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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules and Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 2, Issue 4 - Dec 1994
Volume 2, Issue 3 - Nov 1994
Volume 2, Issue 2 - Aug 1994
Volume 2, Issue 1 - Apr 1994
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Role of Central Monoaminergic Nervous System in Regulation of Blood Pressure: Spontaneously Hypertensive Rats
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 1~10
Studies on the Metabolism of Sinigrin in Rat
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 11~15
The detoxifying properties of cruciferous vegetables components have been the subject of several recent investigations. Evidences from many biochemical and pharmacological studies indicated that higher consumption of cruciferous vegetables is associated with lower incidence of harmful actions such as hepatotoxicity and oxidative stress in animal and human populations. Recently, it has been reported that drug metabolizing and detoxifying enzyme activities were increased by cruciferous vegetable extract in which sinigrin is known to be a main active component, accounting for about 2 to 3 percents of total extract. The detoxifying effect of sinigrin has been well reported in several literatures. The metabolism of sinigrin in animal, however, has not been reported yet. That led us to study the metabolism of sinigrin in rat. Sinigrin is nown to be metabolized into three compounds, i.e., allyl isothiocyanate, glucose and potassium phosphate in cruciferous vegetables. Allyl isothiocyanate was formed in rat hepatic mitochondrial fraction in dose and incubation time dependent manner, that was confirmed by HPLC. Glucose formation was came up with results similar to that of allyl isothiocyanate. Three hours after i.p. administration of sinigrin to rat, allyl isothiocyanate appeared in rat liver, and five hours later it was detected in liver and blood. The above results suggested that sinigrin might be metabolized into allyl isothiocyanate, glucose and potassium phosphate in rat.
Effects of Dopamine Agonists on Primary Cultured Neurons from Various Brain Regions
Kim, Kyeong-Man ;
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 16~22
Using 2 to 4 day-old postnatal rats, primary brain cell cultures were made from various brain regions (substantia nigra, hippocampus, striatum, and nucleus accumbens). Whole-cell patch clamp technique was used for electrophysiological studies. Neurons cultured from substantia nigra were characterized more in detail to test whether these cultured neurons were appropriate for physiological studies. Immunocytochemical and electrophysiological properties of these cultured neurons agreed with those from other in vivo or in vitro studies suggesting that cultured neurons maintained normal cytological and physiological conditions. Modulation of ionic channels through dopamine receptors were studied from brain areas where dopamine plays important roles on brain functions. When neurons were clamped near resting membrane potential (-74mV), R(+), R(+)-SKF 38393, a specific D
receptor agonist, activated cultured striatal neurons, and dopamine itself produced biphasic responses. Responses of cultured hippocampal neurons to dopamine agonists were kinds of mirror images to those from striatal neurons; D
receptor agonists inhibited hippocampal neurons but quinpirole, a D
receptor agonist, activated them. Neurons cultured from nucleus accumbens were inhibited by dopamine.
Evaluation of Topical Drug Containing Solcoseryl and Micronomicin on Surgical Wound in Mice
Chung, Kae-Jong ; Chang, Man-Sik ; Chun, Jong-Ok ; Chun, Jae-Kwang ; Kim, Sung-Chul ; Park, Wahn-Soo ; Lee, Hyang-Woo ;
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 23~27
Wound healing and antibacterial effects of solcoseryl-micronomicin combination gel on an open wound were studied in mice. A simple model was designed for assessing the effects. Using the model, we compared the efficacy of a combined topical gel of solcoseryl and micronomicin with those gels of solcoseryl or micronomicin alone. From the results of our experiment, the wound healing effect of open wounds by treatment with the combination gel was significantly enhanced when compared with those by treatment with solcoseryl gel or micronomicin gel alone. And the antibacterial effect of the combination gel was higher than those of solcoseryl gel or micronomicin gel alone.
Study on the Structure of DNA Containing a Thymine Dimer and
Endonuclense V * DNA Complex
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 28~33
In order to obtain insight into the repair mechanism of DNA containing thymine photo-dimer, the conformation of the duplex d(GCGGTTGGCG).d(CGCCAACCGC) with a thymine dimer incorporated has been studied by proton NMR. NOE data show that, although the local environment around the thymine dimer is altered, the gross structural changes are relatively small. T
endonuclease V exhibited a conformational change on complex formation with DNA. This conformational change occurred around histidine 16 which was close to tyrosine 129 located in the aromatic segment (WYKYY) near the C-terminus. It is likely that the interaction between T
endonuclease V and DNA is strong since the complex was not dissociated up to 1.6 M NaCl.
Structure-Activity Relationships Study of Angiotensin Converting Enzyme Inhibitor Captopril Derivatives: Importance of Solution Moleculnr Dynamics Study
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 34~38
In order to investigate the structure-activity relationships of the stereoisomers of angiotensin converting enzyme inhibitors, captopril and its derivatives were selected as model compounds. In vitro enzymatic activities of them depend on the symmetry at the asymmetric carbons. Especially, the alanyl carbon should have the S configuration to be biologically active. But the demethylated captopril having the achiral carbon also shows the activity although it is less active than captopril. Seven stereoisomers of captopril and its derivatives were chosen and their acidic and ionic forms were used for molecular dynamics simulations. Four computer simulations were practiced for each model compound in order to obtain the good condition for simulation to explain the experimental structure-activity relationships. From the computer simulation results, relativistic movements of three well-known pharmacophoric sites, carboxylate carbon, carbonyl oxygen, and sulfur atoms, were analyzed. Good results were obtained from the aqueous solution molecular dynamics simulation with ionic forms of model compounds. Active model compounds have the pharmacophoric areas of 6.08 to 6.38
and the similarity in the geometrical data. But inactive ones have the largely deviated values of 4.51 to 4.87
from those of active ones.
Bradykinin-Mediated Stimulation of Phospholipase D in Rabbit Kidney Proximal Tubule Cells
Park, Kyung-Hyup ; Jung, Jee-Chang ; Chung, Sung-Hyun ;
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 39~46
The present study was undertaken to demonstrate whether or not bradykinin activates a phospholipase D in rabbit kidney proximal tubule cells. By measuring the formation of [
H]phosphatidic acid and [
H]phosphatidylethanol we could elucidate the direct stimulation of phospholipase D by bradykinin. Bradykinin leads to a rapid increase in [
H]phosphatidic acid and [
H]diacylglycerol, and [
H]phosphatidic acid formation preceded the formation of [
H]diacylglycerol. This result suggests that some phosphatidic acid seems to be formed directly from phosphatidylcholine by the action of phospholipase D, not from diacylglycerol by the action of diacylglycerol kinase. In addition, the other mechanisms by which phospholipase D is activated was examined. We have found that phospholipase D was activated and regulated by extracellular calcium ion and pertussis toxin-insensitive G protein, respectively. It has also been shown that bradykinin may activate phospholipase D through protein kinase C-dependent pathway. In conclusion, we are now, for the first time, strongly suggesting that bradykinin-induced activation of phospholipase D in the rabbit kidney proximal tubule cells is mediated by a pertussis toxin-insensitive G protein and is dependent of protein kinase C.
Correlation between Protein Methylation and Hepatotoxicity
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 47~53
The methylation response as well as the level of methyl donor substance, 5-adenosyl-L-methionine (SAM) has been suggested to be related to hepatotoxicity including hepatocarcinogenesis. But direct correlation between protein methylation and hepatotoxicity has not been established to the present. To observe relationship between protein methylation and short-term hepatotoxicity induced by chemical substances, the activities of protein methylase I and II (PM I, PM II) were examined in cytosolic fraction of SD rat treated orally with acetaminophen(AA),
-naphtyl-isothiocyanate (ANIT) and tetracycline (TC) that was known to produce necrosis, cholestasis and steatosis respectively. To evaluate the degree of hepatotoxicity induced by each chemicals, we observed the serum levels of indicative parameters and histopathological alteration. In AA treated group, the activities of PM I were increased at 6, 12 hours after administration, prior to the appearance of the hepatotoxicity by clinical parameters. It was suggested that the levels of PM I were related with the initial stage of hepatotoxic mechanism induced by AA. In ANIT treated group, though most of clinical parameters were significantly increased at 24, 48 hours after administration, the activity of PM I was not changed, indicating that ANIT induced hepatotoxicity was not coupled to protein methylation.
The Effect of Methamphetamine on the Immune Organs and the Antibody Production
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 54~58
BALB/C mice were intraperitoneally injected with methamphetamine (5 mg/kg) to observe the effect of methamphetamine on the immune system. Body weights were decreased in both acutely treated group (twice for 2 weeks with 7 days interval) and subchronically treated group (daily injection for 14 days). The relative spleen weights and the numbers of splenocytes were unexpectedly increased (p<0.05) in acutely treated group, but subchronically treated group showed the trend of decrease without significance. But there was no significant effect on antibody formation to hen egg Iysozyme which was immunized during the treatment of methamphetamine and on plaque forming cell number. The relative thymus weights of both groups were significantly decreased by the treatment of methamphetamine (acutely treated group, p<0.05; subchronically treated group, p<0.01). These results suggest that the effect of methamphetamine on the immune system may be caused by thymic dysfunction.
Effect of the Water Extract of Pilose Antler of Cervus nippon var. mantchuricus on Acute-Phase Proteins in Rat Blood
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 59~64
The water extract of pilose antler of Cervus nippon var. mantchuricus (WEC) was investigated in respect of its effect on ceruloplasmin and
-cysteine protease inhibitor (CPI), which are acute-phase proteins showing increased synthesis following inflammatory stimulus in rat. Ceruloplasmin and CPI were spectrophotometrically determined by the oxidase activity and the inhibitory activity on papain, respectively, and their changes in the concentrations in plasma or serum were examined after oral administration of 0.04% WEC to rats during 7 days following inflammation by subcutaneous injection of turpentine oil or lipopolysaccharide (LPS). WEC suppressed the maximum increases in ceruloplasmin and CPI on the 4th day after injection of turpentine oil, but the suppression in ceruloplasmin was more potent than that in CPI. On inflammation by LPS the suppression of the maximum increase in ceruloplasmin by WEC was found on the 2nd day, but the result was less significant from that obtained by the treatment with turpentine oil. Administration of WEC for at least 4 days was required to suppress the maximum increase in ceruloplasmin due to inflammation by turpentine oil. When WEC was administered to rats after injection of turpentine oil, a high dosage (0.36% of WEC) was requisite for the suppression on the maximum increase in ceruloplasmin.
Effects of Brazilin on Glucose Metabolism in Epididymal Adipocytes from Streptozotocin induced Diabetic Rats
Lee, Soo-Hwan ; Won, Hyeon-Soon ; Lee, Yong-Khil ; Moon, Chang-Hyun ; Chung, Jin-Ho ; Moon, Chang-Kiu ;
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 65~70
Hypoglycemic mechanism of brazilin was investigated in the streptozotocin induced diabetic rats. Plasma glucose levels of diabetic rats were significantly ame]iorated by the treatment of brazilin, but there were no changes in plasma insulin levels. Brazilin increased insulin binding capacity to epididymal adipocytes, and Scatchard analysis revealed that this increase in insulin binding was not due to the increase of insulin binding sites but that of binding affinity. 2-Deoxyglucose uptake of epididymal adipocytes was significantly augmented by the intraperitoneal administration of brazilin and the same result was obtained in in vitro study. Glucose oxidation and lipogenesis in epididymal adipocytes were significantly enhanced by the treatment of bracilin.
Anti-inflammatory and Analgesic Activities, and Skin Irritation Test of Piroxicam Patch
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 71~76
Anti-inflammatory and analgesic activities and skin irritation of piroxicam patch were investigated. Piroxicam patch increased the pain threshold in rat hind paw inflamed by carrageenan and inhibited writhing induced by acetic acid in mice. Piroxicam patch also inhibited the carrageenan-induced edema in rat hind paw as well as the increased vascular permeability induced by histamine in rats. In adjuvant arthritis of rats, piroxicam patch showed anti-inflammatory effects. Skin irritation of piroxicam patch was tested in Newzealand White rabbits and evaluated by Primary Irritation Index of Draize. The results from skin irritation test showed that piroxicam patch seemed practically non-irritating. The result from the present study indicates that piroxicam may be useful without serious side effects as anti-inflammatory analgesics in this patch form.
Acute Toxicity of Recombinant Human Epidermal Growth factor, DWP-401 in Mice
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 77~81
The acute toxicity of recombinant human epidermal growth factor, DWP-401 was evaluated in ICR mice of both sexes. Six groups of mice were administered orally or subcutaneously with 0, 0.125, 0.25, 0.5, 1 and 2 mg/kg of DWP-401. Abnormal clinical signs related to the compound were not observed, and no deaths occurred. Gross findings of necropsy revealed no evidence of specific toxicity related to DWP-401. LD
values for both male and female mice were evaluated to be over 2 mg/kg, which is approximately 2, 000 fold of presumed clinical dose.e.
Reproductive Toxicity Study of DA-125, A New Anthracycline Anticancer Agent: (I) Teratogenicity Study in Rats
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 82~93
DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.1, 0.3 and 1.0 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of Fl fetuses, as well as growth, behaviour and mating performance of Fl offspring were examined. 1. At 1 mg/kg, one out of the 10 dams showed difficult delivery. A decrease in food consumption, a loss in body weight and a decrease of spleen weight were found in this dose level group. At 0.3 mg/kg, difficult deliverys were observed in two out of the 10 dams. 2. At 1 mg/kg, an increased resorption rate and a decreased fetal weight were found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. 3. At 1 mg/kg, body weight reduction, small eyeball, hydrocephalus and atrophy of sexual organs were observed in Fl offspring. One male pup receiving 0.3 mg/kg died on day 2 of lactation. The results show that the no-effect dose levels (NOELs) for dams and Fl offspring are 0.1 mg/kg/day and NOEL for Fl fetuses is 0.3 mg/kg/day.
Reproductive Toxicity Study of DA-125, A New Anthracycline Anticancer Agent: (II) Fertility Study in Rats
Biomolecules and Therapeutics, volume 2, issue 1, 1994, Pages 94~101
DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.03, 0.1 and 0.3 mg/kg/day administered intravenously to Sprague-Dawley male rats from premating to mating period and to females from premating to early gestation period. Effects of test agent on general findings and reproductive performance of parent animals and embryonic development were examined. No treatment-related changes in clinical signs, body weight, food consumption and necropsy findings were observed in all groups of both sexes. At 0.3 mg/kg, a decrease in the weight of spleen was found only in male rats. Mating performance and fertility of parent animals were not adversely affected by all doses tested. Fl fetuses showed no changes related to treatment of DA-125, except that at 0.3 mg/kg, an increase in the resorption rate was seen. The results show that the no effect dose levels (NOELS) for general toxicity of parent animals and fetal development are 0.1 mg/kg/day and NOELS for reproductive capability are over 0.3 mg/kg/day.