantiomers of chiral drugs, food additives, agrochemicals, cosmetic products, etc. represents a driving force in this field. The enantiomers of all chiral bioactive compounds have to be isolated and to be tested. Besides the ethical or environmental reasons for developing single enantiomers, it may be a real therapeutic benefit and in some cases, it has been used as a strategy for extending patent life. (omitted)

In the past two decades, separations of enantiomers (optical isomers) by high-performance liquid chromatography (HPLC) have remarkably advanced ［1］. Among many commercially available chiral stationary phases (CSPs) for HPLC, polysaccharide-based CSPs are the most popular ones, which can cover the resolution of a wide range of the chiral compounds ［2, 3, 4］. Here, I will explain mainly the HPLC separation of enantiomers using these CSPs. (omitted)

Because of the differences between biological and pharmacological properties of chiral drugs in human body, accurate determinations of their optical purities have been in great need. There are two major approaches in chiral separation: indirect method performed under achiral condition, and direct method under the chiral environment. We have been conducting chiral separation of acidic chiral compounds and also amino acidic chiral compounds employing indirect GC methods and direct CE enantiomeric separation methods. (omitted)

It has been well known for the stereoselectivity in pharmacodynamic effects of many xenobiotics including therapeutic agents, which have lead to the development of enantiomer drugs. Compared to pharmacodynamic stereoselectivity, stereoselective pharmacokinetics of each enantiomer has not been seriously considered in the development of enantiomer drugs although many reports have been demonstrated the stereoselective absorption and metabolism of racemic drug (e.g verapamil). (omitted)

Immune responses to infectious microbes and foreign antigens are regulated by a series of interactions among T cells, B cells, and antigen-presenting cells (APCs) such as macrophages (M$\square$) and dendritic cells (DCs). The inverse relationship between antibody production and cell-mediated immune responses such as delayed type hypersensitivity (DTH) was experimentally manipulated by varying the dose, route of administration, and form of antigen used to immunize animals. (omitted)

Oxidative modification of cellular structures and functions by redox imbalance is the basis of the current oxidative stress hypothesis of aging. The experimental support for this hypothsis has been generated from recent molecular probing on the interrelation between the age-related functional impairments and the pathogenesis. (omitted)

Airway inflammation is a characteristic of many lung disorders including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. All these diseases involve the recruitment of immune and inflammatory cells to the lungs leading to systemic and local chronic inflammation and oxidative stress. (omitted)

Chemoprevention, one of the most innovative and promising areas of cancer research, refers to the prevention of cancer through pharmacologic or nutritional intervention. Recently, considerable attention has been focused on the role of cyclooxygenase-2 (COX-2) in the carcinogenesis as well as inflammation. Inappropriate up-regulation of COX-2 is implicated in the pathophysiology of certain types of human cancers. (omitted)

The phospholipase $A_2$($PLA_2$) family represents a diverse group of enzymes that hydrolyze sn-2 fatty acid from the cell membrane. Several mammalian cytosolic $PLA_2$ and secretory $PLA_2$(s$PLA_2$) have been characterized and classified into different families. At present, 12 distinct sPLA$_2$s have been identified in mammals and classified into different groups, depending on their primary structures as characterized by the number and position of cysteine residues. (omitted)

Recentadvancesin '-omics ' technologies enable us to discover more diverse disease- relevant target proteins, which encourages us to find out more target-specific novel lead compounds as new drug candidates. Therefore, high-throughput screening (HTS) becomes an essential tool in this area. Among many HTS tools, in silico HTS is a very fast and cost-effective tool to try to derive a new lead compound for any new targets, especially when the target protein structures are known or readily modeled. (omitted)

The discovery of new ligands with affinity and selectivity for the dopamine $D_2$ receptor subtypes is an important area in medicinal chemistry. The distribution of the $D_2$ receptors in the limbic areas of brain suggests that these receptors may be particularly an attractive target for the design of potential selective antipsychotic drugs without causing extrapyramidal side effects. (omitted)

S- Adenosylhomocysteine hydrolase $(SAH)^1$ catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L-homocysteine. Inhibition of this enzyme accumulates S-adenosylhomocysteine, which in turn inhibits S-adenosyl-L-methionine dependent transmethylation, resulting in no formation of the capped methylated structure at the 5'-terminus of viral mRNA. Thus, S-adenosylhomocysteine hydrolase has been an attractive target for the development of broad spectrum of antiviral agents. (omitted)

Since capsaicin was found as an excellent vanilloid receptor agonist, considerable efforts toward the development of a novel analgesic have been continued. However, the small therapeutic window between these effects and the excitatory side effects, such as hypothermia, bronchoconstriction, increased GI mobility, and hypertension, precluded the development of capsaicin as a systemic agent. (omitted)

Methylmercury causes severe central nervous system disorders. Despite the efforts of many researchers, the mechanisms involved in methylmercury toxicity and the defense against this toxicity remain unknown. We focused on the fact that drug resistance is sometimes involved in elevation of the concentration of the intracellular target of the drug. (omitted)

Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.

Cadmium (Cd) is an environmental pollutant and categorized as a human carcinogen, which has a tendency to accumulate in the human body. The level of Cd in renal cortex and liver are good indicators as an index of Cd exposure in general population. Geometric mean concentration of Cd is 27.4 and 3.1 /g wet weight in renal cortex and liver, respectively, in Korean. Cd is toxic to a number of tissues, notably the liver, kidney, testis, lung, lymphoid tissue and lung. (omitted)

It is generally accepted that the immune system is one of the major target organs for many toxic chemicals. In addition, many toxic chemicals require metabolic activation by cytochrome P450s for their toxicity. Although the immune cells possess a limited amount of drug metabolizing capacity, metabolic activation of certain toxicants in liver and immune organs may have a significant role in immunosuppression. In the present studies, the possible role of metabolic activation by cytochrome P450s in chemical-induced immunosuppression was reviewed, with a particular emphasis on the methodological techniques to detect immunotoxicants requiring metabolic activation in vivo and in vitro. (omitted)

Methylmercury (MeHg; $CH_{3}HgCl$) is, second only to cadmium as being, the most toxic on the earth. Inorganic mercury from various waste sources can be easily methylated by bacteria in water and subsequently ingested by fishes and then highly accumulated in human. Although toxicity from mercury exposure occurs with both organic and inorganic forms, organic mercury is more potently toxic to central nervous system. Minamata disease is an example of organic mercury toxicity. (omitted)

A number of polycyclic aromatic hydrocarbons (PAHs), such as benzo［a］pyrene, are carcinogenic and thought to contribute to the overall burden of human cancer (1). PAHs are ubiquitous in the environment and humans are exposed to them via multi-pathways, e.g. air or soil of urban areas, exposure to direct or indirect tobacco smoke, and ingestion of food or water polluted by combustion effluents (2-3). (omitted)

Using the isolated perfused rat heart this study investigated 1) the cardiac uptake of idarubicin (IDA), 2) the role of P-glycoprotein (P-gp) in the uptake process, 3) the formation of IDOL from IDA in the heart, and 4) the effect of P-gp inhibitors (verapamil, amiodarone, PSC 833), doxorubicin, hypothermia, xanthine derivatives (caffeine, theophylline) and metabolism inhibitors (rutin, phenobarbital) on the pharmacokinetics and pharmacodynamics of IDA using a mathematical modeling approach. A minimal model was constructed; the differential equations were numerically solved and fitted to the data using the ADAPT II-software package using maximum likelihood estimation assuming that the measurement error has a standard deviation which is a linear function of the measured quantity［1］. (omitted)

Cyclosporin A (CSA) is a poorly water-soluble cyclic peptide comprising 11 amino acids. It inhibits T-lymphocyte function that plays an important role in the induction of immune response. The potent immunosuppressive activity of CSA has been used for the prevention of rejection following transplantation of liver, kidney and bone marrow, etc. The use of CSA has been often limited by several disadvantages including low bioavailability, narrow therapeutic window, nephrotoxicity, hepatotoxicity and neurotoxicity. Moreover, CSA injection is limited to patients who are unable to take the oral preparations, because it has a risk of anaphylactic shock and nephrotoxicity due to Cremophor EL$\textregistered$, a solubilizing agent used in the commercial intravenous formulation. Owing to above mentioned disadvantages of commercial products, there is a great interest in the development of the alternative dosage forms. (omitted)

In the past, the development of pharmacokinetic/pharmacodynamic (PK/PD) models for quantitating the time course of drug responses was mainly based on two types of models, the empirical effect compartment model that simply accounts for the delay between effect and plasma concentration (hysteresis) and the mechanism-based so-called indirect response model. The first approach traces back to a paper by Segre (1) and its application was popularized by Holford and Sheiner (2); indirect response models were introduced by Jusko's group (3). (omitted)

The concentration effect relationship (pharmacokinetic pharmacodynamic model, PKPD) of drugs used for Parkinson's disease is complex. The benefits and adverse effects of drug treatment have to be considered in terms of short term and long term effects. Acute effects, observed over hours and days, reflect symptomatic benefit while chronic effects, observed over months and years, also reveal influences on the progress of the disease. (omitted)

Pharmacokinetic (PK) and pharmacodynamic (PD) study of a new reversible proton pump inhibitor (YH1885, Yuhan Pharmaceutical Co.) was done as a phase 1 clinical trial in Seoul national University Hospital Clinical trialcenter. Single dose of 60, 100, 150, 200, and 300mg were administered to total 20 healthy subjects under fasting state. Six subjects were given 100 mg after food and 12 subjects were given multiple doses of 150 and 300 mg every day for 7 days under fasting state. (omitted)

Although hepatocellular dysfunction occurs during sepsis. the mechanism responsible for this remains unclear. Since Kupffer cells provide signals that regulate hepatic response in endotoxin and inflammation. the aim of this study was to investigate the role of Kupffer cells in the alterations in the hepatic microsomal drug metabolizing function during sepsis. Rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP)followed by fluid resuscitation. (omitted)

Creatine phosphokinase (CPK) was a marker in diagnosis of rhabdomyolysis. The CPK abnormality could be induced by intake of HMG CoA reductase inhibitors (statins). The objective of this study was to estimate the incidence rate of CPK abnormality by each statin. (omitted)

Radiation synovectomy is an useful alternative treatment to rheumatoid arthritis and Re$\^$188/ is suggested as an ideal radiopharmaceutical agents because beta ray (2.1 MeV) emitted from Re$\^$188/ is appropriate for synovial cell ablation and gamma ray (155 KeV) is ideal for dosimetry. Its' ideal particle size (2-5 mm) was achieved by conjugation with tin-colloid, In this study, we investigated the toxicity, stability and biodistribution to evaluate the suitability of DA-7911 as a synovectomy agent. (omitted)

Diazepam (DZ) is one of the most frequently prescribed drugs as an antianxiety agent. muscle relaxant. and anticovulsant and sometimes causes intoxication due to accidental overdose, misuse or abuse. DZ is metabolized to nordiazepam (NDZ, desmethyldiazepam), oxazepam (OX) and temazepam (TM) which are also pharmacologically active, although OX and TM do not accumulate in blood or plasma to an appreciable extent. (omitted)

Drug used in hospital is allowed marketing through after pharmacological and toxicological tests using various animals and clinical test of human in developing state. But as pre-marketing clinical study take short period with relatively a few of patients and strict selection criteria of people, pediatric, geriatric. pregnancy, liver and kidney patients may be excluded. As the safety of drug isn't completely evaluated before launching. it is important to collect and evaluate drug adverse reaction newly reported by medical practitioners and pharmacists. (omitted)

Cyclooxygenase (Cox-2) is involved in tumorigenesis. hence. considered to be a molecular target for chemoprevention and chemomodulation. Selective Cox-2 inhibitors including Celecoxib and Nimesulide have been studied for their anticancer activity when given alone and in combination with radiation or cytotoxic agents. In this study, we synthesized more than 140 analogues of Celecoxib and Nimesulide. and evaluated their inhibitory effects on Cox-l and Cox-2 activity as well as cytotoxicity in order to find promising anticancer agents having selective Cox-2 inhibitory effect. (omitted)

ZD1839 is a new anticancer agent which selectively inhibits EGFR tyrosine kinase. Oxaliplatin (LOHP), 5-FU (FU), and paclitaxel (PTX) have shown to be highly active against the gastric carcinomas. and ZD1839 is considered as a good candidate for the treatment of gastric cancers when combined with cytotoxic agents. In this study, we evaluated the antitumor effects of these agents in SNU-l human gastric cancer cells either alone or when given as a doublet. (omitted)

Hypoxia in solid tumors is known to contribute to intrinsic chemoresistance. Tirapazamine(TPZ). a hypoxia-selective cytotoxin. showed synergism with radiation or cytotoxic agents. Paclitaxel(PTX) is a highly active anti-cancer agent against Non small cell lung cancer(NSCLC), however. due to poor penetration into central hypoxic region of tumor tissue. combination with TPZ has been suggested to enhance its efficacy. (omitted)

Methylmercury (MeHg). a potent neurotoxicant. produces neuronal death that may be partially mediated by glutamate. Glutamine synthetase (GS), a glial-specific enzyme. catalyzes the synthesis of glutamine from glutamate and ammonia and is associated with ischemic injury and neurological diseases. Objectives of this experiment are to investigate whether in vivo and in vitro MeHg exposure have adverse effects on GS and whether duration of exposure to MeHg and glutamate co-treatment playa role in MeHg-induced toxicity. (omitted)

In this study, anti-cancer effect of N-phenyl-O-phenylthionocarbamate (PPTC) substitutes was investigated. and the apoptotic mechanism by these substrates was examined on SK-MEL -28 human skin cancer cell line. SK-MEL -28 cell was treated at various concentrations for 48hr. and then MTT assay was performed to gain IC$\sub$50/ value and examine cytotoxicity of PPTC substitutes, and quantitative structure-activity relationship (QSAR) between cell and these PPTC substitutes was examined. (omitted)

Genistein has been shown to possess chemopreventive potential. but its underlying molecular mechanisms are largely unclear. In the present study, we have investigated the effects of genistein on induction of cyclooxygenase-2 (COX-2) that plays an important role in the pathophysiology of carcinogenesis as well as in mediating inflammation. 12-Ο-Tetradecanoylphorbol-13-acetate(TPA) caused transient increases in cox-2 expression and prostaglandin E$_2$(PGE$_2$) production in MCF 10A cells, which was inhibited by genistein pretreatment. (omitted)

The anaerobic pathway for unsaturated fatty acid biosynthesis was established in the 1960s in Escherichia coli. The double bond is introduced into the growing acyl chain by FabA., an enzyme capable of both the dehydration of ${\beta}$-hydroxdecanoyl-［acyl carrier protein］ (ACP) to trans-2-decenoyl-ACP. and the isomerization of trans-2 to cis-3-decenoyl-ACP. However. there are a number of anaerobic bacteria whose genomes do not contain a fabA homolog, but these organisms nonetheless produce unsaturated fatty acids. (omitted)

The synthesis of chiral 1,2-amino alcohols has been an area of intense study in the synthetic and industrial fields, because of their important roles in organic synthesis as fundamental building blocks and their occurrence in a number of natural products. drugs. and chiral auxiliaries or ligands. General methods for the synthesis of these compounds can be divided into two large categories: functional group transformations and the C-C or the C-N bond formations. (omitted)

Methods of 14C-radio isotope labeling of quinolone intermediates at four different sites are described. 14C-radio isotope labeled quinolone intermediates can be synthesized from 14C-1-malonic acid, 14C-2-malonic acid, 14C-benzene ring. and 14C-trimethyl orthoformate. The major site of 14C-radio isotope labeled quinolone intermediates is from 14C-2-malonic acid. We want to help customers to choose the best way for synthesis of 14C-radio isotope labeled quinolone derivatives. and give a general comprehension for 14C-radio isotope labeled pharmaceutical compounds. (omitted)

Corticosteroids have been used most frequently for inflammatory bowel disease. They are well absorbed and only a limited fraction of the dose is delivered to the inflammatory site in the colon. To reduce side effects by the systemic absorption. colon-specific delivery is highly desirable. We designed dexamethasone 21-sulfate sodium (DS) as a cOlon-specific prodrug of dexamethasone (D) expecting that it might be stable and non absorbable in the upper intestine and dissociate in the colon by the sulfatase, an enzyme solely found in the colon. (omitted)

Azasugars, which have been called the "sugar-shaped" alkaloids from plants. are reversible. competitive inhibitors of glycosidases. The purpose of these natural products is possibly to inhibit the carbohydrate metabolism and consequently the growth of plant consuming pests. Since selective glycosidase inhibitors have a large number of interesting potential applications including treatment of AIDS, diabetes. and tumor metastasis. they have received a considerable attentions. (omitted)

Apio nucleosides whose 4'-hydroxymethyl group moves to 3'-position exhibit interesting biological activity such as antitumor or antiviral activity. On the other hand. neplanocin A is the representative of the carbocyclic nucleosides and has been recognized as a potent antitumor and antiviral agent. Based on these findings. it was of great interest to design apio neplanocia A which combined the properties of apio nucleosides and neplanocin A. (omitted)

SB31, an extract of Pulsatilla koreana, has been tried as an antitumor agent by traditional medicine pratitioner in Korea for the past 30 years, SB31 was evaluated for cytotoxic and antitumor activity against a variety of cancer cell lines. The SB31 exhibited 5-6 fold less cytotoxic activity against normal mononuclear cells (ED$\sub$50/. 1.1 mg/$m\ell$) than against cancer cell lines (ED$\sub$50/ 0.14-0.19mg/$m\ell$). (omitted)

Any food additive as a chemical synthetic compound. whose criteria and standards are not notified publicly and foods using an food additives containing such a chemical synthetic compound or foods containing it shall not be sold. or manufactured. imported. processed. used. prepared. stored. transported. or displayed for the purpose of sale. Some food manufacturers have illegally added drugs to foods not notifying this. Moreover. structure-modified new drugs could be added. But it is almost impossible to detect these by ordinary laboratory inspection. Thus the study about the identification of analogues of pending drugs is imminent. (omitted)

An efficient method for the simultaneous profiling analysis of organic acids and amino acids combined with a simple graphic pattern recognition method was developed for more objective diagnosis of organic acidurias and amino acidurias. In this method, extractive ethoxycarbonly (EOC) reaction of amino and sufhydry groups with ethyl chloroformate was followed by methodime (MO) formation of carbonyl group in aqueous solution (omitted)

In previous study, we showed the feasibility of the in vivo use of portable near infrared system for the determination of human skin moisture. In order to optimize the acquiring condition of NIR spectrum of skin. skin depth profiling was investigated changing the distance and gap size between illumination and receiving of radiation in the terminal of fiber probe. The colleted light information could be controlled depending the distance and gap of fiber optic probe. (omitted)

The alkylphenols, chlorophenols and bisphenol A were determined by gas chromatography/mass spectrometry-selected ion monitoring mode followed by three work-up methods for comparison: EPA method, isoBOC derivatization method and TBDMS derivatization method. Eleven phenols in water samples were extracted with dichloromethane. (omitted)

Mucosal administration of drug or therapeutic gene is emerging as a new route of delivery for systemic and local therapeutics. Previously. in situ gelling system has been applied to chemical drug such as acetaminophen. insulin. prostaglandin E1. and clotrimazole. Plasmid DNA has not been delivered in form of in situ gelling vehicles. To improve the intranasal absorption of plasmid DNA. we designed delivery systems composed of provide of in 냐셔 gelling and mucoadhesive polymers. (omitted)

Proximal femur fracture is known as one of the major medical problems in terms of mortality. disability and economic costs. To assess the association between the use of corticosteroids and proximal femur fracture. a cohort study was conducted upon Korean elderly women. (omitted)

Tolperisone hydrochloride is used as a muscle relaxant. Very few assay methods of tolperisone were reported. such as potentiometry. spectrophotometry and high performance thin layer chromatography. In addition. there is no report related to HPLC method to determine the tolperisone level in biological sample. In this study, A very sensitive reverse phase high performance liquid chromatographic (RP-HPLC) method for the determination of tolperisone HCI in plasma has been developed. (omitted)

A various 2-arylmethylpropionic acds(profen) have been widely used as non-steroidal anti-inllammatory drugs for the relief of acute and chronic rheumatoid arthritis and osteoarthritis. as well as for other connective tissue disorders and pains. Example is fenoprofen. ibuprofen, ketoprolen, and naproxen. All are chiral and, except for naproxen. are marketed in racemic form. Enantioseparations of profens have been of considerable interest because their anti-inflammatory and analgesic effects have been attributed almost exclusively to their (S)-enantiomer. (omitted)

Expression of phase II detoxifying genes is regulated by NF-E2-related factor 2 (Nrf2)-mediated antioxidant response element (ARE) activation. Phosphatidylinositol 3-kinase (PI3-kinase) plays an essential role in ARE-mediated rGSTA2 induction by oxidative stress and controls microfilaments and translocation of actin-associated proteins. This study was designed to investigate the P13-kinase-mediated nuclear translocation of Nrf2 and the interaction of Nrf2 with actin. (omitted)

H$_2$O$_2$ has been shown to act as a signaling molecule involved in many cellular functions such as oxidant-induced stress, apoptosis, proliferation. In this study, we investigated the action mechanisms of H$_2$O$_2$ on activation of Extracellular Signal-Regulated Protein Kinase(ERK) in cultured feline ileal smooth muscle cells(ISMC). Western blot analysis done with phospho-specific MAP kinases antibodies demonstrated that potent activation of ERK and moderate activation of SAPK/JNK occurred within 30 min of H$_2$O$_2$ treatment. (omitted)

We have previously reported that activation of $K^{+}$-$Cl^{-}$-cotransport (KCC) by N-ethylmaleimide (NEM) induces apoptosis through generation of reactive oxygen species (ROS) in HepG2 human hepatoblastoma cells. In this study we investigated the possible role of phospholipase $A_2$($PLA_2$)-arachidonic acid (AA) signals in the mechanism of the NEM actions. (omitted)

Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis by matrix degradation. To analyze the effect of 2-amino-3-ethoxycarbonyl-1-methyl pyrolo (3,2-b) naphtho-4,9-dione (compound 1) on the invasion or metastasis of cancer cells the expression of matrix metalloproteases (MMPs) was investigated in human fibrosarcoma HT 1080 cells by AT -PCR or gelatin zymographic methods. (omitted)

Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic enzymes. which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Thirty subtypes of PTPs have been identified in human genomes. Among PTPs, PTP1 B has been suggested as a negative regulator of insulin signaling. Overexpression of this enzyme has been known as a cause of obesity and type II diabetes, so it is a target for drug discovery. (omitted)

Cyclooxygenase-2 ( COX-2 ) is an inducible enzyme which produces prostanoids by various stimuli. Overexpression of COX-2 in many tumor types indicates its association with tumor progression, which has been a promising target for chemoprevention and chemomodulation. We studied conc- and time-dependency of COX-2 inhibition, growth inhibition, and cell cycle arrest induced by celecoxib, a selective COX-2 inhibitor, in human non-small cell lung cancer (NSCLC) A549 cells. (omitted)

4-Hydroxy nonenal (HNE) is a lipid peroxidation product derived from oxidized $\omega$-6 polyunsaturated fatty acids, such as arachidonic acid. HNE is widely used as a marker of lipid peroxidation. To study the hypothesis that HNE may induce apoptosis and cell cycle arrest, we estimated cytotoxicity of HNE in BAE (bovine aortic endothelial) cells. Anti-proliferative effects were examined by morphological changes and MTT assay after exposure to different time (0-3 hr) and concentration (3-7 ${\mu}$M of HNE. (omitted)

It has been known that resveratrol, a phytoalexin present in grapes mainly, has antioxidant. anti-inflammatory, and cancer chemopreventive activity. One mechanism of its anti-inflammation and cancer prevention is considered to modulate cyclooxygense-2 (COX-2) activity. Since COX-2 plays an important role in inflammation and carcinogenesis, the potential COX-2 inhibitors have been considered as anti-inflammatory or cancer chemopreventive agents. (omitted)

We studied on the antiproliferative effects of bile acids and their derivatives on HepG2 human hepatocellular carcinoma cells. Ursodeoxycholic acid (UDCA) and its synthetic derivative HS-1030. and chenodeoxycholic acid (CDCA) and its synthetic derivatives. HS-1199 and HS\ulcorner200, were used. We focused on the regulation of cell cycle and induction of apoptosis by these bile acid derivatives. (omitted)

We studied the effects of ursodeoxycholic acid (UDCA) and its synthetic derivatives. HS-l030 and HS-1183. and chenodeoxycholic acid (CDCA) and its synthetic derivatives, HS-1199 and HS-1200. on the human colon adenocarcinoma cell line. HT -29 (p53 mutant type). The effects on cell viability and growth were assessed by MTT assay and cell growth study. While UDCA and CDCA exhibited no significant effect, their novel derivatives inhibited the proliferation of HT-29 cell line in a concentration- and time-dependent manners. (omitted)

In this study. we tried to investigate whether polymerized basic amino acid e.g. poly-L-lysine(PLL) which has the molecular weight under 10 kD significantly affects the physiological and stimulated mucin release from cultured hamster tracheal surface epithelial cells. Confluent primary hamster tracheal surface epithelial(HTSE) cells were metabolically radiolabeled with 3H-glucosamine for 24 hr and chased for 30 min in the presence of either PLLs or adenosine triphosphate(ATP) and PLL to assess the effects on basic or ATP-stimulated 3H-mucin release. (omitted)

A number of patients suffering from atrial fibrillation are increasing and many cardiologists are trying to develop the ideal antiarrhythmic drugs for atrial fibrillation. Previously, we found out that CW-2202, a furanocoumarin derivative inhibited the hKvl.5 current expressing predominantly in human atrium without affecting the HERG current expressing mainly in ventricle. (omitted)

A synthetic naphthoquinone alkaloid. 2-amino-3-ethoxycarbonyl-l-methyl pyrolo (3,2-b) naphtho-4,9-dione (compound 1), showed a potent cytotoxicity in a panel of cancer cell lines with an IC50 ranged from 0.1 to 0.3 microgram/mL. Prompted by a potent cytotoxic activity, the mechanism action study was performed with cultured A549 of human lung cancer cells. Flow cytometric G2-M cell cycle arrest and microscopic investigation was also characterized with apoptotic morphological features. (omitted)

It has been shown that C2-ceramide (C2), short chain ceramide, plays a role in mediating contraction of cat esophageal smooth muscle cells. We examined the effect of newly synthesized ceramide analogues on the C2-ceramide induced contraction in esophageal smooth muscle cells isolated with collagenase. C2-ceramide produced contraction of smooth muscle cells in a dose dependent manner. (omitted)

This study reports depigmenting potency of 1,3-selenazol-4-one derivatives. which would be based upon the finding of direct inhibition to mushroom tyrosinase. 1,3-Selenazol-4-one derivatives exhibited inhibitory effect on dopa oxidase activity of mushroom tyrosinase. In this study. inhibitory effects of six kinds of 1,3-selenazol-4-one derivatives (3a, 3c, 3d, 3e, 3g and 3i) on mushroom tyrosinase were investigated. (omitted)

Nitric oxide (NO) has been shown to play an important role in the regulation of vascular tone. platelet function. neurotransmission. and immune function. NO is synthesized from the L-arginine by NO synthase (NOS). Three distinct isoforms of NOS have been identified: calcium/calmodulin-dependent endothelial (eNOS) and neuronal (nNOS) isoforms which are constitutive and produce small quantities of NO, and an inducible isoform (iNOS) which is markedly induced in response to lipopolysaccharide (LPS) or inflammatory cytokines. (omitted)

This study was carried out to demonstrate the effects of oral administration of DA-8159. a selective phosphodiesterase 5 inhibitor. on development of pulmonary hypertension induced by monocrotaline (MCT). MCT-treated rats(60mg/kg) were divided into three groups and orally administered vehicle, 1 mg/kg or 5 mg/kgg of DA-8159 twice a day for 3 weeks. Increased right ventricular weights, medial wall thickening in pulmonary arteries. myocardial fibrosis, decrease of plasma cyclic guanosine monophosphate (cGMP) level and body weight gains were shown in MCT group. (omitted)

Tolerance and pharmacolinetics after single-dose administration of DA-8159, a new selective PDE5 inhibitor under phase 1 study, were examined in 42 healthy male volunteers in a six-period, double-blinded placebo-controlled study. Participants received single oral tablet of DA-8159 (12.5 to 300mg) or placebo. Adverse effects and pharmacokinetic parameters were monitored during experiments. DA-8159 was well tolerated and the frequency of adverse events was dose-related. (omitted)

DA-8159. a selective inhibitor of phosphodiesterase type 5 (PDE5: IC$\sub$50/ 5ng/$m\ell$). is being developed as a new treatment for erectile dysfunction. Since DA-8159 has been shown to inhibit PDE6 enzyme (IC$\sub$53ng/$m\ell$). we evaluated the effect of DA-8159 on electroretinogram (ERG) and retinal histopathology in rabbits. The effect of oral DA-8159 (5 to 30mg/kg) on ERG recordings was investigated at pre-treatment. 1 and 5 hrs after administration in rabbits. (omitted)

DA-8159 is a new. highly selective. potent cyclic-GMP phosphodiesterase 5 inhibitor developed by Dong-A Pharmaceutical Company(Kyunggi, Korea) as an oral drug for the treatment of erectile dysfunction. NO- cGMP signal transduction pathway plays a key role for relaxation of corpus cavernosal smooth muscle. In this study. the efficacy of DA-8159 was evaluated by measuring the length of uncovered penile mucosa in spinal cord injury(SCI) rabbits. (omitted)

Capsaicin and analogues are valuable analgesic agents when administered to mammals. including humans. However. their pungency. hypothermia and the effects on the cardiovascular and respiratory systems through their general activation of primary afferents severely limit their use. So competitive antagonists have been pursued as a novel pharmacological agent for analgesics. rather than agonists. We have identified a new class of potent and selective vanilloid receptor (VR) antagonists. (omitted)

2-Methylaminoethyl- 4,4' -dimethoxy- 5, 5',6,6' -dimethylenedioxybiphenyl- 2' -carboxy- 2-carboxylate (DDB-S) is a synthetic compound derived from DDB. which is protects liver against carbon tetrachloride-, D-galactosamine-, thioacetamine-, and prednisolone- induced hepatic injury in experimental animals. We assessed the use of liquid chromatography/electrospray iontrap tandem mass spectrometry (LC/MS/MS) method to identify and quantify in vivo metabolites and to measure excretion. (omitted)

The present study was performed to compare the cardiovascular adverse effects of verapamil. KR30031 and their each optical isomers, and also to measure their ability to overcome multidrug resistance (MDR). R-isomer of KR30031 (R-KR30031) was equipotent with S-isomer of KR30031 (S-KR30031) and 25 fold less potent than R-isomer of verapamil (R-verapamil) in relaxing the aorta isolated from rat (EC50: 11.8, 10.2 and 0.46 ${\mu}$M, respectively). (omitted)

DA-8159 is a new PDEV inhibitor, synthesized by Dong-A Pharm, as an oral agent to treat male erectile dysfunction. DA-8159 and sildenafil are mainly metabolized by cytochrome P450 enzyme CYP 3A4. In this study. we compared the metabolism of DA-8159 with sildenafil in vitro and in vivo. First, we quantified the remaining gatio of original compound, DA-8159 and sidenafil., after we incubated drugs for 30 minutes with human liver microsome cytochrome P 450 3A4. (omitted)

Apicidin. a natural product HDAC inhibitor. is recently isolated from Fusarium sp. at Merk Research Laboratories, induces therapeutic applications as a broad spectrum antiprotozoal agent to muti-drug resistant malaria and a potential antitumor agent. The biological activity of apicidin appears to be apicocomplexan HDAC at low nanomolar concentrations. (omitted)

In boiling aqueous solution, D-amygdalin usually begins to convert into neoamygdalin in 3 min and more than 30% of the initial D-amygdalin is found as neoamygdalin after 30 min. In this report, we establish methods for simple HPLC analysis and the inhibition of D-amygdalin conversion. D-Amygdalin and its conversion product, neoamygdalin, were clearly separated on reverse-phase column chromatography by an optimized eluent of 10mM sodium phosphate buffer (pH 3.8) containing 6% acetonitrile. (omitted)

The effects of aporplline isoquinoline alkaloids such as liriodenine. anonaine and asimilobine on dopamine biosynthesis in PC12 cells were investigated. Treatment of PC12 cells with liriodenine (10 ${\mu}$M), anonaine (0.05 ${\mu}$M) and asimilobine (0.15 ${\mu}$M) showed 33.6%, 37.7% and 35.1 % inhibition of dopamine content for 12 h. The IC$\sub$50/ values of liriodenine. anonaine and asimilobine were 8.4 ${\mu}$M. 0.05 ${\mu}$M and 0.13 ${\mu}$M. respectively. (omitted)

Mast cells play an important role in inflammation by functioning as a source of histamine, tryptase, and proinflammatory cytokines. Lonicera Japonica (Caprifoliaceae. Lc) has been used to treat inflammation. We investigated whether the water extract of Lonicera Japonica(Lc) inhibit production of inflammatory mediators such as tryptase and tumor-necrosis factor (TNF)-${\alpha}$, and phosphorylation of extracellular signal-regulated kinase(ERK) in trypsin-stimulated HMC-1. (omitted)

We investigated the anti-proliferative effects of lxeris sonchifolia H. (godulbaegi) root extracts. luteolin(3'. 4', 5. 7-Q-glucoside and 3'. 4', 5, 7-tetrahydoxyflavone) and apigenin (3', 4'. 5. 7-O-gluconic acid) on HepG2 (p53 wild type) cells. Hep3B (p53 null) cells, and Chang liver cells. In MTT assay 3', 4'.5. 7-tetrahydoxyflavone showed the most efficient anti-proliferative effects on these three cell lines. However, there was no significant anti-proliferative effect on Chang liver cell line in MTT results. (omitted)

The present study was designed to investigate the effects of green tea extract (GTE) and epigallocatechin gallate (EGCG) on secretion of catecholamines (CA) in the isolated perfused rat adrenal gland. In the presence of GTE (100 ${\mu}$g/$m\ell$) into an adrenal vein for 60 min. CA secretory responses evoked by ACh (5.32 mM), high K＋ (56 mM) and Bay-K-8644 (10 ${\mu}$M for 4 min) from the isolated perfused rat adrenal glands were greatly inhibited in a time-dependent fashion. (omitted)

In the previous studies. we confirmed the anti-inflammatory components of Kalopanax pictus bark using activity-guided fractionation in vivo. For the elucidation of anti-inflammatory mechanism, we evaluated the effects of these components on the inhibition of NF-$\sub$K/B activity and human leukocyte elastase. A cell-based assay system developed in our laboratory was used in transfectant RAW 264.7 cells. (omitted)

We investigated the anti-proliferative effects of a new compound. ircinin-1. from the sponge Sarcotragus sp. on SK-MEL -2 human skin cancer cells. From the data of MTT assay, cell viability was decreased by ircinin-1 in a dose-dependent manner. We observed that the anti-proliferative effect of ircinin-1 was due to the induction of apoptosis, which was confirmed by observing the morphological changes. the increased ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2, and cleavage of poly(ADP-ribose) polymerase protein, via activation of caspase-3. (omitted)

Intestinal epithelial cells can produce cytokines and chemokines that play an important role in the mucosal immune response. Regulation of this secretion is important to prevent inflammatory tissue damage. Lonicera japonica have been shown to inhibit inflammation. We tested the effect of luteolin, a major ingredient of Lonicera japonica, on TNF-${\alpha}$-stimulated IL-8 secretion from lntestinal epithelial cells. (omitted)

Many polysaccharides isolated from plants have been shown to enhance various immune responses in vivo and in vitro. Here we demonstrate that polysaccharide isolated from the root of Acanthopanax koreanum (AK) has a unique mode of immunostimulation with regard to its cell-type specificity. AK was found to markedly increase polyclonal 1gM antibody production and the proliferation of B cells. (omitted)

This research was performed to investigate the protective effect of Yangguksanwha-tang(YST) agaist ischemic damage in PC 12 cells. To elucidate the mechanism of the protective effect of YST on ischemic insult. cell viability and changes in activities of Superoxide dismutase. Glutathione Peroxidase. Catalase. capase 3 and the production of Malondialdehyde were observed after treating PC12 cells with YSt which was metabolized by rat liver homogenate. (omitted)

Piperine (piperinoyl-piperidine) is a nitrogenous pungent substance contained in black pepper. the well know spice obtained from Piper nigrum L. (Piperaceae). Pharmacological studies have shown that piperine reduces inflammation and pain. possesses anticonvulsant and antiulcer activity. protects the liver and has deleterious effects on testis function. Prostaglandins(PGs) are a family of intercellular and intracellular messengers derived from arachidonic acid(AA) by phospholipase(PL) and cyclooxygenase(COX). (omitted)

In our previous study. we reported that PG. a polysaccharide isolated from Plyatycodon grandiflorum, activated macrophages and B cells. but not T cells. Here. we investigated in more detail the mechanism of action of PG in macrophage activation. Since PG cannot penetrate cells due to the large molecular mass, it should bind to membrane receptors of macrophages. We showed that some antibodies to cell surface molecules (CD14, CD11b. TLR2, and TLR4) inhibited RAW264.7 macrophage activation, suggesting the possible binding sites of PG. (omitted)

Many polysaccharides isolated from plants are considered to be biological response modifiers and have been shown to enhance various immune responses in vivo and in vitro. Here we demonstrate that a polysaccharide isolated from cell culture of Acanthopanax senticosus (AS) has a unique mode of immunostimulation with regard to its cell-type specificity. AS was found to markedly increase polyclonal IgM antibody production and the proliferation of B cells. and to activate iNOS transcription and NO production in macrophages. (omitted)

The purpose of the present study was to determine the effects of platycodin D and D3 on the contractile force of the isolated rat aorta and blood pressure of the anesthetized rat. and also to establish the mechanism of action. The phenylephrine (10 $\mu$M)-induced contractile responses were greatly inhibited in the presence of platycodin D (4 ∼ 24 $\mu$g/$m\ell$) in a dose-dependent fashion. (omitted)

Green tea contains several antioxidants including polyphenols of the catechin. which have been shown to act in vitro and in vivo as anti-inflammatory. anti-viral and anti-tumor drugs. Prostaglandins (PGs) are a family of intercellular and intracellular messengers derived from arachidonic acid(AA) by phospholipase(PL) and cyclooxygenase(COX). These mediators exert a wide range of effects on processes such as smooth muscle tone. vascular permeability, cellular proliferation. and inflammatory/immune function. (omitted)

SPH-2 is a herbal medicine composing oriental prescription. We have studied the antidiabetic effect and mechanism of SPH-2 in insulin-resistant diabetic db/db mice. Mice were grouped and treated for 3 weeks as follows: control group was administrated with tap water orally: treated group was administrated with SPH-2 orally at dose of 500 mg/kg. SPH-2 lowered plasma glucose level by 43% as compared to the diabetic control. Total cholesterol. triglyceride and free fatty acid were all reduced in SPH-2 treated group. (omitted)

The leaves of Clerodendron trichotomum Thunberg(CTL) is used in Chinese folk medicine for anti-inflammatory properties. We studied on the anti-inflammatory effects of CTL extracts in rat. mouse and Raw 264.7cell. 1 mg/kg of 30%. 60% methanol fraction of CTL and 1 mg/kg of indomethacin as the standard anti-inflammatory drug were administrated into rats, respectively. Carrageenan was injected subcutaneously to induce hind paw edema in rats. (omitted)

Hypoglycemic effect of GRA was examined in multiple low dose(MLD) streptozotocin(STZ)-induced diabetic rats with regard to time of administration. Experimental methods: 20 mg/kg of STZ in 100 mM citrate buffer(pH 4.5) was injected intraperitoneally for 5 consecutive days. In co-treatment groups, GRA was administered intraperitoneally for 3 weeks at dose of 150 or 300 kg/kg. (omitted)

The herbal combination allergina has been used for the treatment of inflammatory diseases in South Korea. In this study. we investigated the immunosuppressive activities of allergina in more detail. Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation. (omitted)

Uncoupling proteins (UCPs) are transmembrane proton transporters present in the mitochondria. In UCPs. UCP1 and UCP3 play an important role in adaptive thermogenesis by uncoupling mitochondrial oxidation of substrates from ATP synthesis. PPARg coactivator 1(PGC-1) regulates transcriptional activity of PPARg and other nuclear receptors and controls the expression of UCPs. (omitted)

The fruits of various Actinidia species are known to be used as a folk remedy for treatment of various inflammatory and analgesic ailments. Effects of the ethanol extracts and fractions from the fruits of Actinidia polygama (Sieb. et Zucc.) Maxim (Actinidiaceae) were studied using various in vivo and in vtro models of inflammation in mice and rats. (omitted)

We have investigated the effect of MeOH extract of cultured ginseng roots on hyperlipidemic rats induced by fat-rich diet. We also analyzed and compared ginsenosides of cultured ginsengs by HPLC. After oral administration of the extract to hyperlipidemic rats for four weeks, the variables including body weight, cholesterol, HDL, LDL, and triglyceride levels in serum were measured. One of the cultured ginseng roots (CBN3) decreased cholesterol and LDL -cholesterol and increased HDL-cholesterol levels in serum.. (omitted)

SPH-l is a herbal medicine composing oriental prescription. We have studied the antidiabetic effect and mechanism of SPH-l in insulin-resistant diabetic db/db mice. Mice were grouped and treated for 3 weeks as follows: control group was administrated with tap water orally: treated group was administrated with SPH-l orally at dose of 500 mg/kg. SPH-l lowered plasma glucose level by 67% as compared to the diabetic control (omitted)

We studied to compare hypoglycemic effect of GRA and MF in multiple low dose streptozotocin(STZ)-induced diabetic rats. 25 mg/kg of STZ in 100 mM citrate buffer(pH 4.5) was injected intraperitoneally for 5 consecutive days. SD rats were randomly divided into diabetic control and treatment groups. Treatment groups were administered with either 500mg/kg of GRA. 500mg/kg of MF. 250mg/kg of GRA＋250mg/kg of MF(GM 250)or 500mg/kg of GRA＋500mg/kg of MF(GM 500) for 3 weeks. (omitted)

Acanthopanax senticosus has been used clinically as tonic. anti-rheumatic and prophylactic purpose for chronic bronchitis. hypertension. ischemic heart disease. and gastric ulcer. We investigated the effects of methanol extracts from Acanthopanax senticosus (KS. KR. MS, MR, HS. HR, SS and SR) on catecholamine and cortisol content of serum after immobilization and on the exercise time to exhaustion in chronic swimming stressed rats. (omitted)

In the previous study. we isolated kalopanaxsaponin A and pictoside A from the EtOAc fraction of Kalopanax pictus extract. In the present study, the BuOH fraction of K pictus extract was hydrolyzed by alkali and antirheumatic effect of the fraction was evaluated. It was found that the hydrolysate of the BuOH fraction showed inhibition of adjuvant-induced arthritis in rats. Of the EtOAc and BuOH fractions of the hydrolysate, only the former exhibited anti-arthritic activity. (omitted)

It is well known that flavonoids are the inhibitory effects on inflammations. This study was designed to determine the anti-inflammatory effects of luteolin-7-O-${\beta}$D-glucuronopyranoside (LGC). newly synthesized flavonoids. which was extracted from Salix gilgiana leaves. We investigated the protective action of LGC on reflux esophagitis and gastritis in rats. Esophagitis and gastritis were induced by surgical procedures and the exposure to indomethacin (50 mg/kg), respectively. LGC was injected intraduodenally immediately after the surgical procedures and the exposure to indomethacin (omitted)

Phellinus linteus has been traditionally used as a folk medicine for centuries in Oriental countries. and attracts a great interest owing to its plausible anti-tumor effect. The 70% ethanolic extract of its fruiting bodies was shown to contain strong anti-angiogenic and antioxidant activities in the previous work. (omitted)

Gardenia jasminoides Ellis has been used in traditional medicine for the treatment of inflammation. jaundice, headache, fever and hypertension. The 70% ethanolic extract of gardenia fruit was previously shown to possess strong anti-angiogenic activity in the CAM assay. In this work, hexane, ethyl acetate. n-butanol and aqueous fractions were prepared in succession from the 70% ethanolic extract. (omitted)

"Chung Wi Dan" is a Chinese patent medicine, which is used for various purposes in Korea. According to traditional publications, they are mixtures of several powders made of herb medicines. Chung Wi Dan of 19 kinds of powder is used for catarrh of the gastrointestines, indigestion, a pain in the chest. nausea. For the identification of individual ingredients in such powdery mixtures, microscopic method may advantageously be used as it requires only a small amount of specimens. (omitted)

The potential allergenicity of the transgene products in genetically modified organisms (GMOs). has been an important issue. As a part of the risk assessment of GMOs. we investigated the physicochemical stability and the immunogenicity of food allergens to determine their allergenicity. We have systematically evaluated the stability of food allergens in the gastrointestinal tract by using simple models of gastric (Stimulated gastric fluid) and intestinal (Stimulated intestinal fluid) digestion. (omitted)

MPP$\^$＋/ is known to be a neurotoxic substance that induces the degeneration of dopaminergic neurons and a Parkinsonism-like syndrome. MPP$\^$＋/ is retained intracellularly or accumulated in dopaminergic neurons via the dopamine-reuptake system. It inhibits mitochondrial electron transport in dopaminergic neurons. In addition. it generates hydroxyl radicals. which cause the peroxidation of membrane lipid or damage DNA. (omitted)

Aggregation of the high affinity 1gE receptor on mast cells results in many biochemical. events leading to the release of histamine. serotonin. prostaglandins arachidonic acid metabolites, and cytokines. Previously we have shown that M2 pyruvate kinase interacts with the gamma chain of 1gE receptor on the ITAM (immunoreceptor tyrosine-based activation motif) region. (omitted)

The G protein ${\gamma}$12 subunit (G${\gamma}$12) is widely-expressed and. given the extensive role of the ${\beta}$${\gamma}$ subunit (G${\beta}$${\gamma}$) in cell signaling. is a uniquely known substrate for protein kinase C. indicating phosphorylation as a potential regulatory mechanism. The mRNAs for numerous subtypes of putative G${\gamma}$s have been identified in mammalian tissues. but little is known about their expression in brain. so that the systemic survey of the localization of mRNAs encoding twelve of G${\gamma}$s in brain is needed to be performed. (omitted)

The recombinant histamine-releasing factor (rHRF) has been reported to induce a secretion of histamine and cytokines from inflammation-related cell types such as basophils and eosinophils. and to function as a growth factor in immune B cells. Recently. decreased expression level of HRF protein was observed in brain of patients with Alzheimer disease and Downs syndrome. suggesting a possible significant role in neurological systems. (omitted)

MPP$\^$＋/ is known to be a neurotoxic substance that induces the degeneration of dopaminergic neurons and Parkinson-like syndrome. Incubation with MPP$\^$＋/ induced the expression of heme oxygenase-l (HO-1) in PC-12 cells and HO-1 revealed a protective effect against MPP$\^$＋/ -induced cytotoxicity. In this study. we tested the effect of pre-conditioning on the MPP$\^$＋/-induced cytotoxicity. The PC-12 cells were incubated with MPP$\^$＋/ for 3 hrs. and then after 12 hrs the cells were exposed to several concentration of MPP$\^$＋/. (omitted)

Atherosclerosis is a main cause of cardiovascular diseases (that is angina. hypertension. cardiac infarction) and stroke. High level of low-density lipoproteins (LDL) in blood has been implicated as an important factor of atherosclerosis progression. Recently researches in endothelial cells unveiled the roles of Iysophosphatidylcholine (LPC). a constituent of oxidized LDL in atherosclerosis. (omitted)

The signaling pathway of D2 dopamine receptor was studied using yeaslt two-hybrid system.. The 3rd cytoplasmic loop of rat D2 dopamine receptor was used to screen the cDNA library of mouse brain. and ALY was found to interact with it. The interaction in the yeast was observed only with the 3rd cytoplasmic loop of D2 dopamine receptor but not with that of D3 or D4 dopamine receptor. The interaction between two proteins was also confirmed by GST pull-down assay. (omitted)

Dopamine D2 and D3 receptors (D2R and D3R) belong to pharmacological D2R family and share similar structural and functional characteristics. Elucidation of their differential functional characteristics is important for understanding their roles in brain. ERK1/2 was chosen as an example of signaling component of D2R and D3R and systemic studies were conducted to understand the regulatory mechanisms on ERK1/2 activation. (omitted)

Sphingolipids have been emerged as bioactive lipid modulators that mediate a variety of cell functions. However. the effects of sphingolipids on the cell growth and survival of melanocytes are not yet known. In the present study, we investigated the actions of sphingolipids in Mel-Ab melanocytes. We observed the cytoprotective effect of sphingosine-1-phosphate (SPP) on UVB-induced cell death. (omitted)

To analyze vasopressin-induced Ca$\sub$2＋/ influx in liver cells, rat hepatocytes were isolated and attached to collagen-coated cover slips. Using fura-2, a Ca$\sub$2＋/-sensing dye, changes in intracellular Ca$\sub$2＋/ concentration by vasopressin were monitored. Results in this communication suggested that vasopressin-induced Ca$\sub$2＋/ influx consists of two distinguishable components. One was present for a short time and the other was for a long time until it happened. (omitted)

This study shows that sphingosine-1-phosphate (SPP) significantly inhibits melanin synthesis in a concentration-dependent manner, and that the activity of tyrosinase was also reduced in SPP-treated cells. In contrast. a specific extracellular signal-regulated protein kinase (ERK) pathway inhibitor, PD98059 increased tyrosinase activity and melanin production, and PD98059 restored the reduced tyrosinase activity and pigmentation induced by SPP. (omitted)

We have carried out collaborative study to evaluate a preparation of antithrombin concentrate whether or not it was suitable to serve as the candidate for a Korea National Biological Standard. Six laboratories. including three manufacturers and three National Control Laboratories. participated in this study. The potency of this candidate preparation was determined using the heparin cofactor chromogenic method. (omitted)

The safety of blood and blood products is ensured by careful selection of donors. screening of donated blood and the use of validated viral inactivation and/or removal steps during the manufacture of blood products. Serologic screening procedures have substantially reduces the risk of transmission of blood-bone viruses. However, there are still residual risks despite these measures due to the inclusion of 'window period'donations. (omitted)

Temperature change is one of the major environmental factors to influence human skin. However. the relationship between temperature and melanogenesis has received little attention. In the present study. we investigated the effects of temperature change including heat shock on melanogenesis using a mouse melanocyte cell line, Mel-Ab. Our results demonstrated that cells maintained at 37$^{\circ}C$ showed maximal melanin synthesis. (omitted)

Human epidermal keratinocytes consist of stem cells. transit amplifying cells. and postmitotic differentiating cells. Among them, stem cells playa critical role in cell renewal. wound healing. and neoplasia. However. till now, specific markers of human epidermal keratinocytes are not clearly defined. In the present study. we separated putative stem cells from other cells using fluorescence activated cell sorting (FACS). based on differences in a6-integrin and CD71 expression. (omitted)

There have been some reports showing that cardiovascular response is affected by exposure to extremely low frequency magnetic field (ELF-MF). In this experiment. we intended to observe if ELF-MF affects the basal level of cardiovascular response and effect of drugs acting on sympathetic nervous system. Rats exposed to MF (60 Hz. 20 G) for 1 or 5 days and sham were anesthetized with pentobarbital-Na. Carotid artery and jugular vein were intubated to measure blood pressure (BP) and inject drug respectively. (omitted)

Some experiments have been reported that magnetic fields can cause the change of numerous neurotransmitters including excitatory and inhibitory transmitters, which are involved in seizures. In this study we aimed to examine the effect of extremely low frequency magnetic field (ELF-MF) on the sensitivity of seizure response to bicuculline, picrotoxin and NMDA in mice. Mouse were exposed to sham or 20 G ELF-MF for 24 hours and then convulsants were administered i.p. at various doses. (omitted)

It has been proposed that G protein interacts with receptor via multiple interaction sites. With regard to this, C-terminus of the G${\alpha}$ subunit is clearly not the only structural determinant on the G proteins that is critical for receptor coupling selectivity, but the extreme N-terminus of Ga subunit and other structural elements were proposed to be responsible for dictating the interaction with receptors. (omitted)

There have been many changes in hospital pharmacy after division of medical practice and dispensing. Many pharmacist leave hospital pharmacy to drugstore. Because reduced number of pharmacist, many of hospital pharmacies are placed in difficulty. Restructuring of hospital pharmacy made us consider substitution hospital admixtured TPN(total parenteral nutrition) with industrial manufactured TPN. But we have no data established to support that, so we have sarried out the comparison of two kinds of TPn formulary. We have divided into groups receiving hospital admixtured TPN and industrial manufactured TPN patients in august. 2002. We have compared with each groups in nutritional related dose, parameters and complication before and after TPN administration and also invertigated the reason of formulary change in each groups. We expect that this study will be good data for selection TPN formulary and substitution hospital admixtured TPN with industrial manufactured TPN.

It is well known that cisplatin. one of chemotherapeutic agents. induces DNA damage and kill cancer cells mainly by apoptosis. We recently synthesized a novel Pt(IV)-based anticancer agent. trans.cis-Pt(acetato)2C12(1.4-butanediamine) (K101) with octahedral structure. To evaluate antitumor activity about human cancer of K101, we have performed histoculture drug response assay in 35 cases of colorectal cancer patients. (omitted)

Glycosaminoglycans(PT -Gag) were isolated from the porcine testis. From the PT -Gag. we obtained two different types of Gag fractions using Dowex macroporous Resin MSA-1 column. PT-Gag-1.5% NaCl and PT -Gag-16% NaCl. Various biological activities of the GAGs were examined in aspect of anticoagulant and immunomodulating activity. The anticoagulant activity of the GAGs was evaluated by activated partial thromboplastin time (aPTT ) assay and thrombin time (TT) assay. The GAGs of porcine testis markedly increased the clotting times of both of aPTT and TT. showing that PT-Gag-16% NaCl was more effective than PT-Gag-1.5% NaCl. The immunomodulating activity of the GAGs was examined in relation to regulation of cytokine production of mutine peritoneal macrophages. Treatment with the GAGs promonently enhanced the prodution of cytokines. IFN-${\gamma}$, from macrophages. Taken together. GAGs isolated from porcine testis possess biological functions such as anticoagulant and immunomodulating activity.

The antimetastatic effect of BCG-CWS. which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells. Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells. was investigated in syngeneic mice. (omitted)

The purpose of this study was to develop PEl-based gene carriers with optimal serum stability and reduced cytotoxicity. PEl is an efficient gene transfer agent with the ability of DNA condensation and endosome escape: however; use of the polymer in vivo is hampered by signigicant reduction in transfection activity by the presence of serum. Chitosan is a non-toxic. biodegradable and biocompatible polymer with hydrophilic functional groups so it may provide a physical stability against challenge by serum proteins. (omitted)

Synthetic vectors have been considered as a safer and more versatile alternative to viral-based gene delivery systems. A variety of simple synthetic vector systems such as cationic lipid- and polymer-complexed plasmid DNA were shown to have a significant transfection activity in vitro but their use in vivo has been hampered by the decrease in transfection efficiency mediated by non-specific electrostatic interactions with serum components. (omitted)

In the previous study, we reported that NQ12, a vitamin K antagonist. showed a potent antithrombotic and antiplatelet activities. In order to elucidate the antiplatelet activity of NQ12. we investigated the effect of NQ12 on arachidonic acid cascade parameters such as cPLA2. cyclooxygenase (COX), and the downstream production such as TxA2, PGD2 and 12-HETE. N012 inhibited COX activity in a concentration-dependent manner in U937 cells. (omitted)

Tetrandrine is a bis-benzyl isoquinoline alkaloid derived from the root of Stephania tetrandra S. Moore. which was reported to elicit in vitro cytotoxic effect on HeLa cells and in vivo supprresive effects on mouse ascite tumor. Tetrandrine also induced apoptosis in a various cell lines. Recent studies have revealed that mitochondria has been shown to play an important role in the regulation of apoptotic processes. (omitted)

Accumulation of ceramide mass in MCF-7 cells by the anti-cancer agent. paclitaxel. was found to occur primarily due to activation of the de novo synthesis pathway. Morever. the addition of paclitaxel resulted in the accumulation of ceramide, which was followed by a prolonged arachidonic acid release. Participation of ceramide de novo pathway in arachidonate signaling was detected since L-cycloserine, an inhibitor of de novo synthesis, was able to inhibit the paclitaxel-induced AA release and cytotoxicity. (omitted)

Ascorbic acid is very well known as one of various ntioxidants and is used very popular in man. Melatonin. an endogenous compound secreted by the pineal gland in human brain has been reported to act as an antioxidant nowadays. The present study was performed to obtain the differences of the radioprotective function of ascorbic acid and combination with melatonin according to the administration dose a day on radiation induced DNA damage in mouse spleen and blood. (omitted)

Mancozeb. a polymeric complex of zinc and manganese salts of ethylean bisdithiocarbamate(EBDC). is used widely in agriculture as fungicides. and herbicides. Macozeb has been reported to induce teratogenic and carcinogenic effect. But the immunomodulating effects of Mancozeb exposure have not been systemically evaluated. The purpose of this study was to investigate the effects of Mancozeb on immunoglobulin production. (omitted)

This presentation reports the trends of the drug abuses(DA) and the mortalities related to drug-toxicants(MDT) in the Central area of Korea in 2001. We surveyed the DA cases and MDT. which were requested to analyze the drug-toxicants in the Central district office of National Institute of Scientific Investigation. he detected drugs on DA cases were methamphetamine. marihuana. opiates. inhalants(toluene. butane. ropane). dextromethorphane. carisoprodol. benzodiazepines, nalbuphine. fenfluamine. and iscellaneous in order of cases. Men are more liable to drug abuses than women. and the most common age group was 30s. Surveys of MDT shows that the defected toxicants are paraquat(sedative). methomy(insecticide). dicholrvos (insecticide). benxodiaxeqines(anxiolytic), and miscellaneous in order do cases. Men's intoxications by the drug-toxicants are more occured than woman's And most common intoxicated age group was 40s. These trends of the DA cases and the MDT in Central Area fo Korea. can help the forensic toxicologists and government to plan the prevention policy of the DA cases and MDT as well as its future estimation.

Psoralen(7H-Furo［3.2-g］ ［1］benzopyran-7-one) and angelicin(2-Oxo-[2H]- furo[2.3-h]-1-benzopyran) are angular furocoumarin with diverse photobiological effects. They are major components of Psoralea corylifolia L.(破古紙). Psoralea corylifolia L. is used for a tonic and nursing one's energy. It can be also used for loss of virility. vitiligo. a skin disease, etc.. But a well known and often appreciated side effects f psoralens is the hyperpigmentation caused by this treatment. A women who used the herbal drug-mixed-medicine named'sobaeksu' to treat her vitiligo made a complaint against the orinetal medical doctor. She complained that her skin got burned to 2nd degree by the liquid. 'sobaeksu' through a medical celtficate. So we analyzed the components of that liquid with gas chromatography and gas chromatography/mass spectometry. It has 57.3% ethyl alcohol and two kinds of psoralens. Psoralens were psoralen and angelicin and each one of their contained quantity was 0.128mg/ml and 0.123mg/ml.

Chan Su the dried toad venom. has been used in Asian countries as the traditional medicine for the purpose of the alleviation of pain, cardiotonic diuresis. hemostasis and et al.. However, Chan Su is the special attention-needed medication because it is known to contain the highly toxic compounds such as bufotenine, an hallucinogen and aphrodisiac, and a series of bufadienolides, cardiotonic steroids that produce physiological symptoms similar to digoxin. (omitted)

Hwang-Chil. a natural resources of Korea. doesn't have a side effects and has excellent bone cell proliferation. We will be able to use Hwang-Chil to cure and develop various disease that require tissue regeneration. such as osteoporosis and bone fracture and be used in the orthopedic area. In this study. we observed the effect of Hwang-Chil extract and concentration on osteoblast proliferation. alkaline phosphatase(ALP) activity and calcification. (omitted)

Paeoniae radix is commonly used for various woman's health problems in traditional korean medicine. In order to develop new antioxidant for woman use. the ethanolic extracts of paeoniae radix (PRE) were prepared and various biological activities were evaluated. PRE showed potent free radical scavenging activity and moderate antioxidative activity in vitro. and also showed the protective effect on H2O2-induced DNA damage in mammalian cell. (omitted)

In situ and circulating estrogen is the most important endocrine hormone that promotes the growth of hormone-dependent breast cancer. Consequently. decrease of estrogen on in situ and circulation can inhibit breast cancer. Estrogen is mainly produced by the ovary in premenopausal women and by peripheral tissues such as adipose tissues in postmenopausal women. The cytochrome p450 (CYP19), aromatase. is a key enzyme in the synthesis of estrogen hormones. (omitted)

The adverse health effects on humans and domestic and wildlife species by exposing to environmental contaminants. which interact with the endocrine system. have he en treated as an important issue without hesitation throughout the 1990s. The chemicals with practical and/or potential interfering actions with the endocrine system functions are called endocrine disrupting chemicals (EDCs). (omitted)

Organochlorine pesticides and polychlorinated biphenyls (PCBs) have been used intensively in agriculture and industry for a long time. They belong to a group of contaminants whose occurrence in the environment is a serious concern to environmental chemists and toxicologists due to their resistance to degradation in the environment as well as their potential toxicity. Also. the lipophilic characteristics of these substances are responsible for their ability to bioaccumulate in tissues and organs rich in lipids of men and animals through food chain. Therefore, the measure of the levels of organochlorine pesticides and PCBs in human tissues are good markers in detemining the extent to exposure and evaluating the hazards. This study was preformed to compare concentrations of organochlorine pesticides(${\alpha}-BHC, {\beta}-BHC, {\gamma}-BHC, {\delta}-BHC$, p.p'-DDT,p.p'-DDD,p.p.'-DDE. endrin. dieldrin. aldrin) and seven marker PCBs(PCB nos. 28. 52. 101. 118. 138. 153. 180) in liver. kidney cortex, lung blood and adipose tissue collected at autopsies of 10men and 10 women using gas chromatography equipped with electron capture detector to express the data on a lipid adjusted basis. From the results, the significant differences in the levels of organochlorines of PCBs between sexes, districts where they had lived and ages were also investigated.

In previous studies, we demonstrated that ambient PM collected from urban site of Korea air could induce DNA damage, Various mutagens and carcinogens present in the urban air differ according to the source of the pollutants. Polycyclic aromatic hydrocarbons (PAHs) and their nitrated compound are produced in the combustion of fossil fuels as diesel emission exhausts. In recent, PAH and nitro-PAH have been identified in urban air particulate matter (PM). and some of them were found to be tumorigenic in experimental animals and humans. (omitted)

Gastric contents and blood samples are generally analyzed for the detection of the Drug-toxic substances(DTS) in the postmortem specimens, but tissue specimens from postmortem for the detection of the DTS are, especially, required in the cases that analysis of DTS in blood or gastric contents is impossible because of insufficient or inaccessible specimens in special cases. (omitted)

Paraquat(methyl viologen) is a bis-quaternary ammonium compound as a wide range herbicide. which was first introduced as an oxidation-reduction indicator dye. When paraquat(fatal dose. 1-2g) was administered to men, the oxido-reduction system of cell was repeatedly acted to perpetuate the cell membrane system, Many death cases had been occurred after ingestion of paraquat around Daejon area for the last six months. (omitted)

Recent industrial society has human widely exposed to PAHs that are comming from the incomplete combustion of organic material as widespread environmental contaminants. Biological activities of PAHs are not known although PAHs are considered as carcinogens. PAHs in the mammalian cells affect CYP 1A1 gene expression as well as other phase II drug metabolizing enzymes as UDPGT, NMOR etc. The mechanism of action of PAHs has been studied extensively, however it is not clear how PAHs turn on CYPIAI in human breast cancer. (omitted)

Oxidative stress and its consequent lipid peroxidation exert harmful effects, which have been currently involved in the generation of carbon tetrachloride(CC14)-induced fibrosis(cirrhosis). In this study, it was investigated whether dried extract of 田螺(Concha Cipangopaludinae: CC) is liver functional improvement, antioxidative and antifibrotic effect under the liver fibrotic(cirrhotic) condition by CC14 administration. The female Sprague-Dawley rats were divided into 3 groups(Normal, AC, AC-CC), and were observed for 3 weeks. (omitted)

To study the expressions of glutamate transporter subtypes in cerebellar astrocytes following the chronic exposure of nicotine from mating, rats were treated with nicotine (25 ppm) from the beginning of mating through drinking water. After delivery. each group was divided into two groups. Groups were exposed to either distilled water or nicotine. From 7 day-old pups at each group. cerebellar astrocytes were prepared. Ten days after culture. the expressions of glutamate transporter subtypes (GLAST and GLT-1) were determined using immunochemistry and immunoblot. (omitted)

The safety pharmacological core battery studies of AS2-006A. a newly developed wound healing drug, were investigated according to the ICH S7A guidelines in compliance with Good Laboratory Practice(GLP) Regulations, The doses given were 0, 100. 300 and 1000 mg/kg and drugs were administered subcutaneously. The animals used for this study were mice, rats and guinea pigs. AS2-006A showed no effects on the central nervous system such as motor activity. behaviotal changes. coordination, sensory/motor reflex responses and body temperature. no effects on blood pressure(BP). heart rate(HR), and ECG profiles and respiratory system. it was concluded that AS2-006A possess no general pharmacological effects at all doses tested. (omitted)

Previously. we reported a novel polymeric micellar solubilizeI'. Aceporol 330. that showed relatively low toxic effects when it was compared with that of Cremophor EL which is currently being used for paclitaxel. In this study. we have developed a new micellar solubilizeI, Aceporol 460. that has 3-4 times higher loding capacity for paclitaxel than Aceporol 330. The single-dose and the repeated-dose toxicity of Aceporol 460 were evaluated in ICR mice. (omitted)

Herbal medicines are increasingly being utilized to treat a wide variety of disease processes. The aim of this study was to evaluate the ability of aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae). Changkil (CK). to affect cellular response in primary cultures of rat hepatocytes to t-butyl hydroperoxide (t-BHP) induced oxidative stress and hepatotoxicity. CK-treated cells showed an increased resistance to oxidative challenge. as revealed by a higher percent of survival capacity in respect to control cells. CK added prior or simultaneously with I-BHP reduced enganced lipid peroxidation measured as production of malondialdehyde and enhnaced intracellular reduced glutathinoe depletion by t-BHP. Furhtermore. CK protected from the t-BHP-induced intracellular generation of reactive oxygen species assessde by montioting dichlorodihydrofluorescein fluorescence. it can be concluded that CK exerts an antioxidant action insice the cell. responsible for the abserved modulation of the cellular response to oxidative challenge. and CK have a marked anitioxdative and hepatoprotective potency.

Herbal medicines are increasingly being utilized to treat a wide variety of disease processes. We previously reported that aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK). had hepatoprotective effects against acetaminophen induced liver injury. In the present study, we assayed the preventive and therapeutic effects of CK on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. (omitted)

Increasing evidence regarding free radical generating agents and inflammatory processes suggests that accumulation of reactive oxygen species can cause hepatotoxicity. A short-chain analog of lipid hydroperoxide, t-butyl hydroperoxide (t-BHP), can be metabolized to free radical intermediates by cytochrome P-450 in hepatocytes. which in turn can initiate lipid peroxidation, affect cell integrity and result in cell injury. (omitted)

Quercetin, one of the most abundant flavonoids in human diet has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of quercetin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant decrease in body and liver weight. Oral administration of quercetin (10 mg/kg daily for 4 weeks) remarkably prevented this DMN-induced loss in body and liver weight and inhibited the elevation of serum alanine transaminase. aspartate transaminase, and bilirubin levels. (omitted)

Choi group reported that Kamijadowhan (KMD). an oriental herbal medicine, has anti-angiogenic effects and it may be a potential agent for clinical chemoprevention since it inhibits angiogenesis. Objectives of this experiment are to investigate acute, genetic and reproductive/developmental toxicities of KMD preparations. Acute toxicity was performed after single administration of KMO (200-500 mg/kg) to mice. Supravital staining micronucleus assay was conducted using peripheral reticulocytes in mice. (omitted)

The surgically ovariectomized rat induces aging by reactive oxyyen species(ROS) generation. Free oxygen radicals have been proposed as important causative agents of aging. The purpose of this study was to investigate the effect of Chondroitin Sulfate(CS) to prevent ovariectomy(OVX) induced oxidative stress and atherosclerosis. The OVX rats were given intraperitoneally CS at dose of 100mg/kg and 200mg/kg daily for fifteen weeks. (omitted)

The protective effects of a Platycodi Radix (Changkil: CK), the root of Platycodon grandiflorum A. DC (Campanulaceae). on carbon tetrachloride-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with CK prior to the administration of carbon tetrachloride significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. (omitted)

A cytosolic. neutral and magnesium-independent Sphingomyelinase (N-cSMase) is known to playa role in vitamin D3-induced differentiation and neurodegeneration such as Alzheimer's disease and stroke through the production of ceramide. a lipid-derived tumor suppressive mediator. However. little is known about its identity and characteristics. (omitted)

For the safety evaluation of adenovirus-mediated gene therapy. we have investigated gene and protein expression after transduction of adenoviral vector (Ad5CMV-p16) which contains tumor suppressor gene. p161NK4$\alpha$ in human non-small cell lung cancer (A549) cells. We compared the differential gene expression level in the A549 cells treated with Ad5CMV (null type) and Ad5CMV-p16 virus. respectively. by using cDNA membrane chip and oligonucleotide chip. (omitted)

Cancer is multifaceted disease that presents many challenges to clinicians and cancer researchers searching for more effective ways to combat its often devastating effects. Among the central challenges of this disease, are the identification of markers for improved diagnosis and classification of tumors, and the definition of targets for more effective therapeutic measures. The objective of this study is to identify potential biomarkers for the early detection of gastric cancer in serum. (omitted)

In order to understand the mechanism of action of TCDD. we have examined the effect of COX-inhibitors on cypla1 activity. We observed the effect of COX-inhibitor on EROD activity in C57BL/6 mouse in vovo. And we also evaluated the effect of COX-inhibitors on cypla1 mRNA. mouse cyplal promoter activity and EROD activity in Hepa cell. When Aspirin were pretreated with 3MC in vivo, the EROD activity that was stimulated by 3MC was inhibited. (omitted)

Pyrethroids are one of the most commonly used insecticides in worldwide. but it remains unclear whether pyrethroid compounds possess endocrine disrupting activity or not. T47D cells, an estrogen receptor positive human breast cancer cell line. is known to induce alkaline phosphatase (AlkP) only in response to progestins. Because the action of estrogen may be changed by the action of progestins (Kraus et al. 1995), it is important to examine the potential to produce progestin-mediated effects for determining endocrine disrupting activity of chemicals(LiLorenzo et al. 1991). (omitted)

Pyrethroids are extensively used as insecticide in agriculture and home. Several studies have reported that yrethroids are relatively safe to humans and wildlife. However. some studies have suggested that pyrethroids ossess estrogen-like activity. Thus. the purpose of this study was to investigate the effects of pyrethroid ompounds on cell proliferation. and expression of ERs and pS2 using estrogen receptor positive human breast ancer cell line (MCF-7 BUS celis). (omitted)

Bisphenol A ［BPA. 2.2-bis(4-hydroxyphenyl)propane］ is reported to have estrogenic activity: however. its influence on cytokine production or immune system function remains unclear. In this study. we investigated the effects of BPA on the production of nitric oxide (NO) and tumor necrosis factor-a (TNF-a), and on the level of inducible nitric oxide synthase (iNOS) and TNF-a gene expression in mouse macrophages. BPA alone did not affect NO or TNF-a production. (omitted)

In the brain, glial cells serve in the role to sequester metal from the neural microenvironment and therefore play an important role as a cellular deposition site. The central nervous system is highly vulnerable to oxidative stress, and free iron can stimulate oxidative stress by the Fenton reaction. Aluminum may upregulates the transferrin-independent iron uptake system and stimulate oxidative stress. Nramp2. also known as DMT 1. is a 12-transmembrane(TM) domain protein responsible for dietary iron uptake as well as metal ions such as iron. lead, mangamese. zinc. copper, and cobait. (omitted)

The effects of estradiol and its metabolites on the regulation of CYP1A1 expression. K.E. Joung and Y.Y. Sheen College of Pharmacy, Ewha womans University, Seoul. 120-750, Korea 2, 3.7.8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity. immune suppression. and reproductive and developmental toxicity. (omitted)

Methylmercury (MeHg: CH3HgCl) is a ubiquitous environmental toxicant that readily bioaccumulates in aquatic foodchains. This toxicant is most highly exposed to humans through the ingestion of contaminated food. and thus is an ongoing health concern. Thus far. MeHg has been suggested to exert its toxicity through its high reactivity to thiols of bioactive proteins. elevation in intracellular Ca2＋ concentration. and generation of reactive oxygen species. but its mechanism remains poorly understood. (omitted)

Metallothioneins (MTs) are a go up of heavy metal-binding proteins characterized by cystein-rich low molecular weight(6000 - 10.000 Da). They plays a major role in the detoxification of heavy metals and also in scavenging of superoxide radicals. They are known to be induced by heavy metals in various organs of different species and represent a potential biomarker of aquatic heavy metal contamination. (omitted)

An organophosphate pesticide terbufos (S-t-butylthiomethyl-O.O-diethyl phosphorodithioate; TBF) has been extensively used as an insecticide. A sexual dimorphism in TBF toxicity was not reported and remains unclear. Objective of the work is to investigate the influence of TBF on sexual dimorphism in rats by using acethlcholinesterase (AchE). (omitted)

Bisphenol A(BPA). a monomer used in the manufacturing epoxy resins and polycarbonates. has been reported to induce estrogenic activity, it has been considered as an environmental endocrine disruptor. But the immunomodulatory effects of BPA exposure have not been systemically evaluated. We investigated whether BPA effects on the ability of immunoglobulin(lg) production of mice. To initiate investigation of BPA-induced alterations of the immune system. BPA at dose of 100. 500,1000 mg/kg b.w./day with or without OVA-antigen for 30 days were orally administered to female ICR mice. Mice were sacrificed and serum was colleted on day 2 following administration of BPA for 30days. Total lgG1. total lgG2a. total lgE. OVA-specific lgG1. OVA-specific lgG2a. and OVA-specific lgE in serum were detetmined and compared with those of non-treated mice. In the groups of BPA with OVA antigen, total 1gG1, total lgG2a, total lgE. OVA-specific lgG1 and OVA-specific lgG2a were significantly decreased at dose of 500mg/kg/day. However, in mice treated with BPA alone, total lgG1, and lgG2 were not much altered and total lgE was significantly increased at dose of 1000mg/kg/day. These results demonstrated the BPA modulates the production of immunoglobulin.

Our previous study demonstrated that 2.3', 4.4'. 5- Pentachlorobiphenyl (PCB 118) showed an antiestrogenic activity in vitro and in vivo. In the present study. we examined the effect of PCB 118 on postnatal reproductive development in female rats. PCB 118 (0.001. 0.01 or 0.1 mg/kg/day) was administered to pregnant female SD rats from gestation day (GO) 6 to 18 via subcutaneous injection. and developmental parameters such as vaginal opening were determined. PCB 118 significantly delayed vaginal opening of female offsprings at dose of 0.1 ${\mu}g$/kg/day. whereas had no effects on body weights. In addition. in utero treatment of PCB 118 caused significant decreases in serum levels of E2, T3 and T4 in female oftsprings at certain doses on postnatal day (PND) 22. Our data of results indicate that in utero exposure to PCB 118 may postnatal reproductive development in female rat through its antiestrogenic activity.

Immunoassays are frequently used for an screening method to detect the presence of drugs in Urine. The main advantages of the method are well known -- simplicity of handling samples. rapidity. sensitivity. and specificity of analysis. However. it is also known that immunoassays exhibit cross-reactivity to related drugs and there are only limited specific immunoassays on the market. This study reports on the ability of TDx to detect urine samples obtained from suspects of taking over-the-counter medications and illegal drugs containing ATS. designer drugs. (omitted)

Previous report showed that histamine release by HCI was mediated via reactive oxygen species (ROS) generation in RBL 2H3 cells. To investigate action of protein kinase on histamine release and ROS generation. we observed effects of protein kinase inhibitors on histamine release and ROS generation in RBL 2H3 cells stimulated by HCI HCI dose-dependently increased both histamine release and ROS generation. HCI-induced histamine release was significantly inhibited by bisindolmaleimide (10 ${\mu}$M). DHC (10 ${\mu}$M). , and wortmannin (10 ${\mu}$M), but not by PD098059 (10 ${\mu}$M). ON the other hand. HCI-induced ROS generation was significantly inhibited by DHC (10 ${\mu}$M). but not by bisindolmaleimide(10 ${\mu}$M). wortmannin (10 ${\mu}$M). and PD098059 (10 ${\mu}$M). However KN-62 did not inhibited both. These results showed that involvement of protein kinase in regulation of histamine release and ROS generation may be different and only tyrosine kinase may be associated with regulation of both histamine release and ROS generation in RBL 2H3 cells.

A benzopyranyl derivative. KR32000. synthesized as a plausible KATP opener. has been shown to exert cardioprotective effect in vivo myocardial infarct model. In this study. we investigated whether KR32000 can produce cardioprotective effect against hypoxia- and reactive oxygen species(ROS)-induced injury in heart-derived H9c2 cells. Hypoxic injury was induced by incubating cells in anaerobic chamber (glucose-free. serum-free DMEM. 85% N2. 5% CO2. 10% H2) and oxidative stress was induced by buthionine sulfoximine(BSO). (omitted)

Tyrosinase (monophenol. 3.4-${\beta}$-dihydroxyphenylalanin oxygen oxidoreductase. EC 1.14.18.1 J. which plays a pivotal role in melanogenesis. It is single chain glycoprotein catalyzing the hydroxylation of tyrosine to ${\beta$\mid$$-3.4-dihydroxyphenylalanin (DOPA) and the oxidation of DOPA to DOPA quinone. To investigate whitening effect of chitosan oligosaccharide. we obtained chitosan oligosaccharide ［(glucosamine)2-6］ by NaNO2 oxidation and measured the effect of chitosan oligosaccharide on tyrosinase activity. Chitosan oligosaccharide dose-dependently inhibited tyrosinase (2 unit) activity and inhibited by 18.8% at dose of 100${\mu}$g/ml. Vitamin C. arbutin and kojic acid that are well known to be inhibitor of melanin production dose-dependently inhibited tyrosinase (2unit) activity. These results suggest that chitosan oligosaccharide may be used as inhibitor of melanin production in melanocyte. which will be further studied.

Bioflavonoids are semi-essential food components that are ubiquitously present in nature. It has been reported that flavonoids act as anti-oxidant as well as anti-cancer agents. Quercetin is one of the most widely distributed bioflavonoids in the plant kingdom. The goal of this study was to investigate effects of quercetin analogs extracted from Lindera erythrocarpa, quercetin 3-O-${\alpha}$-arabinofuranoside and quercetin 3-O-${\alpha}$-L -rhamnoside, on oxidatie stress-induced cell death. (omitted)

Failure of the hepatic microcirculation is a major component of reperfusion injury in the liver. However. the vasoactive mediators involved in the regulation of sinusoidal flow during reperfusion following hepatic ischemia remain to be identified. We investigate the role of Kupffer cells in hepatic ischemia/reperfusion (l/R)-induced imbalance of vasoregulatory gene expression. Rats were subjected to 60 min hepatic ischemia, followed by 5 h of reperfusion. (omitted)

For the activity-guided separation on anti-asthmatic action from 4 fractions as n-hexane (yield. 0.09%), EtOAc (0.48%), BuOH (3.0%) and H2O (5.17%) fractions from MeOH extract (11.64%) of powdered Gastrodia elata Rhizoma (GER), some biological active agents were isolated by column chromatography (column, silica gel: elution solvent. CHCl3 : MeOH) according to the method of Junko Hayashi et. al. and Heihachiro Taguchi et. al. (omitted)

Both of Semen (OF-Se) or stem (OF-Sf) of Opuntia ficus-indica Semen have been used as a healthful food or folk medicine in korea for the treatment of asthma. diabetes mellitus. aging, osteoporosis, rheumatic arthritis. constipation, cancer. gastric ulcer. constipation. toxic state, edema, etc, There are many reports that OF have the anti-gastric damage, wound healing, diabetes mellitus, monoamine oxidase B inhibitor etc. (omitted)

From 4 fractions as n-hexane (yield. 0.09%), EtOAc (0.48%). BuOH (3, 0%) and H2O (5.17%) fraction from MeOH extract (11, 64%) of powdered Gastrodia elata Rhizoma (GER) for the activity-guided separation on anti-inflammatory action. some biological active agents were isolated by column chromatography (column. silica gel: elution solvent. CHCl3 : MeOH) according to the method of Junko Hayashi et. al. and Heihachiro Taguchi et. al. Compound I, II, III, IV, V as phenolic derivatives were isolated in the EtOAc and BuOH fractions. (omitted)

HCV is transmitted via various plasma-derived medicinal products. The transmission of HCV could. however, be prevented by screening plasma pools with NAT and validating HCV viral clearance during the manufacturing of plasma derivatives, Although various screening methods including commercial kits are available. it is yet to develop an analytical method to detect HCV in both plasma and plasma derivatives. The objective of this study was to develop a reliable in house method for reliable for the HCV RNA detection from plasma and plasma derivatives. (omitted)

The aim of present study was to investigate effects of blunt trauma on alterations in cytochrome P-450 (CYP)-dependent drug metabolizing function and to determine the role of Kupffer cells in the hepatocellular dysfunction Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia. Control animals received only anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride (GdCl3) was injected intravenously via the tail vein at 7.5 mg/kg body wt. 1 and 2 days before surgery. (omitted)

The present study was done to determine the effect of trolox C. a hydrophilic analogue of vitamin E. on alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion. Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehicle (PBS. pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after ischemia and reperfusion. This increase was significantly suppressed by trolox C. (omitted)

Sepsis remains the leading cause of morbidity and mortality following trauma. Although hepatocellular dysfunction occurs during trauma and sepsis. the mechanism responsible for this remains unclear. We investigated the role of Kupffer cells in the alterations in microsomal drug metabolizing function during trauma and sepsis. Rats were subjected to trauma by femur fracture (FFx). After 72h, polymicrobial sepsis was induced by cecal ligation and puncture(CLP). (omitted)

Adenosine has been associated with protection of neurons from noxious stimuli both by receplor- and non receptor-mediated mechanisms. Previously we have reported that immunostimulated astrocytes were highly vulnerable to glucose deprivation. In the present study we investigated the effect of adenosine and related nucleotides on the susceptibility of immunostimulated astrocytes to glucose deprivation. (omitted)

Oxidative stress has been implicated in the pathophysiology of many neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Baicalein. baicalin and wogonin. the major constituents of Scutellaria baicalensis. have been reported to exhibit antioxidant properties in many different bioassay systems. The present study evaluated neuroprotective effects of these flavonoids on various neuronal injuries induced in primary cultured rat cortical cells by oxidative stress. NMDA. oxygen-glucose deprivation. and $A{\beta}$(25-35). (omitted)

Recent studies have suggested that the cerebral ischemia induced the neuronal cell death by mediating multiple mechanisms with necrosis and/or apoptosis. The present study examined neuroprotective mechanism of aloesin against transient focal cerebral ischemia. Aloesin. main component of aloe possesses various biological activates such as wound healing. anti-gastric ulcer. and chemopreventive activity. Transient focal cerebral ischemia was induced by 120 min MCAO. (omitted)

Wogonin. a flavonoid originated from the root of Scutellaria baicalensis Georgi. is known to exhibit potent anti-inflammatory effects and variable degrees of antioxidant and free radical scavenging effects depending on the experimental systems. In addition. wogonin has been reported to protect neurons from excitotoxic and oxidative injuries in primary cultured rat cortical cells. (omitted)

Brain injury resulting from cerebral ischemia remains a major public health problem. Aloesin. main component of aloe possesses various biological activities such as wound healing, anti-gastric ulcer, and chemopreventive activity. In this study we investigated whether treatment with aloes in could protect brain injury induced by permanent focal cerebral ischemia in rats. We also compared aloes in with other neuroprotective. drugs such as MK801 and ebselen. (omitted)

In central nervous system. matrix metalloproteinases (MMPs) are produced by neuron as well as glia and implicated in physiological events such as neurite outgrowth and myelination etc. In addition. MMPs also contribute to the pathogenesis of several CNS diseases such as multiple sclerosis, Alzheimer's disease and malignant glioma. In spite of their functional importance, little is known about the signal transduction pathways leading to the induction of MMPs in CNS. Here. we investigated whether the activation of Erk(1/2) is involved in the induction of MMP-9 in LPS-stimulated primary astrocytes. (omitted)

The present study investigated the passive avoidance and spatial learning in the ${\mu}$-opioid receptor gene knockout mice and wild type mice. In the step-through passive avoidance task. the ${\mu}$-opioid receptor knockout mice did not differ from the wild type mice. In Morris water maze. however. the ${\mu}$-opioid receptor knockout mice showed significant memory deficit compared to wild type mice. (omitted)

The temporal profiles of the changes of dopaminergic cell and microglial activation induced by transient cerebral ischemia was investigated in the substantia nigral region which lay outside ischemic areas of rat brain after middle cerebral artery occlusion (MCAO). Transient cerebral ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 hand reperfusion was continued for 1, 2. 3. 7. 10. 14. 30, 60. and 120 days. Activated microglial cells were visualized with immunohistochmistry using OX-43 antibody. (omitted)

In recent studies on cefodizime, it may potentially have the capability of stimulating chemotactic activity of neutrophils and monocytes as well as the strong immuno-modulator. In turn, infection can result in a drastic change of mediators. which lead to initiate an immune response in an indirect way. With this backgrounds, we have studied to see if cefodizime can be a potential substance to induce an immunological function in dendritic cells and peritoneal macrophages. (omitted)

Cefodizime has originally been developed for treating infections as antibiotics. However. according to some of recent studies. cefodizime. a third generation cephalosporin. may potentially have the capability of stimulating chemotactic activity of neutrophils and monocytes as well as the strong immuno-modulator. In this study. we studied to learn about the expressive effect of dentritic cells and macrophage. With this background. We have studied to see if cefodizime can be a potential substance inducing an immunological function in dendritic cells and peritoneal macrophages. IL-12 activates NK cell and macrophage, and shows antiviral effect by excreting INF-${\gamma}$. In vitro. total RNAs were extracted from murine dentritic cell at 4, 8, 12, 24hr after the application of 10, 50, 100${\gamma}g$/ml of cefodizime wighout other stimulators. And we analyzed IL-12 mRNA using RT-PCR method. In conclusion. IL-12 mRNA was increased. and the results suggest that cefodizime activate TH1 cell induction, CTL differentiation as well as accelerating the increase of NK. LAK cell.

The main targets for the immunosuppressive calcineurin inhibitors. tacrolimus (FK-506) and cyclosporine A (CsA). have been considered to be activated T cells. but not antigen presenting cells (APCs). In the present study. we examined the effects of these drugs on the MHC-restricted presentation of exogenously added antigen. ovalbumin (OVA). in dendritic cells (DCs). Particulate form of OVA was efficiently captured. processed and presented on class I MHC molecules (cross-presentation) as well as on class II MHC molecules. (omitted)

According to recent studies. cefodizime. a third generation cephalosporin antibiotic agent. may potentially have the capability of stimulating chemotactic activity of neutrophils and monocytes as well as the strong immuno-modulator. We have studied to see if cefodizime can be a potential substance inducing an Immunological activities on immune cells. such as dendritic cells and macrophages. In experimental process. dendritic cell and macrophage were taken from mice and mixed with 10${\mu}\ell$/$m\ell$. 50$${\mu}\ell$/$m\ell$, 100${\mu}\ell$/$m\ell$.cefodizime and 1$${\mu}\ell$/$m\ell$ IFN-${\gamma} 10U/$m\ell$＋LPS. (omitted)

Inflammation is a frequent radiation-induced following therapeutic irradiation. Since the upregulation of adhesion molecules on endothelial cell surface has been known to be associated with inflammation. interfering with the expression of adhesion molecules is an important therapeutic target. We examined the effect of allicin. a major component of garlic. on the induction of intercellular adhesion molecule-1 (lCAM-1) by gamma-irradiation and the mechanisms of its effect in gamma-irradiated human umbilical vein endothelial cells (HUVECs). (omitted)

Acharan sulfate. a new glycosaminoglycan(GAG) isolated from the giant African snail Achatina fulica. was shown to have antitumor activity in vivo. To elucidate the mechanisms for the antitumor activity. we examined its impact on professional antigen presenting cells such as macrophages and dendritic cells (DCs). Acharan sulfate stimulated cytokine production (TNF-a and IL -1b). nitric oxide release. and morphological changes in a dose dependent manner on a macrophage cell Line Raw 264.7 cells. The differentiation-inducing activity of acharan sulfate was examined on immature DCs. Immature DCs were generated from mouse bone marrow (BM) cells by culturing with GM-CSF and IL-4, and then stimulated with acharan sulfate. The resultant DCs were then examined for funcional and phenotypic properties. It was found that acharan sulfate could induce functional maturation of immature DCs as determined by increased allogenic mixed lymphocyte reaction (MLR) and IL-12 production. Phenotypic. analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2 and CD40 also confirmed that acharan sulfate could induce maturation of immature DCs. These results suggest that that the antitumor activity of acharan sulfate is at least in part due to activation adn induction of differentiation of professinal antigen presenting cells. (omitted)

In drugs for neutropenia. which suppress born marrow and which are needed to control their dosage and the therapy periods, there has been lots of emphasis on drug development to increase blood cells. In order to see the effects of an impact to hematopoietic cells. the hematopoietic effect of Phellinus linteus polysaccharide by segregating the study levels in matured cells both in born marrow cell and splenocyte were examined. (omitted)

Tissue macrophages produce at least two groups of protein mediators of inflammation. interleukin 1(IL-1) and tumor necrosis factor (TNF) when they were activated. Recent studies have emphasized that TNF and IL-1modulate the inflammatory function of endothelial cells. leukocytes. and fibroblasts, Aloe vera has been claimed to have several important therapeutic properties including acceleration of wound healing, immune stimulation, anti-cancer and anti-viral effects. (omitted)

Even though radiotherapy and chemotherapy. which have been generally used in anti-cancer treatment. show a superior inhibition effect on cancer cells. those are very toxic to normal tissues and body organs. which cause a secondary side effect. In order to see the effects of an impact to hematopoietic cells. the hematopoietic effect of ginsenoside Rg3 by segregating the study levels in matured cells both in born marrow cell and splenocyte were examined. (omitted)

Ginsan, a polysaccharide extracted from Panax ginseng. was earlier scrutinized for a biological-response modifier. We further studied the protective and restorative activity of Ginsan against sublethal dose irradiation owing to increase production of endogenous hematopoietic growth factors such as IL-1. TNF-${\alpha}$. IL-6, GM-CSF. Which induce strong redox-emzyme elevation. Exposing to radiation induces reactive oxygen species (ROS). which play an important causative role in radiation damage. (omitted)

The FimH subunit of type l-fimbriated Escherichia coli has been determined as a major cause of urinary tract infection. To produce a possible vaccine antigen against urinary tract infection, the fimH gene was genetically coupled to the ctxa2b gene, which was then cloned into pMAL -p2E expression vector. The chimaeric construction of pMALfimH/ctxa2b was transformed into Escherichia coli TB1 and its N-terminal amino acid sequence was analyzed. (omitted)

The fusion (F) protein of respiratory syncytial virus(RSV) is an important antigen in including cross-protective immunity with neutralizing activity. Two peptides homologous to amino acid 205-225(F/205-225) and 255-278 (F/255-278) of the F glycoprotein of RSV containing B cell and T cell epitope were synthesized and then conjugated with KLH. (omitted)

Macrophage activated by LPS/IFN-${\gamma}$ playa important role in imflammation. innate immunity and tumor immunity. The recent report has indicated that LPS treated bone marrow macrophages were induced apoptosis. but IFN-${\gamma}$ protects from apoptosis induced by several stimuli in complete medium condition (Jordi et al.. Immunity. Vo1.11. 103-113. 1999). (omitted)

Macrophages have been known to play an essential role in tumor angiogenesis and produce a number of growth stimulators and inhibitors. Thus macrophages appear to influence every stage of angiogenesis. In this report, TNF-$\alpha$ was able to induce the production of IFN-${\gamma}$ in cancer cell-contanted macrophage. TNF-${\gamma}$ alone released relatively little IFN-${\gamma}$ whereas live tumor cells (3LL) alone releasd IFN-${\gamma}$ markedly from macrophage. (omitted)

Crystal structure of TRAF6 in complex with TRAF6-binding sites from CD40 was previously determined. The structure revealed a distinct TRAF6-binding groove of CD40. the key structural determinant of interaction. The structural information leads to a proposed TRAF6-binding motif. This allows the identification of TRAF6-binding sequences in the hlRAK protein, whose functional requirement in IL-1 mediated signal transduction is further demonstrated using site-directed mutagenesis. The mutational in IL-1 mediated signal transduction is further dimonstrated using site-directed mutagenesis. The mutational effects of hlRAK on the down-stream NF-${\kappa}$ signaling shows the importance of the TRAF6 interface for signaling by IL-1.

L -ascorbic acid (LAA) was shown to modulate the in vitro growth of leukemic-colony forming cells from patients with acute myelogeneous leukemia (AML). Dendritic cells (DCs) were successfully cultured from the leukemic blasts by us and others. The effects of LAA on the ex vivo cultured leukemic-DC were studied. Plastic adherent cells from the leukemic blasts were cultured with GM-CSF and IL -4 (each 103 U/$m\ell$) with or without LAA (300 ${\mu}$M) for 7 days and harvested. (omitted)

Previous studies have demonstrated that 2,3',4,5' -tetramethoxystilbene (TMS) and 3,3',4',5,5'-pentamethoxystilbene (PMS) showed selective inhibition of human cytochrome P450 1 Bl and 1A1 in vitro., respectively, In the present study, the effects of synthetic stilbene analogs on the expression of cytochrome P450 1Al or lBl were investigated in human tumor cell lines such as HepG2, MCF-7 and MCF-l0A, TCDD caused a dramatic increase in the amount of P450 1A1 or 1B1 proteins and mRNA levels. (omitted)

The metal-ligand complex, ［Ru(phen)$_2$(dppz)]^{2＋}$ (phen = 1.10-phenanthroline, dppz = dipyrido［3.2-a:2', 3'-c］phenazine) (RuPD), was used as a spectroscopic probe for studying nucleic acid dynamics. The RuPD complex displays a long lifetime and a molecular light switch property upon DNA binding due to shielding of its dppz ligand from water. (omitted)

Recently we have reported that various hydroxystilbenes show strong inhibition of human P450 1 activity. A series of synthetic trans-stilbene derivatives were prepared and their inhibitory potentials were evaluated with the bacterial membrane of recombinant human P450 1A1, 1A2 or 1B1 coexpressed with human NADPH-P450 reductase to find new candidates for cancer chemoprevention, Of the compounds tested. SY-021 (3.5-dimethoxyphenyl vinyl thiophene) exhibited a potent inhibition of human P450 181 with an IC$_{50}$ value of 2 nM. SY-021 also showed the inhibitrion of P450 1A1 with IC$_{50}$ value of 61 nM and P450 1A2 with IC$_{50}$ value of 11 nM. SY-021 showed 31-fold selectivity for P450 1B1 over P450 1A1 and 6-fold selectivity for P450 1B1 over 1A2. We have further investigated the inhibition kinetics of P450 1A1. 1A2 and 1B1 by SY-021. The modes of inhibition by SY-021were non-compeitive for all three P450 1 enzymes. Effect of preincubation with NADPH on inhibition of P450 1B1 by SY-021 was determined. These results suggest that SY-021 is one of the mostj potent inhibitor of human P450 1 enzymes and may be considered as a good candidate for a cancer chemopreventive agent in human

Nitric oxide (NO) production through the inducible nitric-oxide synthase (iNOS) pathway has been implicated in inflammatory diseases and cellular injury. Inhibition of various genes related to inflammation, including iNOS is one of the major roles of well-known anti-inflammatory drugs. In the present study, the effects of ceramide analogs on iNOS expression and NO production were evaluated to investigate how ceramide and its structurally related analogs modulate NO-mecliated cellular signals and inflammation. (omitted)

Environmentally benign protein staining method in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using both an acidic dye, zincon (ZC) and a basic dye. ethyl violet (EV) is described. It is based on a counter ion-dye staining technique that employs oppositely charged two dyes to form an ion-pair complex. The selective binding of the free dye molecules to proteins in an acidic solution produces bluish violet colored bands. It is a rapid procedure, involving only fixin and staining steps that are completed in 45 min. (omitted)

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in response to a variety of cytokines and other proinflammatory stimuli. It has been known that aberrant up-regulation of COX-2 is associated with resistance to apoptosis. Contrary to the above notion. treatment of MCF10A-ras cells with the anti-tumor agent ET -18-O-$CH_3$ caused increased expression of COX-2 and its mRNA transcript. while inducing apoptosis as revealed by proteolytic cleavage of poly(ADP-ribose)polymerase. caspase-3 activation, and positive TUNEL staining. (omitted)

Bacterial ${\beta}$-lactamases provide resistance to ${\beta}$-lactams by hydrolyzing the ${\beta}$-lactam bond, On the basis of their catalytic mechanisms. ${\beta}$-lactamases are divided into two major groups. Class A. C and D which belong to the first group require serine in the active site and class B which is the second group require Zn(II) for their activity. Among class B enzymes, Bacteroides fragilis ${\beta}$-lactamase (CcrA enzyme) require two Zn(II) ions per monomer for maximal enzymatic activities. (omitted)

DNA topoisomerases catalyze changes in DNA topology through cycles of transient DNA strand breakage and religation. During this process. the active site tyrosine in human DNA topoisomerase Ⅰ(Top Ⅰ) becomes covalently linked to the 3'-ends of a single-stranded nick in the DNA duplex, Stabilization of the Top Ⅰ-DNA cleavable complex is the common initial event leading to the cytotoxicity of top 1 inhibitors. (omitted)

DNA topoisomerases I (topo I) and II are essential enzymes that relax DNA supercoiling and relieve torsional strain during DNA processing. including replication. transcription. and repair. Topo I relaxes DNA by cleaving one strand of DNA by attacking a backbone phosphale with a catalytic lyrosine (Tyr723. human topo I). This enzyme has recently been investigated as a new target for antineoplastic drugs. Inhibitors to the enzyme intercalate between the DNA base pairs. interfering religation of cleaved DNA, therefore inhibit the activity of topo I. (omitted)

The translationally controlled tumor-associated proteins (TCTPs) are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in both cell growth and human acute allergic response but whose intracellular biochemical function has remained elusive. There are reports that antimalarial drug, artemisinin. binds to Plasmodium falciparum TCTP. however, its 3D structure has not been known. (omitted)

A universal set of genes encodes the components of dissociated. type II. fa11y acid synthase system that is responsible for producing the multitude of fa11y acid structures found in bacterial membranes. We examined the biochemical basis for the production of fatty acids by bacteria. Several genes from HaemophHus influenzae Rd and three genes from Enterococcus faecalis V583 were predicted to encode homologs of the ${\beta}$-ketoacyl-acyl carrier protein synthases I or II or III of Escherichia coli(FabB or BabF, or FabH)were identified in the genomic database. The protein products were expressed. purified, and biochemically characterized. efFabH and hF abH carried out the initial condensation reaction of fatty acid biosynthesis with acetyl-Coenzyme A as a primer. and hFabB and efFabF1 carried out the elongation condensation reaction of fatty acid biosynthesis with myrixtoyl-ACP.

Dermatan sulfate (DS) was isolated from eel skin (Anguilla japonica) bv actinase and endonuclease digeslions followed by ${\beta}$-elimination reaction and DEAE-Sephacel chromatography. DS was a major glycosaminoglycan in eel skin with 88% of the total uronic acid. The content of IdoA2S$\alpha$1longrightarrow4GalNAc4S sequence in eel skin. which is known to be a binding site to heparin cofactor II. was two times higher than that of dermatan sulfate from porcine skin. The anti-lla activity of eel skin dermatan sulfate mediated through heparin cofactor ll(NCL) was 25 units/mg. whereas DS from porcine skin shows 23.2 units/mg. The average molecular weight was determined as 14 kDa by gel chromatography on a TSKgel G3000SWXL column. Based on H1 NMR spectroscopy. we suggest that 3-sulfated and/or 2.3-sulfated ldoA residues are present in the chain.

Manassantin B classified into dineolignans have been isolated from Saururus chinensis Manassantin B was found to induce apoptosis in human promyelocytic leukaemia HL -60 cells with characteristic apoptotic features like increase of nucleosomalladder. apoptotic body ormation. flipping of membrane phosphatidylserine. Manassantin B induced FAS and FAS ligand expression, and activated caspase 8 which cleaved bid to tbid in cytosol. The release of cytochrome c to sytosol was accompanied with decrease of bcl-2 protein and incresase of tbid and bax protein in mitochondria. Released xytochrome c activated caspase 9 and-3. but these effects were completely attenuated by the treatment of broad caspses ingibitor. Z-VAD fmk. These results indicate that manassatin B induce apoptosis through upregulation of FAS. caspase family and mitochondria-related proteins.

In previous reports, we exhibited that acteoside showed significant cytotoxicity against various cancer cells. In this study we investigated that acteoside is capable of inducing differentiation in HL -60 human leukemia cell line. After being treated with acteoside, the growth curve was decreased remakably in a dose- and time-dependent manner, and cell doubling time was delayed. Exposure of cells to 20 $\mu\textrm{g}$/m$\ell$ acteoside induced differentiation of HL-60 cells to monocyte/macrophage-like cells by cell surface antigen expression. The percentage of NBT reducing activity was increased in a time-dependent manner. In addition. the protein lever of p21 and p16 increased and ppRb decreased in western biot analysis. Theas results suggest that acleoside possess the activity of inducing differentiation in HL-60 cells.

The action of epigallocatechin-3-gi:lllale (EGCG). polyphenol compound from green lea, on the release pattern of glycosylphosphatidylinositol (GPI)-anchored renal dipeptidase (RDPase) from renal proximal tubules (PTs) was examined. EGCG had a stronger inhibitory effect on the release of RDPase than alkaline phosphatase (APase), another GPI-anchored ectoenzyme used as a reference protein. The effect of EGCG on cell viability as assessed by MTT test was found to be intact, and moreover, was indicative of potent cell activation or proliferation. (omitted)

Peroxynitrite, formed from the reaction of .O2- and .NO, is a cytotoxic species that can oxidize several cellular components such as proteins. lipids and DNA. Oxidative stress is considered to be the major cause of aging and many age-related diseases including Alzheimer's disease. rheumatoid arthritis. cancer. and atherosclerosis. ONO-, a powerful oxidant, can cause damage of proteins, lipid and DNA through nitration and oxidation. (omitted)

We found that 23-hydroxyursolic acid, triterpenoid was isolated from Cussonia bancoensis have a significant cytotoxic activity against HL -60 human promyelocytic leukemia cells. The IC of 23-hydroxyursolic acid was 32.83 $\mu$M. These anti-proliferative activity was due to induction of apoptosis. The effect of apoptosis was identified by DNA laddering, DAPI assay. PI staining, and Annerxin V-FITC binding assay. (omitted)

The effects of oxidative stress on the alterations of different antioxidant enzyme activity on mouse melanoma cells(B16F10) was investigated. Oxidative stress was induced by the exposeure to hydrogen peroxide(H2O2). B 16F 10 cells were exposed Phellinus linteus Ex. in combination with H2O2 and measured the time course of changes in cell viability and antioxidant enzyme activity. CAT activity peaked at 12 hr. On the contrary, SOD and GPX activity was maximum at 6 hr. The cell viability of Pheltinus linteus extracts in combination with hydrogen peroxide was higher than hydrogen peroxide alone.

Peroxynitrite(ONOO-), formed from the reaction of superoxide(O2-) and nitric oxide(NO), is a potent oxidant that contributes to oxidation of various cellular constituents including lipids. amino acids, sulphydryls and nucleotides. It can cause cellular injury such as DNA fragmentation and apoptotic cell death. Also. the toxicity of ONOO- has been reported to be involved in inflammatory and nurodegenerative diseases such as Alzheimer's disease, Parkinson's disease. and atherosclerosis. (omitted)

Yomogin. an eudesmane sesquiterpene isolated from Artemisia princeps, was found to induce apoptosis in human promyelocytic leukaemia, HL -60 cell with characteristic apoptotic features like nuclear condensation, apoptotic body formation, flipping of membrane phosphatidylserine, release of mitochondrial cytochrome c and caspase-8. -9. and -3 activation. Furthermore. early yomogin-induced cytochrome c release was not affected by the caspase inhibitor Z-VAd fmk and preceded loss of mitochondrial membrane potential. The results suggest that induction of apoptosis by yomogin may provide a pivotal mechanism for their cancer chemopreventive function.

Chitin is a major component of the shells of crustacea such as crab. shrimp and crawfish. Renal dipeptidase (RDPase. EC 3.4.13.19), an ectoenzyme of renal proximal tubules. is covalently bound to outer leaflet of lipid bilayer via glycosylphosphatidylinositol (GPI)-anchor. The biological role of RDPase was suggested as the hydrolysis of dipeptide into free-amino acids before renal reabsorption. The underlying biochemical mechanism of decreased RDPase release was suggested as nitric oxide (NO) production. (omitted)

Saururus chinensis Baill (Saururaceae) is a perennial plant that has been used in the treatment of edema. jaundice and gonorrhea in Korean folk medicine. Houttuynin sodium bisulphate (HSB), alpha hydroxyl-capryl-ethyl-sodium-sulphonate. is a product formed by reacting sodium bisulphate with houttuynin. which is obtained from a medicinal herb Houttuynia cordata Thunb. (omitted)

We investigated the effect of various triterpenoids isolated from the Cussonia bancoensis. such as ursolic acid. 23-hydroxyursolic acid. 3-O-${\alpha}$-L -arabinopyranosyl-23 -hydroxyursolic acid. 3-O-${\beta}$-D-glucopyranosyl-23-hydroxy-ursolic acid and 28-O-${\alpha}$-L -rhamnopyranosyl(1-4)-${\beta}$-D-glucopyranosyl( 1-6)-${\beta}$-D-glucopyranosylester of 23-hydroxyursolic acid. have been evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) release by the macrophage cell line RAW 264.7. (omitted)

Macrophages activated by lipopolysaccharide (LPS) are known to induce several proinflammatory proteins including COX-2. iNOS and TNF which produce chemical mediators involved in inflammatory response. Sophoricoside and its analogs (genistin, genistein and orobol) from Sophora japonica (Leguminosae) showed differential inhibitory effects on COX-1 and 2 activities. Sophoricoside and genistin shwoed IC50 values of 4 uM and 6 uM on COX-2 activity and of 1,497 uM and 135 uM on COX-1 activity, respectively. Genistein and orobol showed IC50 values of 3 uM on COX-2 activity and of 28 uM and 18 uM on COX-1 activity. respectively. Therefore. the legume isoflavonoids to be selective COX-2 inhibitors. However. sophoricoside and its analogs did not show inhibitory effects of COX-2, iNos and TNF transcripts. which were identified by the RT-PCR.

Nuclear factor ${\kappa}$B (NF-${\kappa}$B) represents a family of eukaryotic transcription factors participating in the regulation of various cellular genes. Since aberrant regulation of NF-${\kappa}$B has been implicated in the pathogenesis of various diseases including inflammation. asthma. atherosclerosis. AIDS. septic shock. arthritis, and cancer. this transcription factor has been shown to be an interesting target of new drug discovery. (omitted)

To indentify inhibitors of melanogenesis. we compared the effect of some natural products on mushroom tyrosinase. human melanocytic tyrosinase activity and melanin content. The cytotoxicity of the component were also tested on cultured mouse melanoma cells, Each extract significantly inhibited tyrosinase activity and melanin synthesis in vitro and B 16 melanoma cell lines. In B 16 cell lines, watermelon's inner shell extract inhibited tyrosinase activity as strong as kojic acid at 150${\um}g$/${\mu}\ell$ concentration. And morning glory'seed extract inhibited melanin synthesis more than kojic acid at 150${\um}g$/${\mu}\ell$ concentration. Each extract were strong inhibitors of tyrosinase activity and total melanin synthesis in B 16 mouse melanoma cell lines at less than 100${\um}g$/${\mu}\ell$ concetration. These result show that extract of watermelon's inner shell. lettuce. morning glory's seed and licorice root could be developed as skin whitening component of cosmetics.

Possible role of anti-inflammatory effects of a new iridoids, patridoid I. II and II-A which were isolated from Patrinia saniculaefolia. examined by assessing their effects on tumor necrosis factor $\alpha$ (TN F$\alpha$) and 2 enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccaride (LPS)-stimulated murine macrophage-like cell line RAW 264.7. Among them. patridoid II consistently inhibited the production of TNF$\alpha$ and NO production in a dose dependent manner. But patridoid I and patrioid ll isomer palrioid ll-A. these compounds very weakly inhibited NO producion. Moreover. treatment of macrophage with these compounds, the decrease in NO products was accompanied by a decrease in iNOS protein level as assessed by Western Blot. But these compounds did not affect COX-2 protein expression in LPS-stimulated macrophage. Our results suggest that patridoid ll could become a leading compound for developing a novel of anti-inflammalory drugs.

Lawsone methyl ether (LME. 2-methoxy-1, 4-naphthoquinone) is a natural compound found in balsaminaceae. In this study the effect of LME on the release of renal dipeptidase (RDPase) and alkaline phosphatase (APase) known as glycosylphosphatidylinositol (GPI) anchored proteins was examined from the renal proximal tubules. Compared with control, LME (0.5mM) increased RDPase release (218%) and APase release (135%). The increase of RDPase release by LME showed concentration-dependent effect but the release pattern of APase did not. (omitted)

Houttuynia cordata Thunb is a traditional medicine which has been used as antidote and antiphlogistic agent. Saururus chinensis is a perennial herb which cultivated as medicinal and decorative use. the aerial part of which have been used for the treatment of edema, jaundice and gonorrhoea in Korean folk medicine. (omitted)

Curcumin derived from turmeric (Curcuma longa L.. Zingiberaceae) has been shown to possess marked chemopreventive activities, but the underlying molecular mechanisms remain unclear. In the present work. curcumin was found to inhibit 12-Ο-tetradecanoylphorbol-13-acetate(TPA)-induced expression of cyclooxygenase-2 (COX-2) in female ICr mouse skin as determined by Western and Northern blot analysis as well as immunohistochemical staining. Curcumin treatment atlenuated TPA-stimulated epidermal NF-${\kappa}$B activation. which was associated with its blockade of degradation and phosphorylation of the inhibitory protein l${\kappa}$ Bu and also of subequent translocation of the p65 subunut to nucleus. (omitted)

Apicidin ［cyclo(N-O-methyl-l -tryptophanyl-L -isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecano y)］. a histone deacetylase inhibitor. has been shown to cause growth arrest and morphological change of cancer cells. resulting from the alternation of protein expression. such as p21WAF1/Cip1 and gelsolin. However. proteome of altered by apicidin are poorly studied. In this study. we used a functional proteornics approach to identify the proteome altered by apicidin in Hela cells at 24hr post-treatment. (omitted)

We previously reported that apicidin induces apoptosis through selective induction of Fas/Fas ligand. resulting in the release of cytochrome C from mitochondria to the cytosol and subsequent activation of caspase-9 and \ulcorner However. we observed that apicidin did not induce the apoptosis in a specific cell line. such as HeLa. which was characterized by nuclear DNA fragmentation. On the basis of these facts, we tested whether JNK activation is involved in cell death induced by apicidin. (omitted)

Histone deacetylases (HDAC) activity is associated generally with transcriptional repression. We have reported previously that apicidin. a histione deacetylase inhibitor. inhibited the proliferation of tumor cells via induction of p21 WAF/C1P1. We extended our study to identify the effect of apicidin on the expression of other cell cycle regulatory protein. such as cyclin E. a critical regulator of the transition from G1 into S phase. (omitted)

Human 5-reductase type II(5AR2) is an important target for the treatment of benign prostatic hyperplasia. In this study we describe the establishment of cell line which stably expressed 3X FLAG tagged human 5AR2. We used this cell line as a cell based assay tool and source for 5AR2 enzyme. First a plasmid (3XFLAGpCMVl0-5AR2) for the expression of 5AR2 was constructed by the use of the vector 3XFLAGpCMV10 and transfected into the HEK 293. By selection with G418 sulfate. ten HEK 293 single cell clones were obtained of which three stably exhibited high 5AR2 activity. (omitted)

Recent studies suggest that inflammatory events are implicated in a variety of human diseases including cancer and neurodegenerative diseases. and non-steroidal anti-inflammatory drugs have beneficial effects in treatment or prevention of these disorders. It has been reported that expression of cyclooxygenase (COX)-2 and nitric oxide synthase and subsequent production of prostaglandin (PG) and nitric oxide (NO). respectively are elevated in many inflammatory disorders. (omitted)

Cell motility plays important physiological roles in embryogenesis. immune defense. wound healing. and metastasis of tumor cells. Cell motility of normal cells is tightly regulated. while tumor cell motility is aberrantly regulated or autoregulated. Autotaxin (ATX) is a 125-kDa glycoprotein. originally isolated from the conditioned medium of human melanoma A2058 cells. ATX stimulates random (chemokinetic) and directed (chemotactic) motility of human tumor cells at high picomolar to low nanomolar concentrations. (omitted)

We investigated the effect of bovine lactoferricin (Lfcin-B) on cell cycle regulation and caspase activation in tumor cells. Treatment with Lfcin-B resulted in the production of intracellular reactive oxygen species (ROS) during apoptosis of THP-1 cells. Biochemical analysis revealed that Lfcin-B-induced apoptosis. the cell cycle arrest and caspase activation were completely abrogated by addition of an antioxidant such as N-acetylcysteine(NAC). (omitted)

An imbalance between matrix metalloproteinase (MMP)-2 and its endogenous inhibitor. tissue inhibitor of metalloproteinase (TIMP)-2 causes the degradation of the extracellular matrix associated with pathological events including invasion. metastasis and angiogenesis. Since TIMPs are secreted molecules. they have the potential to be used for gene therapy of certain tumors. (omitted)

We applied serological analysis of cDNA expression library technique to identify cancer-associated genes. We screened cDNA expression libraries of human testis and gastric cancer cell lines with sera of patients with gastric cancers. We identified a gene whose expression is testis-specific among normal tissues. We cloned and characterized this novel gene. It contains D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. It showed wide expression in various cancer tissues and cancer cell lines. (omitted)

Glial cell-derived neurotrophic factor (GDNF) is a potent neurotrophic factor that enhances survival of midbrain doparminergic neuron. GDNF and its receptors are widely distributed in brain and are believed to be involved in the control of neuron survival and differentiation. In this study, we examined the effect of GDNF on proliferation and migration of Hs683 human glioma cells. GDNF markedly enhances proliferation and migration of Hs683 cells in a dose-dependent manner. (omitted)

Glycosaminoglycans(PT -Gag) were isolated from the porcine testis. From the PT -Gag, we obtained two different types of Gag fractions using Dowex macro porous Resin MSA-1 column, PT -Gag-1.5% NaCl and PT -Gag-16% NaCl. Various biological activities of the GAGs were examined in aspect of anticoagulant and immunomodulating activity. The anticoagulant activity of the GAGs was evaluated by activated partial thromboplastin time (aPTT ) assay and thrombin time (TT) assay. The GAGs of porcine testis markedly incresed the clotting times of both of aPTT and TT. showing that PT-Gag-16% NaCl was more effective than PT-Gag-1.5% NaCl. The immunomodulating activityof the GAGs was examined in relation to regulation of xytoxine prodution of murine peritoeal maerophages. Taken together. GAGs isolated from porcine testis possess bilolgical functions such as anticoagulant and immunomodulating activity.

Inflammatory as well as oxidative tissue damage has been associated with pathophysiology of Alzheimer's disease (AD), and nonsteroidal anti-inflammatory drugs have been shown to retard the progress of AD. In this study, we have investigated the molecular mechanisms underlying oxidative and inflammatory cell death induced by beta-amyloid (Abeta), a neurotoxic peptide associated with senile plaques formed in the brains of patients with AD, in cultured PC12 cells. (omitted)

Transforming growth factor-${\beta}$ (TGF-${\beta}$), a hormonally active polypeptide found in normal and transformed tissues. regulates cellular growth and phenotyphic plasticity. We have previously shown that H-ras. but not N-ras. induces invasive phenotype in MCF10A human breast epithelial cells. In this study. we wished to examine the effect of TGF-${\beta}$ on H-ras-induced invasion and motility in MCFI 10A cells by performing in vitro invasion assay and wound migration assay. (omitted)

A major lipid-signaling pathway in mammalian cells implicated the activation of sphingomyelinase (SMase), which hydrolyses sphingomyeline to generate ceramide and phosphocholine. Sphingomyelinase is divided into many isoform groups dependent on optimal pH, and essential cation especially magnesium in their activation. Such as acidic sphingomyelinase, neutral sphingomyelinase and alkaline sphingomyelinase. Ceramide is known as a crucial second messenger in cell responses like cell proliferation. cell cycle arrest. cellular senescence, and apoptosis. (omitted)

This paper presents stability of tyhoid vaccine -attenuuated vaccine(oral) and killed vaccine{vi polysaccharide)- 5 classes with various temperature(3 points: iced temperature, refrigeration temp.. indoor temp.). Analytical techniques -vi polysaccharide content. pH. sterility. assay - have been used for the quantity of pharmacologically active chemical entries. From this study. we have found the attenuated vaccine is show iced temp. 258% and indoor temp. 0.02% compare with refrigeration temp. in assay examination and the killed vaccine is not found different. (omitted)

A convenient bioassay of nerve growth factor(NGF) is essential for assessing its potency during the course of product development and quality controls afterwards. We have set up a cell-based bioassay for determining the potency of recombinant NGF using rat pheochromocytoma (PC12) cells. Cell survival was measured by monitoring the reduction of the alamarBlue$^{TM}$ dye by living cells. (omitted)d)

Expressions of adhesion molecules (AMs) are closely related to the formation of early atherosclerosis. an age-dependent process. However. previous research only provided limited and conflicted reports about alternated AMs expressions during aging and even much less is known about modulation of AMs by calorie restriction (CR), the only established anti-aging experimental paradigm. (omitted)

This study was intended to establish test methods equivalent to those of "Interferon alfa-2 concentrated solution" monograph in European Pharmacophoeia(EP). Two recombinant interferon alfa concentrated solutions manufactured in Korea were tested according to the monograph of EP. Tests of identification(biological activity. isoelectric focusing. SDS-PAGE under reducing condition, peptide mapping). related proteins. impurities of moducular masses differing from that of interferon alfa-2(SDS-PAGE under reducing and non-reducing condition). bacterial endotoxin, protein, potency, host-cell-derrved proteins. and host-cell-derived DNA were performed in the laboratories of manufacrues and division of biotechnology. KFDA. The results of this study showed that specitications of interfenon alfa concentrated solutions manufactured in Korea were within the aceptance criteria of EP. Based on the study. specitications and test methods for interferon alfa concentrated solution can be established according to the monograph of EP suggesting the revision of Minimum requirements for biological products

Arginine methylation is a common post-translation protein modification in eukaryotic cells. Protein-arginine N-methyltransferase transfer methyl groups from S-adenosyl-L-methionine to the guanidino group of arginine residues. However. The significant of this modification has been questionable. because it occurs rarely and is present at very low abundance. Recently, the discovery of two protein arginine methyltransferase, PRMT1 and CARM1, as cofactors required for responses to muclear Hormone receptors provided an indicationthat arginine methylationhave an important role in transcriptional regulation. (omitted)

The conformational study on cyclic Ac-Cys-Pro-Xaa-Cys-NHMe (Ac-CPXC-NHMe: X = Ala, Val. Leu. Aib. Gly. His. Phe, Tyr. Asn. and Ser) peptides has been carried out using the ECEPP/3 force field and the hydration shell model in the unhydrated and hydrated states. This work has been undertaken to investigate structural implications of the CPXC sequence as the chain reversal for the initiation of protein folding and as the motif for active site of disulfide oxidoreductases. The backbone conformation DAAA is in common the most feasible for cyclic CPXC peptides in the hydrated state. which has a type 1${\beta}$-turn at the Pro-Xaa sequence. The proline residue and the hydrogen bond between backbones of two cystines appear to play a role in stabilizing this preferred conformation of cycilc CPXC peptides. However. the distributions of backbone conformations and ${\beta}$-turns may indicate that the cyclic CPXC peptide seems to exist as an ensemble of ${\beta}$-turns and coiled conformations. The intirnsic stability of the cyclic CPXC motif itself the active conformation appears to play a role in determining electrochemical properties of disulfide oxidoreductases.

Actinomycetes CS0703 has been isolated in soil sample from location in the Jeju province. Korea. and produces alkaline extracellular proteases. To maximize protease production, initial pH of the culture medium was adjusted to 12.0 with NaOH and incubated at $48^{\circ}C$ on a rotary shaking incubator(180rpm). Actinomycetes CS0703 produced high level of protease at late exponential phase when grown in OSYM medium (oatmeal 2.0%. soybean meal 1%. dried yeast 1%. mannitol 1%). (omitted)

Actinomycetes CS0707 has been isolated in soil sample from location in the Jeju province. Korea, and produces thermostable extracellular proteases. Actinomycetes CS0703 showed the highest protease activity at late exponential phase when grown in OSYM medium (oatmeal 2.0%, soybean meal 1 %, dried yeast 1 %, mannitol 1 %) at $48^{\circ}C$. Three forms of protease(Ta-1, TA-2 and Ta-3) were fractionated by Ultrogel AcA 54 column chromatography, and further purified through ammonium sulfate fractionation, ultramembrane filtration, and DEAE-sepharose CL-6B column chromatography. (omitted)

A novel penicillin G acylase (PGA)-producing bacterial strain was isolated from soil by using the Serratia marcescens overlay technique. The isolated strain was identified as Leclercia adecarboxylata based on the analyses of the biochemical characteristics (API 20E). the cellular fatty acid profile. and the 16S rDNA sequences. The gene encoding the PGA (pac gene) was cloned into the pHSG399 vector and the recombinant E. coliHB101 clones harboring the pac gene were isolated on agar plates containing phenylacetyl-L -leucine and penicillin G. (omitted)

Streptococcus vestibularis is a urease-producing oral bacterium. frequently isolated from vestibular mucosa of human oral cavity. Ureolysis by S. vestibularis and other ureolytic oral bacteria is believed to be crucially involved in oral microbial ecology and oral health. Genomic library of the S. vestibularis ATCC49124 was constructed in an E. coli plasmid vector and the urease-positive transformants harboring the urease gene cluster were isolated on Christensen-urea agar plates. The minimal DNA region required for the urease activity was located on a 5.6 kb DNA fragment. (omitted)

Three alkaline proteases. designated JB-1. JB-2, and JB-3, are extracellular enzymes produced by Bacillus spp. JB411 which was isolated korean soil. They were separated by DEAE-sepharose CL-6B gel. and further purified using ammonium sulfate precipitation. ultra membrane filtration. and Ultrogel AcA gel filtration. The optimun pH values of proteases IB-1. JB-2. and JB-3. were shown to be 9.5. 9.5 and 7.5. respectively. All three proteases were stable in the pH range of 5-11. (omitted)

Streptomyces tendae JC412 secreted two forms of protease(ST -1 and ST -2) when grown in OSY medium (oatmeal 1.5%. soybean meal 2%. dried yeast 1 %) supplemented with glucose(0.5%) and KH2PO4(0.05%). Initial pH of the culture medium was adjusted to 10.0 with NaOH and incubated at $27^{\circ}C$ on a rotary shaking incubator (180rpm). High- molecular-weight protease ST-1 was heat labile. whereas low molecular protease ST-2(22.000 Da) was reported to be heat stable. (omitted)

Kakkalide from Puerariae Flos expresses pharmacological actions after biotransformation to irisolidone by intestinal bacteria. B. breve K-110 was isolated as a bacterium metabolizing kakkalide. Therefore. we purified kakkalide-metabolizing p-Xylosidase from B. breve K-110. ${\beta}$-Xylosidase from B. breve K-110 (isolated from Korean intestinal microflora) was induced by kakkalide. We used defined medium contating 1mM kakkalide for the cultivationof B. breve K-110. (omitted)

Streptomyces scabiei subsp. chosunensis M0137. nonadecanoic acid producer. showed the highest protease activity when grown in OSY medium (oatmeal 1.5%, soybean meal 2%, dried yeast 1 %) supplemented with. glycerol (1 %) and CaCO3 (0.1 %). Two forms of protease(SS-1 and SS-2) were fractionated and purified through Ultrogel AcA 54 gel filtration and DEAE-sepharose CL-6B column chromatography. Both proteases were practically stable in the pH range of 6-10. The optimal pH for the activities of both protease 88-1 and 8S-2 were 7.5 and 8.0. respectively. (omitted)

As the part of our continuing study for antihyperlipidemic agents from the herbal medicinal resources. we examined the possibility of the ethylacetate fraction of Alpinia officinarum water extract in vitro and in vivo. We isolated some compounds from the ethylacetate fraction of Alpinia officinarum and measured their antihyperlipidemic activities. The active components isolated by silicagel column lmproved serum TG. HDL and LDL level in corn oil feeding and triton WR-1339 induced hyperlipidemic mice. The most active compound was 3-Methylethergalangin. Consequently. these biologically active gerbal functional foods could be used for preparing the healthy food which might diabetas. hyperlipidemia and other disease.

Ginseng(the root of Panax ginseng C.A. Meyer, Araliaceae) has been used for thousands of years as a traditional medicine in Asian countries. The main components of Ginseng are ginsenoside Rb1, Rb2 and Rc. These compounds are transformed by intestinal microflora. The main metabolite of ginsenosides was compoud K (IH-901). The transformed compound K shows an antimetastic or anticarcinogenic effect by blocking tumor invasion or preventing chromosomal aberration and tumorigenesis. Therefore. we isolated and characterzed ginseng saponin-metabolizing bacteria from human intestinal microffora. Among 200 tested intestinal bacteria. we found 78 bacteris to transform glnseng senseng saponins to compound K. These bacteria were seperated into three group: the first group highy produced ginsenside Rd (29) the second grop produced potently ginsenoside F2 (21) and the third produced compound K(28)

The ermK gene from Bacillus lichenformis encodes an inducible rANA methylase that confers resistance to the macrolide-lincosamide-streptograminB antibiotics. The ermKmANA leader sequence has a total length of 357 nucleotides and encodes a 14-amino acid leader peptide together with its ribosome binding site. The secondary structure of erm leader RNA and a leader peptide have been reported as the elements that control expression. (omitted)

Despite the use of antibiotics and vaccines, Streptococcus pneumoniae remains a serious cause of morbidity and morality in human. In this study, pathogenic and immunological natures of alcohol dehydrogenase (ADH) in S. pneumoniae were elucidated. In vitro cytotoxicity test determined by lactate dedydrogenase release from A549 cells revealed that adh mutation significantly reduced cytotoxicity although in vivo intraperitoneal challenge of the adh mutant to BALB/C mouse exhibited marginal increase of survival time than the wild type. (omitted)

To find ${\alpha}$-Glucosidase Inhibitors produced by Actinomycetes, 20 soil samples were tested and 53 Actimycetes were isolated. One of 53 Actinomycetes (strain PM718) showed very potent inhibitory activity in vitro. The morphological and physiological characteristics of strain PM 718 were investigated. The spore morphology. spore chain morphology and spore surface were observed by scanning electron microscope. The inhibitory activity of strain PM718 in vivo has been studied in mice made hyperglycemia by Streptozotocin treatment. The strain PM718 showed signficant reduction of blood glucose level(more than 30%) in mice loaded with maltose.

HSP100/Clp family functions as molecular chaperone and ATP dependent protease. The Streptococcus pneumoniae ClpL. a homologue of bacterial ClpB and yeast cytosolic HSP 104. is one of major heat shock proteins but its biochemical properties are unknown. In this study. ClpL in Streptococcus pneumoniaewas characterized using histidine tagged recombinant ClpL. When ATP hydrolysis activity was compared in the presence or absence of a variety of nucleotides or divalent ions. either ATP or Mn$2^＋$ ion was found to increase significantly the rate of ATP hydrolysis. Furthermore. glutaraldehyde cross-linking and subsequent native-PAGE analfysis showed that ClpL forms dimer. but in the presence of 4 mM concentration of $Mn^{2＋}$ion as a cofactor for ATP hydrolysis and oligormerization in vitro.

Several 1 A-naphthoquinone derivatives have been reported to possess many pharmacological effects such as anti-viral. anti-fungal. anti-cancer and anti-platelet activities. We have reported that 2-chloro-3-［4-(ethyICarbOxy)-phenyl］-amino-1.4-naphthoquinone(NQ12) had a potent inhibitory effect on the platelet aggregation in vitro and thrombosis in vivo. However. little has been known about functional roleot NQ12 on vascular smooth muscle cells (VSMCs). (omitted)

We previously reported that a synthetic naphthoquinone analog. 2.3-dichloro-5.8-dihydroxy-1, 4-naphthoquinone (NA). effectively induces apoptosis in human leukemic HL-60 cells. However. the cellular mechanism by which NA induces cell death remain unclear. In this study. we show that NA induces activation of capases. release of cytochrome c and upregulation of proapoptotic Bax protein. Futhermore. NA suppressed phosphorylation of Akt and Bad. suggesting that Akt regulates NA-induced apoptosis. Expresson of a dominant negative Akt enhancde NA-induced apoptosis. suggesting that naphthoquinone analog induces apoptosis through activating proapoptotic pathway and by the inactivation of antiapoptotic pathway.

Hypertrophy and the alteration of renal cell growth have been reported as early abnormality in diabetic nephropathy. However, the effects ot high PKCglucose and its action mechanism in renal proximal tubular cell (PTC) have not been elucidated. High glucose condition increases diacyl glycerol (DAG) and activates protein kinase C (PKC) in renal tubular cells. The PKC activates mitogen-activated protein kinases (MAPK), such as extracellular regulated kinase (ERK) and p38 MAPK. (omitted)

Conjugated linoleic acid (CLA) is a potent inhibitor of mammary carcinogenesis. Cancer cells produce various angiogenic factors which stimulate host vascular endothelial cell mitogenesis and chemotaxis for their growth and metastasis. Basic fibroblast growth factor (bFGF) is a potent angiogenic factor that is expressed in many tumors. In this study. we found that CLA decreased bFGF-induced endothelial cell proliferation and DNA synthesis in a dose-dependent manner. However, CLA did not inhibit endothelial cell migration. Furthermore CLA showed a potent inhibitory effect on embryonic vasculogenesis and bF GF-induced angiogenesis in vivo. Collectively. these results suggest that CLA selectively inhibis the active proliferating endothelial edll induced by bFGF. which may explain its anti-carcinogenix properties in vivo.

UV-B irradiation increases the synthesis of matrixmetalloproteinase-1 (MMP-1) that degrades skin collagen in human skin. In this work, we investigated the photoprotective effect of decursinol angelate (DEA) extracted Irom Angelica gigas on human skin libroblasts. DEA inhibited UVB-induced MMP-1 induction, which was conlirmed by western blot and ELISA. We examined upstream signal transduction pathway and the action mechanism of DEA on UVB induction of MMp in human skin fibroblasts. (omitted)

The efficient Erythropoietin(EPO)-expression system in mammalian cells is required for massive production for therapeutic use. Ammonium ion is a major problem in the production of useful proteins by cultured animal cells and therefore it is of importance to devise a system by which a high productivity of human therapeutic recombinant protein can be maintained or enhanced under low ammonium concentration. (omitted)

Ceramide is a lipid second messenger that is involved in apoptotic cell death. In this study, we show that p38 MAPK plays an important role in the regulation of ceramide-induced apoptosis. We found that SB203580, a p38 kinase inhibitor, blocked the effects of ceramide to induce Bax translocation to mitochondria, activation of caspase-3, and DNA fragmentation. Furthermore. expression of a dominant negative form of p38 MAPK suppressed ceramide-induced Bax translocation, suggesting that p38 kinase activity is essential for Bax translocation. (omitted)

Since two selective COX-2 inhibitors. celecoxib and rofecoxib, showed good biological activity as antiinflammatory agents. many medicinal chemists are interested in specific COX-2 inhibitors. The distinguished feature of these drugs is that the 5-membered heterocycle ring is substituted with two aryl groups. Therefore, in this study, we designed a new hydantoin derivatives via the reaction of unnatural amino acids as selective COX-2 inhibitors, In systematically steps. 5-phenyl-1 (or substituted) hydantoin derivatives were prepared through esterification. bromination, C-N bond formation, cyclization from phenyl acetic acid. Particularly. a novel hydantoin ring was converted from unnatural amino acids with potassium isoyanate. In last step. the final analogs were synthesized the substitution at 3-position with alkyl reagents.

Interest in the synthesis and chemistry of multidentate macrocyclic ligands is currently very high. Synthetic macrocycles arise from the fact that many biologically important molecules are metal complexes of macrocyclic organic systems: and in order to understand the mechanism of action of the naturally occurring complexes. chemists have resorted to the synthesis and study of so-called model systems. (omitted)

Capsaicin is hot taste ingredient of chili pepper and was isolated in 1876 and in 1919 its structure is sympathized compound. induces pain and when persistently dosed. the fact will bring insensible condition to other chemical and mechanical thermal stimulation by incapacitating sensory neuron is known. The analgesic effect by desensitization of such capsaicin is differ from the mechanism by analgesic action by opiate receptor of the existing analgesia or by prostaglandin mediation and the efficacy was known as similar with morphine. (omitted)

Centella asiatica is an herbal plant used on different continents by diverse ancient cultures and tribal groups. Historically. the extract has been used as a wound healing agent, The extract has three different triterpenoid ingredients: asiaticoside. asiatic acid, and madecassic acid. It has been reported that its wound healing activity is associated with the modulation of collagen synthesis in the skin dermis. The wound healing property of the extract has led to its commercial introduction under the trade name, Madecrlssol. As part of our program toward the development of new wound healing agents. structere activity relationship (SAR) studies have been performed by modifying asiatic acid. In this communication. the SAR study of esiatic acid for the development of an efficient woind healing agent is reported.

As a part of our continuing studies directed toward the synthesis of the medium to macrolactam alkaloids, we have been interested in the versatile functionalization of the lactam carbonyl. Synthetic routes involving cyclic N-acyliminium ions are generally useful strategies that have been applied for a wide variety of synthetic transformation. Especially, the use of a-alkoxy azacycles as precursors to cyclic N-acyliminium ions was well reviewed. (omitted)

During the research for the development of antitumor agents. we found the 3-arylisoquinoline derivatives exhibited potent cytotoxicity against human tumor cell lines. For extending our study on these compounds. indeno［1.2-c］isoquinolines were chosen as the next research target due to previous studied data of the compounds that showed potent topoisomerase I inhibition activity as well as cytotoxicity against many kinds of tumor cell lines. Retrosynthetic consideration of indeno[1.2-d]isoquinolines indicates that the coupling of o-methyltoluamide with o-hydroxymethylbenxonitrile might afford 3-arylisoquinoline which could be translerred to the aldehtde. Indeno [1.2-c]isoquinolines can be formed by and inframolecular ring cyclization method. Various derlvatives of this compound including 11-alkoxy-6-methyl-6H. 11H-indeno[1.2-c]isoquinolin-5-one and biological activity will be presented with the docking model with topisomerase 1 enzyme.

Apio nucleosides belong to unique classes of nucleosides in that 4'-hydroxymethyl group moves to 3'-position. Among thse compounds. we found that apio dideoxyadenosine (apio-ddA) exhibited potent antiviral activity and apio-d4A showed potent anti-HCMV activity. Based on thse findings. it was of great interest to design and synthesize Anio nucleoside anlogues with various substituents such as fluorn or azido group. In order to synthesize apio analogues. the glyxosyl dondr. D-. and L-apio sugar acetates were first synthesized. starting from D-gallas. condensed whth silylated N4-benzoylcytosine. and then convenged to the linal D-andL-nucleosides. Synthesist of the D-and-apio nucieosides will be prssented in detail aht th the meeting.

An efficient process for the solution-phase synthesis of biaryl amides has been developed. Girard's reagent T. an inexpensive scanvenger. was found to be very efficient in trapping excess aromatic acid chlorides. resulting in water soluble by-products. which were easily removed from the products by liquid-liquid extraction. The ease of use. and the excellent purity of the amide libraries obtained are important features of this protocol. (omitted)

The interest in polyhydroxyamines is based in their biological activity as enzyme inhibitors. and as starting materials in the synthesis of more complex compounds. Polyhydroxyamines is that amine group is continuing structurally with hydroxy groups and has become important target of the synthesis strategy because of the chirality control of amine group and each hydroxy groups. (omitted)

6.7-Dicholroquinoline-5.8-dione reacted with 2-aminopyridine derivatives, Out of the four possible products which could be achieved in this reaction. condensation and rearrangement product. 4a.10.11-triazabenzo［3.2-a］ fluorine-5.6-dione was obtained as major product. The definite structure was identified with X-ray crystallographic study. (omitted)

The ${\beta}$-turn has been implicated as an important conformation for biological recognition of peptides or proteins. Benzodiazepine classes have been known as one of the non peptide ${\beta}$-turn mimic scaffolds. We have developed an efficient approach for the synthesis and derivatization of a scaffold of hydroxytetrahydrodizepinone class in order to screen compound library in various protein targets for new lead generations as well as for structure activity relationships of the scaffold. (omitted)

Non-insulin dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia, hyperinsulinemia. and impaired insulin action. Insulin resistance is considered to be the underlying mechanism in the pathogenesis of type 2 diabetes. which also leads to dyslipidemia, hypertension. and obesity. Thazolidinediones are a class of oral insulin-sensitizing agents that improve glucose utilization without increasing insulin release. They significantly reduce glucose, lipid and insulin levels in rodent models of NIDDM and obesity, and recent clinical data support theri efficacy in obese diabetic patients. (omitted)

Nonsteroidal antiinflammatory drugs(NSAIDs) are widely used to treat pain. fever and inflammatory condition. But chronic-disease patients suffer from gastro-intestinal disturbances such as discomfort. nausea. peptic ulcer and severe bleeding because NSAIDs inhibit not only COX-2 associated with anti-inflammatory activity but also COX-1 associated with adverse gastro-intestinal effects. On the basis of this fact. specific COX-2 inhibitors such as celecoxib and rofecoxib are introduced in the drug market. (omitted)

Ranunculin (RAN). isolated from Ranunculaceae. exhibited significant cytotoxic activity against KB and Bel-7402 cells with ED$_{50}$ values of 0.21 and 0.35).${\mu}4M respectively. Under physiological condition. the ranunculin was deglycosylated to be protoanemonin. an active form containing ${\alpha}{\beta}$-unsaturated ketone moiety. which successively dimerized to be anemonin inactive form. (omitted)

We report the synthesis of several new 3-aminohydantoinyl-1.2-benzothiazine derivatives and propose an another mechanism of the cyclization to the hydantoins for the development candidates of COX-2 inhibitors. 3-Aminohydantoins 3a-d were prepared through cyclization of the condensation products that were formed by heating amino acids and tert-bytyl carbazate in quinoline according to the method of Lalezari. (omitted)

Sophoricoside analogs are natural isoflavonoids isolated from fruits of Sophora japonica L. and exhibited an inhibitory effect on IL -5. Many synthetic variations on isoflavonoids has been reported. but relatively few examples of quinolone analogs have been described. As part of our endeavor to develop novel and effective IL-5 inhibitor, we have synthesized azaisoflavones by cyclization of the key intermediate, 2'-aminochalocone obtained from substituted aniline. The synthesized azaisoflavones were evaluated for their inhibitory activtities on IL-5 comparing with natural Sophoricoside analogs. None of the azaisoflavones showed promixing inhibitory effects In the assay. Nevertheless. assay data Indicated that 5.7-phenolic hycroxy groups on the A-ring and alkyl subsitiuent on N1 seemed to play an importnt role in the IL-5 bioassay.

For the development of novel anticancer agent. we have designed. synthesized. and tested novel 4-phenyl-1(N)-arylsulfonylimidazolidinones. As a result. much more potent cytotoxicities of these compounds against the various cancer cell lines than those of doxorubicin were demonstrated. Elaboration on aryl motif on sulfonyl moiety led us to find highly potent 4-phenyl-1-(N-acylindoline-5-sulfonyl)imidazolidinones. Among them, 4-phenyl-l- ［N-(p-aminobenzoyl)indoline-5-sulfonyl］imidazolidinone (PA) was proved to have good pharmacological profile. (omitted)

${\alpha}$-terthienyl the first isolated from natural products shows potent antitumor activity, which encouraged us to study terpyridine and its biological properties. Terpyridine has also been reported as having carcinogenicity, and it's erivatives showed high cytotoxic activities against several human cancer cell lines and topoisomerase I inhibitory ctivity. Mannich free base from condensation reaction was allowed to react with pyridinum salts to give activity. (omitted)

Recently. 4'${\alpha}$-C homologated furanose nucleosides. especially alkyl branches. are molecules of considerable current interest. One of reasons for this prominence arises from the notable biological activities as antiviral and antitumor agents. as shown in 4'${\alpha}$-C-methyl-2-deoxythymidine (EC$_{50}$ = 7.2$\mu$M against HIV in MT-4 cell), 4'${\alpha}$-C-fluoromethyl-2-deoxycytidine. 4'${\alpha}$-C-hydroxymethylthymidine and 4'${\alpha}$- -C-azidomethyl-thymidine. (omitted)omitted)

In connection with the asymmetric synthesis of chiral l.2-diol. we report here the total synthesis of (＋)-frontalin using diastereoselective alkylation featuring tridentate chelation-controlled asymmetric alkylation of a-hydroxyketone, in which the chiral auxiliary is attached to the hydroxyl group as ether linkage. The starting D-glyceraldehyde acetonide was converted (S)- ［(4R)-2.2-dimethyH,3-dioxolan-4-yl］ (4-methoxyphenyl) methanol. (omitted)

FXR (farnesoid X-activated receptor) is a member of nuclear steroid hormone receptor superfamily and especially a orphan receptor, which are able to control mevalonate pathway upon activation by binding of the specific ligands. We. have launched our study for development of FXR specific ligands getting on in lead discovery. A promising lead stilbene analog was obtained through the screening of a set of library compounds which was previously targeted for other nuclear receptors. And then synthetic modilication of the lead was perfoumde. In addition. fishing a new pharmacophore was fried by UNITT aearch. which brought new structural features.

Recently, several branched-nucleosides have been synthesized and evaluated as potent antitumor or antiviral agents. Among them, 4'${\alpha}$--C-ethenyl and 4'${\alpha}$-C-ethynyl nucleosides which having an additional double or triple bond at 4'-position were reported to be as potent antiviral and anlitumor activities. Encouraged by these interesting structures and antiviral activities, it was determined to synthesize novel classes of nucleosides comprising branched carbocyclic nucleosides with an additional aryl group at 4'${\alpha}$-position using versatile reiterative three-step sequences from simple acyclic precursor '2-hydroxyacetophenone. Our efforts toward the synthesis of novel nucleosides analogues are reported herein.

The polyamine pathway represents a logical target for chemotherapeutic intervention, since depletion of polyamines results in the disruption of a variety of cellular functions, and may in specific cases result in cytotoxicity. Polyamine interaction with DNA has also long been thought to be an important function of the natural polyamines and as more is learned about the specific interactions and the resultant conformational changes which can be influenced by the polyamine binding to DNA the potential for regional and gene-specific changes are becoming more evident. We have prepraed the elaborate polyamines by the reaction of simpler polyamines with polyalkyating agents. Synthesized polyamines were separated and purified by metal complex formation and ion-exchange chromatography. They were characterized by X-ray crystal structure determinations of their metal complexes.

In cancer chemotherapy. it is becoming increasingly clear that the DNA topoisomerases play an active role in the expression of the cytotoxic action of drugs. The amino substituted azaanthraquinones have attracted much interest due to their possible role as topoisomerase inhibitors. In connection with our interests in the design and synthesis of potent topoisomerase inhibitor. we herein described the preparation of a series of benzoquinoxalinedione derivatives. These were designed based on the SAR of azaanthraquinones and structural analysis of products which are fitted with doxorubicin.

The unusal keto amino acid. (s)-2-amino-8-oxodecanoic acid(Aoda) is a biologically important constituent of the naturally occurring cyclic tetrapeptides such as apicidins. Consequently extensive chemical modifications of Aoda residue of apicidin were studied, and we are obtained the practical and versatile synthesis of the long-chained keto amino acids in enantlomerically pure form by alkylation with bromoketone and chiral Scholkopf auxiilary. (omitted)

Recent study indicated that terpyridine and its derivatives displayed highly active antitumor properties. In this presentation. derivatives of terpyridines having three pyridine moieties at 2',4',6'-position of central pyridine skeleton were prepared, and evaluated their cytotoxicity against several human cancer cell lines and topoisomerase I inhibitory activities. Most of the prepared compounds showed strong cytotoxicity compared to doxorubicln. In addition. several compounds displayed better cytotoxicity than that of doxorubicin. In addition, several compounds displayed better cytotoxicity than that of doxorubicin. Structure-activity relationship study was perfomed to be indicated that [2.2':6',2']terpyidine skeleton is important to show strong xytotoxicity. Significant topoxicity. Significant topoisomerase I inhibitory activity was not observed for prepared compounds.

Recently it has been demonstrated that selective cyclooxygenase-2 (COX-2) inhibitors retain the antiinflammatory effect but with markedly reduced GI toxicity compared to non selective inhibitors such as traditional NSAIDs. As a consequence, intense efforts have been made to develop selective COX-2 inhibtors during the last decade. Two compounds in this class. celecoxib and rofecoxib. are already in the market and are proved as potent and selective COX-2 inhibitors with much better gastric tolerance. However. there are still strong domands for a COX-2 inhibitor with improved efficacy and safety profiles. Here we report the synthesis and biological profiles of 1.5- and 4.5-disubstituted imidazole analogues as structural equivalents of cefecoxib and refecoxib. The imidazole analogues are overlapped well whth the 3D srructures of celecoxib and rofecoxib.

We synthesized various catechol ether type derivatives substituted by the hydrazine moiety and evaluated for their ability to inhibit PDE Ⅳ (Phosphodiesterase Ⅳ). These new compounds were synthesized from 4-methoxy-3-hydroxy benzaldehyde through 5 or 7 steps. Some of them have similar or more potent inhibitory activity against PDE Ⅳ than known PDE Ⅳ inhibitor. Ariflo (SB 207499). Structure activity relationship (SAR) and biological studies of described compounds will be discussed in detail. (omitted)

The significant antitumor activities of 3-arylisoquinolines promoted us to explore the structure-activity relationship of these compounds. A series of 3-Arylisoquinoline derivatives, which related to Benzo［c］ phenanthridine alkaloids. were evaluated for antitumor cytotoxicity against human lung tumor cell (A 549). We tried to study structure-activity relationship (SAR) of 3-Arylisoquinolines using the comparative molecular field analysis (CoMFA) method. (omitted)

(－)-${\alpha}$-narcotine( 1 R.9S) is one of the major bases in Papaver somniferum L.. the sourse plant for opium. while (－)-${\beta}$-narcotine(1R.9R) is a synthetic phthalideisoquinoline alkaloid. Although some advanced methods for the preparation of $\alpha$-narcotine have been developed using modified Bischler-Napieralski cyclization. the facile synthesis of $\beta$-narcotine has not further been attempted. supposingly because of its no clinical efficacy contrary to $\alpha$-narcotine having an antitussive effect. (omitted)

Capsaicin. the pungent component of chili pepper. opens a novel cation selective ion channel in the plasma membrane of peripheral sensory neurons. Capsaicin channel agonists induce pain upon topical application in the early stage. which is followed by a period of desensitization. Although the agonists have been studied as a analgesics, their initial irritancy became sever side effect. So competive antagonists have been pursued as a novel pharmacological agent for analgesics, rather than agonists. (omitted)

Deprotection of the benzyl group has been widely used in multi-step organic synthesis with a variety of reaction conditions. including catalytic hydrogenolysis. Lewis acids such as FeCl$_3$ or MgBr$_2$ and lithium naphthalenide. However. these procedures sometimes can be problematic with multifunctional substrates. such as unsaturated bonds during hydrogenolysis. an acid-labile moiety in FeCl$_3$ and a easily reducible functional group in lithium naphthalenide. (omitted)

A series of diaralkylthiourea derivatives was prepared and tested for its antagonistic activity against vanilloid receptor. In this study we explored the possibility of selected compound type (Ⅰ) with tetrahydronaphthyl group as rigid pendant moiety. Our premise for antagonistic activity of molecules was modeled on the capsazepine. the first antagonist for vanilloid receptor. These compounds (Ⅰ) showed less potent antagonistic activity than that of capsazepine. but they were devoid of agonistic activity. (omitted)

The reaction of N-acyliminium ion with a variety of nucleophiles is one of the powerful method to introduce various substituents at the a-carbon of an amine. Particularly this type of inter and intramolecular C-C bond formation can be effectively applied to the synthesis of the bioactive natural or unnatural compounds as well as many bioactive peptidomimetics. Accordingly. much attention has been devoted to the practical and efficient methods for the generation of acyliminium ion precursors though there are many important aspects in the reaction involving N-acyliminium ions. (omitted)

2-Arylthio-, 2-arylthio-5-methoxy-, 2, 3-bisarylthio-juglones and 2, 3-bisarylthio-5, 8-dimethoxy-1, 4-naphthoquinones were newly systhesized for the evaluation of antifungal activities. These derivatives were prepared by methylation of juglone and 2, 3-dichloro-5, 8-dihydroxy-1, 4-naphthoquinone. and by resioselective nucleophilic subsitution with arylthiols. All compounds were tested in vitro for their growth inhibitory activities against pathogenic fungi by the standard method. The MIC values were determined by comparison to flucytosine as a fungicidal standard agent. In general. In general. most juglone derivatives shows in vitro antifungal activities. Among them. 2-arylthio-5-methoxy-juglones showed most potent antifungal activities against all pathogenic fungi.

Heterocyclic compounds with oxygen atoms are known to have potent biological effect. The flavonoids. isoflavonoids. and coumarins which form the bulk of these compounds are very polar and have limited use as drugs which have to pass through membranes. The non-polar property is increased by exchange oxygen to selenium as a part of heterocyclic compound. Our group is focused on synthesizing selenoheterocyclic compound with the above property. (omitted)

We have previously reported the synthesis and cytotoxic activities of a series of azaanthraquinone derivatives on the model of doxorubicin(Dox). Dox is known to intercalate into DNA and to inhibit topoisomerase II activity. But in the case of Quinone compounds like Dox. its use is limited because of systemic toxicities. primarily cardiotoxicity and myelosuppression. In this study. we describe the synthesis of benzoquinoxaline derivatives as DACA analogue. DACA has a neutral chromophore and acridine moiety and posions both topoisomerases I and ll with DNA intercalating activity. In order to delineate the SAR of benzoquinoxaline derivatives. an effcient sythetic rout to the target compounds without quinone group. Various attempted removal of quinone from benzoquinoxlinedione was unsuccessful. Diels-Alder rout applied for the synthesis of the target compounds will be discussed.

Oxygen radicals are produced in many pathophysiologic states whether the event is a causal factor of illness or is a result of their progression. Oxygen radicals including superoxide anions. hydrogen peroxide are thought to be involved in a number of type of acute. and chronic pathologic condition in the brain and neural tissue. So the antioxidants have recently received much attention as therapeutic agent for the treatment of neurodegenerative disease. In this study. we describe synthesis of a series of chromenone derivatives as antioxidant agents. The target compounds are designed to include the structural frature of caffeic acid. flavoniod. and focopherol known as antioxidants.

2.5-Disubstituted-6-arylamino-4.7-benzimidazolediones were synthesized and tested for in vitro antifungal activities against pathogenic fungi. The 2-aryl-6-arylamino-5-chloro-4.7-benzimidazolediones were prepared by nucleophilic substitution on 2-Aryl-5.6-dichloro-4.7-benzimidazolediones with appropriate arylamines in good yields. TIte synthesized 4.7-benzimidazolediones were tested in vitro for their growth inhibitory activities against pathogenic fungi by the standard method. The MIC values were determined by comparison to llucytosine as a fungicidal standard agent. The most active potential among the 4.7-benzimldazoledione series was found for 6-arylamino-2-(2-pyridyl)-4.7-benzimidazolediones. which showed generally good activities against all tested Candida apecies and A. niger.

5-Arylamino-6-chloro-4.7-dioxoindazoles (DZs) were newly synthesized for the evaluation of antifungal activities. The compounds DZs were prepared by regioselective nucleophilic substitution of 5.6-dichloro-4.7-dioxoindazoles with appropriate arylamines in high yield. DZs were tested for their growth inhibitory activities against Candida species and Aspergillus niger. The MIC values were determined by the two-fold dilution method. In general. DZs showed in vitro antifungal activities. Among the tested compounds, DZ1, 3, 6, 7 and 12 showed potent antifungal activities against Candida species and Aspergillus niger. DZ7 was the most effective in preventing the growth of Candida species.

The reverse transriptase (RT) of HIV-1 is a proven target for inhibition of HIV-1 replication. Many nonnucleoside RT inhibitors (NNRTls) are in development stage for the clinical use: Among them. trovirdine (PETT). (thiophene) ethylpyridylthioureas (TET). and phenylethylpyridylureas (urea-PETT) are simple and flexible arylalkylarylureas. These are now considered to be very important as a potential therapeutics with remarkable antiviral activity against various mutant strains. (omitted)

Carbocyclic nucleosides are unique class in which a methylene group replaces the oxygen in the furan, which result in metabolic stability to endogenous phosphorylase. The biologically active natural carbocyclic nucleosides such as aristeromycin and neplanocin were found to possess interesting biological properties including antiviral and antitumor activity. (omitted)

Fifty of 3.4-diaryl-2(5H)-furanone derivatives were synthesized and evaluated for their cytotoxicity in a small panel of cancer cell lines. Eleven compounds in this series, were found to have significant cytotoxic activities with ED$_{50}$ values of less than 1 4{\mu}$M in most of the cell lines tested. Compound RTMSI, 3-(3.4, 5-trimethoxyphenyl)-4-(3-amino-4-methylamino)-2(5H)-furanone exhibited the most potent cytotoxic activity with ED$_{50}$ value of 0.003 4{\mu}$M and antitumor activity on BDF1 mice bearing Lewis lung carcinoma cells with inhibition ratio of 72 %.%.

Interleukin (IL)-5 appears to be one of the main proinflammatory mediators among a growing number of cytokines and chemokines that induce eosinophilic inflammation. Sophoricoside and their analogs isolated from Sophora japonica show relatively potent inhibitory activity of interleukin (IL)-5 as a small molecule. To identify structural requirements of this isoflavonone for its inhibitory activity against IL -5. isoflavonones. isoflavanones, and their glycosides were prepared and tested their inhibitory activity against IL-5. (omitted)

Recently. we have reported that several lipoxygenases products directly activate the capsaicin-activated channel as intracellular messengers in neuron. In particular, 12-(S)-hydroperoxyeicosatetraenoic acid turned out to be the most potent endogenous VR activator. This finding prompted us to search for a novel non-vaniloid VR agonists and antagonists. We have designed and synthesized a series of non-vanilloid VR binding ligands based on the structural simllarity between 12-HPETE and capsaicin, the natural VR agonist. Our recent studies on the development of selective vanilloid receptor agonists and antagonists will be presented.

Benzo［c］ phenanthridine alkaloids occurring in the Fumariaceae, Papaveraceae, and Rutaceae. posses numerous pharmacological activities, such as antitumor. antimicrobal and antifungal activities. Thus, they have attracted much interests of chemists and as the result, several total syntheses of these heterocycle structure were accomplished. Among that, procedures which involve 3-arylisoquinoline intermediates are useful methods and these synthons could be also applied to the preparation of other alkaloids. (omitted)

Prostaglandins are synthesized by the enzyme cyclooxygenase (COX). Both constitutive (COX-1) and inducible (COX-2) isoforms have been identified. COX-2 expression is stimulated by inflammatory mediators such as growth factors and cytokines. Most non-steroidal anti-inflammatory drugs (NSAIDS) inhibit both isoforms of COX. Recent evidence suggests that selective inhibitors of COX-2 may possess diminished side effects reletive to common NSAIDS. Novel isothiazoles and isoxazoles were identified as selective inhibitiors of cycloxygenase-2(COX-2). (omitted)

The carbocyclic nucleosides have extensively studied as a promising antiviral agents having chemical and metabolical stability. In our research program for discovery of antiviral drugs. some novel dimethylcyclopropyl nucleosides possessing additional methyl spacer between purine bases and the ring was synthesized. The important intermediate, dimethylcyclopropyl alcohol was synthesized from ethyl chrysanthemate via its ozonolysis, isomerization reduction. (omitted)

The structure of 1-phenyl-2-substituted thiourea derivatives have been studied and optimized for their cytotoxic activity. The three dimensional quantitative structure activity relationship (3D-QSAR) was investigated using comparative molecular field analysis (CoMFA). The result suggested that electrostatic and steric factors of 2-alkylureido-1-phenyl propanol derivatives were correlated well with cytotoxic activity. (omitted)

Metoprolol (MT) is one kinds of adrenergic beta-blockers. Its (S)-enantiomer is known to be more active than the (R). Recently. the x-ray structure of beta-blocker. (S)-propranolol (a-naphthyl analogue), complexed in a mould fungal cellulase. Cel7A. was reported and the (R)-form did not build any complex. And in our previous study the conformation and stability of MT in carboxymethylated beta-cyclodextrin (BCD) complex was determined by NMR. HPLC, UV and electrophoresis measurement. (omitted)

Three-dimensional quantitative activity relationship (3D-QSAR) study for a series of arylsulfonylimidazolidinone derivatives with antitumor activity was conducted using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices anaysis (CoMSIA). The in vitro cytotoxicity against human lung carcinoma (A549) exhibited a strong correlation with steric and electrostatic factors of the molecules. (omitted)

Corticosteroids have been used most frequently for inflammatory bowel disease.They are well absorbed and only a limited fraction of the dose is delivered to the inflammatory site in the colon. To reduce side effects by the systemic absorption. cOlon-specific delivery is highly desirable. We prepared prednisolone 21-sulfate sodium (PDS) and investigated its suitability as a colon-specific prodrug of prednisolone(PD). (omitted)

The 20 thiourea derivatives had been investigated for their cytotoxic activity using MTT assay. Cytotoxic activity was strongly influenced by the substituted alkyl chain length. but not by configuration of Cl and C2. The optimal alkyl chain length for cytotoxicity was C12. The 9 thiourea derivatives showed stronger activity than reference compound. B13. some of them gave 2-3 times stronger activity than B13. (omitted)

Platinum(II) coordination complex(cisplatin) has been currently used as one of the most effective compounds in the treatment of various solid tumors. However. its use has been limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program has been aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. (omitted)

We recently synthesized new platinum(II) complex analogs containing trans-1 and cis-l.2-diaminocyclohexane (DACH) as carrier ligands and L -3-phenyllactic acid(PLA) as a leaving group. Our platinum-based drug discovery program has been aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. (omitted)

In mammalian species, CpG dinucleotides are highly methylated with 60-90% methylation at the 5-position of cytosine. The pattern of DNA methylation in a cell dramatically affects the function of the DNA by switching genes on or off. Abnormal methylation events occur during aging and in the development of many cancers. Methylated CpG was reported recently to affect the reactivity of agents (mitomycin C and benzo ［a］pyrenediolepoxide) that can fromguanine adducts in DNA. (omitted)

In the previous study, we reported that 2'-hydroxy-4'-methxoychalcone, synthetic chalcone inhibited PGE2 production in TPA- stimulated rat peritoneal macrophages by inhibiting the induction of COX-2 protein. The present study was carried out to clarify whether 2'-hydroxy-4'-methoxychalcone inhibit angiogenesis by the experimental methods in vitro and in vivo. 2'-Hydroxy-4'-methoxychalcone decreased angiogenesis of both chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation inthe mouse Martigel plug assay. (omitted)

Protein-tyrosine phosphatase 1 B(PTP-l B). which plays a key role in insulin signaling. is rising as a fascinating target for type 2 diabetes and obesity. Many scientists in structural biology solved the three dimensional X-ray Crystal structure of this type of enzyme, so we could easily get the active site structure of PTP-1 B or complex structure with ligand. Our virtual screening study for PTP-1B exactly based on these crystal strucutures from public database. (omitted)

Pancratistatin is a highly oxygenated phenanthridone alkaloid. exhibits a high level of in vitro and in vivo cancer cell growth in inhibitory activity. and antiviral activity. The asymmetric synthesis of this alkaloid has been. accomplished from the commercially available (R)-(＋)-3-Butyn-2-ol. We utilized the Claisen rearrangment and metathesis to install stereogenic centers in the cyclohexene ring that has absolute chemistry. (omitted)

Antofine belongs to the Phenathroindolizidine group of alkaloids. This natural products exhibit interesting biological properties such as antitumour activity. and anti-inflammentory. Wittig reaction of phenathrenealdehyde with the phosponium salt provided the phenathreneazidealkene in good yield. Intramolecular 1.3-dipolar cycloaddition of the resulting azidealkent in refluxing benzene proceeded the imine. It was reduced with cyanoborohydride of Noyori's Asymmetric Hydrogenation. (omitted)

The Polyoxin complex is an antifungal antibiotics produced by Streptomyces cacaoi var. asoensis that exhibit marked and selective activity against pytopathogenic fungi. They incorporate carbamoylated dipeptides attached to the sugar moiety. Controlled alkaline hydrolysis of polyoxins result in several products. one of which has been identified as (＋)-(2S. 3S, 4S)-2-amino-3. 4. 5-trihydroxypentonic acid(polyoxamic acid). A variety of chemical syntheses of polyoxamic acid have been developed over several years. (omitted)

Costunolide which is known as a chemopreventive drug is a sesquiterpene compound isolated from Magnolia Sieboldii. and has antitumor and antiinflamatory activities. it is very hard to collect enough amount of natural extracts of costunolide for the activity studies. therfore. synthesis of costunolide derivatives is honestly needed. the aim of this research is to develope new methods for costunolide synthesis and to test biological activities. (omitted)

Costunolide. a sesquiterpene lactone is isolated from Magnolia Sieboldi. It is known to possess antitumour and anti-inflammatory activities. This compound is synthesized from Ihe easily available decalin dione using the ring cleavage approach to construct the ten-membered ring system. The two keys points in this work are the chiral inductionon the allyl alcohol moiety using Sharpless epoxidation reaction and opening of the eopxide with an organocuprate reagent which leads to a $\alpha$-exomethylene lactone. (omitted)

A number of 2',3'-deoxynucleosides have been discovered to possess significant antiviral activity against HIV-1 and other viruses. Since it has been suggested that proper conformation of the dideoxynucleosides in terms of ring puckering of the five-membered sugar moiety is required for them to exhibit antiviral activity a number of nucleoside analogues to fix sugar-ring puckering have been synthesize and evaluated for antiviral activity. (omitted)

Unmodified nucleosides exist in either S-type or N-type conformation, but due to the low energy barrier between this two dominating conformers a fast equilibrium between them exists in solution state. Therefore. many approaches to lock the puckering of the furanose ring in N-type or S-type have been made since HIV-1 reverse transciptase is able to discriminate between two conformationally locked carbocyclic AZT triphosphate analogues. (omitted)

2-Chloro-N6-(3-iodobenzyl)-adenosine-5'-methylcarboxamide (2-CI-IB-MECA) has been recognized to be one of the most selective agonists (Ki = 1.0 nM) for rat adenosine A3 receptor. On the basis of the high binding affinity of 2-CI-IB-MECA to adenosine A3 receptor. it was interesting to find out whether 2'- and/or 3'-hydroxyl group of 2-CI-IB-MECA is essential for the binding affinity to the receptor. (omitted)

(S) and (R) 12-HETE. endogenous eicosanoids. have recently been discovered to be implicated in a number of important biological activities. In particular. it has recently been reported by us that both the capsaicin-activated channel of sensory neurons and the cloned capsaicin receptor (VR1) are activated by the eicosanoids including these metabolites. We report herein a novel and efficient asymmetric synthesis of highly enantiomerically enriched 12(S)-HETE via enzymatic kinetic resolution of the key allylic alcohol synthon. (omitted)

Since adenosine A3 receptor has been cloned from rat brain. a number of compounds have been synthesized and evaluated for the binding affinity to this receptor. Among these. 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-methylcarboxamide (2-CI-IB-MECA) has been found to be one of the most selective agonists (Ki = 1.0 nM) for rat adenosine A3 receptor. On the basis of the high binding affinity of 2-CI-IB-MECA to adenosine A3 receptor. it was interesting to find out whether 2'-hydroxyl group of 2-CI-IB-MECA is essential for the binding affnity to the receptor. (omitted)

S-Adenosylhomocysteine hydrolase (SAH) catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L -homocysteine and has been an attractive target for the development of broad spectrum antiviral agents. Neplanocin A and 9-(dihydroxycyclopent-4' -enyl)adenine (DHCeA) have been known to inhibit SAH by cofactor (NAD＋) depletion mechanism and their inhibition is reversed by the addition of NAD＋ or dialysis. (omitted)

New and improved preparations of structurally modified nucleosides are important goals in synthetic organic chemistry because of the potential utility of these compounds as synthetic precursors of many biologically active molecules in cells. In our program to synthesize the bioactive nucleosides, such as AdoHcy hydrolase inhibitors and cyclic adenosine diphosphoribose(cADPR) analogues. (omitted)

Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defective site to initiate de novo tissue regeneration. In this respect. the availability of an appropriate biomaterial scaffold is crucial to allow chondrocyte growth and cartilaginous matrix deposition in a three-dimensional geometry. Hyaluronic acid (HA) molecules are anchored to the chondrocyte membrane via receptors, such as CD44. (omitted)

In an effort to search for the chemically and enzymatically stable carbonucleoside. we designed ［1'-fluoro-2', 2'-bis-(hydroxymethyl) cyclopropyl methyl］ purines. The underlying concept for our design is to seek relatively conformationally-locked compound with minimal structural disturbance from acyclic carbonucleoside such as acyclovir or penciclovir. To meet such a requirement. we need to introduce cyclopropane and fluorine moiety. (omitted)

Flavo.no.ids are a diverse group of phytqchemicals that are produced by various plants in high quantities. Dietary flavonoids in edible plants can be further subdivided into. several structural groups. The large number of compounds arises from various combinations of multiple hydroxyl and methoxyl groups substituting the basic flavonoid skeleton. The chemopreentive activity of flavonoids is dependent on their structural features. (omitted)

Cnidium Rhizome is a frequently prescribed herbal medicine in Korea, Japan as well as China, which has been successfully used in these countries for the treatment of diseases related to. gynecology, blood circulations and dental troublers in the name of 천궁. And it is circulated as the same chinese character, which is 천궁, although original plants are different as Cnidium officinale in pharmacopoeia of Korea or Japan and Ligusticum chuanxiong Hort. In that of China. (omitted)

The ginsenosides content of ginseng radices extracts were investigated in the Food Code and the Shibata methods. Crude saponins and each ginsenosides content of the manufactured ginseng radix alba extracts were revealed to be higher than those of the manufactured ginseng radix rubra extracts. A large amount of a ginseng radix rubra specific component(ginsenoside Rg3) was shown in the manufactured ginseng radix rubra extracts. Also a large amoung of ginsenoside Rg3 was shown in the manufactured ginseng radix alba extracts. (omitted)

Mesaconitine and hypaconitine were isolated from Cho O and identified by the spectroscopic methods. The contents of alkaloid (mesaconitine. aconitine and hypaconitine) in the Cho O and its processed products were determined by high performance liquid chromatography. Processed 1 and 2 methods reduced the contents of alkaloid than those of processed 3 and commercially processed Aconiti Tuber powder. (omitted)

Fruits of Hovenia dulcis T. (Rhamnaceae) was called ′jiguja ′ in oriental medicine which has been used for diuresis, remove of hangover and leaves has been used for detoxified the alcohol. From the MeOH Extraction. five compounds were isolated by column chromatography and elucidated as quercetin quercetin-3-O-rhamnose. quercetin-3-O-gal(6"1") rha, quercetin-3-O-glc(6"${\rightarrow}$1")glc, and kaemferol through specroscopic methods. (omitted)

Pharbitis nil Choisy (convolvulaceae) is an annual vine plant and grows at the wayside of Korea. Japan. China and India. The seeds of blue or red Pharbitis nil Choisy. Pharbitidis Semen, is black or red-brown. This seeds have been used as a purgative. From a preliminary experiment. Pharbitidis Semen exhibited anti-cancer activity. MeOH extract of this seeds was subsequently fractionated into four parts: methylene chloride, ethylacetate, n-butanol and water fractions. (omitted)

In our previous study, the leaves of Ixeris sonchifolia afforded two new and two known guaiane type sesquiterpene lactones by activity-guided fractionation. Now we report additional isolation of sesquiterpene lactones from the roots of Ixeris sanchi!a!ia. They are glucozaluzanin C and ixerin H. Ixerin H is germacranolide type sesquiterpene glucuside. Theil structures were determined by 1 D and 2D NMR spectroscopy. (omitted)

Rumex crispus (Polygonaceae) is a well known perennial plant. which is called So-Ri-Jaeng-Yi. growing in the field and on the roadside. It has been used as a Korean Folk medicine in treating of acute and chronic cutaneous disease. cathartics, fever and jaundice. Also, the seed of this plant has been used as only a folk medicine for the treatment of digestion problems, liver diseases and many sorts of tumor. So we examined analgesic activity, anti-inflammatory activities and hepatoprotective activity using MeOH extraction and BuOH fraction in this plant. (omitted)

Albizzia julibrissin Durazz (Leguminosae) is a small domed to flat-topped, spreading tree with smooth. gray-brown bark and doubly pinnate leaves. It grows abundantly in Korea. The dried stem bark of A. julibrissin is used as a tonic in China, Japan and Korea. From the stem bark of A. ju/ibrissin, a new unsaturated hydroxy fatty acid was isolated and characterized as 4-hydroxy-dodec-2E-enedioic acid on the basis of several data including 2D-NMR. (omitted)

Prunella vulgaris var. lilacina (Labiatae) has been used as a Korean traditional medicine for the treatment of. fever. inflammation. urinary disadvantage and cancer. We previously isolated three $\alpha$-amyrin triterpenoids from n-butanol-I extract. They are 3$\alpha$-hydroxyurs-12-ene-28-oic acid (ursolic acid). 2$\alpha$, 3$\alpha$-dihydroxyurs-12-ene-28-oic acid and 2$\alpha$. 3$\alpha$. 19$\alpha$ trihydroxyurs-12-ene-28-oic acid (euscaphic acid) exhibiting cytotoxicity and topoisomerase I inhibition. (omitted)

This study was carried out to obtain basic informations that can be used in index for Korea ginseng (Panax ginseng C.A. Meyer) cultivated in East Asia (Geumsan. Ganghwa. Punggi. Umsong, Jinan, Hongchon. Jilin. Nagano). Ginsenosides composition in various Panax ginseng roots cultivated in different places and years were carried by the Shibata method. The average about total saponins and each ginsenosides content of four year-age Ginseng Radix aquosa cultivated in Korea were higher than those of ginseng cultivated for its longer period. (omitted)

On the quality control of commercial Zingiberis Rhizoma and its processed product. quantitative determination of 6-gingerol using HPLC method has been conducted. Quantitative analysis of 6-gingerol in Zingiberis Rhizoma showed average 0.359% in 14 samples collected throughout the regions of Korea. The contents of 6-gingerol in Zingiberis Rhizoma were decreased during the processing procedure(0.306%). (omitted)

The roots of Juglans mandshurica Maximowicz (Juglandaceae) have been used as a folk medicine for treatment of cancer in Korea. Several naphthoquinones and naphthalenyl glucosides from Juglans species have been reported (1-7). In the course of isolating cytotoxic compounds from the roots of this plant. we have isolated six naphthalene glycosides. four tetralone, one naphthalene carboxylic acid glucoside and nine diarylheptanoids (8-13). (omitted)

Triterpenoids. Ursolic acid (1). 23-hydroxyursolic acid (2). and tormentic acid (3) were obtained by the hydrolysis of BuOH fraction of Cussonia bancoensis extract and further chromatographic isolation to test antinociceptive and anti-inflammatory effect of C. bancoensis (Aratiaceae). Compound 1 and 2 exhibited anti-nociceptive effects, which were determined by acetic acid-induced writhing test and hot plate test. However. the effect of tormentic acid was not significant (omitted)

Bioassay-directed chromatographic fractionation of a methylene chloride extract of Ailanthus altisshima indicated the presence of 20(S). 24(R), epoxy-25-hydroxydammarane-3-one(compound 1. ocotillone). which was isolated from this plant for the first time. Antimicrobial activity of compound 1 was measured by its degree of growth inhibition against bacterial and fungal cells and by a hemolytic assay with human erythrocytes, respectively. (omitted)

We have reported cytotoxicities based on several types of sugar linkage in saponins in addition to antitumor and antiinflammatory effects. In order to find further structure-activity relationship on the cytotoxicity of saponins. we intended to isolate oleanane disaccharides Irom the saponin-containing extract of Akebia Quinata (Lardizabalaceae). (omitted)

AIzelin (1) and quercitrin (2) isolated from the EtOAc-soluble fraction of the leaves of Litsea japonica Jussieu (Lauraceae) showed inhibitory activity against classical pathway complement system with 50% inhibitory concentration ($IC_{50}$/) values of 112.2 and 198.2 $\mu\textrm{g}$/$m\ell$. respectively. For the structure-activity relationship of flavonoids on anti-complement system. myricitrin (3) from JUQ/ans mandshurica Maximowicz (Juglandaceae) also tested anti-complement activity. while this was devoid of any significant activity. (omitted)

A novel triterpene saponin (1). deapioplatycoside E ［3-O-$\beta$-D-glucopyranosyl-(1$\rightarrow$6)-$\beta$-D-gluco- pyranosyl-(1$\rightarrow$6)-$\beta$-O-glucopyranosYI-2$\beta$.3$\beta$.16$\alpha$.23.24-pentahydroxyolean-12-ene-28-oic acid 28-O-$\beta$-D-xylopyranosyl-(4$\rightarrow$1)-$\alpha$-L -rhamnopyranosyl-(1$\rightarrow$2)-$\alpha$-L -arabinopyranoside］ including seven known saponins (2-7) was isolated from the water extract of the roots of Platycodon grandoflorum (Campanulaceae). The chemical structure of 1 was determined based on the spectral and chemical evidence. (omitted)

Twenty Artemisia species are distributed in South Korea and rich in terpenoids. Artemisia rubripes (Compositae) has been used as a Korean traditional medicine for stomachache. vomiting. diarrhea and hemostatic agent. The antimutagenic effect and essential oils of Artemisia rubripes were reported, but phytochemical study has not been fully investigated. As part of our systematic study on the terpene constituents of Artemisia species. we have investigated A. rubripes (1 kg) collected at Dae-Kwan ryung. Gangwon Province on Aug. 1997. (omitted)

In search for plant-derived cytotoxic compounds, it was found that the MeOH extracts obtained from Amanita pantherina(DC. ex Fr.) Krombh exhibited significant cytotoxic activity against human tumor cell line. The classical fractionation on the basis of the inhibitory activity upon the growth human tumor cell line. in vitro, and repeated column chromatography afforded several cytotoxic compounds from Amanita pantherina (DC, ex Fr.) Krombh. (omitted)

Alismatis Rhizoma is originated from the rhizome of Alisma plantago-aquatica L. var. orientale Samuelson or A. canaliculatum A. Br. et Bouche (Alismataceae). Prostane-type triterpenes, guaiane-type sesquiterpenes, and kaurane-type diterpenes have been reported as the main canstituents from these plants. Four prostane-type triterpenes. alisol B 23-acetate (1). alisol C 23-acetate (2), alisol B (3). and alisol A 24-actate (4). were isolated from the EtOAc-soluble fraction of this dried rhizome. (omitted)

The barks o.f Pinus densiflara representative Pinus species graws in Korea, have been used for oriental traditional medicine as the remedies for rheumatitis. hemorrhage and cancer. Water soluble fraction of 80% acetone extracts from the barks af Pinus densiflera (PDB) showed nitrogen monoxide(NO) production inhibitory activity in IFN-${\gamma}$. LPS stimulated RAW 264.7 cell. (omitted)

Siegesbeckia pubesence (Cempesitae). a perenial herb, is widely distributed in our country and has been used for rheumaic arthritis, hypertension, malaria. neurasthnia and snake-bite in traditional Chinese medicine. On reviewing the literatures of this plant. diterpenoids and alkaloids were isolated and some pharmacological activities were investigated. As part of our systematic study fer Korean Compositae plants, we have investigated Siegesbeckia pubesence (7kg), cellected from Mt. Odae on Aug. 2001. (omitted)

As part of a research program on the bioactive terpene constituents of Korean compositae plants. we have investigated Cacalia koraiensis (compositae). collected from Gangwon Province on August 2001. On reviewing the literatures of this species. triterpenes and pyrrolizidine alkaloids were isolated and some pharmacological activities were investigated. This species have been used for tinea and spasmolysis However. chemical constituents of this plant have not been reported. (omitted)

S.deltoides (Compositae) distributed widely in Korea. China. It is edible as a food additive. but there has been no study on chemical constituents. Therefore. we isolated nine compounds from S.deltoldes. On the basis of spectroscopic evidence. the structure of these compounds were characterized as lupeol( 1), $\alpha$-amyrin(2).$\beta$-amyrin (3), ursolic acid(4), nonacosanol(5), nonacosanoic acid(6). mixture of $\beta$-sitosterol. stigmasterol and campesterol (7), $\beta$-sitosteryl-3-O-$\beta$-D-glucopyranoside(8), stigmasteryI-3-O-$\beta$-D-glucopyranoside(9). (omitted)

In continuing search for BChE-inhibitory compounds from Korean marine algae. we found a highly potent inhibitory activity in the methanolic extract of Sargassum species. After partition of the MeOH extract between $CHCl_3$ and 30% MeOH. the former layer was subjected to a series of ODS flash chromatography. silica column chromatography. and preparative TLC to afford three compounds (1-3). Detailed structural elucidation of them is in progress. Compound 1 showed potent BChE-inhibitory activity with $IC_{50}$ values of 11 ng/mL. (omitted)

Acyl CoA:diacylglycerol acyltransferase (DGAT) is a key enzyme involved in triacylglycerol synthesis. Too much accumulation of triacylglycerol in certain organs and tissues of the body causes high risk conditions of fatty liver. obesity and hypertriglyceridemia. leading to serious diseases of atherosclerosis. Therefore, DGAT inhibition may be worthwhile strategy for the treatment of triglyceride metabolism disorders. such as obesity or hypertriglyceridemia. (omitted)

Phytochemical examination of Barks of Ulmus macrocarpa isolated two flavanone, three flavanonol, three flavan 3-ol and one procyanidin compounds. We also determinated the antioxidative activity of these compounds by measuring the radical scavenging effect on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Three flavan 3-ol (catechin, epicatechin and catechin-7-O-$\beta$-O-xylopyranoside) and procyanidin B1 showed significant antioxidative activity. (omitted)

Some of the dammarane-type saponins. ginsenosides of Panax ginseng C.A. Meyer (Araliaceae) are now well established as a potent chemotherapeutic agent against a wide variety of aliments. Its various pharmacological and biological activities have been thoroughly reviewed (S. Shibata, 2001). The limited supply of the drug from the original source. the hairy root of the Panax ginseng promoted intense efforts to develop alternate sources and means of production. (omitted)

Neuroscience and molecular biology studies show that inappropriate butyrylcholinesterase (BuChE) activity as well as acetylcholinesterase (AChE) activity increases the risk and/or progression of Alzheimer's disease. BuChE may also regarded to participate in the transformation of Abeta (${\beta}$-amyloid) from an initially benign form to an eventually malignant form associated with neuritic tissue degeneration and clinical dementia. (omitted)

The MeOH extract of the twig of Marus alba L. (Moraceae) inhibited strong lipid peroxidation activity. Five antioxidative compounds were isolated through activity-guided fractionation. and identified as 6-geranylapigenin (1). 6-geranylnorartocarpetin(2). resveratrol (3). oxyresveratrol (4). quercetin (5) by physicochemical and spectrometric methods. In order to evaluate the antioxidant effect of these compounds. the lipid peroxidation inhibitory activity test were performed. Compounds 1-5 showed greater activity than tocopherol. (omitted)

Eight compounds were isolated from the MeOH extracts of Erythrina senegalensis for HIV-1 protease inhibitors. Their structures were elucidated as eight isoflavonoids by spectroscopic analysis. These compounds showed dose dependent inhibitory activities on HIV-l protease with $IC_{50}$ values from 0.5 to 30.0 ${\mu}$M. (omitted)

Prostaglandins (PGs) and nitric oxide (NO) are essential to maintain homeostasis and defensa systems in human beings. However. overproduced PGs and NO by inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS), respectively. cause tissue damages. chronic inflammation. and carcinogenesis. In this view. the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory or cancer chemopreventive agents. (omitted)

Phellinus linteus has been used as anti-tumor and immuno stimulating agents in folk remedies. From precipitate of MeOH ex. by activited guided fractionation. 5.8-epidioxy ergosta-6.22-dien-3ol. palmitic acid. linoleic acid, and methyl linolate. 3.4-dihydroxybenzoic acid methylester and 4-(3'4'-Dihydroxyphenyl)-3-butene-2one were isolated. DPPH method was used to examine of antioxidative activity of the isolated compounds. As the result, 3.4-dihydroxybenzoic acid methylester, and phenolic compound. 4-(3'4'-Dihydroxyphenyl) -3-butene-2one were found to be a scavenger of 1,1-diphenyl-2-picrylhydrzyl radical. (omitted)

Prunus serrulata var. spontanea(Rosaceae) is a large sized tree widely distributed throughout Korea. The red fruits are edible and are used in traditional folk medicine against heart failure from beriberi. dropsy. mastitis, an emmenagogue, and toothache. Also. the bark of P. serrulata var. spontanea has been used for detoxification. and relaxation and as an antitussive in traditional Korea medicine. (omitted)

As described previously. we reported twenty two compounds including one naphthoquinone. eight diarylheptanoids, two tetralone. one sesquiterpenoid. one diarylheptanoid glucoside, two tetralone glucosides. one naphthalene carboxylic acid glucoside and six naphthalenyl glycosides were isolated from the roots of Juglans mandshurica (17-22). Here we report that al of these compounds and a known triterpene are tested for the inhibitory effects against DNA topoisomerases I and II activities. (omitted)

Angelicae tenuissimae ia a plant often used in traditional Korean medicine. It has been used as analgesic. antipyretic and anti-inflammatory agent. However its component and precise modes of neuropharmacological action have not been reported. In the present study, we investigated the protective effects of A. tenuissimae and it's component on ischemic damage induced by oxygen and glucose deprivation in rat hippocampal slice. (omitted)

Polygoni Radix. the root of Polygonum cuspidatum (Polygonaceae) has been used as treatments of dermatitis. gonorrhrea. favus athlete's foot. inflammation in traditional medicine. Oxygen free radical injury and lipid peroxidation have been suggested as major causes of atherosclerosis. cancer. liver disease. and the aging process. In order to evaluate antHipid peroxidative effect. Polygoni Radix was fractionated and then its fractions were examined by liver homogenate MDA by TBARS assay and DPPH (1.1-diphenyl-2-picrylhydrazyl) radical scavenging activity. (omitted)

Peroxisome proliferator-activated receptor (PPAR)-$\gamma$ is a nuclear hormone receptor family that plays an important role in the transcriptional regulation of genes in cellular lipid and energy metabolism. In our search for Iigands for PPAR-$\gamma$ from natural resources. two phenylpropanoids. 3.4.5-Trimethoxy cinnamylalcohol (1) and 3.4.5- Trimethoxy cinnamaldehyde (2). were isolated as PPAR-$\gamma$ agonists from the MeOH extracts of Zanthoxylum schinifolium Sieb. & ZUCCo (Rutaceae) by activity-guided fractionation. These two compoundS bind and activated PPAR-$\gamma$ transcriptional activity in a dose dependent manner assessed by ligand-binding assay. While the maximum activities for PPAR-$\gamma$ of these compounds were comparable with that of rosiglitazone. which is currently used in the treatment of Type II diabetes. the potency of these compounds were much weaker than rosiglitazone ($ED_{50}$=t.2$\mu\textrm{M}$) with the $ED_{50}$ values of 9.08 and 4.08 $\mu\textrm{M}$. respectively. To examine the structure-activity relationship of phenylpropanoids. we prepared several phenylpropanoid derivatives and measured the activity. We observed that substituents at 4'- position could playa key role in determining the potency for PPAR-$\gamma$ agonistic activity .

Rhus verniciflua Stokes (RVS) is a widely used herbal plant with various biological properties. Our previous study using in vitro platelet aggregation in whole blood showed that ethyl acetate layer of RVS had strong anti-aggregatory activity. In this study. to investigate the anti-aggregatory activity and antioxidative effects of RVS ethyl acetate layer. the layer was subsequently fractionated by ODS columm chromatograph (50% MeOH). As a result. the fraction 3 was most inhibited the aggregation of platelet in rat whole blood induced by thrombin and all fraction of RVS was detected strong antioxidative effect. (omitted)

Gleditsia sinensis Lam. (Leguminosae) is a perennial shrub distributed in Gyeongju in Korea and throughout China. Its thorns called "Jo Gak Ja" (Korean name) or "Zao Jia Ye (Chinese name) have been known to possess an antiinflammatory effect. Korean "Jo Gak Ja". a speciality of Gyeongju. is much longer and thicker than that of Chinese one. (omitted)

There is now increasing evidence that free radicals and active oxygen species are involved in a variety of pathological events. often associated with ageing. Free radical-mediated cell damage and free radical attack on polyunsaturated fatty acids result in the formation of lipid radicals. These lipid radicals react readily with molecular oxygen to produce peroxy radicals responsible for initiating lipid peroxidation. The peroxidation of cellular membrane lipid can lead to cell necrosis and considered to be implicated in a number of pathophysiological conditions as well as in the toxicity of many xenobiotics. (omitted)

Free radical-mediated cell damage and free radical attack on polyunsaturated fatty acids result in the formation of lipid radicals. These lipid radicals react readily with molecular oxygen to produce peroxy radicals responsible for initiating lipid peroxidation. The peroxidation of cellular membrane lipid can lead to cell necrosis and considered to be implicated in a number of pathophysiological conditions as well as in the toxicity of many xenobiotics. DPPH is known to abstract labile hydrogen and the ability to scavenge the DPPH radical is related to the inhibition of lipid peroxidation. (omitted)

Blood monocytes are the precursors for the lipid-laden foam cells of early atherosclerotic lesions. Monocyte chemoattractant protein-1 (MCP-1), a CC chemokine. and chemokine receptor 2 (CCR2) playa crucial role in the recruitment of monocytes to the vascular lesion. Using the human monocyte THP-1 cell line. we investigated the inhibitory effects of methanol extracts of 127 medicinal herbs on MCP-1-induced chemotaxis. (omitted)

Melanin biosynthesis inhibitors are useful not only for the materials used in cosmetics as skin-whitening agents but also for the remedy of hyperpigmentation. In order to find the new skin-whitening compounds from the natural products. screening of tyrosinase and melanin biosynthesis inhibitory activities in vitro has been carried out. The MeOH extracts and/or fractions of Polygoni multiflori Radix, Dalbergiae odoriferae Lignum. Solnani nigri Herba. Polygoni cuspidati Radix. POlygoni multiflori Ramulus. Salviae Radix showed tyrosinase inhibitory effects. Four methanolic extracts also showed melanin biosynthesis inhibitory effects in B-16 melanoma cell line.

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in the arteries. Monocytes/macrophages are involved in many aspects of the development of atheroscleotic plaques. It is known that the intercellular adhesion molecule-1 (ICAM-1) expressed preferentially on endothelial cells of atheroscleotic plaque. promotes local adhesion and transendothelial migration of monocytes, neutrophils. and lymphocytes. Using the human promyelocytic leukemia HL-60 cell line, we investigated the inhibitory effects of methoanol extracts of 175 plants on ICAM-1/LFA-1 mediated cell adhesion. Eight kinds of methanol extracts of tested plants inhibited PMA-induced homotypic aggregated cell adhesion. Eight kinds of methanol extracts of tested plants inhibited PMA-induced homotypic aggregation of HL-60 cells without cytotoxicity at the concentration of 6.25 ${\mu}$g/ml. $CHCl_3$ extracts (1.0 ${\mu}$g/ml) of Saururus chinensis and Chloranthus japonicus significantly inhibited agregation of HL-60 cells without cytoxicity.

In connection with our studies on the isolation of hepatoprotective constituents from natural products. we have recently reported hepatoprotective compounds including phenolic bakuchiol. diarylheptanoids. furocoumarins. In the course of continuing efforts. the aqueous extract of the roots of Agrimonia pilosa Ledeb. (Rosaceae) was found to exhibit promising hepatoprotective activity. A. pilosa is a perennial herb distributed throughout South Korea. and its roots have been used as the hemostatic. antimalarial. and antidysenteric agent in oriental medicine. Chemical investigation of the aqueous extract of the roots of this plant. as guided by hepatoprotective active catechin (2). Compound 1 showed hepatoprotective effects on both tacrine-induced cytotoxicity in human level derived Hep G2 cells and tert-hydroperoxide-induced cytotoxicity in rat primary hepatocyles with $EC_{50}$ values of 66.2 $\pm$ 2.8 and 22.9 $\pm$ 2.6 $\mu\textrm{M}$ respectively.

Diabetic nephropathy is major chronic complication of diabetes mellitus. Advanced glycation endproducts(AGEs) are largely involved in the pathogenesis of diabetic nephropathy. The irreversibly formed AGEs do not return to normal even if hyperglycemia is corrected and continue to accumulate over the lifetime of protein. The AGEs inhibitor. aminoguanidine(AG), is the only protein glycation inhibitor currently under development. its safety however is desirable. To find possible AGEs inhibitor in herbal medicines, bovine serum albumin was added to a mixture of sugars and some of processed. unprocessed herbal medicines or AG. Cyperi rhizoma was processed in four different methods according to chinese pharmacopoeia and traditional literatures. In comparision to the negative control with no inhibitor and positive control with AG. alcoholic extracts of these processed cyperi rhizoma proved to have more potent inhibitory activities than that of unprocessed cyperi rhizoma. These results revealed that some processed herbal medicines have a more potent in vitro inhibitory action on AGEs formation than AG. suggesting the possible candidate for diabetic nephropathy from the processed herbal medicines.

Rosmarinic acid (1) and methyl rosmarinic acid (2), isolated from the ethyl acetate soluble fraction of the methanolic extract of Salvia miltiorrhiza Bunge (Lamiaceae) were found to be the tyrosinase inhibitors and scavengers of 1, 1-diphenyl-2-picrylhydrzyl (DPPH) radical. Compounds 1 and 2 inhibited the oxidation of L-tyrosine catalyzed by mushroom tyrosinase with $IC_{50}$/ of 16.8 $\mu\textrm{M}$ and 21.5 $\mu\textrm{M}$. respectively. It compared well with kojic acid. a well-known tyrosinase inhibitor. with an $IC_{50}$ of 22.4 $\mu\textrm{M}$. The inhibitory kinetics, analyzed by a Lineweaver-Burk plot, found rosmarinic acid and its methyl ester to be competitive inhibitors with $K_{i}$ of $2.35{\times}10^{-5}M$ and $1.52{\times}10^{-5}M$ respectively. In addition, compounds 1 and 2 showed the scavenging activities on DPPH radical, with $IC_{50}$ of 4.27 $\mu\textrm{M}$ and 3.05 $\mu\textrm{M}$. respectively. These scavenging effects were more potent than that of L-ascorbic acid ($IC_{50}$ = 11.75$\mu\textrm{M}$).

The antifungal activities of the essential oils from Citrus borgamia. Ciderus atlantica. Cymbopogon ditratus, Eucalyptus globulus. Juniperus communis. Lavandula angustifolia. Melaeuca aterinfolia. Pelargonium graveolens. Pogestemon patchouli. Rosmarinus officinalis. Styrax tonkinensis. and Thymus vulgaris, which are recommended for the treatment of microbial infections in aromatherapy and complementary medicines. were tested against Trichophyton spp. The activities were measured by broth dilution method and disk diffusion assay. As the results, most of the test oils inhibited growth of T. tonsurans. T.mentagrophytes. T. ferugineum. and T. rubrum. Eapecially, the essential oils from C. atlantica. C. ditratus. e. globulus, and P. graveolens showed the strongest activity among the tested herb oils showing MICs between < 0.09 and 0.39 mg/ml.

This research was undertaken to find the in vitro anti-inflammatory action of the essenetial oil (CS-oil) extracted from Chrysanthemum sibiricum (Compositae) herbs. We investigated the effects of the CS-oil not only on the formation NO and $PGE_2$ and TNF-$\alpha$ but also on inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage 264.7. The data obtained were consistent with the modulation of iNOS enzyme expression. (omitted)

Head of Panax ginseng C. A. Meyer indicates its growth number of years and has been widely used for supplying energy to weaklings or used as vomit. Butanol fraction of Panax ginseng head was significantly effective on gastritis and ulcer models in rats. and also had anti-oxidative properties in the previous study. It has been well established that gastric ulcer is induced by imbalance between aggressive factors and protective factors. and the oxidative reaction makes the lesions on gastric mucosal injury severer. (omitted)

Cordyceps has been used as a tonic for replenishing vital function in Chinese traditional medicines. As an attempt to obtain fundamental data for the kidney function, MeOH Ex. and its hexane. ethyl acetate, butanol and water fractions of cultivated Cordyceps pruinosa on mercuric chloride induced renal failure rats were investigated. Urin volume. blood parameters(urea nitrogen. uric acid. creatinine) and urinary electrolytes content (natrium. potassium. chloride) were determined. MeOH extract and butanol fraction showed diuretic effect. (omitted)

Cornus officinalis has been used as protective drug for liver and kidney function. In order to evaluate the effect on renal function of Corni Fructus. We measured urine volume, chemical parameters(urea nitrogen. creatinine, uric acid). electrolytes($Na^{+}$, $K^{+}$, $Cl^{-}$) in serum and urine. Furosemide showed significant urine volume. serum and urine parameters, but Corni Fructus showed normal level parameters by dose increasing in rats.

Current therapeutics for osteoporosis are often associated with adverse effects with long-term use. The purpose of this study was to find out herbal drug interaction and to apply an alternative drug candidate for osteoporosis based on a traditional medicinal herb that may have fewer side effects and less uterine hypertrophy. Effect of 219-H. a mixed herbal extract including Astragali Radix. was investigated on osteoporosis in vitro and in vivo models. (omitted)

The H2O and 50% extracts of herbal medicines(HM) combinations which were consisted of Acanthopanacis Cortex. Phragmitis Rhizoma. Chaenomelis Fructus. Pruni pseudocerasi Semen and rice bran were prepared and administered orally before 40% ethanol administration in the males S.D rats. The 50% ethanol extract of HM (HM50E) showed blood alcohol decreasing activity and was fractionated again into HM50El and E2 by Sephadex LH-20 gel column chromatography. HM50E2 showed more effective blood ethanol decreasing activity than HM50El. (omitted)

We investigated the effect of tectorigenin (1) with hypoglycemic and hypolipidemic effects on Phase I and II enzymes and TF activity to elucidate the action of an immunosuppressive compound (1) in the diabetic rat. Compound 1 was obtained from the hydrolysis of tectoridin easily isolated from the flower of Pueraria thunbergiana(Leguminosae). Puerariae Flos has been used as therapeutics for diabetes mellitus in traditional medicine of Korea. (omitted)

Aging and estrogen cleficiency after menopause induce bone loss and result in osteoporosis. This study was investigated effects of n-hexane fraction (Hx) extracted from Astragali Radix on osteoporosis with osteoblast-like cell line (MG-63 and Saos-2) and an ovariectomized (OVX) rat model. Proliferation of osteoblast-like cells. MG-63 and Saos-2. was tested with MTT and alkaline phosphatase (ALP) assays. (omitted)

The rhizomes of Cnidium ollicinale Makino (Umbelliferae) has been used as sedatives and analgesics in the Traditional Medicine in Korea. The essential oil of this rhizomes has been reported to possess CNS depressant activity. however, its analgesic activity has not yet been investigated. (omitted)

The plant Ligularia fischerivar. spiciformis(Compositae) is a candidate for available functional foods. It has been used to treat diabetes mellitus and rheumatoid arthritis. We have reported the isolation of a new eremophilanolide named 6-oxoeremophilenolide and cytotoxic intermedeol together with the isolation of hydrophilic constituents. chlorgenic acid. 3.4-di-O-caffeoylquinic acid(1). and 5-O-［1-butyl］-3.4-di-O-caffeoylquinic acid. (omitted)

Aconiti Tuber (Aconitum spp. tuber, Ranunculaceae) which contains bioactive but toxic alkaloids has been used as analgesic. cardiotonic, diuretic. and stimulant. We have previously reported two new C-19 norditerpenoid alkaloids and five known norditerpenoid alkaloids. Further study has now led to the isolation of two new norditerpenoid alkaloids. 14-O-anisoylneoline and 14-O-veratroylneoline. (omitted)

Quercus species have been used for diarrhea. dysentery, dermatitis. haemoptoe, and haemorrhagia in Korean folk medicine. Specially Quercus salicina have been used for diuretic. anti-inflammatory. antiedemic. and litholytic agent. In order to investigate the efficacy of antioxidative activity the activity guided fraction and isolation of physiologically active substance were performed. (omitted)

Kyonin(Armeniacae Semen)is the herb medicine that contains amygdalin as a major ingredient. Amygdalin in water is decomposed into benzaldehyde. HCN. and glucose by emulsin. a hydrolysis enzyme in kyonin. A useful and practical method for the optimum extraction condition of amygdalin without enzymatic hydrolysis is required. The extraction yield of amygdalin of natural formula kyonin was 0.5% from crude powers. 0.7% from small pieces. 1.2% from half pieces and 2.7% from whole pieces. (omitted)

A high-performance liquid chromatographic method was developed to determine the quantities of curcumin and glycyrrhizin in two different oriental herbal preparations of Kamijadowhan (KMD. NKMD). Two compounds were separated in less than 10 min with a Nova-Pak $C_{18}$ column ($3.9{\times}150$ mm ($5{\mu}$ particle size) by linear gradient elution using 0.03% (v/v) phosphoric acid-acetonitrile (60:40. v/v% at 0 min; 40:60 v/v% at 6 mini as the mobile phase at a flow-rate of 0.8 ml $min^{-1}$. (omitted)

Tonin(Persicae Semen)is the herb medicine that cntains amygdalin as a major ingredient. Amygdalin in water is decomposed into benzaldehyde. HCN. and glucoseby emulsin. a hydrolysis enzyme intonin. A useful and practical method for the optimum extraction condition of amygdalin without enzymatic hydrolysis is required. The extraction yield of amygdalin of natural formula tonin was 0.1 % from crude powers. 1.4% from small pieces. 3.5% from half pieces and 2.4% from whole pieces. (omitted)

Gastrodia elata Blume belongs to Orchidaceae, its steamed and dried rhizomes are very important herbal medicines used for the medical treatment of headaches. migraine. dizziness, epilepsy, rheumatism. neuralgia. paralysis and other neuralgic and nervous disorders. Although phytochemical studies of the rhizome have revealed the presence of several phenolic compounds. in which a phenolic glycoside. gastrodin (C13H18O7). is a major consituent, so far, there is no report on the studies of its aerial part. (omitted)

The fruits of cardamon (family Zingiberaceae) are used in traditional medicine for the treatment of several ailments. such as stomach disorders, liver abscess, and infection of the throat, and as a common spice as well, Amomum tsao-ko Crevost et Lemarie. a Zingiberaceous plant called "초과" in korea, is an oriental folk medicinal herb for the treatment of stomach illness. The present paper reports the isolation of the constituents of the fruits of this plant and their antifungal activity. (omitted)

Nuclear-kappa B(NF-$\kappa$B) plays a role in the regulation of genes responsible for inflammatory and immune responses as well as growth control of cells. A cell-based assay system for guiding NF-KB activity was developed to determine the influence of activated NF-KB in human keratinocytes. It suggested that this system could be used to determine the quantitative measurement of NF-$\kappa$B activity in the human skin and allow the monitoring of anti-inflammatory agent for dermatological means from various environmental stimuli. (omitted)

Acanthopanax species (Arelaceae) are widely distributed in Asia. which used as tonic and sedative as well as a drug with ginseng-like activities from olden time. There are many reports on the studies of these plants. but there seems no reported about components from the leaves of Acanthopanax sessiliflorus. which is indigenous plant to Korea. We have now characterized three triterpenoid compounds from MeOH extract of the leaves of this plant. (omitted)

The inhibitory activity of several crude drugs on $\alpha$-glucosidase, which are the key enzyme for carbohydrate digestion and the prevention of diabetic complications. was investigated. This experiment was designed to examine the hypoglycaemic effect of four water extracts crude drugs. We found two drugs. Mori radicis Cortex and Cudraniae radicis Cortex in several crude drugs remarkably inhibited $\alpha$-glucosidase. Two crude drugs were examined in streptozotocin induced high blood glucose mice. (omitted)

Melanin is a main pigment found in skin. hair and eyes, and tyrosinase plays an important role in the process of melanin polymer biosynthesis. Caesalpinia sappan L.(C. sappan) has been commonly used in Oriental folk medicines to promote blood circulation and as analgesic as well as remedy for thrombosis. This present study was designed to investigate the effect of ethyl acetate extract from C. sappan on melanogenesis in Melan-a cells. (omitted)

One of the important functions of skin is protection from harmful environments. There has been many studies for keeping skin healthy from wrinkling and pigmenting. Skin wrinkle and pigmentation could be caused by the disruption of connective tissue, free radicals and ultraviolet irradiation. In this study, the extracts obtained from 25 kinds of medicinal plants were screened. All the extracts examined were obtained by using 70% (v/v) ethanol at $60^{\circ}C$. (omitted)

Cytotoxic activity against the P388 cell line was seen in a crude extract of Anisotome lyallii. A bioactivity guided isolation led to the isolation of a deterpene. which displayed strong Cytotoxic activity against the P388 cell line (IC50 2.3 $\mu$g/ml), as well as antimicrobial activity against Bacillus subtilis. The structure of de terpene 1 was elucidated by spectroscopic methods. (omitted)

The increase of triglyceride in blood can be a signal of an increasing danger of arterial diseases when insulin resistance. diabetes. HDL -cholesterol decrease is accompanied. It is adjusted to triglyceride level in blood by a balance. which seems to be absorbed from VLDL metabolism in liver and by lipoprotein lipase activity. The hyper-triglyceride disease treatment proposal role should match with suppression does into liver or elimination of a triglyceride. (omitted)

Present study was performed for development of a new supplementary product with gastroprotective effect. Natural Products mentioned that have GI protective property on Dongeuibogam were evaluated anti-bacterial activity against Helicobacter pylori. then five herbs were selected. The material used for the test were water extract of Alpima oxyphylla (AO). Astragalus membranaceus (AM). Cinnamomum loureirii(CL). Citrus aurantium (CA), Amomum villosum (AV). (omitted)

Benzodiazepine is a widely used anxiolytic agent. However it has been reported that most anxiolytics have side effects such as hypotension, depression of respiration. dizziness. headaches. chronic sleep disorders. drug poisonings. and withdrawal symptoms. In this report. we want to evaluate the anxiolytic effect of Albizia julibrissin (AJ), There are various reports that AJ has several biological activities such as sedative action. insomnia. irritability, anorexia and diuretic action. (omitted)

A thrombus is a mass formed from the constituents of the blood within the vessels or the heart during life. The process of formation is known as thrombosis. A vegetable warms producing fibrinolytic enzyme was isolated from chines traditional medicinal mushrooms. Cordyceps militairs and Paecilomyces tenuipes. The fibrinolytic enzyme of Cordyceps militaris and Paecilomyces tenuipes was purified from fruiting body by -70 prechilled ethanol precipitation. ion-exchange chromatography. gel filtration. (omitted)

A sensitive and selective reversed-phase LC-ESI-MS method to quantitate pseudoephedrine in human plasma was developed and validated. Phenacetin was used as an internal standard. Samples were prepared simply by acetonitrile precipitation without an evaporation step. Chromatographic separation was achieved on a XTerra MS C18 column ($150{times}2.1$ mm I.D.. 3.5 $\mu\textrm{m}$ particles). using gradient elution with 0.5% (v/v) trifluoroacetic acid (TFA) in water and 0.5% (v/v) TFA in methanol at a flow-rate of 0.1 ml/min. (omitted)

Dextromethorphan (Romilar. DEX) is a synthetic analogue of codeine. is not classified as a narcotic and is used only for its antitussive effects in Korea. The daily intake by adults range up to 120mg. Usually in the case of traffic accident. alcohol concentration of blood is analyzed in Korea. but drug tests (medicine, narcotic. alcohol) are submitted in Australia. In crimes of violence (2 examples), a traffic and a murder accident. drug testing in urine and blood was performed. (omitted)

Many of the chiral NSAIDs are marketed as racemates. There is an increasing interest in developing the enantiomerically pure forms of the NSAIDs because the anti-inflammatory activity of NSAIDs have previously been shown to be largely sterospecific for the (S)-(＋)-enantiomer. Therefore, simple and economic preparative method to identify the (S)-(＋)-enantiomer of NSAIDs (aryl propionic acids) as diastereomeric solvation complex was developed using several chiral solvating agents by recrystallization of racemate and solvent fractionation. (omitted)

The determination method for 11 corticosteroids (betamethasone, cortisol. cortisone, cortisone acetate. dexamethasone. cortisol acetate, isoflupredone acetate, methylprednisolone. prednisone, prednisolone, and triamcinolone acetonide) in a herbal medicinal preparation (Sibjeondaibotang) by a gas chromatography-mass spectrometric (GC-MS) method with selected ion monitoring (SIM) mode is described. Samples (4 mL) were extracted by liquid-liquid extraction with diethyl ether. (omitted)

A simple, rapid and reliable high performance liquid chromatography (HPLC) method has been developed for the measurement of lansoprazole in human plasma, and the application of pharmacokinetic study has been evaluated. Omeprazole was used as an internal standard. After adding methyl tert-butyl ether, samples were stored at －7$0^{\circ}C$. The extracts were easily obtained only with pouring the organic phase. The mobile phase was prepared using acetonitrile and water at the volume ratio of 38:62. (omitted)

HPTLC(High Performance Thin Layer Choromatography) method was developed for rapid and precise analysis of Sildenafil and modified Sildenafils(Vardenafil. Homosildenafil, Tadanafil). Chromatographic conditions were Optimized for simultaneous analysis of them and each specific UV spectra were obtained. The calibration curve of Sildenafil and modified Sildenafils had a linearity in the range of 1.0 ~ 56.5 $\mu$/ml at 254nm. The Limit of Detection(LOD) and the limit of Quantification(LOQ) of Sildenafil and modified Sildenafils were 0.8$\mu$/ml and 1.0$\mu$g/ml. (omitted)

Analytical results during the proficiency test managed by Kyungin Regional Korea Food ＆ Drug Administration were proposed to be influenced by several factors. Data of several factors were collected along with the test results with ibuprofen and sobrerol formulations. The collected data were the use of internal standard, academic background and career of analytical personnel, production size of the company and location of the participating laboratory. (omitted)

Because of the differences in biological and pharmacological properties between enantiomers of chiral acidic non-steroidal antiinflammatory drugs (NSAIDs) in human body. accurate determinations of their optical purities have been in great need. Racemic ibuprofen. tiaprofen. suprofen. flubiprofen and napoxen were reacted with (1R. 28. 5R)-(－)-menthol to convert them to corresponding diastereomeric (1R. 2S. 5R)-(－ )-menthyl esters. (omitted)

A human immune globulin preparation (histobulin\ulcorner) are made to bind a small amount of histamine (0.15 $\mu$g) to the protein (12 mg) to increase the resistance of histamine susceptibility in the treatment of allergic diseases. Strict control of histamine content of the drug are required since intake of histamine might result in hypo- or hypertension. headache. or anaphylactic shock syndromes. HPLC analytical method with pre-column fluorescent derivatizalion after clean-up by solid-phase extraction (SPE) was developed. (omitted)

Sildenafil citrate(SC. Viagra(equation omitted)) is the oral treatment for erectile dysfunction. Vardenafil hydrochloride. tadalafil and modified sildenafil have anti-impotent effect and have possibility to be used illegally. The aim of this study was to set up simultaneous determination method of anti-impotent drugs using TLC and HPLC. The anti-impotent drugs were extracted with 50% methanol and then diluted with mobile phase for HPLC and also extracted with developing solvents as sample solutions for TLC. (omitted)

A new chiral derivatization agent with sugar moiety. 2, 3.4, 6-tetra-O-acetyl-D-galactopyranosyl isothiocyanate (GATC) was synthesized. Several $\beta$-blockers were investigated for the possible separation of the enantiomers by reversed-phase HPLC after derivatization with this new chiral derivatization agent (GATC). GATC was reacted readily with $\beta$-blockers at room temperature and the reaction mixture could directly be injected into the HPLC system. (omitted)

A column switching HPLC assay was developed to allow the separation and quantitation of cetirizine in human plasma by ultraviolet (UV) detection. Plasma samples were prepared by liquid-liquid extraction. After drying, the residue was reconstituted in 20 mM phosphate buffer (pH 2.8) containing 15% acetonitrile. The samples were initially injected onto a clean-up Capcell Pak MF C18 column. (50 mm $\times$ 4.6 mm I.D.), and the chromatographic region containing the peaks of interest was followed in an analytical C18 microcolumn (250 mm$\times$1.5 mm I. D.) via column switching device. (omitted)

Quality control by analytical ability with a certain level of precision and accuracy is important. This is true especially in pharmaceutical industries. for a failure in quality control can result in a failure in drug medication. in turn. sometimes a heavy damage to patient's health condition andlor the worst damage to company's reputation. On this backgroun, Kyungki KFDA prepared test pharmaceutical products, which were distributed to 114 pharmaceutical companies in kyungin Province in year 2000. (omitted)

The chiral stationary phase derived from (＋) (18-crown-6)-2.3, 11.12-tetracarboxylic acid (18-C-6- TA) as a chiral selector has been employed for resolution of several $\alpha$-amino acids in HPLC. In a quest for the origin of chiral recognition of $\alpha$-amino acids in the presence of 18-C-6- T, A, as a chiral selector, these interactions responsible for the differential affinities shown toward enantioners were investigated by NNR spectroscopy. (omitted)

Capillary electrophoretic direct chiral separation method is described for the determination of the absolute configuration of chiral aromatic acids, The enantiomeric separation was achieved by capillary electrophoresis using HP $\beta$-cyclodextrin (CD) as the chiral selector. The effect of CD concentration was investigated to optimize the chiral separation and resolution. When applied to microbial culture fluid. the present method allowed positive identification of chiral aromatic acids and their chirality as well.

Near-infrared (NIR) system was used to determine rapidly and simply indomethacin in buffer solution for a dissolution test for tablets and capsules. Indomethacin standards were prepared ranging from 10 to 50ppm using mixture of phosphate buffer(pH 7,2) and water(1:4), The near infrared(NIR) transmittance spectra of indomethacin standard solutions were collected by using a quartz cell in 1 mm and 2mm pathlength, Partial least-square regression (PLSR) was explored to develop calibration models over the spectral range 1100-1700nm. (omitted)

Because of the differences in pharmacological properties between enantiomers of chiral acidic non-steroidal antiinflammatory drugs (NSAIDs) in human body. accurate determinations of their optical purities have been in great need. An efficient capillary electrophoretic (CE) profiling method was developed for the enantioseparation of NSAIDs. Capillary electrophoretic conditions were optimized using TM$\beta$-cyclodextrin as the chiral selectors under MES buffer. (omitted)

Near-infrared(NIR) reflectance spectroscopy was employed to qualify various ploymorphs. We collected 8 potential polymorphs forms of Medicine T for this study. Near-infared spectra of the powder samples contained in glass vials were obtained over the wavelength region of 1100-1750nm. There were the peak around 1560nm in the 6 spectra among 8 spectra. Principal component analysis(PCA) has been performed to examine the qualitative difference of 8 polymorphs PC space. (omitted)

Levosulpiride is the levo-enantiomer from of racemic sulpride. abenzamide derivative selectively inhibition doparninergic D2 receptos at the trigger zone both in the central nervous system and in the gastrointestinal tract. We report a rapid and sensitive HPLC method using reverse phase C 18 column with fluorescence detection for separation and quantitation of levosulpiride in plasma. Tiapride was used as an internal standard. After adding an internal standard. levosulpiride in 800 ${\mu}l$ of plasma was extracted under basic conditions with ethyl acetate and methylene chloride. (omitted)

Potentiometric sensors are important and viable devices for use in pharmaceutical analysis. liquid polymeric membrane electrodes for many basic drugs and a few acidic drug were reported. The acidic drug-metal(Ⅱ)-triethylene tetramine ion pair complexes were prepared and used in poly(vinyl chloride) membrane electrodes to analyze anionic drugs such as mefenamic acid and ibuprofen. Metal ion used were Fe2＋. Co2＋. Ni2＋ and Cu2＋. Plasticizer used was o-nitrophenyl octyl ether.. (omitted)

To study the pharmacokinetics of triflusal, more reliable and sensitive analytical method of triflusal in plasma sample was developed. Analytical method of triflusal in human plasma was developed using semi-microbore HPLC equipped with automated column switching system. p- Toluic acid, which is structural analogue of triflusal. was used as an internal standard and 2 M HCI was employed as a stabilizer. The load phase and mobile phase were prepared using acetonitrile and 20 mM $KH_{2}PO_{4}$ with the volume ratios of 10:90 (pH 2.5) and 43:57 (pH 2.3), respectively. (omitted)

Enalapril (ENP) maleate is effective drug for the treatment of renivascular hypertension and heart failure. ENP acts as inhibitor of the enzyme angiotensin-convertase (ACE-inhibitor) and metabolized to enalaprilat (ENPT), which is the active metabolite that is really responsible for the therapeutic action. In the present study, a sensitive and rapid liquid chromatography/ electrospray ion trap tandem mass spectrometry (LC/MS/MS) method combined with high-throughput solid phase extraction (SPE) has been developed and validated for the simultaneous quantitative determination of ENP and ENPT in human plasma. (omitted)

The LC/MS/MS method for the simultaneous determination of sildenafil and its active metabolite N-demethylsildenafil in human plama was developed. Sildenafil. its active metabolite and the internal standard. DA-8159 were extracted form human plasma by liquid-liquid partitioning. A reverse-phase HPLC separation was performed on Luna phenylhexyl column with the mixture of acetonitrile-5 mM ammonium formate (55:45. v/v) as mobile phase. (omitted)

An algorithm for finding the best regression models has been developed using NIR spectral data. In cases of regression analysis for quantitation with NIR spectral data, it is very critical to find essential features from the spectral data. This task was accessed in two ways. The first one was to use all-possible combinations of varibles (wavelengths). Correlation coefficients at each spectral points were calculated to get initial set of variables and all of the possible combinations of variable sets were tested with SEC. SEP and/or $R^2$. (omitted)

Cilostazol. a quinolinone derivative that inhibits phosphodiesterase. is used for the treatment of intermittent claudication resulting from peripheral arterial disease. In order to perform pharmacological and pharmacokinetic studies of cilostazol, specific. sensitive and reproducible analysis methods are demanded. Therefore. in the present study. an analytical method of cilostazol in human plasma was developed using semi-microbore HPLC equipped with automated column switching system. (omitted)

Combination of two or more preservatives are commonly used in cosmetic creams to prevent alteration and degradation of the product formulation. but preservatives are one of the main causes of allergic contact dermatitis from the use of cosmetics. (omitted)

A high performance liquid chromatographic method was developed for the determination of DA-6034 in biological fluids using fluorescence detector. The method involved deproteinization of biological sample with the same volume of acetonitrile, 0.2M zinc sulphate. and 0.15M barium hydroxide. The aliquot of supernatant was injected onto Nova-pak C18 column and detected by fluorescence detector. Emission and excitation wavelength of detector were 336nm and 440nm. (omitted)

Dimethyl phthalate(DMP). diethyl phthalate(DEP), di-n-butyl phthalate (DBP). butyl benzyl phthalate(BBP). bis(2-ethylhexyl)phthalate(DEHP) and di-n-octyl phthalate(DOP) in lotions was determined by gas chromatography. and benzyl benzoate was used as the intermal standard. The separation of the six phthalates and internal standard was optimized, and the optimal analytical conditions were as follows: column. DB-1701 (I.D. 0.25mm): mobile phase. helium: oven temperature 20$0^{\circ}C$ (10 min) ${\rightarrow}10^{\circ}C$/min ${\rightarrow}260^{\circ}C$/min(30min), injector temperature 23$0^{\circ}C$, detector temperature 28$0^{\circ}C$. (omitted)

A LC/MS/MS method for the simultaneous determination of the activities of seven major human drug-metabolizing cytochrome P450s (CYP3A4. CYP2D6. CYP2C9. CYP1A2, CYP2C19, CYP2A6. and CYP2C8) was developed. This method used an in vitro cocktail of specific substrates (midazolam. bufuralol. diclofenac, ethoxyresorufin. S-mephenYlOin. coumarin. and paclitaxel) and LC/MS/MS. The assay incubation time is 20 min and the analysis time is 8 min/sample. (omitted)

The present study was undertaken to develop the in vitro sun protection factor(SPF) test method having good correlation with in vivo method using human. 8% homomentyl salicylate. P3 reference standard and commercially available sunscreen products were measured by the in vitro method using SPF 290S analyzer. and the SPFs were compared with the SPFs measured by in vivo test method. In vitro SPFs of 8% HMS and P3 reference standard were 4.59$\pm$0.12 and 14.94$\pm$0.83. (omitted)

Cupressaceae plants are used in traditional folk medicine. whose extracts have been found to possess some bioactivities. (－)-Yatein is a lignan of the dibenzyl-butyrolactone type. that has been isolated from some Cupressaceae plants. It was reported that (－)-yatein. isolated from plants. showed different activities from the synthetic yatein ［3］. Hence. the enantiosetective determination of yatein from synthetic materials and natural products would be necessary. (omitted)

The amount of water for the cultivation of citrus is different based on the growing period. The water content in the leaves of citrus can be a index for watering during cultivation. The purpose of this study is to determine non-destructively the water content of Citrus leaves by using near infrared spectroscopy (NIRS). Citrus leaves were prepared from satsuma mandarin leaves (Citrus unshiu Marc. var. okitsu) ranging from 62.20 to 69.98% of water content by loss on drying, NIR reflectance spectra of Citrus leaves were acquired by using a fiber optic probe. (omitted)

A near infrared (NIR) method was developed to analyze specious diversity for morphologically similar umbelliferous herbal medicine. Cnidium officinale Makino. This herbal medicine has been widely used as 'chungung' without any discrimination of its quality and original plants. though it has the ambiguous origins of plants between various countries especially Korea. China and Japan. It is named by Cnidium officinale Makino in Korea and Japan. in comparison with Ligusticum chuanxiong Hort. in China. (omitted)

The anti-oxidant activities of the various fractions from the herbs of Artemisia apiacea were investigated. The n- hexane and n-butanol fractions were found to cause significant free radical scavenging effects on DPPH. their scavenging potencies as indicated in $IC_{50}$ values. being 230.1 and 183.7 g/ml. respectively. The n-butanol fraction exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by $CCl_{4}$-intoxication in rats. All fractions tested exhibited a lipid peroxidation causing a significant decrease in MDA production in TBA-reactant assay. (omitted)

Special attention has been paid to human chorionic gonadotropin (hCG) for athlete doping control because it stimulates the endogenous production of testosterone and epitestosterone without increasing the T/E ratio which is a doping indicator for the exogenous administration of testosterone. Even though the IOC banned the use of hCG. a detection method has not been decided upon since there are a variety of immunoassay kits available on the market. We evaluated three kits in terms af their performance characteristics. (omitted)

Analysis of interferon alpha (IFN) modified with high molecular weight branched PEG was performed by capillary electrophoresis (CE) and MALDI-TOF mass spectrometry (MALDI-TOF MS). IFN was modified by the reaction of amine residues with an active ester of monomethoxy polyethylene glycol at various molar ratios. As a CE method. capilary electrophoresis sodium dodecyl sulfate nongel sieving (CE-SDS NGS) was performed using an uncoated capilary filled with a hydrophilic replaceable polymer network matrix. (omitted)

To develop immunostrip of DDT (4.4'-dichlorodiphenyl-2.2,2-trichloroethane) and its metabolites, DDT derivatives (DDA-. DDHP-. DDCP-. DDHH-. and DDHHAP-) were conjugated to carrier proteins (OVA and BSA) and three DDT derivatives (DDA. DDHP. DDCP) were conjugated to KLH for the use of coating ligand and immunogen. respectively. To screen the immunoreactivity of antibody to DDT derivatives, the coating ligand was evaluated by a competitive ELISA and DDHP-OVA was selected. (omitted)

We have been studing sensitive non-enzymatic chemiluminescence (CL) imaging methods for the detection of DNA. For one of our methods, a unique chemical derivatization reagent. 3'. 4', 5'-trimethoxyphenylglyoxal (TMPG) was utilized. This reagent reacted specifically with guanine bases in nucleic acids to quickly produce a chemiluminescent derivative under mild reaction conditions. (omitted)

A portable near infrared (NIR) system which was newly integrated by our lab has been used to develop a non-invasive blood glucose monitoring. The portable NIR system includes a tungsten halogen lamp, a photo diode array type-InGaAs detector, and specialized reflectance fiber optic probes. The shape of probes is composed of two parts. one for illumination into sample and the other for receiving the radiation from sample. Three kinds of probes with different distance between illumination and receiving part. such as 0.03. 0.1. and 0.5mm, were investigated for optimization. (omitted)

A interpolymer complexes composed of poly(acrylic acid)(PAA) and po!y(vinyl alcohol)(PVA) were prepared by template polymerization of acrylic acid in the presence of PVA for mucoadhesive drug delivery. FT -IR results showed that the PAA/PVA interpolymer complex was formed by hydrogen bonding between the carboxyl groups of PAA and the hydroxyl group of PVA. The dissolution rate or the swelling ratio of the PAA/PVA interpolymer complexes was dependent on the pH and molecular weight of PVA that was used as a template. (omitted)

The aim of this study is to prepare biodegradable microspheres without use of any kind of surfactants or emulsifiers for a novel sustained delivery carriers of protein drugs. Poly(e-caprolactone)/poly(ethylene glycol)/poly(e-caprolactone) (CEC) triblock copolymer was synthesized by ring-opening of e-caprolactone with dihydroxy poly(ethylene glycol) and was used to make surfactant-free microspheres. (omitted)

For the development of a biocompatible nano-scale drug carrier. hydrophilic polysaccharide pullulan was hydrophobized by the conjugation with fatty acid. The synthesized polymers were characterized by the measurements of fourier transform infrared (FT -IR) spectroscopy and 1H -nuclear magnetic resonance (NMR) spectroscopy. In aqueous solution. hydrophobically modified puliulan was self-assembled and structured into the core-shell type nanoparticles. (omitted)

Retinol is widely used for skin care. the improvement of the appearance of aging. photo-damaged or oxidatively stressed skin. and especially for the improvement of the appearance of wrinkled skin. Retinol. however. is extremely sensitive to atmospheric oxygen. and easily decomposed by exposure to air. Retinol is commonly formulated as the ointments or creams for cosmetic preparations. (omitted)

Microencapsulations of piroxicam using the mixture of Eudragit RS with RL or Eudragit L or E or S according to Eudragit RS were carried out. The Eudragit microspheres of piroxicam were prepared by solvent method. Piroxicam and Eudragit polymer were dissoved in methylene chloride and dispersed in 0.5% pOlyvinyl alcohol solution and solvent evaporated. The average diameters of various Eudragit microspheres were from 40 to 43${\mu}{\textrm}{m}$. A good and smooth surface of microspheres observed by SEM were shown in all type of microspheres. (omitted)

Local anesthetics are used to reduce pain. but they are so frequently injected to patients. So we prepared lidocaine solid lipid nanopaticles for long acting subcutaneous injection to decrease the number of times of injection. Solid lipid nanoparticles were prepared by spray drying method. First. drug. lipid. plasticizer and surfactant were dissolved in methylene chloride. and we operated spray dryer using this solution at setting value. (omitted)

Ketoprofen (KP), a potent analgesic and non-steroidal anti-inflammatory drug, has some disadvantages such as gastro-intestinal irritation. short half-life (1.5-4 hour) in plasma and low solubility in aqueous solution. In order to minimize these disadvantages. we have recently prepared a KP prodrug, KP-polyethylene glycol conjugate (KPEG750, PEG Mw=750), and investigated its pharmacokinetic behavior. anti-inflammatory and analgesic effect. (omitted)

The purpose of this study was to investigate the effect of quercetin on the bioavailability of paclitaxel orally coadministered in rats Paclitaxel is reported to be metabolized by cytochrome p-450(CYP3.A,)in both the liver and epithelial cells of small intestine and also absorption of paclitaxel is inhibited by p-glycoprotein efflux Pump in the intestinal mucosa. This resulted in poor orall bioavailability of paclitaxel. Area under the plasma concentration-time curve (AUC) of paclitaxel in combination with quercetin were significantly (p＜ 0.01) higher than those of control. (omitted)

In order to develope an optimum formulation for iontophoretic delivery of vitamine-C-2 phosphate. we have prepared 3 different formulations using hydrophilic polymers, such as poloxamer, carbo pol and HPMC and iontophoretic flux through skin from these hydrogel formulations was carried out. The effect of current density, drug concentration and current profile on flux was investigated. In-vitro flux study was performed at 36.5$^{\circ}C$, using side-by-side diffusion cell. Full-thickness hairless mouse skin was used for this work. (omitted)

On the basis of recognizing that physicochemical properties (lipophilic/hydrophilic), intestinal absorption clearance and pharmacokinetic characteristics of drug are the fundamental parameters controlling the rate and the extent of drug absorption, the biopharmaceutics classification system for the correlation between drug lipid- solubility and intestinal absorption clearance is proposed. (omitted)

Purpose. To prepare PVP-based solid dispersions containing lovastatin (LOS) and solubilizers (sodium lauryl sulfate. Tween80. oleic acid) to enhance dissolution of practically insoluble LOS. Methods. Solid dispersions containing LOS were prepared by dissolving two different organic solvent systems (acetone/ethanol or acetonitrile/ethanol). Results. The stickiness and flowability of solid dispersion powders were dependent on the composition and ratio of the solubilizers. (omitted)

Purpose. To prepare polymer based physical mixtures or solid dispersions containing solubilizing compositions using a spray-dryer. Methods. Lovastatin.simvastatin.aceclofenac and cisapride were selected as poorly water-soluble drugs. Dextrin. poly(vinylalcohol). poly(vinylpyrrolidone)and polyethylene glycol were chosen as solubilizing carriers for solid dispersions. The solid dispersions containing solubilizing compositions without drug were prepared without using organic solvents or tedious changes of formulation compositions. (omitted)

Purpose To investigate the physico-chemical properties of CB-ph ［2-benzoyloxycinnamaldehyde］, an anticancer drug obtained from Cinnamomum cassia using methylenechloride. and its stability in various aqueous solutions. Results CB-ph was rarely soluble in water but soluble in methanol and very soluble in ether. Kinetic salt effect on degradation of CB-ph in buffer solutions at pH 4.0 and 6$0^{\circ}C$ showed a linear relationship having a positive slope that means reactions between hydronium ions and protonated substrates. (omitted)

Paclitaxel is an antitumor agent with poor water solubility and its pharmacokinetics are nonlinear. Cremophor EL. a surfactant used in the formulation of paclitaxel. may cause adverse effects. New solubilizer(Aceporol 460) was developed to reduce side effects of Cremophor EL and to increase the effect of drug as surfactant used in the intravenous micelle formulation of anticancer drug paclitaxel. We studied easy, rapid quantitative determination of Aceporol 460 in mouse plasma samples. which was achieved by complexation of the compound with the Coomassie brilliant blue G-250 dye in protein-free extracts. (omitted)

Paclitaxel is a diterpenoid isolated from Taxus brevifolia and is an active anticancer drug for the treatment of ovarian cancer, breast cancer and Kaposi's sarcoma. Due to its low solubility in water, it is dissolved in Cremophor EL(polyethoxylated castor oil) and ethanol, which cause serious side effects including hypersensitivity. BLK460 was developed as a novel polymeric micellar paclitaxel formulation containing Aceporol460 as solubilizer (omitted)

To improve the compliance of oral administration of drugs in cancer patients, who are unable to swallow tablets, FDT containing ondansetron HCI($Onseran^{TM}$) was developed with a low-cost manufacturing process. $Onseran^{TM}$ was prepared from ondansetron. mannitol, crospovidone. and others with a direct compression method. The disintegration time and dissolution rate of $Onseran^{TM}$ were assessed according to the USP method. The results were compared with those of the reference drug ($Zofran^{TM}$). (omitted)

To secure the safety of drugs without compromising drug efficacy, it can not be more important to administer the exact intended amount of active ingredients to patients. Even if the correct amount of drugs are taken in the correct manner, drug can be overdosed or less-dosed without intention unless the content uniformity of the unit dose were secured. Especially, it can be a serious problem when it comes to drugs with narrow therapeutic windows or a strong pharmacological activity at a small dose. (omitted)

Apical to basal transport of organic cations (OCs) such as tributylmethylammonium (TBuMA), triethyimethylammonium (TEMA). 1-methyl-4-phenylpyridinium (MPP), and berberine across Caco-2 cell monolayers was measured to elucidate the intestinal absorption of OCs. Basal to apical transport of MPP and berberine was larger than apical to basal transport and showed temperature dependency and concentration dependency. indicating that MPP and berberine are secreted into the inteslinal lumen. (omitted)

We investigated the absorption enhancing effect of BuOH extract of the root of Aralia elata (BERAE) in Caco-2 cell monolayers and rats. At the concentration of both 0.04% and 0.08% (w/v). BERAE decreased the transepithelial electrical resistance (TEER) values and increased the permeability of intact chondroitin sulfate (CS) and its digestion products as hydrophilic macromolecules in a dose dependent manner. We also evaluated the cytotoxicity of BERAE for the determination of a proper concentration as an absorption enhancer. (omitted)

To improve the stability of recombinant human epidermal growth factor (rhEGF) as therapeutic agent. the N-terminal PEGylated rhEGF (N-PEG-rhEGF) was prepared by site-specific bioconjugation and the stability was investigated in rat skin wound homogenates. Two different N-PEG-rhGEFs (N-PEG5K- and N-PEG20K-rhEGF) were successfully prepared with the yields of above 70%. The PEGylation site was directly confirmed by determining the molecular mass of Lys-C digested samples using MALDI- TOF MS. (omitted)

Biodegradable PLGA microspheres(MS) have been widely studied for delivering antigens because PLGA has the characteristics of various degradation rate. In general. since MS have shown potential for single-dose vaccines. the degradation rate of PLGA is determined by their molecular weight. polymer composition, etc. We studied the influences of molecular weight of PLGA. polymer composition and surfactant on in vitro release and in vivo effects. (omitted)

Transfersomes are highly detormable hydrophilic lipid vesicles that are able to penetrate the skin barrier so that they can be used to carry low- and high-molecular weight molecules into the body. Until recently. it has been reported that molecules such as insulin. interleukin-2 and several other large molecules have been transported into the body using Transfersomes as a delivery system. Here however, for the very first time, genes (GFP) have been transported into the mice non-invasively using the Transtersomes as a delivery vehicle. (omitted)

Among the promising cancer therapy is targeting of the drug to tumor cells via receptor specific ligands. CR2945, $\beta$-2-( ［2-(8-azaspiro ［4.5］ dec-8-ylcarbony!)-4.6-dimethylphenyl］amino-2-oxoethyl］ -(R)-1-naphthalenepropanoic acid. is known to have an inhibitory effect on a gastrin receptor of colorectal cancer cells. As the human pancreatic cancer cells (BxPC-3) express gastrin receptors. interruption of binding of gastrin with gastrin receptor of human pancreatic cancer cells by CR2945 inhibits the growth of human pancreatic cancer cells. (omitted)

The in vitro release of rhGH from PLGA microspheres was characterized. rhGH-loaded PLGA microspheres were prepared with 50:50 poly(D.L-lactide-co-glycolide) (PLGA) polymers using a double emulsion process. To simulate rhGH release under physiological conditions. the microspheres were suspended in a physiological buller at 37$^{\circ}C$. Quantification of the rhGH released and its molecular form analysis were carried out using SE-HPLC. (omitted)

The rhGH-loaded PLGA microsphere formulation was prepared using a double emulsion process from hydrophilic 0:50 poly(D.L-lactide-co-glycolide) (PLGA) polymers. To investigate the sustained efficacy of this formulation, ts pharmacodynamic characteristics were analyzed. It showed particle size of ca 53.1 $\mu\textrm{m}$ with high drug ncorporation efficiency and it was sucutaneously administrated to hypophysectomized rats and whole body rowth responses of this formulation were compared to those of the different dosing patterns of rhGH. (omitted)

Recombinant interferon alpha is widely used for the treatment of diseases including chronic hepatitis C. However. it has drawbacks such as relatively short serum half-life and rapid clearance like other therapeutic proteins. Using PFGylFltioo which is one of the well-established methods to fulfill the requirements of a long-lasting form of protein. wIe prepared mono-PEG modified interferon alpha-2a in which polyethylene glycol moiety was covalently attached to the amino groups of interfelon alpha-2a. (omitted)

With the Sunshine policy. exchange of goods and cultures inter Koreas is broaden and expectancy of reunification is getting higher. Especially. medical supplies and medicines is one of the biggest parts in the exchanges. So. need for preparing new medical administration system for reunification is needed. We are going to compare inter Koreas drug administration system in medical services. (omitted)

Enalapril. a prodrug. is the ethyl ester of a long-acting angiotensin converting enzyme inhibitor. enalaprilat. Because enalapril does not contain any appreciable chromophore. detection of the drug in a complex matrix (e.g.. biological fluids) has been problematic with conventional detection systems in high-performance liquid chromatography (HPLC). As a result. determination of enalaprillevel in blood samples has been typically carried out using HPLC-MS/MS in the literature. (omitted)

The purpose of this study was to report the pharmacokinetic changes of cyclosporine after oral administration of cyclosporine. 10 mg/kg. in rabbits coadministered or pretreated twice per day for 3 days with nimodipine. dose of 5 mg/kg, The area under the plasma concentration-time curve (AUC) of cyclosporine was significantly higher in rabbits pretreated with nimodipine than in control rabbits (p＜0.01). showing about 149% increased relative bioavailability. (omitted)

Caco-2 is a cell line derived from the human colon adenocarcinoma and often used as a model for studying intestinal drug absorption. It has been well-known that a strong correlation holds between in vitro permeability across Caco-2 cell monolayers and in vivo bioavailability for various drugs. but the correlation curves varied depending on laboratories. The permeabilities of drugs across Caco-2 cell monolayers have been measured under different agitation conditions. (omitted)

The purposes of this study were to evaluate bioequivalence (BE) using In-transformed pharmacokinetic parameters obtained from two tiropramide HCI products and to develop the analytical methods for the quantitative determination of tiropramide in human serum. In addition. the in vitro dissolution profiles of the two tiropramide HCI products in various dissolution media: pH 1.2, 4.0. 6.8 and water (KP Ⅶ Apparatus II method) were assessed. BE was evaluated in 20 healthy male Korean volunteers in randomized crossover study. (omitted)

A validated UV determination of loratadine in human plasma was developed and the pharmacokinetic profiles of single dose of loratadine were determined in 8 healthy volunteers. Human serum samples (1.0 mL) spiked with known concentration of loratadine and 50 ng diazepam as an internal standard were alkalinized with 500 ${\mu}\ell$ ${\mu}\ell$ of 10% $Na_{2}CO_{3}$ and extracted with 7 mL of mixture of isopentane and hexane (2 : 1. v/v) for 5 min. Extracts were centrifuged and 6 mL of organic layer was back-extracted with 150 ${\mu}\ell$ of 12.5% $Na_{2}PO_{4}$ for 1 min. (omitted)

The purposes of this study were to evaluate the population pharmacokinetics of terbinafine according to two-compartment model will, lag time and to investigate the influence of characteristics or subjects such as body weight and age on the pharmacokinetic parameters of terbinatine. Serum data from 73 healthy male Korean subjects were used for this analysis. After overnight fast. each subject received a single 125 mg oral dose of terbinafine. (omitted)

Recent studies show that KR-31378 ［(2S.3SAR)-N"-cyano-N-(6-amino-3A-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N${\cdots}$-benzylguanidine］ has the neuroprotective effect as evidenced by the limitation of the size of infarct of the ischemia-reperfusion injury after an administration of KR-31378. In the literature. however. kinetics of KR-31378 distribution into the brain has not been systematically studied. (omitted)

Carvedilol is a nonselective $\beta$-adrenoblocking agent with vasodilating activities. The pharmacokinetics and pharmacodynamics of carvedilol were studied in healthy volunteers following single oral administration. After oral administration of carvedilol 25mg. blood samples were collected for a period of 30 hours. Plasma concentrations of carvedilol were determined by HPLC with spectrofluorometric detection. The effects of carvedilol on systolic and diastolic blood pressure (BP) and heart rate (HR) were measured during the same period. (omitted)

This study examined the pharmacokinetic disposition of SJ-8029. a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities. in mice. rats. rabbits and dogs after i.v. administration. The serum concentration-time curves of SJ-8029 were best described by tri-exponential equations in all these animal species. The mean CI. $V_{ss}$ and $t_{1/2}$ were 0.3 L/h. 0.1 Land 63.2 min in mice. 1.5 L/h. 1.6 Land 247.7 min in rats. 13.8 L/h. 39.6 Land 245.9 min in rabbits. and 29.2 L/h. 44.6 Land 117.4 min in dogs. respectively. (omitted)

The purpose of the present study was to investigate the hepatic uptake and biliary excretion of IH-901. a potential anticancer agents. in rats. IH-901 was mainly distributed into the liver after its iv administration at the dose of 10-30 mg/kg. The liver concentration of IH-901 at 7 min after its Iv administration was comparable with its initial concentration of the plasma. Moreover. recovery ratio of IH-901 in the bile for 6 hr was more than 40% after its iv administration. (omitted)

A simple. specific and sensitive method for the determination of cyclosporine A (CsA) in human serum has been developed by a high performance liquid chromatography/diode array detector (DAD) and applied to pharmacokinetic study of CsA. This method involves the use of solid phase extraction procedure following rapid protein precipitation with zinc sulphate from 1 $m\ell$ of human serum, using a disposable $C_{18}$ extraction cartridge. (omitted)

The present study evaluates the pharmacokinetics and tissue distribution of GX-12, a multiple plasmid DNA vaccine for the treatment of HIV-1 infection. PCR analysis after i.v. injection in mice showed that plasmid DNA was rapidly degraded in blood with a half-life of 1.34 min and was no longer detectable at 90 min post-injection. Plasmid DNA concentration also rapidly declined at the injection site after i.m. injection. with less than 1 % of the initial concentration remaining at 90 min post-injection. (omitted)

Interferon has therapeutic potential for a wide range of infectious and proliferative disorders such as chronic hepatitis C and malignant melanoma. However. it has some therapeutic problems as other protein therapeutics do. A variety of approaches have been developed to circumvent these problems. Among them. the attachment of a polyethylene glycol (PEG) moiety 10 interferon is considered as one of the most promising solutions for its ability of extending the plasma residence time. (omitted)

The in vivo release characteristics of rhGH-loaded PLGA microsphere prepared using a double emulsion process from hydrophilic 50:50 poly(D.L-lactide-co-glycolide) (PLGA) polymers were analyzed. This formulation showed particle size of ca 53.1$\mu\textrm{m}$ with high drug incorporation efficiency. To investigate in vivo release kinetics without the interference of formation of antibodies to rhGH in the experimental animals, the animals were immunosuppressed by treatment with Cyclosporin. (omitted)

Nanoparticles of polylactic acid (PLA) and polyethylenimine (PEI) as an effective gene delivery agent were prepared and characterized. As a model plamid DNA. PME185/$\beta$-gal. a mammalian expression vector. and fluorescence enhancing protein (pEGHP) were used. The effects of PEI type on the physical properties of nanoparticles and transfection efficiency were examined. (omitted)