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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules and Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 6, Issue 4 - Dec 1998
Volume 6, Issue 3 - Sep 1998
Volume 6, Issue 2 - Jun 1998
Volume 6, Issue 1 - Mar 1998
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Studies on Mechanism of Antidiuretic Action of N
Nitro-L-Arginine, Nitric Oxide Synthase Inhibitor, in Dog
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 225~231
This studies were performed for investigation of mechanism on central antidiuretic action of L
-Nitro-L-arginine (L-NOARG), nitic oxide systhase inhibitor, in dog. Antidiuretic action of L-NOARG infused into the carotid artery was not affected by renal denervation but inhibited by pretreatment with arginine, NO Precusor. Furthermore, L-NOARG inhibited the diuretic action of dopamine induced by hemodynamic development. Above results suggest that antidiuretic actions of L-NOARG mediated by endogenous substances not associated with renal nerve. Therefore, it is demonstrated that those endogenous substances might be associated with NO which mediate the diuretic action of dopamine.e.
A Study on Anti-Stress Activities of Cholic Acid Derivatives
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 232~241
This study was done to investigate whether cholic acid derivatives have anti-stress activity in various stress models. Two cholic acid derivatives, ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (WDCA), were used. physical, psychological, chemical and environmental stress models were performed. Adrenal weight, serum glucose levels and ALP activity were elevated in restraint stress model, but this elevation was prevented by UDCA treatment. Moreover, UDCA and TUDCA inhibited exploratory and spontaneous movements in oscillation stress model. In alcohol-induced stress model, TUDCA improved rotarod performance. UDCA and TUDCA significantly reduced the involution of lymphoid organs and the increment of WBC counts in cold stress model. These findings suggest that choric acid derivatives have antistress effects in various stress models.
Inhibitory Effect of Silkworm Urine on the Rat Intestinal Glycosidase
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 242~246
The inhibitory activities of Amberlite active fraction, which was obtained from methanol soluble fraction of freeze dried slikworm urine, on the rat intestinal glycosidase-catalyzed enzymatic reaction were examined in in viro and in vivo experiments. Amberlite active fraction showed significant inhibitory effects on the hydrolysis of o-glycosidic bond, especially
-1,4 bond. On the other hand, the inhibition on the hydrolysis of
-glycosidic bond was very weak. Oral administration of Amberlite active fraction resulted in a dose-dependent decrease in the blood glucose after an oral maltose load, and postprandial hyperglycemia in carbohydrate-loaded mice was suppressed by Amberlite active fraction at 60 mgHg in decreasing order of maltose, starch, sucrose and lactose. 60 mg/kg of Amberlite active fraction lowered the blood glucose level markedly after 18, 35, and 60 min after an oral maltose load and the antihyperglycemic activity was maintained upto 90 min. In alloxan-induced hyperglycemic mice, Amberlite active fraction at a dose of 100 mg/kg also significantly lowered blood glucose after an oral maltose load, and its efficacy was almost equivalent to that of acarbowe.
Effect and Histopatbologic Examination of Calcium Channel Blocker on Carbon Tetrachloride-induced Hepatotoxicity in Rats
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 247~255
Carbon tetrachloride (CCI
) induces the hepatotoxicity due to the reactive free radicals generated by cytochrome P-450 (CYP-450) enzyme, which result in destabilization of cellular membrane. Diltiazem, a calcium channel blocking agent, has been known to suppress the CYP-450 enzyme activities. To study the effect of diltiazem in
-treated rats, we measured the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutathione S-transferase (GST), contents of bilirubin, albumin, total protein, cholesterol, triglyceride, blood urea nitrogen, creatinine malondialdehyde and calcium. Also we conducted liver histopathologic examinations. Diltiazem, when administered 1 hour prior to CCI
treaeent, significantly reduced the activities of ALT and AST, the contents of microsomal malondialdehyde and calcium in liver and microsome as compared with those of
-treated rats. In addition, histopathologic examination showed that diltiazem prevented the development of centrilobular necrosis induced by CCI
in liver tissue. Our results suggested that diltiazem could inhibit the formation of free radicals and the influx of calcium. Therefore diltiazem may be applied to suppress the liver damage caused by
Properties and Anti-diabetic Effect of 7-O-p-Fluorobenzoylchrysin
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 256~260
-7-o-p-Fluorobenzoylchrysin was synthesized by condensing p-flouorbenzoic acid with chrysin in organic solvent, and its structure was identified by NMR, MS, UV, and IR. We also investigated the physicochemical properties, hypoglycemic effect, and the quantitative analysis method of this compound. The correlation coefficient of calibration curve on this compound was approximately 0.9945 by absorption spectrophotometry and 0.9989 by high perfornance liqid chromatography 7-o-p-Fluorobenzoylchrysin was resolved in 6.014 min by reversed-phase HPLC column with solvents consisting of methanol (80%) and 10mM phosphoric acd. Its blood glucose inhibition rate is 20.7%.
Studies on the Efficacies of Water Extract of Propolis
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 261~268
Propolis is a lipophilic, natural product prepared by mixing the exudates collected from various plants by honeybees with beeswax for the purpose of using to seal hive walls and to strengthen the borders of combs. Because of its versatile bioactivities, propolis has been attracting many investigators'interest. But the pharmacological studies on propolis has, to date, been exclusively performed for an alcohol extract, there is few information of water extract. Therefore, in this study, we investigated the various effects of water extract of Chinese propolis. The water extract of propolis and its fractions of organic solvents showed strong antioxidative activities, especially ether and ethylacetate fractions, and reduced the lipid peroxidation of rat liver in viro. Additionally the ether fraction of propolis (10 mg/ml) inhibited the activity of hyaluronidase by 50%. In vivo, the water extract of propolis considerably decreased s-GOT, s-GPT and s-LDH activities which represent for the hepatotoxicity induced by
in rats, and prolonged the MST (Medium revival tinge) and ILS (Increasing in MST over control) by 18% in mice which inoculated with sarcoma 180 ascites cells. These results suggest that the water extract of propolis has various bioactivities as well as the alcohol extract.
Studies on the Antiinflammatory Effects of Natural Products
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 269~275
These studies were conducted to investigate the antiinflammatory effects and the mechanism of action of natural products. We used the methods of "carrageenan induced foot edema" , "PAF (platelet activating factor) induced foot edema" , "inhibition test of vascular permeability" , "inhibition test of white blood cell migration" , "formation of granuloma" and "adjuvant induced arthritis" to examine the antiinflammatory erects of Angelica gigas, Ledebouriella seseloides, Ginkgo biloba and Bamboo salt (Jukyom). The oral administration of the water extract of Angelica gigantis radix, the methanolic extract of Ginkgo folium and the aqueous solution of Bamboo salt showed antiinflammatory effect on carrageenan and PAF induced foot edema in SD rat at a dose of 1 g/kg. The same administration of methanolic extract of Ginkgo folium also inhibited the vascular permeability in mice. The aqueous solution of Bamboo salt inhibited the formation of ganuloma in SD rats at a oral dose of 1 g/kg. Angelica gigantis radix seems to have antiinflammatory effect by inhibition of PAF.
A Retinoid Antagonist Inhibits the Retinoic Acid Response Element that Located in the Promoter Region of the Cytomegalovirus
Lee, Mi-Ock ; Ahn, Ju-Mi ; Han, Sun-Young ;
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 276~282
Retinoids regulate a wide variety of biological processes such as cellular proliferation and differentiation in many cell types. They have also shown to stimulate replication of several viruses including human cytomegalovirus (CMV). Retinoid signalling pathway involves two distinct subfamilies of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that bind to specific retinoic acid response elements (RAREs) in the promoter regions of retinoid-target genes. Here, we characterized RAREs in the regulatory regions of the CMV and of the hepatitis B vi.us (HBV). The viral RAREs, i.e., CMV-RARE and HBV-RARE, are composed of two consensus RARE half-sites (A/GGGTCA) arranged as a direct repeat separated by 5-bp and 1-bp, respectively. The RAREs were activated by both RAR/RXR heterodimers and RXR homodimers in transient transfection experiments. We also found that COUP-TF
(chicken ovalbumin upstream promoter-transcription factor u) and COUP-TF
repressed the retinoid response of the viral elements. Further we demonstrated that previously known retinoid antagonist, SRI 1330, repressed retinoid-induced transactivation of the CMV-RARE. These results implicate Vitamin A, it's nuclear receptors and COUP-TFs as important regulators of the CMV and HBV pathogenesis and the SRl1330 as potential negative modulator of such retinoid-dependent processes.
Metabolism of YH1885 by Rat, Dog, Monkey and Human Liver S9 Fractions
Kim, Eun-Joo ; Roh, Jung-Koo ; Green, Carol ;
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 283~288
YH 1885 (5,6-dimethyl -2-(4-fluorophenylamino)-4-(1-methyl -1,2,3,4-tetrahydroisoquinolin -2- yl) pyrimidine hydrochloride) was developed as an antiulcer drug. The objective of this study was to examine a comparative metabolism of YH1885 in rat, dog, monkey and human liver tissues and to determine the metabolite profiles produced by the four species. YH1885 was metabolized by liver 59 fractions from all four species. Control incubations containing 59 fraction but no cofactors, contained essentially no metabolites. Metabolism of YH1885 apparently became saturated in the concentration range studied because the % of YH 1885 metabolized decreased with increasing drug concentration for all four species. Six to nine metabolite peaks were detected in the incubations and the particular profile of metabolites varied with species. The total amount of metabolites formed by liver microsomes from human and monkey were less than microsomes from rat or dog. The major metabolite peak formed by rat liver 597actions fluted near the solvent front on the HPLC or remained at the origin in TLC, indicating that it contained one or more polar metabolites. Dog liver 59 fractions incubations contained four major metabolites that each accounted for about 15 to 20 % of the total radioactivity at the low concentration of YH1885. The metabolite profiles of YH1885 appeared to be similar in incubations with rhesus monkey and human liver 59 fraction. The amount of metabolites formed by rhesus monkey liver preparations was greater than that of human liver that contained prominent metabolite peaks with approximate relative retention time of 0.14 and 0.43.
Bioequivalence of Two Nilvadipine Tablet
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 289~295
The bioequivalence of two nilvadipine products was evaluated in 16 normal male volunteers (age 22-32 yr, body weight 57-80 kg) following sidle oral dose. Test product was Overca
tablet (Choong-Wae Pharm. Corp., Korea) and reference product was Nivadi
tablet (Hyundai Pharm. Corp., Korea). Both products contain 4 mg of nilvadipine. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2
2 Latin square method). The determination of nilvadipine was accomplished using a validated capillary column GC with electron-capture detection. As a result of the assay validation, the quantiflcation of nilvadipine in human plasma by this technique was possible down to 0.5 ng/ml using 1 ml of plasma. Absolute overall recovery from five replicate analyses of nilvadipine-spiked sample were 88.4
5.D.) for human plasma of 10 ng/ml. The coefficients of variation (C.V.) were less than 20% and the actual concentration of nilvadipine measured by GC ranged from 80 to 99% in all plasma. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve from time zero to 8 hr (AUCo-
5.90 vs 22.2
6.10 ng . hr/ml), maximum plasma concentration (
2.85 vs 9.3
3.28 ng/ml) and time to reach maximum plasma concentration (
0.31 vs 1.3
0.47 hr). The differences of mean AU
between the two products (2.25, 7.65, and 10.30%, respectively) were less than 20%. The power (1-
) and treaeent difference (7) for AU
were more than 0.8 and less than 0.2, respectively. Although the power for Tmax was under 0.8, Tm\ulcorner of the two products was not significantly different from each other (p>0. 05). These results suggest that the bioavailability of Overeat tablet is not significantly different from that of Nivadil tablet. Therefore, two products are bioequivalent based on the current results.sults.lts.lts.lts.
Bioequivalence of Cyclosporin A Hard Capsules
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 296~302
The bioequivalence of two cyclosporin A products was evaluated in 26 normal male volunteers (age 25 ~33 yr, body weight 56~84 kg) following single oral administration. Test product was a hard capsule containing the granule of cyclosporin A (Chong Kun Dang Corp., Korea) and reference product, Sandimmun", was a soft capsule containing surfactant, oil, alcohol and cyclosporin A (Sandoz, Swiss). Both products contain 100 mg of cyclosporin A. Four capsules of the test and the reference product were administered to the volunteers, respectively, by randomized two period cross-over study (2
2 Latin square method). Average drug concentrations at each sampling time and pharmacokinetic parameters were not significantly different between two products (p>0.05); the area under the concentration-time curve to last sampling time (24 hr) (AU
1760.6 vs 4635.4
1158.9 ng . h/ml), maximum plasma concentration (
353.1 vs 980. 4
171.7 ng/71), and mean residence time (MRT) (6.16
0.81 vs 5.64
0.50 h). The differences of mean AUC 7-,4,7~, T_ and MRT between the two products (7.93,2.22,16 and 8.39%, respectively) were less than 20% given as a guideline. The power (1-
) and treatment difference (
) for AU
and MRT were more than 0.8 and less than 0.2, respectively. Although
of the two products was significantly different each other (p<0.05),
might be an insignificant parameter because cyclosporin A generally requires long-term administration. From these results, the two products are bioequivalent.alent.t.
General Pharmacology of the New Platinum (II) Anticancer Agents with Diaminocyclohexane as a Carrier Ligand
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 303~311
The general pharmacological properties of new platinum (II) coordination complexes, SA : [Pt(trans-ι-DACH)(DPPE)] . 2NO
, SB : [Pt(cia-DACH)(DPPP)] 2NO
and SC : [Pt(cia-DACH)(DPPE)] 2NO
on central nervous, respiratory, cardiovascular and digestive systems were studied in various experimental animals. These platinum (II) anticancer agents had no effects on analgesia, thiopental-induced sleeping time, body temperature, strychnine-induced convulsion, inflammation and local anesthetic action in mice and rats. Intestinal motility, stomach-ulcer induced by serotonin and bile-secretion of rats were not influenced by the dose of 30 mg/kg. However SB and SC induced a mild decrease in heart rate in anesthetized rats. Based on these results, these new platinum (II) complexes may be regarded as a valuable lead compound in the development of new anticancer chemotherapeutic agents with marked antitumor activity and low toxicity.
Efficacy of Recombinant Human Erythropoietin(rhu-EPO)
Kim, Dong-Hwan ; Ahn, Byoung-Ok ; Park, Jang-Hyeon ; Lee, Sung-Hee ; Kim, Won-Bae ;
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 312~316
Efficacy and in vivo bioassay of recombinant human erythropoietin (rho-EPO), was investigated. Efficacy studies were conducted in normal, and cisplatin-induced anemic rats. Normal and anemic animals were treated intravenously with rhu-EPO for 5 days, and the changes in the number of red blood cells (RBC), hemoglobin concentration (Hb), hematocrit value (Hct) and percentage reticulocyte value (Ret, reticulocyte/RBC) were examined. In normal rats, rho-EPO significantly increased RBC, Hb, Hct and Ret at the doses of 50∼ 1,250 lU/kg/day in a dose-dependent fashion. Cisplatin-induced anemic rats showed significant increase of RBC, Hb, Hct and Ret after administration of rho-EPO (50-200 lU/kg/day) in a dose-dependent manner. These changes of hematological parameters disappeared gradually after cessation of the treatment. The in vivo bioassay results in polycythemic mice showed that rho-EPO had 90% of bioactivity compared to NIBSC standard rhu-EPO. These results suggest that rho-EPO might be useful for the therapy of anemia originated from renal failure and chemotherapy-induced anemia.
Subchronic Intravenous Toxicity of Recombinant Human Erythropoietin (rHuEPO) in Beagle Dogs
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 317~327
The subchronic toxicity study of rHuEPO, a newly developed recombinant erythropoietin, was investigated for 13 weeks in Beagle dogs intravenously treated with doses of 100, 500 and 2,500 lU/kg/day. There were no significant changes in body weight, food intake, physical and opthalmic examination, urine analysis, etc. Any toxic response was not observed except for enlarged spleen and extramedullary hematopoiesis. These results indicate that the no-observed adverse effect level (NOAEL) of rHuEPO is 100 lU/kg in Beagle dogs.
Subacute Oral Toxicity of DWP-311 in Sprague-Dawley Rats
Biomolecules and Therapeutics, volume 6, issue 3, 1998, Pages 328~336
The subacute oral toxicity study of DWP-311 was carried out in Sprague-Dawley rats of both sexes. We daily examined clinical signs, body weights, hematological and biochemical parameters, and histopathological examinations for 30 days after administration of DWP-311 with different dose levels (0, 0.04, 0.2, and 1.0 g/kg). There were no clinical signs and pathological changes compared with control group except slight decreases in spontaneous motor activities and locomotions at high dose group of DWP-311. Body weights were not significantly changed in animals treated with DWP-311, In histopathological examinations, there were 2 cases of pneumonia in control group for one male and one female, but it was not directly related to DWP-311. These results indicate that subacute oral toxicities of DWP-311 were low and the no-observed a dverse effect level (NOAEL) was considered to be 1.0 g/kg in rats.