• The Journal of the Korean bone and joint tumor society
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• v.15 no.2
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• pp.111-121
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• 2009

Background: Osteosarcoma is one of the most common primary malignant tumors of bone occurring mainly in children and adolescents. Although surgery combined with chemotherapy has markedly improved patient survival during the last years, the use of anticancer drugs is still associated with serious problem, such as the frequent acquisition of drug-resistant phenotypes and occurrence of "secondary malignancies". Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs) are inhibitors of bone resorption, and widely used to treat osteoclast-mediated bone diseases. Also they appear to possess direct antitumor activity. Methods: One osteosarcoma cell line (U2OS) was treated with ibandronate (0, 0.1, 1, $10{\mu}M$) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MT1-MMP were detected by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MT1-MMP protein were measured by Westernblot, the activities of MMP-2 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after ibandronate treatment. Results: The invasiveness of U2OS cell line was reduced dose-dependently following 48 hour treatment of up to $10{\mu}M$ of the ibandronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MT1-MMP were also suppressed by increasing ibandronate concentrations. Conclusion: Given that MMP-2 is instrumental in tumor cell invasion, it is very likely that the reduction in osteosarcoma cell invasion by ibandronate is a consequence, at least in part, of suppressed expression of both MMP-2 and MT1-MMP. Isolation of a molecule (s) responsible for the bisphosphonate inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.

• The Korean Journal of Nuclear Medicine
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• v.18 no.2
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• pp.17-23
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• 1984

For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human mind in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On May 25, 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuro-receptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. The growth of any scientific field is based on a paradigm or set of ideas that the community of scientists accepts. The unifying principle of nuclear medicine is the tracer principle applied to the study of human disease. Nineteen hundred and sixty-three was a landmark year in which technetium-99m and the Anger camera combined to move the field from its latent stage into a second stage characterized by exponential growth within the framework of the paradigm. The third stage, characterized by gradually declining growth, began in 1973. Faced with competing advances, such as computed tomography and ultrasonography, proponents and participants in the field of nuclear medicine began to search for greener pastures or to pursue narrow sub-specialties. Research became characterized by refinements of existing techniques. In 1983 nuclear medicine experienced what could be a profound change. A new paradigm was born when it was demonstrated that, despite their extremely low chemical concentrations, in the picomolar range, it was possible to image and quantify the distribution of receptors in the human body. Thus, nuclear medicine was able to move beyond physiology into biochemistry and pharmacology. Fundamental to the science of pharmacology is the concept that many drugs and endogenous substances, such as neurotransmitters, react with specific macromolecules that mediate their pharmacologic actions. Such receptors are usually identified in the study of excised tissues, cells or cell membranes, or in autoradiographic studies in animals. The first imaging and quantification of a neuroreceptor in a living human being was performed on May 25, 1983 and reported in the September 23, 1983 issue of SCIENCE. The study involved the development and use of carbon-11 N-methyl spiperone (NMSP), a drug with a high affinity for dopamine receptors. Since then, studies of dopamine and serotonin receptors have been carried out in over 100 normal persons or patients with various neuropsychiatric disorders. Exactly one year later, the first imaging of opitate receptors in a living human being was performed [1].

• The Korean Journal of Pharmacology
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• v.22 no.1 s.38
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• pp.34-44
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• 1986

In our previous studies, we had clarified many pharmacological effects of majarine: the bacteriostatic effect in vitro; the potentiation of hypnotic action of alcohol; hypotensive effect in rats and hypothermic effect in mice. This study was undertaken to search for a new antihypertensive drug. Red crystalline was obtained from majarine (which was extracted from Berberis koreana Palibin) by chemical methods. And this crystalline was identified as $C_{19}H＿{16}NO＿4$ contained one hydroxy group instead of methoxy group of majarine in isoquinoline ring and named 'Majarol' (5,6-Dihydro-9-hydroxy, 10-methoxybenzo-[g]-1,3-benzodioxolo [5,6-a] quinolizinium). We examined the effects of majarol on blood pressure and heart rate in urethane ancsthetized rats and the rate and amplitude of contraction of isolated frog heart. Several drugs: atropine sulfate, diphenhydramine chloride, hexamethonium bromide, phentolamine, epinephrine, propranolol and isoproterenol were used to clarify the mechanism of the hypotensive action of majarol. The results of experimints were as follows; 1. In low dose (0.5-2mg/kg, i.v.), majarol showed a typical transient hypotensive effect and slight decrease in heart rate. In high dose (5-10 mg/kg, i.v.), majarol showed a typical transient and a subsequent prolonged hypotensive effect and a significant prolonged decrease in heart rate was followed. 2. The hypotensive effects of majarol was not abolished by the pretreatments with atropine sulfate, hexamethonium bromide and diphenhydramine. The pretreatment with phentolamine inhibited significantly the hypotensive effects of majarol and the pretreatment wtih majarol blocked markedly the hypertensive effect of epinephrine. The positive chronotropic effect of isoproterenol was not blocked by the pretreatment with majarol. 3. In low dose, majarol increased the amplitude and decreased rate of contraction, but in high dose, majarol inhibited the amplitude and rate of contraction of isolated frog heart.

• Korean Chemical Engineering Research
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• v.58 no.4
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• pp.541-549
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• 2020

The Drug Delivery System (DDS) is defined as a technology for designing existing or new drug formulations and optimizing drug treatment. DDS is designed to efficiently deliver drugs for the care of diseases, minimize the side effects of drug, and maximize drug efficacy. In this study, the optimization of tripolyphosphate (TPP) concentration on the size of Chitosan nanoparticles (CNPs) produced by crosslinking with chitosan was measured. In addition, the characteristics of Fe₃O₄-CNPs according to the amount of iron oxide (Fe₃O₄) were measured, and it was confirmed that the higher the amount of Fe₃O₄, the better the characteristics as a magnetic drug carrier were displayed. Through the ninhydrin reaction, a calibration curve was obtained according to the concentration of γ-aminobutyric acid (GABA) of Y = 0.00373exp(179.729X)-0.0114 (R² = 0.989) in the low concentration (0.004 to 0.02 wt%) and Y = 21.680X-0.290 (R² = 0.999) in the high concentration (0.02 to 0.1 wt%). Absorption was constant at about 62.5% above 0.04 g of initial GABA. In addition, the amount of GABA released from GABA-Fe₃O₄-CNPs over time was measured to confirm that drug release was terminated after about 24 hr. Finally, GABA-Fe₃O₄-CNPs performed under the optimal conditions were spherical particles of about 150 nm, and it was confirmed that the properties of the particles appear well, indicating that GABA-Fe₃O₄-CNPs were suitable as drug carriers.

• Applied Chemistry for Engineering
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• v.8 no.4
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• pp.560-567
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• 1997

A new approach to obtain stable $W_1/O/W_2$ multiple emulsions has been studied ; The basis of the interfacial interaction between a PCL-PEO-PCL triblock copolymer and a lipophilic emulsifier in the dispersed oil phase was examined. $W_1/O/W_2$ multiple emulsions were prepared by the two-step method. Arlacel P-l35 was used as a liphophilic emulsifier and Synperonic PE/F 127 as a hydrophilic one. Eutanol-G was used as an oil phase. NaCl was encapsulated within the multiple emulsion droplets as the internal marker and its release rate studies were carried out. The suability of the multiple emulsions have been assessed by measuring Separation Ratios(%) and microscopic observations. The release of NaCl was significantly reduced in $W_1/O/W_2$ multiple emulsions containing PCL-PEO-PCL triblock copolymer(2k-4k-2k or 6k-4k-6k) in the oil phase. It may be concluded that the copolymer and the emulsifier form effective interfacial complex to enhance stability and to control the release rate. The effective diffusion coefficients of the NaCl were estimated as $2.64{\times}10^{-15}s$and $3.23{\times}10^{-16}gcm^2/s$ for the $W_1/O/W_2$ multiple emulsion containing 1.2 wt % of PCL-PEO-PCL triblock copolymers with compositions of 2k-4k-2k and 6k-4k-2k, respectively. The rate of release decreased with the increase of the initial concentration of NaCl. The results were examined in view of Higuchi mechanism. A kinetic model which is similar to the model for release of dispersed drugs from a polymeric matrix was found to be suitable for the release of NaCl from $W_1/O/W_2$ multiple emulsions.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.67-75
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• 1995

Background: Although we gain new knowledge, the problem of pneumonia will not be eliminated. We should understand who is at risk, why these people develop this problem, what causes the pneumonia, and how to manage and prevent respiratory infection. To clarify the alterations of the etiologies of bacterial pneumonia we analysed the recent causative organisms and evaluated the therapeutic implications. Methods: A retrospective four-year study of bacterial pneumonia was conducted in Soon Chun Hyang University Hospital. 190 episodes of bacterial pneumonia was investigated. Results: 1) The causative organisms were isolated in 173 cases on the sputum culture: 154 cases (89%) were gram negative bacilli and 19 cases(11%) were gram positive cocci. The major organisms were Pseudomonas species 49 cases(28%), Klebsiella pneumoniae 29 cases(17%), Enterobacter species 25 cases(14%), and Acinetobacter species 20 cases(12%) in decreasing order. Pseudomonas species(13 cases, 34%) were frequently found in nosocomial pneumonia. 2) The causative organisms were isolated in 16 cases on the blood culture: 7 cases(43%) were gram negative bacilli and 9 cases(57%) were gram positive cocci. The major organisms were Staphylococcus aureus(6 cases, 38%), Pseudomonas species(3 cases, 19%) in decreasing order. 3) In the susceptibility test of causative organisms to antimicrobial drugs, Pseudomonas was susceptible to amikacin, ciprofloxacin, aztreonam, ceftazidime(more than 50%) and resistant to piperacillin, gentamicin, carbenicillin(more than 60%). Klebsiella was susceptible to chloramphenicol, gentamicin, cefotetan(more than 70%) and resistant to carbenicillin, ampicillin(more than 70%). Staphylococcus was susceptible to methicillin(64%), and Streptococcus pneumoniae was susceptible to oxacillin(94%). 4) The response rate after antibiotics therapy was 81% and the mortality rate was 19%. Conclusion: As considering the changes of causative organisms and antibiotic resistance, it behooves us to exercise caution in dispending antibiotics in order to maximize their continued efficacy and to do appropiate antibiotics therapy based on cultures and susceptibility test.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.122-134
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• 2001

Background : Some chemotherapeutic drugs induce NF-${\kappa}B$ activation by degrading the $I{\kappa}B{\alpha}$ protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting $I{\kappa}B{\alpha}$ degradation would block NF-${\kappa}B$ activation and result in increased tumor cell mortality in response to chemotherapy. Methods : The "superrepressor" form of the NF-${\kappa}B$ inhibitor was transferred by an adenoviral vector (Ad-$I{\kappa}B{\alpha}$-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MIT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. Results : EMSA showed that $I{\kappa}B{\alpha}$-SR effectively blocked the NF-${\kappa}B$ activation induced by cisplatin. Transduction with Ad-$I{\kappa}B{\alpha}$-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of $IC_{50}$. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. Conclusion : The blockade of chemotherapeutics induced NF-${\kappa}B$ activation by inducing Ad-$I{\kappa}B{\alpha}$-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of $I{\kappa}B{\alpha}$-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.234-241
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• 2004

Background : There has been a gradual increase in the number of newly diagnosed cases of Mycobacterium avium complex (MAC) pulmonary disease. However, the optimal therapeutic regimen for the disease has not yet established and there is no report about the treatment outcome of MAC pulmonary disease in Korea. This study examined the effect of clarithromycin-based regimen in patients with pulmonary MAC disease without a HIV infection. Materials and Methods : Fifty-six patients with pulmonary MAC disease were diagnosed according to the American Thoracic Society criteria from January 2000 to December 2003 at this hospital. Of these patients, 15 were treated with clarithromycin, rifampin, and ethambutol for more than 6 months, together with streptomycin initially (first 6 months) in 8 patients. Results : Six months after the treatment, the sputum cultures converted from positive to negative in 8 patients (53%) and the radiological findings improved in 10 (67%). At 12 months 4 patients (44%) achieved sputum negative conversion and 6 patients out of 9 patients (67%) who were treated for more than 12 months showed radiological improvement. Overall, the sputum findings converted to negative in nine patients (60%) who underwent medical treatment. A pulmonary resection was successfully performed in one patient. Only one patient discontinued the treatment due to side effects such as gastrointestinal intolerance and optic neuritis. Conclusion : A combined regimen containing clarithromycin is relatively safe and tolerable even in the elderly outpatients. However, the results of this combined chemotherapy were unsatisfactory and new companion drugs for MAC pulmonary disease are needed. A resection may be considered for localized disease.

• Journal of the Korean Chemical Society
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• v.51 no.1
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• pp.43-50
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• 2007

Liposomes having particle size from several tens to hundreds nanometers are efficient carriers for injectable drug delivery. Enhancement of liposome stability in bloodstream has been studied because of its relatively short circulation time and fast clearance from human body by reticuloendothelial system (RES) in blood vessel. In this study, new disaccharide-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) derivatives in which lactose or sucrose as the disaccharide molecule was conjugated covalently to DSPE were synthesized. Liposomes of which surface had disaccharide molecules were prepared by incorporating the disaccharide-DSPE into liposomes as one of their lipid components. Particle size of the prepared liposomes was approximately 100 nm. The liposomes of which surface were modified with the disaccharide-DSPE showed -25 mV of zeta potential value due to the presence of hydroxyl groups on their surface, while the unmodified control liposomes showed -10 mV of zeta potential value. Loading efficiency of model drug, doxorubicin, into liposomes was about 90%. Stability of the disaccharide-modified liposomes in vitro was evaluated by monitoring the amount of protein adsorption and particle size of the liposomes in serum. Disaccharide-modified liposomes were more stable in serum than unmodified control liposomes or polyethyleneglycol (PEG)-modified liposomes due to less adsorption of serum protein and hence less increase of their particle size. The liposomes of which surface was modified with disaccharide-DSPE conjugate can be used as long-circulating carriers for drugs having high toxicity or short half-life time due to their enhanced stability in blood circulatory system.

• Clinical and Experimental Pediatrics
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• v.50 no.2
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• pp.138-142
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• 2007

Purpose : The purpose of this study is to find out the changing pattern of drug or foreign body ingestion between 1990s and 2000s in Wonju Christian Hospital, which is located in one of the most rapidly urbanizing cities in Korea. Methods : We retrospectively reviewed the medical records of patients with acute drug intoxication and foreign body ingestion from January 1991 to December 1994 and from January 2001 to December 2004. We performed clinical analysis and compared the results of the 1990s and 2000s. Results : There were 43 cases of acute drug intoxication in the 1990s, and 35 cases in the 2000s. Foreign body ingestion was 47 cases in the 1990s and 22 cases in the 2000s. The ingested foreign bodies were chiefly coins (46.8 percent), Weiqi chips (14.9 percent), plastic toys (6.4 percent) and others (31.9 percent) in the 1990s. In the 2000s, others (58.2 percent) were the most commonly ingested foreign body with mercury batteries (23.8 percent), nails (9 percent), pins (9 percent) following. The most common cause of drug intoxication was medical drugs (37.2 percent) others (23.2 percent), agricultural agents (13.9 percent), carbon monoxide (11.6 percent), rodenticide (9.3 percent), insecticide (9.3 percent) in the 1990s. In the 2000s the most common causes were others (34.3 percent), medical drug (31.4 percent), agriculture agents (20 percent), detergent (11.4 percent), insecticide (2.9 percent) and carbon monoxide (2.9 percent). The highest incidence age group was the 1-3 year old group, both in acute drug intoxication and foreign body ingestion. There were no changes in the incidence age group between the 1990s and the 2000s. Conclusion : There were some significant changes in the cause of acute drug intoxication and foreign body ingestion between the 1990s and 2000s. New education programs for preventing acute drug intoxication and foreign body ingestion are important and necessary.