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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules & Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 7, Issue 4 - Dec 1999
Volume 7, Issue 3 - Sep 1999
Volume 7, Issue 2 - Jun 1999
Volume 7, Issue 1 - Mar 1999
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Effects of Morphine and Panax ginseng on the Opioid Receptor-G protein Interactions
Kim, Young-Ran ; Kim, Ae-young ; Kim, Kyeong-Man ;
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 1~6
Effects of Panax ginseng on the morphine toxicity were studied in relation to its effects on the opioid receptor-G protein interactions. Morphine treatments (3 days) reduced the body weight increment rate and the weight of the thymus and spleen. These changes were usually recovered by the concomitant administration of ginseng total saponin (GTS) but occasionally further deteriorated. This discrepancy was studied in relation to the opioid receptor coupling to G protein, that is, the effects of morphine and GTS on the opioid receptors were studied using the antagonist-agonist competitive binding studies. When GTS recovered the morphine toxicity, morphine shifted the striatal
receptors to slightly higher affinity state, and this was partly recovered by the GTS treatment. However, morphine did not have any effect on the affinity state of
receptor from NG108-15 cells, suggesting that additional factors were needed for the modulation of the affinity states of
receptor. Effects of morphine and GTS on
receptor were complicate and variable, and we could not reach a clear conclusion. The morphine toxicity might accompany complicate biological involvements, and the modulation of the affinity states of the opioid receptors might explain a part of the effects of GTS on the morphine toxicity.
Accelerated Wound Healing by ]Recombinant Human Basic Fibroblast Growth Factor in Healing-impaired Animal Models
Kang, Soo-Hyung ; Oh, Tae-Young ; Cho, Hyun ; Ahn, Byoung-Ok ; Kim,Won-Bae ;
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 7~13
The stimulatory effect of recombinant human basic fibroblast growth factor (bFGF) on wound healing was evaluated in healing-impaired animal models. Full-thickness wounds were made in prednisolone-treated mice, streptozotocin (STZ)-induced diabetic rats and mitomycin C (MMC)-treated rats. Saline or bFGF at a dose of 1, 5, or
per wound was applied to the open wound once a day for three to five days. The degree of wound healing was assessed using wound size and histological parameters such as degree of epidermal and dermal regeneration. Local application of bFGF accelerated wound closure significantly in a dose-dependent manner in all healing-impaired wounds (p<0.05). The wound healing effect of bFGF was further confirmed by histological examination in MMC-treated rats. Epidermal and dermal regeneration were enhanced in bFGF-treated wounds with a dose-related response. Dermal regeneration parameters such as collagen matrix formation and angiogenesis were significantly increased in
of bFGF-treated wounds when compared to saline-treated wounds (p<0.05). pectin immunostaining on day 8 for vascular endothelium showed an increased number of neovessels in bFGF-treated wounds. These results suggest that topical application of bFGF has beneficial effects on wound healing by angiogenesis and granulation tissue formation in healing-impaired wounds.
Immunogenicity Study of Recombinant Human Basic Fibroblast Growth Factor
Kim, Dong-Hwan ; Cho, Hyeon ; Kang, Kyung-Koo ; Ahn, Byoung-Ok ; Kang, Soo-Hyung ; Kim, Won-Bae ;
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 14~21
The immunogenicity of the recombinant human basic fibroblast growth factor (rh-bFGF) was investigated by tests for active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and guinea pig maximization test (GPMT) in mice or guinea pigs. Guinea pigs were sensitized with rh-bFGF (
) or rh-bFGF-CFA mixture (
). All animals sensitized with rh-bFGF alone or mixture with CFA showed symptoms of anaphylactic shock. IgE antibodies to rh-bFGF were detected in sera obtained from rh-bFGF and rh-bFGF-Alum (
) sensitized mice, indicating that rh-bFGF has immunogenicity eliciting potential. IgG and/or IgM antibodies to rh-bFGF were also detected in all the sera obtained from sensitized mice by PHA. In the GPMT for delayed type skin reaction, no skin reaction was observed in sensitized guinea pigs after intradermal injection and dermal application of 0.01% rh- bFGF. However, these positive reactions were consistent with the results of another rh-bFGF, showing that rh- bFGF is a heterogenous protein to rodents. Considering the fact that rh-bFGF is a genuine human protein of which structure is identical to the endogenous human bFGF, it is thought that rh-bFGF is rarely associated with immunological problems in clinical use.
Comparison between Doxorubicin and Anti-Fas Antibody induced poptosis in Promyelocytic Leukemia Cell Line HL-60
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 22~28
Induction of apoptosis is considered to be the underlying mechanism that accounts for the efficiency of chemotherapeutic drugs. It has recently been proposed that doxorubicin (DOX) can induce apoptosis in human leukemic cells via the Fas/Fas Ligand (FasL) system. Comparison of Fas and FasL mRNA expression between drug- and anti-Fas antibody(Fas-Ab)- induced apoptosis was analyzed for examining the role of Fas/FasL system in the mediation of drug-induced apoptosis. After HL-60 cells were routinely cultured, MTT assay was performed for cytotoxicity test. Giemsa staining was carried out to monitor the apoptosis morphologically. By semiquantitative RT-PCR analysis, the expression of Fas and FasL at 4, 10, 24 hours was determined after DOX and Fas-Ab treatment. Dose-dependent cytotoxicity was induced by DOX-treatment, while Fas-Ab treatment showed the similar dose-dependent pattern but the cytotoxicity is not reached at LD
at 100 ng/ml concentration of Fas-Ab. In the 10ng/m1 DOX and 10ng/m1 Fas-Ab treated group, typical apoptotic cell morphology was shown such as fragmented nuclei and cell membrane budding in the Giemsa-stained slide. Fas mRNA expression was not changed significantly in the both groups. But, FasL mRNA expression was induced significantly at initial period of apoptosis. In this study, Fas/FasL interaction assumed to be involved in drug-induced apoptosis.s.
Anticancer Activity of Natural Products including Salvia miltiorrhiza
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 29~34
The cellular growth inhibition of 20 natural products was screened using SRB (sulforhodamine B) assay against 4 human cancer cell lines(SNU-1, SNU-C
, Hep3B, Kato III). Ethanol extracts of Salvia miltiorrhiza, Saussurea lappa and Chelidonium majus showed potent anticancer activity among them, and further, it was fractionated into methylene chloride, hexane and methanol. Methylene chloride and methanol fraction of Salvia radix showed significant inhibitory activity against 4 human cancer cell lines. The effect of Salvia miltiorrhiza on anticancer activity in vitro models was evaluated with methylene chloride fraction of Salvia miltiorrhiza. Life span of ICR mice implanted with sarcoma-180 was increased by 40-61% and BDF
mice implanted with L1210 was increased by 66-89% upon intraperitoneal administration with methylene chloride fraction of Salvia miltiorrhiza. Based on these result, we suggested that Salvia miltiorrhiza showed anticancer activity on the in vivo and in vitro models
Protective and Therapeutic Effects of Malloti Cortex Extract on Carbon Tetrachloride- and Galactosamine-induced Hepatotoxicity in Rats
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 35~43
Hepatoprotective effects of Malloti cortex extract (MCE) from Mallotus japonicus against the carbon tetrachloride (CCl
) and galactosamine (GalN) were investigated. Whereas serum aspartate aminotransferase and alanine aminotransferase levels were markedly elevated after CCl
and GalN administration, pretreatment and posttreatment with MCE before and after the injection of CCl
and GalN resulted in decreases in elevated serum aminotransferase activities. Whereas CCl
and GalN treatment caused 3~7 fold increases in sorbitol dehydrogenase and
-glutamyltransferase activities, pretreatment and posttreatment with MCE resulted in the blocking of CCl
and GalN-induced liver toxicity. The hepatoprotective effect of MCE was in part due to MCE-induced elevation of hepatic glutathione levels. Pretreatment and posttreatment with MCE also reduced increased lipid peroxidation induced by CCl
and GalN. These results suggest that MCE may be useful for the prevention and therapy of hepatotoxic pathogenesis. It is presumed that protective and therapeutic effects of MCE due to be inducible glutathione S-transferase and glutathione reductase activities, involving in glutathione-medicated detoxication and maintainment of glutathione content, respectively.
Comparative in vitro and in vivo Antibacterial Activities of Cefatrizine/clavulanic Acid Combination and Other
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 44~53
The resistant strains due to the extended-spectrum
-lactamase (ESBL) were susceptible to cefatrizine combined with clavulanic acid. The purpose of this study was to evaluate the in vitro and in vivo antibacterial activities of cefatrizine/clavulanic acid (CTRZ/CV) combination at a ratio of 2 : 1 in comparison with cefaclor (CCLO), cefuroxime (CRXM), cefuroxime axetil (CRXMA) and amoxicillin/clavulanic acid (AMXCCV). CTRZ/CV showed good activity against laboratory strains of gram-positive and gram-negative bacteria and exhibited excellent antibacterial activity against
-lactamase-producing strains. The bactericidal activity of CTRZ/CV was superior to that of CCLO and CRXM, and almost equal to that of AMXCCV against the
-lactamase-producing strains. The in vitro results were substantiated. by in vivo mouse experimental infection studies with
-lactamase-producing and non-producing strains. In mixed experimental infection due to
-lactamase-producing and non-producing strains, the therapeutic efficacy of CTRZ/CV was superior to that of CTRZ, CCLO, CRXMA and AMXCCV. In respiratory tract infection in mice due to Klebsiella pneumoniae EB4O, CTRZ/CV was more erective than CCLO, CRXMA and AMXCCV and also more efficacious than CCLO, CRXMA and AMXCCV in urinary tract infection in mice due to Escherichia coli EB13. These results indicate that CTRZ/CV is a useful drug for the treatment of infection caused by
-1actamase-producing strains including ESBL-producing strains.
Pharmacokinetic and Pharmacological Evaluation of Topical Microemulsion Preparation Containing Piroxicam
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 54~58
The pharmacological activities and pharmacokinetic aspects of a topical microemulsion (KDPM) containing 0.5% piroxicam were evaluated after its topical application compared with a commercially available 0.5% piroxicam gel (R gel). When the pharmacological activities were evaluated with the carrageenan-induced paw edema model, KDPM showed 55.6% edema inhibition, while R gel resulted in 37.1%. With the adjuvant-induced arthritis model, KDFM also resulted in the better pharmacological activities than R gel. The relative bioavailability of KDPM based on R gel was 176% in rabbits.
Bioequivalence Evaluation of the Cisapride Formulation Produced by Dong Wha Pharmaceutical Co.
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 59~65
A bioequivalence study of the Dong Wha Cisapril tablets(Dong Wha Pharm. Ind. Co., Ltd.) to the Prepulsid tablets(Janssen Korea Ltd.), formulations of cisapride, was conducted. Twenty four healthy Korean male subjects received each formulation at the dose of 5 mg as cisapride in a 2
2 crossover study. There was a 1-week washout period between the doses. Plasma concentrations of cisapride were monitored by an LC/MS method for over a period of 36 h after each administration. AUC(area under the plasma concentration- time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method.
(maximum plasma drug concentration) and
(time to reach
) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC,
between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 6.8, -6.6 and 1.8% for AUC,
, respectively). Minimum detectable differences(%) at
=0.05 and 1-
=0.8 were all less than 20% in these parameters between the formulations (i.e., 16.5, 11.4 and 16.4% for AUC,
, respectively). The 90% confidence intervals for these parameters were also within 20% (i.e., -2.9~ 16.4, -13.2~0.1 and -7.8~ 11.4% for AUC,
, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the two formulations of cisapride are bioequivalent and, thus, may be prescribed interchangeably.hangeably.y.hangeably.
Pharmacological Actions of New Wonbang Woohwangchungsimwon Liquid on Cardiovascular System
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 66~78
In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10
M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD
at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.s.
Pharmacological Actions of New Wonbang Woohwangchungsimwon Liquid on Cerebral Ischemia and Central Nervous System
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 79~88
In order to investigate pharmacological properties of New Wonbang Woohwangchungsimwon Liquid(NSCL) and Wonbang Woohwangchungsimwon Liquid(SCL), the effects of NSCL and SCL on cerebral ischemia and central nervous system were compared. Cerebral ischemia insult was performed using unilateral carotid artery occlusion in mongolian gerbils. The histological observations showed a preventive effect of NSCL and SCL treatments with ischemia-induced brain damage. The ATP in brain tissue was decreased in vehicle-treated ischemic gerbils. This decrease was prevented by NSCL and SCL treatment. In contrast to what was seen with ATP, lipid peroxide were elevated in vehicle-treated ischemic gerbils. This elevation was inhibited by NSCL and SCL treatments. While NSCL and SCL had no effects on the hexobarbital-induced sleeping time, they showed sedative effect in rotarod and spontaneous activity test. NSCL and SCL prevented the seizures induced by electric shock and strychnine, but the effect of NSCL was less than that of SCL. Furthermore, NSCL and SCL showed anti-stress effect. Our findings suggest that the pharmacological profiles of NSCL on cerebral ischemia and central nervous system are similar to those of SCL.
General Pharmacology of CJ-50002, an Oral Vaccine against Vibrio vulnificus Infection
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 89~96
CJ-50002 is an oral vaccine against V.vulnificus infection composed of whole cell lysate of V. vulnificus. The general pharmacological properties of CJ-50002 were evaluated in various animals and in vitro system. CJ-50002 at oral doses of 0.2, 2 and 20 mg/kg had no effect on general behavior in mice, chromo- and electro-convulsions in mice, writhing syndrome induced by acetic acid in mice, body temperature in rats, charcoal meal propulsion in mice and urine and electrolytes excretion in rats. However, oral administration of CJ-50002 at dose of 20 mg/kg prolonged the hexobarbital-inuced sleeping inducing time in mice. In anesthetized dogs, CJ-50002 showed no effect on blood pressure, heart rate and ECG but decreased the respiratory rate and femoral blood flow at dose of 20 mg/kg. p.o. CJ-50002 had no effect on the contractile response of the isolated guinea pig ileum to various spasmogen at concentrations of 0.2, 2 and 20
/ml, respectively. Since these pharmacological effects of CJ-500o2 were observed at dose much greater than those in clinical use (approximately 0.16 mg/kg, p.o.), it is likely that this vaccine may be relatively free of undesirable effects in clinical practice.
General Pharmacology of the Active Ingredients of New Antibiotic Bead (CJ-40003)
Biomolecules & Therapeutics, volume 7, issue 1, 1999, Pages 97~104
A new antibiotic bead, CJ-40003 is a combination of three antibiotics, tobramycin, vancomycin and cefazolin embedded in bone cement, for the treatment of osteomyelitis. To evaluate the general pharmacological properties of CJ-40003, the effects of its active ingredients were investigated in mice, rats, dogs and isolated guinea pig ileum. The combination of three antibiotics (CA) did not affect general behavior, central nervous system, smooth muscles, gastrointestinal system, cardiovascular and respiratory system and water and electrolytes excretion when administered intravenously at the doses of 0.3, 1 and 3 mg/kg, respectively, into experimental animals. The CA had no effect on the contractile response of the isolated guinea pig ileum to various spasmogen at concentrations of 1, 3 and 10
/ml, respectively. In conclusion, the active ingredients of CJ-40003 showed no pharmacological effect in these studies.