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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules and Therapeutics
Journal Basic Information
Journal DOI :
The Korean Society of Applied Pharmacology
Editor in Chief :
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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The Stability and Mutagenecity of
-Sitosterol Glycoside, Antimicrobial Compound from Schima wallichii sp. liukiuensis
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 205~209
Stability of the
-sitosterol glycoside from Schima wallichii sp. at various physical conditions were investigated, mutagenecity of the steroid saponin was determined by Ames test. When exposed in pH 3 to pH 8, the
-sitosterol glycoside was stable on antimicrobial activity against yeasts. The antimicrobial activity of the
-sitosterol glycoside also stable in high temperature,
gas and light exposure, and metal ion. Ames test result revealed that
-sitosterol glycoside did not have any mutagenic activity. These results suggest that the
-sitosterol glycoside might be a promising candidate as a natural antimicrobial compound.
Effect of Various Herbal Extracts on Nitric Oxide Production in Lipopolysaccharide-induced Murine Peritoneal Macrophages
Ko, Young-Kwon ; Seo, Dong-Wan ; Ahn, Seong-Hoon ; Bae, Gyu-Un ; Yoon, Jong-Woo ; Hong, Sung-Youl ; Lee, Hoi-Young ; Han, Jeung-Whan ; Lee, Hyang-Woo ;
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 210~215
Nitric oxide (NO) can mediate numerous physiological processes, including vasodilation, neurotransmission, cytotoxicity, secretion and inflammatory response. The regulation of NO production by inducible NO synthase (iNOS) is considered to be the possible target of the development of anti-inflammatory agent, based on the observation that NO can activate cyclooxygenase, which results in the synthesis of prostaglandins. In an effort to screen new inhibitor of NO production from about 352 species of herbal extracts, we found 9 species with 50% or more inhibitory effect on NO production. Especially, the dose-dependent inhibition of NO production in lipopolysaccharide-treated macrophages by two of the herbal extracts (Artemisiae asiaticae Herba and Saussureae Radix) was due to the decrease in the expression of iNOS.
Levels of Viral Glycoprotein Provide a Measure of Modulated Chemotherapeutic Effect
Shin, Jaeyong ; Yoon, Yeon-Sook ; Pyo, Suhkneung ;
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 216~220
A chemosensitivity assay with small replicate Mm5mt/cl C3H mammary tumor cell cultures was developed to determine whether changes in viral antigen expression and release into culture fluids could be utilized as an in vitro measure of modulating drug effect. The 52,000 MW viral envelope glycoprotein (gp52) of the mouse mammary tumor virus (MMTV) was measured in culture fluids of control and drug-treated cultures while cell density was simultaneously determined by cell staining and OD 664 nm determination. While extra-cellular gp52 levels and cell density progressively increased over 72 hours for control cultures, declines in both parameters provided dual measures of effect for combination [N(phophonacetyl-L-aspartic acid)+5-fluorouracil], combination 〔N(phophonacetyl-L-aspartic acid )+5-fluoro-5'-deoxyuridine〕and single component treatment of this combination. At each treated time point, thesecombinations begin to produce a greater decline in both cell density and gp52 levels as compared to single drug treatments. These results indicate that N(phopho-nacetyl-L-aspartic acid) in combination can enhance the effectiveness of single drug.
The Flowers of Carthamus tinctorius : Potential Agent for Postmenopausal Disorder
Heo, Moon-Young ; Kim, Cheon-Ho ; Kang, Jae-Sung ; Ur, Kyung-Nam ; Kim, Hyun-Pyo ;
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 221~226
In this study, 75% ethanol extract from the flowers of Carthamus tinctorius was prepared and biological activities were examined. The extract showed the inhibitory activity of vascular smooth muscle contraction and antithrombotic activity judged by bleeding time measurement. It also showed anti-inflammatory and potent analgesic activities in vivo. By oral administration of the extract, no acute toxicity was observed up to 5 g/kg in mice and rats. All these results strongly suggest that this extract may be beneficial for postmenopausal disorder by enhancing blood circulation.
Antiplatelet Actions of 2-Bromo-3-(.3,5-tert-butyl-4-hydroxylphenyl)-1,4-naphthaleneflione (TPN2)
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 227~233
The effects of 2-bromo-3-(3,5-tert-butyl-4-hydroxylphenyl)-1,4-naphthalenedione(TPN2), a synthetic vitamin K derivative, on platelet aggregation and its action mechanisms were investigated in rat platelet. TPN2 inhibited the platelet aggregation induced by collagen(
/ml), thrombin(0.1 U/ml), A23187(
) and arachidonic acid(
) in concentration-dependent manner with
values of 6.5
2.37 and 2.9
, respectively. Collagen-induced serotonin release was significantly reduced by TPN2. The elevation of intracellular free
]i) by collagen stimulation was greatly decreased by the pretreatment of TPN2, which was due to the inhibition of calcium release from intracellular store and influx from outside of the cell. TPN2 also significantly reduced the thromboxane
) formation in a concentration-dependent manner. The collagen-induced arachidonic acid (AA) release in [
]-AA incorporated platelet, an indicative of the phospholipase
activity, was decreased by TPN2 pretreatment. TPN2 significantly inhibited the activity of thromboxane synthase, but did not affect the cyclooxygenase activity. From these results. it is suggested that TPN2 exert its antiplatelet activity through the inhibition of the intra-cellular
mobilization and the decrease of the
Effect of PAF Antagonists on the Alterations in Cerebral Hemodynamics in Transient Cerebral Ischemia
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 234~241
The present study assessed the cerebroprotective effect of platelet-activating factor(PAF) antagonists in transient cerebral ischemia of rats. Right middle cerebral artery (MCA) of Sprague-Dawley rats was occluded for 2 hours using an intraluminal filament technique, and was reperfused for 6 hours following cerebral ischemia. The infarct area of seven coronal brain slices was measured morphometrically following stain ing in the 2% 2,3,5-triphenyltetrazolium chloride solution. The changes in regional cerebral blood flow (rCBF) and pial arteriolar diameter were measured by laser-Doppler flowmetry and by a videomicroscopy, respectively. The infarct size was significantly reduced by PAF antagonists, BN 52021 and CV-6209, which were administered i.p. 10 min before MCA occlusion. Pretreatment with PAF antagonists significantly restored the changes in pial arterial diameter as well as those in rCBF during the period of cerebral ischemia-reperfusion. PAF antagonists significantly inhibited the inducible nitric oxide synthase activity in the pial arteries ipsilateral to ischemia. These results suggest that PAF antagonists exert a cerebroprotective effect against ischemic brain damage through an improvement of postocclusive cerebral blood flow.
Pharmacodynamic Interactions of Diazepam and Flumazenil on Cortical Eeg in Rats
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 242~248
Diazepam, a benzodiazepine (BDZ) agonist, produces sedation and flumazenil, a BDZ antagonist, blocks these actions. The aim of this study was to examine the effects of BDZs on cortical electroencephalogram (EEG) in rats. The recording electrodes were implanted over the frontal and parietal cortices bilaterally, and the reference and ground electrodes over cerebellum under ketamine anesthesia. To assess the effects of diazepam and flumazenil, rats were injected with diazepam (1 mgHg, i.p.) and/or flumazenil ( 1 mg/kg, i.p.), and the EEG was recorded before and after drugs. Normal awake had theta peak in the spectrum and low amplitude waves, while normal sleep showed large amplitude of slow waves. The powers of delta, theta and alpha bands were increased during sleep compared with during awake. Diazepam reduced the mobility of the rat and induced sleep with intermittent fast spindles and large amplitude of slow activity, and it produced broad peak over betaL band and increased the power of gamma band, which were different from EEG patterns in normal sleep. Saline injection awakened rats and abolished fast spindles for a short period about 2-5 min from EEG pattern during diazepam-induced sleep. Flumazenil blocked both diazepam-induced sleep and decreased the slow activities of delta, theta, alpha and betaL, but not of gamma activity for about 10 min or more. This study may indicate that decrease in power of betaL and betaH bands can be used as the measure of central action of benzodiazepines, and that the EEG parameters of benzodiazepines have to be measured without control over the behavioral state by experimenter.
Effects of Glibenclamide, an ATP-dependent
Channel Blocker, on Renal Function in Dog
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 249~256
Glibenclamide(GLY)(1.0 and 3.0 mg/kg), an ATP-dependent
channel blocker, when given into the vein in dogs, produced the diuretic action accompanied with the increase of osmolar clearance(
), urinary excretion of
), and with the decrease in reabsorption rates for
in renal tubules (
), and then ratios of
) were decreased. GLY did not affect mean arterial pressure at any doses used. At a low dose(0.1 mg/kg), GLY injected into a renal artery brought about the diurectic action in both experimental and control kidney, however at a higher dose(0.3 mg/kg), GLY appeared significant diuretic action in the control kidney, but not in experimental kidney and the decrease of glomerular filtration rates(GFR), renal plasma flow(RPF),
, and the increase in
. In the control kidney, these changes in renal function exhibited the same aspect as shown in intravenous experiments. In experiments given into carotid artery of GLY(0.5 and 1.5 mg/kg), changes in all renal function included the increase in urine volume were the same pattern as shown in intravenous experiments. The above results suggest that glibenclamide produces diuretic action through central function and the action site of the GLY in kidney is the renal distal tubules in dogs.
Optimization of the Capsular Polysaccharide Production from streptococcus pneumoniae Type 23
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 257~262
Streptococcus pneumoniae (pneumococcus) is the most frequent causative agent of acute bacterial pneumonia. Outstanding characteristic of pneumococcus is an ample polysaccharide capsule that is highly anti-genic agent and is the major factor for classification of pneumococcus into more than 94 serotypes. In this study, production of capsular polysaccharide from Streptococcus pneumoniae type 23 was optimized by supplementation of metal ions or by modulation of culture conditions. When brain heart infusion (BHI) broth was supplemented with 1 mM concentration of
, growth of pneumococcus as well as polysaccharide yield were stimulated. Also slight aeration gave rise to better polysaccharide yield.
Enhanced Transmucosal Permeation of Thyrotropin-releasing Hormone
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 263~270
The in vitro permeation of thyrotropin-releasing hormone (TRH) through rabbit nasal, rectal and duodenal mucosae was studied in the absence and presence of an enzyme inhibitor and permeation enhancer. TRH in the donor and receptor solutions was assayed by HPLC. When thimerosal (TM, 0.5 mM) was added to the donor cell as an inhibitor, the permeation rate of TRH (200
/ml) increased linearly as a function of time. Fluxes of TRH through the nasal, rectal and duodenal mucosae were found to be 33.3
1.9 and 9.6
/hr, respectively. The addition of sodium glycocholate, glycyrrhizic acid ammonium salt, sodium taurodihydrofusidate or L-
-lysophosphatidylcholine to the donor solution containing TM did not result in the significant increase of permeation flux except for the duodenal mucosa, comparing with that in the presence of TM alone. Consequently, it was suggested that the nasal route was advantageous for systemic delivery of TRH, and the addition of TM and/or an enhancer was necessary to maximize the transmucosal permeation of TRH.
General Pharmacology of LB71350, a New HIV-1 Pretense Inhibitor
Kim, Hee-Jin ; Oh, Jeng-In ; Park, Hee-Dong ; Kang, Ju-Seop ; Ko, Hyun-Chul ; Lee, Chang-Ho ;
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 271~277
Safety evaluation of LB71350, a new HIV-1 protease inhibitor, was performed in mice, rats and dogs. For the general behavior of mice, LB71350 at an oral dose of 200 mg/kg did not show any significant effects on muscle tone and locomotor activity. In terms of central nervous system, at oral doses of 200 mg/kg and 1000 mg/kg, LB71350 inhibited acetic acid-induced pain response approximately 41% and 83% of control. respectively. At oral doses of 200 mg/kg and 500 mg/kg, it reduced the rectal body temperature in rats. Pentylenetetrazole-induced seizure in mice was slightly potentiated by oral administration of LB71350 at doses ranging from 200 mg/kg to 1000 mg/Ag. Single or five day treatment of LB71350 doubled the hexobarbital- induced sleeping time in mice at oral doses ranging from 50 mg/kg to 500 mg/kg. It did not cause any effects on gastric secretion and acidity in rat at oral doses of 200 mg/kg and 1000 mg/kg and also it did not change intestinal motility in mice up to 1000 mg/kg. Blood coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) in rats were not affected by the treatment of LB71350 up to 500 mg/kg. LB71350 caused no significant effects on the cardiac output, stroke volume, heart rate, and mean blood pressure when infused intravenously to the anesthetized rats and dogs. Taken together, LB71350 at high oral doses caused significant pharmacological effects on the central nervous system and the hexobarbital-induced sleeping time.
Opioid Receptor Selectivity and General Pharmacology of DK1001, New Alkaloid Analgesic
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 278~284
DK1001 is a thebain derivative, which is newly synthesized as an alkaloid analgesic. This study was designed to study effects of DK1001 on the ligands binding to the opioid receptor subtypes, and general pharmacology of DK1001. DK1001 inhibited the binding of [
]DAMGO, a selective mu-subtype agonist, to the opioid receptor of rat forebrain in a concentration-dependent manner.
of DK1001 was significantly lower than that of morphine. DK1001 inhibited the binding of 〔
H〕DPDPE, a selective delta-subtype agonist concentration-dependently. DK1001(0.5 mg/kg) had no effects on behavior, body temperature, blood pressure. respiratory rate, and intestinal charcoal propulsion of mice. In addition, DK1001 did not affect on the contractilities of isolated muscle strips of aorta, ileum, and trachea of rats. These results suggest that DK1001 might be a potent analgesic without serious side effects.
General Pharmacology of DA-7101, a New Antibiotic Composition
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 285~291
DA-7101 is a new combined formulation of cefatrizine:clavulanic acid (2:1) under development as oral abtibiotics. The general pharmacological properties of DA-7101 on central nervous, cardiovascular, gas-trointestinal and other organ systems were studied by oral administration, in vivo and in vitro. DA-7101 had no marked effects all tests studied such as general behavior, hexobarbital-induced sleeping, spontaneous activity, anticonvulsion, body temperature, acetic acid-induced writhing, rotarod performance, heart rate and blood pressure in cats, isolated ileum movement, intestinal transition, gastric juice secretion and urine volume and electrolytes in rats. But exceptionally at the highest dose of 900 mg/kg, DA-7101 increased hexobarbital-induced sleeping time, caused a slight hypotension and decreased the secretion of gastric juice. These results suggest that at the estimated clinical dose DA-7101 would not bring about any serious acute adverse effects clinically.
Teratogenicity Study of SKI 2053R, a New Platinum Anticancer Agent, in Rabbits
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 292~299
SKI 2053 R, cis-Malonato [(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II), is a newly developed antitumor platinum complex derived from cisplatin. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than cisplatin. Effects of test agent on general toxicity of does and embryonic development of Fl fetuses were investigated in rabbits. Sixty eight New Zealand white rabbits were distributed among three treated groups and a control group. SKI 2053R was administered intravenously to pregnant rabbits from days 6 to 18 of gestation at dose levels of 0, 0.67, 2.0, or 6.0 mg/kg/day. The pregnant does were subjected to the caesarean section on day 28 of gestation. No treatment-related changes in clinical signs, body weight, food consumption, and necropsy findings were observed in all groups. Fl fetuses showed no changes related to the treatment of SKI 2053R, except that an increase in the incidence of skeletal variations were observed at 6.0 mg/kg. There were no signs of material toxicity or embryotoxicity at 0.67 and 2.0 mg/kg. The results show that the administration of 6.0 mg/kg SKI 2053R induces skeletal variations in fetuses and that the no observed adverse effect levels(NOAELS) of SKI 2053R are considered to be over 6.0 mg/kg for does and 2.0 mg/kg for Fl fetuses in rabbits.
Antigenicity Tests of BR92021, a Vi polysaccharide Typhoid Vaccine, in Guinea Pigs
Biomolecules and Therapeutics, volume 7, issue 3, 1999, Pages 300~306
To study the antigenicity of BR92021(Vi polysaccharide typhoid vaccine), active systemic ana-phylaxis and passive cutaneous anaphylaxis were tested in guinea pigs. The groups were as follows: group I(low dose, 30
/kg), group II(high dose, 300
/kg), group III(300
/kg plus complete Freund's adjuvant), group IV(positive control, ovalbumin plus complete Freund's adjuvant) and group V(saline-treated control). Male Hartley guinea pigs at 7 weeks of age were sensitized subcutaneously with the test article or saline three times per week for three weeks(j.e., total 9 times). For groups III and IV, animals were sensitized subcutaneously with either the test article or ovalbumin plus complete Freund's adjuvant once per three week for 6 weeks(i.e., total 3 times). Twelve days after the last sensitization, the blood was collected from the sensitized animals for the passive cutaneous anaphylaxis test. In addition, the sensitized animals were subjected to the active systemic anaphylaxis test on fourteen days after the last sensitization by an intravenous challenge with either the test article or ovalbumin. In group I, mild(1/5) or moderate(4/5) symptoms of anaphylactic shock were observed. In group II, no sign(1/5), moderate(3/5) and severe(1/5) symptoms were observed. In group III, four animals of revealed moderate signs and one of 5 showed no signs of anaphylactic shock. In group IV, all 5 animals showed severe signs of shock. In group V, one of 5 revealed moderate and four of 5 showed no signs. The necropsy findings related to the active systemic anaphylaxis were observed in most animals of groups I to V In the passive cutaneous anaphylaxis test, the antiserum was diluted 10- to 5120- fold and was injected intradermally on the clipped back of recipient animals, followed by an intravenous challenge with either the test article or ovalbumin. No animals in groups I, II, III and V showed the positive reaction, whereas all animals in group IV, the positive control, showed the positive reaction at the dilution range of x1280 to x5120. Our results indicate that the test article, BR92021, may have weak antigenic potential in male guinea pigs.