• Toxicological Research
• /
• 제32권2호
• /
• pp.133-140
• /
• 2016

Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

• International Journal of Industrial Entomology and Biomaterials
• /
• 제8권2호
• /
• pp.135-138
• /
• 2004

In order to find potential anticancer agents, we extracted pheophytin from silkworm feces according to various dry and storage methods such as sun dry, shade dry, fresh freezing dry and freezing dry after freezing storage (for 1∼3 years). The pheophytin extracts, mainly 10-hydroxypheophytin a, little b, of various storage silkworm feces were analyzed by reversed-phase high-performance liquid chromatography with photodiode array and fluorescence detection. The content of those pheophytih in old silkworm for 3 years (freezing storage and freezing dried in use, or freezing dried and cold storage) was better than others. The cytotoxicity of the pheophytin extracts and ethanol extracts of various storage silkworm feces were measured using Jurkat cells originated from human leukemia, using dye uptake assay (MTT) in order to find effective photodynamic therapeutic agents. The anticancer activity of those pheophytin extracts in various storage methods showed little difference among them. But ethanol extracts of fresh freezing dried silkworm in the current year was good cytotoxic activity than those of any other silkworm feces. With regards to these results, fresh ethanol extracts of silkworm feces were better than old ones. On the other hands, the pheophytin extracts of old silkworm feces contained the highest percentage of pheophytin content and showed good cytotoxicity against cancer cells by changing the pheophytin into pheophobide in the degradative process.

• Childhood Kidney Diseases
• /
• 제19권2호
• /
• pp.143-147
• /
• 2015

Purpose: Burkholderia cepacia is an aerobic, glucose-non-fermenting, gram-negative bacillus that mainly affects immunocompromised and hospitalized patients. Burkholderia cepacia has high levels of resistance to many antimicrobial agents, and therapeutic options are limited. The authors sought to analyze the incidence, clinical manifestation, risk factors, antimicrobial sensitivity and outcomes of B. cepacia urinary tract infection (UTI) in pediatric patients. Methods: Pediatric patients with urine culture-proven B. cepacia UTI between January 2000 and December 2014 at Samsung Medical Center, a tertiary referral hospital in Seoul, Republic of Korea, were included in a retrospective analysis of medical records. Results: Over 14 years, 14 patients (male-to-female ratio of 1:1) were diagnosed with B. cepacia UTI. Of 14 patients with UTI, 11 patients were admitted to the intensive care unit, and a bladder catheter was present in 9 patients when urine culture was positive for B. cepacia. Patients had multiple predisposing factors for UTI, including double-J catheter insertion (14.2%), vesico-ureteral reflux (28.6%), congenital heart disease (28.6%), or malignancy (21.4%). Burkholderia cepacia isolates were sensitive to piperacillin-tazobactam and sulfamethoxazole-trimethoprim, and resistant to amikacin and colistin. Treatment with parenteral or oral antimicrobial agents including piperacillin-tazobactam, ceftazidime, meropenem, and sulfamethoxazole-trimethoprim resulted in complete recovery from UTI. Conclusion: Burkholderia cepacia may be a causative pathogen for nosocomial UTI in pediatric patients with predisposing factors, and appropriate selection of antimicrobial therapy is necessary because of high levels of resistance to empirical therapy, including aminoglycosides.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제23권2호
• /
• pp.121-131
• /
• 2020

Purpose: To determine the long-term efficacy of the anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADA), in pediatric luminal Crohn's disease (CD) by performing a systematic literature review. Methods: An electronic search was performed in Medline, Embase, and the Cochrane Library from inception to September 26, 2019. Eligible studies were cohort studies with observation periods that exceeded 1 year. Studies that reported time-to-event analyses were included. Events were defined as discontinuation of anti-TNF therapy for secondary loss of response. We extracted the probabilities of continuing anti-TNF therapy 1, 2, and 3 years after initiation. Results: In total, 2,464 papers were screened, 94 were selected for full text review, and 13 studies (11 on IFX, 2 on ADA) met our eligibility criteria for inclusion. After 1 year, 83-97% of patients were still receiving IFX therapy. After 2 and 3 years the probability of continuing IFX therapy decreased to 67-91% and 61-85%, respectively. In total, 5 of the 11 studies subgrouped by concomitant medication consistently showed that the probabilities of continuing IFX therapy in patients with prolonged immunomodulator use were higher than those in patients on IFX monotherapy. Conclusion: This review of real-world evidence studies confirms the long-term therapeutic benefit of IFX therapy in diverse cohorts of children with luminal CD. Moreover, it supports the view that combination therapy with an immunomodulator prolongs the durability of IFX therapy in patients who previously failed to recover following first-line therapy. The limited number of time-to-event studies in patients on ADA prevented us from drawing definite conclusions about its long-term efficacy.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1997년도 춘계학술대회
• /
• pp.40-47
• /
• 1997

New quinolones generally have a broad antibacterial spectrum against gram-positive, gram-negative, glucose-nonfermenting and anaerobic bacteria. Some of newly developed quinolones have potent activities against S. aureus including MRSA, S.pneumoniae including PRSP, B. fragilis, chlamydiae, mycoplasmas and mycobacteria as well, and show good activities against various strains resistant to antibacterial agents of other classes. Quinolones display postantibiotic effects in vitro and are bactericidal at concentrations similar to or twice that of the minimum inhibitory concentrations (MICs) for susceptible pathogens. In experimental murine infection models including systemic infections with various pathogens such as S. aureus, S. pyogenes, S. pneumoniae, E. coli and P. aeruginosa, quinolones have shown good oral efficacy as well as parenteral efficacy. Good oral absorption and good tissue penetration of quinolones account for good therapeutic effects in clinical settings. The target of quinolones are two structurally related type II topoisomerases, DNA gyrase and DNA topoisomerase IV. Quinolones are shown to stabilize the ternary quinolone-gyrase-DNA complex and inhibit the religation of the cleaved double-stranded DNA. Bacteria can acquire resistance to quinolones by mutations of these target enzymes. Mutation sites and amino acid changes in DNA gyrase and DNA topoisomerase IV are similar in the organisms examined, suggesting that the mechanism of quinolone resistance in the target enzymes is essentially the same among various organisms. Quinolones act on both the target enzymes to different degrees depending on the organisms or agents tested, and bacteria become highly resistant to quinolones in a step-wise fashion. Incomplete cross-resistance among quinolones in some strains of E. coli and S. aureus suggests the possibility of finding quinolones active against quinolone-resistant strains which are prevailing now. To find such quinolones, the potency toward two target enzymes and the membrane permeability including influx and/or efflux systems should be taken into account.

• Journal of Applied Biological Chemistry
• /
• 제44권1호
• /
• pp.1-5
• /
• 2001

The methanol extracts of 25 leguminous seeds in vitro was evaluated for inhibitory activities against the small intestinal $\alpha$-glucosidase of Sprague Dawley male rats. The responses varied both with leguminous seed types and concentrations used. At the concentration of 0.5 mg/ml, the methanol extracts of Cassia obtusifolia, Glycine max var. yagkong, Glycine max var. hooktae, Glycine max var. geumdu, Glycine max var. mejukong, Glycine soja, Phaseolus multiflorus, Pisum sativum, and Vigna sinensis inhibited over 50% of the enzyme activity. The extracts of G. max var. yagkong and V. sinensis showed relatively strong inhibitory activities against $\alpha$-glucosidase at the concentration of 0.1 mg/ml. The activity of each solvent fraction from G. max var. yagkong and V. sinensis was determined, and potent activities were detected from chloroform and butanol fractions, respectively. $IC_{50}$ values of G. max var. yagkong and V. sinensis were 0.06 and 0.19 mg/ml, respectively. As a naturally occurring therapeutic agents, leguminous seeds examined could be useful for developing new types of antidiabetic agents.

• 대한임상독성학회지
• /
• 제9권2호
• /
• pp.105-108
• /
• 2011

Aconitine is an anti-inflammatory agent with therapeutic uses in oriental medicine as an analgesic and for treatment of stroke. Because of its sodium channel effect, aconitine can promote undesirable, wide complex tachyarrhythmia. If tachycardia develops during use of aconitine, class Ia and class III anti arrhythmic drugs can be utilized for treatment. However there are no single anti-arrhythmia agents which are uniformly effective. We report a case, characterized by wide complex tachyarrhythmia and severe hypotension, which was successfully treated by simultaneous injections of amiodarone and lidocaine. A 59-year-old woman exhibiting clinical signs of drowsiness as a result of ingesting 6 g of aconitine, was admitted to the emergency department. Initially, wide complex tachyarrhythmia (ventricular tachycardia and pulse rate of 180 beats/min) and severe hypotension (blood pressure of 53/26 mmHg) was observed. After simultaneous injection of amiodarone and lidocaine, the patient's rhythm pattern changed to an accelerated junctional rhythm with ventricular premature complex. Two hours later, the patient's heart pattern became a sinus rhythm. As demonstrated by this case, simultaneous injections of amiodarone and lidocaine can be useful in treating ventricular arrhythmia induced by aconitine.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권4호
• /
• pp.1757-1762
• /
• 2014

Development of drugs from natural products has been undergoing a gradual evoluation. Many plant derived compounds have excellent therapeutic potential against various human ailments. They are important sources especially for anticancer agents. A number of promising new agents are in clinical development based on their selective molecular targets in the field of oncology. D-pinitol is a naturally occurring compound derived from soy which has significant pharmacological activitites. Therefore we selected D-pinitol in order to evaluate apoptotic potential in the MCF-7 cell line. Human breast cancer cells were treated with different concentrations of D-pinitol and cytotoxicity was measured by MTT and LDH assays. The mechanism of apoptosis was studied with reference to expression of p53, Bcl-2, Bax and NF-kB proteins. The results revealed that D-pinitol significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner, while upregulating the expression of p53, Bax and down regulating Bcl-2 and NF-kB. Thus the results obtained in this study clearly vindicated that D-pinitol induces apotosis in MCF-7 cells through regulation of proteins of pro- and anti-apoptotic cascades.

• Bulletin of the Korean Chemical Society
• /
• 제26권2호
• /
• pp.285-291
• /
• 2005

The nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is the viral RNA-dependent RNA polymerase (RdRp), which is the essential catalytic enzyme for the viral replication and is an appealing target for the development of new therapeutic agents against HCV infection. A small amount of serum from a single patient with hepatitis C was used to get the genome of a Korean HCV isolate. Sequence analysis of NS5B 1701 nucleotides showed the genotype of a Korean isolate to be subtype 1b. The soluble recombinant HCV NS5B polymerase lacking the C-terminal 24 amino acids was expressed and purified to homogeneity. With the highly purified NS5B protein, we established in vitro systems for RdRp activity to identify potential polymerase inhibitors. The rhodanine family compounds were found to be potent and specific inhibitors of NS5B from high throughput screening (HTS) assay utilizing the scintillation proximity assay (SPA) system. The binding mode of an inhibitor was analyzed by measuring various kinetic parameters. Lineweaver-Burk plots of the inhibitor suggested it binds not to the active site of NS5B polymerase, but to an allosteric site of the enzyme. The activity of NS5B in in vitro polymerase reactions with homopolymeric RNA requires interaction with multiple substrates that include a template/primer and ribonucleotide triphosphate. Steady-state kinetic parameter, such as Km, was determined for the ribonucleotide triphosphate. One of compounds found interacts directly with the viral polymerase and inhibits RNA synthesis in a manner noncompetitively with respect to UTP. Furthermore, we also investigated the ability of the compound to inhibit NS5B-directed viral RNA replication using the Huh7 cell-based HCV replicon system. The investigation is potentially very useful for the utility of such compounds as anti-hepatitic agents.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권7호
• /
• pp.3185-3189
• /
• 2014

Background: Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and $6.25{\mu}M$ concentrations of sorafenib and 200, 100, 50 and $25{\mu}M$ concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and $IC_{50}$ values are calculated according to the absorbance data Results: Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an $IC_{50}$ value of $32.0{\mu}M$; in contrast with lapatinib the $IC_{50}$ was $136.6{\mu}M$. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells. Conclusions: Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.