• Journal of fish pathology
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• v.14 no.1
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• pp.31-36
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• 2001

A novel clonidine binding sites were characterized in the intestinal membrane isolated from seawater eels, Anguilla japonica. The specific clonidine binding sites consisted of at least two classes, high affinity ($K_d=1.4{\pm}0.3$ nM n = 5) and low affinity ($K_d=175{\pm}34$ nM n = 5) sites. The specific binding of 2 nM [$^3H$]clonidine was most enhanced at $20^{\circ}C$ and pH 7.5, and reversed by unlabelled clonidine. Such binding was hardly inhibited by adrenaline, yohimbine or rauwolscine, indicating that most binding sites are distinct from $\alpha_2$-adrenoceptor. The specific clonidine binding sites was inhibited by various imidazoline/guanidinium drugs, indicating existence of imidazoline/guanidinium receptive sites (IGRS) or imidazoline receptors in the eel intestine. Competition experiments revealed that rank order to displace 2 nM [$^3H$]clonidine from their binding sites was as follows : guanabenz > cirazoline = naphazoline = UK14,304 = ST587 $\geq$ clonidine $\geq$ idazoxan = RX821002 = tolazoline > ST93 = oxymetazoline = amiloride = ST91 > yohimbine = efaroxan = rauwolscine $\geq$ adrenaline = ST567 = histamine = agmatine. Although physiological role of IGRS is not clear yet even in mammalian cell/tissues, eel intestine may be a good model to elucidate how the IGRS act in the cell and to decide what is the endogenous ligand for the IGRS.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.90-99
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• 2011

Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC's 95% confidence interval was greater than 0 and RR's 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as $Micromedex^{(R)}$ and 2010 Drug Interaction $Facts^{TM}$. Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

• Korean Journal of Biological Psychiatry
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• v.7 no.2
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• pp.191-197
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• 2000

Objectives : Risperidone is a new antipsychotic drug developed to overcome the therapeutic limitation of conventional antipsychotics. It responses to negative as well as positive symptoms by blocking both dopaminergic and serotonergic receptors, causing no significant side effects such as agranulocytosis and seizure. It is, however, not known whether it induces any serious cardiovascular side effects as evoked by other conventional antipsychotic drugs. The aims of this study were to evaluate the effect of risperidone on cardiovascular function, and to discuss the factors affecting the cardiovascular function. Methods : For 42 patients(22 males and 20 females) diagnosed as schizophrenia, schizophreniform disorder or schizoaffective disorder according to the DSM-IV classification, the cardiovascular fuctions such as heart rate, systolic and diastolic blood pressure, PR interval, QRS interval and QT interval were successively checked before and after 2 weeks and 4 weeks risperidone administration. Furthermore, variables such as body weight, Brief Psychiatric Rating Scale(BPRS), Clinical Global Impression(CGI), Extrapyramidal Symptom Rating Scale(ESRS), Anticholinergic Rating Scale(ARS), serum cholesterol level, serum triglyceride level, serum high-density-lipoprotein level, serum WBC, serum Hb, serum platelet level, prothrombin time and partial thromboplastin time were also analyzed before and after 2 weeks and 4 weeks risperidone administration. Results : 1) Risperidone treatment resulted in a significantly decreased heart rate and increased QT interval after 4 weeks administration(p<0.005 respectively). 2) The scores of BPRS and CGI were significantly decreased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). The scores of ESRS and ASRS were significantly increased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). 3) There were positive correlations between heart rate after 4 weeks and total dose(P<0.05). Blood pressure was significantly(p<0.05) correlated with sex(higher in male) and significantly(p<0.05) positive correlated with body weight. QT interval was significantly(p<0.05) correlated with sex(longer in female) and smoking history(shorter in smokers). Conclusions : Risperidone could induce significant change in heart rate and Q-T interval. Therefore, the cardiovascular safety for risperidone should be reconsidered according to the duration and dosage increase.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.54-58
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• 2007

Purpose: Luciferase is one of the most commonly used reporter enzymes in the field of in vivo optical imaging. D-luciferin, the substrate for firefly luciferase has very high cost that allows this kind of experiment limited to small animals such as mice and rats. In this current study, we validated local injection of D-luciferin in the articular capsule for bioluminescence imaging in rabbits. Materials and Methods: Chondrocytes were cultured and infected by replication-defective adenoviral vector encoding firefly luciferase (Fluc). Chondrocytes expressing Fluc were injected or implanted in the left knee joint. The rabbits underwent optical imaging studies after local injection of D-luciferin at 1, 5, 7, 9 days after cellular administration. We sought whether optimal imaging signals was could be by a cooled CCD camera after local injection of D-luciferin. Results: Imaging signal was not observed from the left knee joint after intraperitoneal injection of D-luciferin (15 mg/kg), whereas it was observed after intraarticular injection. Photon intensity from the left knee joint of rabbits was compared between cell injected and implanted groups after intraarticular injection of D-luciferin. During the period of imaging studies, photon intensity of the cell implanted group was 5-10 times higher than that of the cell injected group. Conclusion: We successfully imaged chondrocytes expressing Fluc after intraarticular injection of D-luciferin. This technique may be further applied to develop new drugs for knee joint disease.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.175-180
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• 2010

Albumin-modification has been viewed as one of the most effective ways of extending the short in vivo lifetimes of peptide drugs by delaying glomerular filtration. In this study, we describe a new type 2 anti-diabetic exendin-4 (Ex4) peptide derivative with significant binding ability to human serum albumin (HSA). This exendin-4 derivative consists of a 4-branched polyethylene glycol $(PEG)_{5k}$ (Mw: 20 kDa) modified with three stearylamines ($C_{18}-NH_2$) and one exendin-4 on its branches. PEG and stearylamine were selected to provide functionality to increase molecular size and bind to albumin, respectively. This derivative ($3C_{18}-4PEG_{5k}$-Ex4) was shown to have larger molecular size (Ca. 152 kDa) than actual (25.0 kDa) when subjected to size-exclusion chromatography, and the fluorescein-tagged $3C_{18}-4PEG_{5k}$-Ex4 displayed significant binding to the HSA-immobilized Sepharose CL-4B resin using confocal laser scanning microscopy. Furthermore, $3C_{18}-4PEG_{5k}$-Ex4 was found to have acceptable anti-hyperglycemic efficacy via three consecutive oral glucose tolerance testings (OGTT) in fasted type 2 diabetic db/db mice. The $HD_{total}$ value ($57.6{\pm}12.3%$) of $3C_{18}-4PEG_{5k}$-Ex4 at a 50 nmol/kg dose was 2-fold greater than that ($31.0{\pm}8.7%$) of native exendin-4 in non-fasted db/db mice. Especially, the blood glucose levels in the mice group treated with $3C_{18}-4PEG_{5k}$-Ex4 did not rebound to ~150 mg/dL until 24 h after the injection, which obviously shows the extended hypoglycemia. We believe that this derivative has great pharmaceutical potential as a novel long-acting type 2 anti-diabetic injection treatment.

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.377-384
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• 1995

We examined the wound healing effect and toxicity of Forsythia suspensa extract to verify the therapeutic usefulness on wound treatment. Additionally, we examined its antibacterial effect. The wound healing effect of Forsythia suspensa extract was compared with the tetrachlorodecaoxygen anion complex (TCDO), protein free haemodialysate (Haemyl), and physiological saline. The wound areas on the 4th, 11th, 14th day of treatment with Forsythia suspensa extract, TCDO, and Haemyl were significantly smaller than with the saline treatment. The wounds on the 8th day of treatment with Forsythia suspensa extract were only siginificantly smaller than the saline treatment. On the 8th day of treatment with Forsythia suspensa extract, TCDO, and Haemyl accerlerlated the wound epithelization more than saline treatment. There was not a significant difference in liver enzyme activity (GOT, GPT) and blood cell count between the Fosythia suspensa extract and the saline treatment. In addition, the Forsythia suspensa extract did not inhibit bacterial proliferation. These results suggest that Forsythia suspensa extract has great possibility of being developed into new wound healing drugs. Its pharmacological effects seem to have no relation with antibacterial effect.

• Journal of Microbiology and Biotechnology
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• v.23 no.8
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• pp.1076-1083
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• 2013

Seventeen compounds derived from traditional Chinese medicines (TCMs) were tested for their antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV) in vitro. Visualization with the cytopathologic effect (CPE) assay and the 3-(4, 5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide test were used to determine the 50% cytotoxic concentration ($CC_{50}$) and 50% effective concentration ($EC_{50}$) in cultured Marc-145 cells. Among the tested compounds, chlorogenic acid and scutellarin showed potential anti-PRRSV activity. The $EC_{50}$ values were $270.8{\pm}14.6{\mu}g/ml$ and $28.21{\pm}26.0{\mu}g/ml$ and the selectivity indexes were >5.54 and 35.5, respectively. The time-of-addition and virucidal assay indicated that the anti-PRRSV activity of the two compounds could be due to their inhibiting the early stage of virus replication and/or inactivating the virus directly. The inhibition of the virus attachment was not observed in the adsorption inhibition assay. The inhibition ratios of chlorogenic acid and scutellarin were, respectively, 90.8% and 61.1% at the maximum non-cytotoxic concentrations. The results have provided a basis for further exploration of their antiviral properties and mechanisms in vivo. We believe that the chlorogenic acid and scutellarin have a great potential to be developed as new anti-PRRSV drugs for clinical application.

• Journal of Microbiology and Biotechnology
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• v.30 no.4
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• pp.540-551
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• 2020

Sporotrichosis is a chronic and subacute mycosis causing epidemiological outbreaks involving sick cats and humans in southeastern Brazil. The systemic disease prevails in cats and in humans, with the symptoms restricted to the skin of immunocompetent individuals. Under these conditions, the prolonged treatment of animals and cases of recurrence justify the discovery of new treatments for sporotrichosis. This work addresses the antifungal activity of silver salts of Keggin-type heteropolyacid salts (Ag-HPA salts) such as Ag₃[PW₁₂O₄₀], Ag₆[SiW₁₀V₂O₄₀], Ag₄[SiW₁₂O₄₀] and Ag₃[PMo₁₂O₄₀] and interactions with the antifungal drugs itraconazole (ITC), terbinafine (TBF) and amphotericin B (AMB) on the yeast and mycelia forms of Sporothrix spp. Sporothrix spp. yeast cells were susceptible to Ag-HPA salts at minimum inhibitory concentration (MIC) values ranging from 8 to 128 ㎍/ml. Interactions between Ag₃[PW₁₂O₄₀] and Ag₃[PMo₁₂O₄₀] with itraconazole and amphotericin B resulted in higher antifungal activity with a reduction in growth and melanization. Treated cells showed changes in cell membrane integrity, vacuolization, cytoplasm disorder, and membrane detachment. Promising antifungal activity for treating sporotrichosis was observed for the Ag-HPA salts Ag₃[PMo₁₂O₄₀] and Ag₃[PW₁₂O₄₀], which have a low cost, high yield and activity at low concentrations. However, further evaluation of in vivo tests is still required.

• Journal of Yeungnam Medical Science
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• v.20 no.2
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• pp.152-159
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• 2003

Background : Hyperlipidemia is the one of the major risk factors causing the atherosclerosis of coronary arteries. Treatment of hyperlipidemia with drugs has been confirmed the effects of therapy showing a decreased incidence of coronary artery disease. Simvastatin is a new drug of HMG-CoA reductase inhibitors and the short-term hypolipidemic effects and safety of simvastatin is evaluated in patients with hyperlipidemia. Methods: We studied 63 patients (39 males and 24 females, mean age 58) for 12 weeks whose plasma levels of total cholesterol were higher than 240 mg/dL or higher than 220 mg/dL with ischemic heart disease. Simvastatin was administered 20 mg/day and measured lipid profile at 12 week interval. Result: 1) Simvastatin significantly reduced the level of the plasma total cholesterol(-29.3%), LDL-cholesterol(-36.9%) and triglyceride(-13%)(p<0.05) but the level of HDL-cholesterol was not changed after 12 weeks simvastatin therapy. 2) the clinical symptoms and laboratory examination before and after simvastatin treatment showed no particular abnormal findings in short term follow up. Conclusion: These results suggested that short-term simvastatin therapy in patients with hyperlipidemia seeems to be very effective and safe.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7045-7056
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• 2013

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.