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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules & Therapeutics
Journal Basic Information
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
Selecting the target year
Effects of Age on Selective Antagonist Binding to Muscarinic Receptors in Rat Striatum
Kim, Hwa-Jung ; Lee, Sun-Hyoung ; Molly H. Weiler ;
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 337~344
The objective of the present study was to investigate the effect of senescence on the binding properties of muscarinic receptors in the neostriatum of young (3 months), middle-aged (18 months) and aged (33 months) male Fischer 344 x Brown Norway hybrid rats by employing direct binding of selective radiolabeled antagonists. Using the selective M, muscarinic receptor antagonist,
AF-DX384, as the ligand, no significant difference in the maximal receptor density (Bmax) was observed in the neostriatum among any age-groups. In contrast, with the selective M, receptor antagonist,
4-DAMP, a significant increase in the number of muscarinic receptors was observed in neostriatal membrane fractions prepared from the aged animals relative to that observed in the young rats. For each ligand there was no age-related change in its affinity (Kd) for the muscarinic receptors. These results indicate that the observed age-related changes in the muscarinic receptor density may not be necessarily decremuntal and depend upon the muscarinic receptor subtype examined.
Chronic Treatment of Ethanol Inhibits Proliferation of Normal Fibroblasts, but Not Oncogenic ras-Transformed Cells
Gu, Young-Hwa ; Park, Mi-Sun ; Jhun, Byung-H. ;
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 345~350
The adverse effects of ethanol on cell proliferation have been described for a variety of tissues and cells. In the present study, we investigated whether chronic ethanol intoxication impairs the cell proliferation and DNA synthesis induced by oncogenic
-transformed cells. Ethanol treatment inhibited the cell proliferation and the DNA synthesis of control parental fibroblasts in a time- and dose-dependent manner. In contrast, ethanol did not suppress the proliferation of either oncogenic
-transformed fibroblasts. Microinjection of oncogenic
protein induces DNA synthesis and ethanol treatment did not interfere with the DNA synthesis. The antiproliferative toxicity of ethanol was rescued by antioxidants, such as N-acetylcysteine and 4-methlpyrazole. These results indicate that the antiproliferative action site of ethanol toxicity lies upstream or is independent of Ras and ethanol exerts its toxicity through a free radical formation.
Comparison between TCDD and 3MC Action on CYPIAI Expression and EROD Activity in the Isolated Perfused Male Rat Liver
Ahn, Mee R. ; Sheen, Yhun Y. ;
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 351~357
In order to understand the mechanism of the regulation of CYPIAI gene expression and ethoxy-resorufin deethylase (EROD) activity in ex vivo system, we have studied the action of TCDD and 3MC in theisolated perfused male rat liver. CYPIAI myNA level and EROD activity were measured in rat liver that wasisolated and perfused with va.ious chemicals such as 2,3,7,8-tet.achlorodibenzo-p-dioxin (TCDD), 3-methyl-cholanthrene (3MC),
), morin. TCDD or 3MC alone perfusion into male rat liver resulted in increase of CYPIAI mRNA level and the magnitude of stimulation was one and half times higher with TCDD treatment than 3MC treatment. However
perfusion into male rat liver showed slight stimulation of CYPIAI mRNA level. When
was perfused concomitantly with either
M TCDD or
M 3MC, stimulated CYPIAI mRNA by either TCDD or 3MC was inhibited. Morin was examined for its effects on CYPIAI mRNA level and result was similar to that was observed with estrogen except that morin alone did not change the level of CYPIAI mRNA. EROD activity was also stimulated with either TCDD or 3MC perfusion, and the magnitude of EROD stiumlation was similar to that of CYPIAI mRNA stimulation in response to TCDD or 3MC perfusion. This data is different from the data that we have obtained with female rat liver. Concomitant perfusion either
or morin with TCDD or 3MC inhibited 3MC perFusion or TCDD perfusion stimulated EROD activity. These data confirm the hypothesis that TCDD and 3MC might act through the same mechanism of action on the regulation of CYPIAI gene expression in male rat liver.
Effect of MCT (medium-chain triglyceride) and LCT (long-chain triglyceride) on Myocardial Ischemia/Reperfusion Injury and Platelet Aggregation in Rat
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 358~363
Intravenous lipid emulsion is used extensively as a major component of parenteral nutrition for patients in the surgical intensive care unit. Abnormal cardiovascular function related to lipid infusion has been reported although conflicting results exist. In the present study, we investigated the effects of intravenous emulsions of long-chain triglyceride (LCT) and medium-chain triglyceride (MCT) on myocardial ischemia/ reperfusion injury and on platelet aggregation in rat. There was no difference between LCT and MCT considering the effects on left ventricular developed pressure (LVDP) and coronary flow rate (CFR) before and after ischemia/reperfusion in isolated rat heart. On the other hand, a difference was found between LCT and MCT with regard to their effects on heart rate (HR) and end diastolic pressure (EDP) after ischemia/reperfusion. After ischemia/reperfusion, HR was significantly (P<0.05) reduced and EDP significantly (P<0.05) inc.eased by LCT (18
2.0% and 42.8
8.9%, respectively), but not by MCT Ex vivo platelet aggregation induced by collagen was reduced by LCT infusion, but not by MCT These findings suggest that MCT may have slightly more favorable effect than LCT on the myocardial function after ischemia/reperfusion in rat.
Isolation of N-Containing Sugars from Silkworm Urine and Their Glycosidase Inhibitory Activities
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 364~370
Glycosidase inhibitors from urine of Bombyx mori were isolated and their inhibitory activities on glycosidases were evaluated. Six compounds were isolated by using several ion exchange columns, and their chemical structures were identified by the physicochemical and spectral data. Compound IV, V and Ⅵ were identified as 1-deoxynojirimycin, fagomine and 1,4-dideoxy-1,4-imino-D-arabinitol, respectively. Among six compounds isolated,1-deoxynojirimycin(IV) was the most potent inhibitor on
-galactosidase of rat intestine, and its inhibitory activities for trehalase and almond
-glucosidase were relatively weak. Compound V and Ⅵl retained a little inhibitory potency toward
-galactosidase. Compound II and III, however, have been found to have no effect on all glycosidases tested in this study.
Effect of Palmiwon on the Streptozotocin induced Prediabetic Model in Panceratic Bita Cells
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 371~377
The aim of the present study was to investigate the effect of Palmiwon on the type 1-prediabetic models induced by streptozotocin (STZ) in RINm5F cells and HIT-T15 cells. Palmiwon increased the cell proliferation and insulin release when pre- and post-treated for the STZ-exposed pancreatic beta cells. The cell proliferation and insulin release of these beta cells were measured by
H-thymidine uptake and RIA, respectively. We also analyzed nutrients such as sugars, fatty acid and amino acids and minerals containing in Palmiwon using by gas chromatography, amino acid analyzer and AA spectrometer, respectively. Palmiwon seems to have protective and recovery properties on the prediabetic model in cellular level, which were ascribe to various nutrients and minerals containing in Palmiwon. From these results, it could be suggested that Palmiwon may be available as preventive and therapeutic prescription of type 1 diabetes mellitus.
Anti-diabetic Activity of Constituents of Lycii Fructus
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 378~382
In the previous screening on antidiabetic effect of Lycii fructus by glucose transport method using
-STZ diabeted rat model, each extracts showed the potent antidiabetic activity. We obtained three compounds isolated from the water fraction, EtOAc fraction and n-BuOH fraction of Lycii fructus in the present work and their structures were identified as 1-carboxy-N,N,N-trimethylmethanaminium hydroxide inner salt, 2,4(1H,3H)-pyrimidinedione and 3,3',4',5,7-pentahydroxyflavone-3-rutinoside . Among the constituents separated from Lycii fructus, 2,4(IH,3H)-pyrimidinedione, 3,3',4',5,7-pentahydroxyflavone-3-rutinoside and ascorbic acid were shown a remarkable antidiabetic effect.
Effect of Rebamipide on nepato-Renal Dysfunction Caused by E.coli Lipopolysaccharide in Rat
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 383~388
The present study was aimed to investigate the preventive effects of rebamipide on the multiple organ dysfunction in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide; LPS) in comparison with that of methotrexate. Endotoxemia for 6 hours resulted in little change in the levels of hemoglobin and neutrophils. However, treatment with methotrexate decreased significantly the numbers of circulating neutrophils. Significant increases in serum alanine aminotransferase (ALT,958
250 lU/L, p<0.001) and aspartate aminotransferase (AST, 1350
295 lU/L, p<0.001) levels induced by endotoxemia were significantly decreased by rebamipide and methotrexate. The increased level of lactic acid dehydrogenase (LDH) by LPS (2850
467 lU/L, p<0.05) was significantly inhibited by rebamipide, but not by methot.elate. The elevated serum creatinine (1.2
0.1, p.0.05) and urea levels (55.3
6.5 mg/dL, p.0.01) by LPS were also decreased by rebamipide, but not by methotrexate. In line with these results, the plasma concentration of tumor necrosis factor-
20 pg/mL) was significantly increased upon injection of endotoxin at 1 hour by 1570
100 pg/mL, and declined to 312
35 pg/mL at 6 hours. The TNF-
level at 6 hours was significantly decreased by rebamipide to 207
8 pg/mL (P<0.05). Taken together, it is summarized that rebamipide inhibits the development of multiple ogran dysfunction by inhibition of neutrophil activation in association with inhibition of TNF-
formation in a murine model of endotoxemia.
Effect of Nicardipine on the Pharmacokinetic Parameters of Cyclosporine in Rat
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 389~394
Cyclosporine (CsA) is a major immunosuppressive drug used widely to prevent organ allograft rejection. fits potential organotoxicity by prolonged use is known to cause both direct tissue damage and indirect pharmacokinetic interactions with other drugs. This study was performed to determine the effect of nicardipine (NCP) on the pharmacokinetic parameters of CsA in Sprague-Dawley rats. Each rat was administered with CsA in saline-treated group or in NCP-treated group which was pretreated with NCP (5 mg/kg/12 hours, i.p.) for 6 days. The plasma CsA concentration were analyzed by reversed HPLC: UV system at 0.5, 1, 2, 4, 6, and 8 hours after bolus injection of CsA (10 mg/kg). Pharmacokinetic parameters (mean
SD, n=7) such as initial plasma concentration (C(0)), mean residence time (MRT), steady-state volume of distribution (Vdss), terminal half-life (t
)) and plasma clearance (CLp) of CsA in each groups (saline-group vs NCP-group) were determined as follows: C(0) (5.66
1.98 vs 17.98
2.36, p<0.01); Vdss (2.68
1.6 vs 0.94
0.25, p<0.01); CLp (0.53
0.18 vs 0.21
0.06, p<0.01). Therefore, Our results indicate that nicardipine significantly affects the pharmacokinetic parameters of cyclosporme, especially C(0), Vdss, and CLp in NCP-treated group. We suggest that the significant pharmacokinetic interaction between cyclosporine and nicardipine should be considered and cyclosporine level should be closely monitored and dosage reduction made as necessary in clinical situation that was coadministered with CsA and NCP.
In Vivo Antitumor Activities and Pharmacokinetics of DW2282 Depending on Vehicles
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 395~399
DW2282, (S)- (+)-4-phenyl -1-[N-(4-am mob enzoyl) -indolin-5- sulfonyl]-4,5- dihydro-2-imidazolone hydrochloride, is a novel anticancer agent thought to have an unique mechanism of action on the inhibition of tumor growth. In this study, we estimated in vivo antitumor activities and pharmacokinetics of Dw2282 depending on various vehicles. The inhibition rate of tumor growth was increased by 50, 100 and 200 mg/kg of Dw2282 in a dose-dependent manner. When Dw2282 dissolved in 4 sorts of vehicles was orally single dosed to rats at 50 mg/kg, Cmax of Dw2282 in 0.5% CMC.Na was a half as high as those in PG, PG+CP and PG+CP+DW. When Dw2282 was orally administered to mice for 5 days, antitumor activity of 130 mg/kg suspended in 0.5% CMC.Na was as effective as that of 65 mg/kg dissolved in the rest of vehicles. Taken together, it is thought that antitumor activities of Dw2282 are resulted from the absorption extent of it and related to the vehicle used.
Pharmacokinetics of CJ-50001i Recombinant Human Granulocyte-Colony Stimulating Factor, in Rats and Dogs
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 400~405
The pharmacokinetics of CJ-50001 (recombinant human granulocyte-colony stimulating factor, developed by R&D center of Cheil Jedang Corp.) were investigated in rats and dogs. The serum concentrations of CJ-50001 were measured by a sandwich enzyme immunoassay. After single intravenous (iv) administration of Cf-50001 to rats at a dose of 5
g/kg, the mean terminal half-life and area under the concentration-time curve (AUC) were 0.96 h and 124.497g . h/ml, respectively. After single subcutaneous (sc) administration at the same dose, maximum serum concentration was observed at about 2 hours after administration, and the mean terminal half-life, AUC and the bioavailability were 1.11 h,63.58
g . h/ml and 51.07%, respectively. In repeated dosing studies, CJ-50001 was administered iv and sc to rats at a daily dose of 5
g/kg for 7 days. The pharmacokinetic parameters, such as mean AUC and terminal half-life, were no significantly different from those of single administration. Following single iv and sc administration of CJ-50001 to dogs at a dose of 5
g/kg, mean AUCs were much higher than those of rats, due to the decreased clearence (CL). After sc administration to dogs, maximum serum concentration was observed at 2~4 hours after administration and the bioavailability was 54.60%.
General Pharmacology of
-Urea Powder Preparation in
Lee, Eun-Bang ; Cho, Sung-Ig ; Jung, Chun-Sik ;
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 406~411
-urea powder preparation in
for test of Helicobacter pylori was evaluated for pharmacological properties. The oral doses of the preparation used in mice were 30-fold as compared to human doses. The results obtained in the present study demonstrate that spontaneous movement, hexobarbital-induced hypnosis, rotarod performance, body temperature, acetic acid-induced writhing syndrome, chemical and electroshock convulsion, pupil size and intestinal propulsion had not been affected at the oral doses of 230, 700 and 2100 mg/kg in mice. The blood pressure was slightly elevated as given intravenously in rats at a dose of 5 mg/kg of the preparation, but respiration was not influenced at the dose. In isolated guinea pig ileum and rat fundus preparation, the preparation at a concentration of
g/ml neither caused any direct effect nor inhibited the contraction produced by acetylcholine, histamine or 5-hydroxytryptamine. These results reported here provide evidence that pre-mixed
13/C-urea powder preparation is free of general pharmacological properties performed in oral administration.
Acute Oral Toxicity of Bifidobacterium breve K-110 K-111 and B. infantis K-525 Isolated from Korean Intestine in Rats
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 412~416
Acute oral toxicity of Bifidobacterium breve K-110, Bifidobacterium breve K-111, Bifidobacterium infantis K-525 were studied in Sprague-Dawley rats of both sexes. In this study, we examined number of deaths, clinical signs, bod weight and gross findings for 14 day after single oral administration of B. breve K-110,B. breve K-111 or B. infantis K-525 with different levels. They did not show any toxic effect in rats and oral LD
value was over 5 g/kg in rats.s.
Bioequivalence Study of Loxoprofen Sodium in healthy Volunteers
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 417~422
Loxoprofen sodium (sodium 2-[4-(2-oxocyclopentylmethyl)phenyl] propionate dehydrate) is a nonsteroidal antiinflammatory drug of
-phenyl propionic acid derivative. To test the bioequivalence of loxoprofen, the pharmacokinetic parameters of new preparation of loxoprofen, LENOX was compared with LOXONIN as a reference drug. Fourteen healthy volunteers were entered to the stydy (Yonsei University College of Medicine, Severance Hospital IRB approval No. 9608). They were administered 60 mg of loxoprofen in 2
2 cross-over design. There was one week of drug-free interval between doses. The blood sample was taken on schedule up to 8 hours, and the plasma concentration loxoprofen was measured by reverse phase high-performance liquid chromatography (HPLC) with UV-detector. There were no significant difference between two preparations when AUC, Cmax, and Tmax were compared by ANOVA. The mean differences of AUC, Cmax, and Tmax were within 20% of the reference drug: the values were 2.22,5.61, and 12.50%, respectively. The confidence limits of AUC and Cmax but not Tmax satisfied the bioequivalence criteria. These results suggest that the tested LENOX is bioequivalent to the reference drug.
Bioequivalence Evaluation of Senafen Tablet and Airtal Tablet Containing Aceclofenac 100 mg
Biomolecules & Therapeutics, volume 6, issue 4, 1998, Pages 423~428
Aceclofenac is an orally effective non-steroidal anti-inflammatory agent of the phenylacetic acid derivative. Bioequivalence study of two aceclofenac preparations, the test drug (Senafe
: Daewon Phar-maceutical Company) and the reference drug (Airta
: Daewoong Pharmaceutical Company), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers, 24
4 years old and 63.9
6.9 kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 100 mg as aceclofenac in a 2
2 crossover study. Plasma concentrations of aceclofenac were monitored by HPLC method for 12 hr after administration. AU
(area under the plasma concentration-time curve from initial to 12 hr) was calculated by the linear trapezoidal method.
(maximum plasma drug concentration) and
(time to reach
) were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there are no differences in AU
between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 0.25, 0.01 and 7.32 for AU
, respectively). Minimum detectable differences (%) between the formulations at
=0.05 and 1-
=0.8 were less than 20% (e.g., 14.65, 12.47 and 15.46 for AU
, respectively). The 90% confidence intervals for these parameters were also within
20% (e.g.,-10.19~10.68, -8.87~8.89 and -3.69~ 18.33 for AU
, respectively). These results satisfy the bioequivalence criteria of KFDA guidelines, indicating that two formulations of aceclofenac are bioequivalent.quivalent.ivalent.ent.t.ent.