• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.205-210
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• 2010

Several studies have shown that plant-derived polyphenols reduce cardiovascular accidents in high-risk patients and the inhibition of platelet function may be responsible for part of this benefit. Lindera obtusiloba is widely used in traditional herbal medicine for the treatment of cardiovascular and inflammatory diseases. Therefore, the antiplatelet and antithrombotic activities of Lindera obtusiloba Extracts (LOE) on in vitro platelet aggregation, radical scavenging activity and in vivo murine pulmonary thrombosis were examined. LOE was able to directly scavenge the stable DPPH radical in a concentration-dependent manner and its $IC_{50}$ value was 3.9 ${\pm}$ 0.1 ${\mu}g$/ml. LOE significantly inhibited collagen- and ADP-induced platelet aggregation in a concentration-dependent manner and its $IC_{50}$ value is 0.9 ${\pm}$ 0.1 mg/ml and 0.4 ${\pm}$ 0.1 mg/ml respectively. The inhibitory effect of LOE was comparable to aspirin ($IC_{50}$ values were 1.0 ${\pm}$ 0.5 and 1.0 ${\pm}$ 0.7 mg/ml, respectively). Furthermore, oral administration of LOE suppressed the death of mice with pulmonary thrombosis induced by intravenous injection of collagen plus epinephrine. Taken together, our results suggest LOE may be a promising candidate for antithrombotic agent, and the antithrombotic effect of LOE may be due to, at least in part, antiplatelet activity.

• Toxicological Research
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• v.18 no.1
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• pp.87-98
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• 2002

This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.67-74
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• 1989

The effect of guanabenz on volume-induced micturition reflex contraction (VIMRC) in urethane-anethetized female rats was examined under adrenalectomy, chemical-sympathectomy, ganglionectomy, alpha-1, or alpha-2 blockade. Intracerbroventricular administration of guanalberz had little effect on VIMRC, but topical application suppressed amplitude and frequency of VIMRC. Guanabenz intravenous injection dose-dependently suppressed amplitude and frequency of VIMRC, with complete inhibition at dose of $100\;{\mu}g/kg$, but phenylephrine had no effect on VIMRC. Intravesicular peak pressure and amplitude of VIMRC were increased by 6-hydroxydopamine (6-OHDA) treatment when compared with control value, but yohimbine-, prazosin-hexamethonium-treatment and adrenalectomy did not show changes in VIMRC. Dose-response curve of guanabenz on amplitude and frequency of VIMRC shifted significantly to the right by treatment of yohimbine and 6-OHDA, and adrenalectomy. Median inhibitory dose $({\mu}g/kg)$ of guanabenz to amplitude of VIMRC showed 27.3 in control group, 381.6 in yohimbine, 294.1 in 6-OHDA and 54.1 in hexamethonium, and 38.8 in prazosin. Those of guanabenz to frequency of VIMRC showed 41.7 in control group, 571.1 in yohimbine, 410.8 in 6-OHDA, 141.4 in adrenalectomy, 59.6 in hexamethoinum and 31.4 in prazosin. These results suggest that guanabenz inhibits VIMRC through alpha-2 receptor stimulation rather than alpha-1 receptor stimulation and that catecholiamines released from sympathetic nerve ending and adrenal gland play a role in the inhibition.

• Journal of Veterinary Clinics
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• v.10 no.2
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• pp.221-226
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• 1993

To study effective dossage and administration route for scaling, ketamine HCl/propionyl promazine HCl(ketamine) combination and tiletamine HCl/zolazepam HCl(zoletil) were administered in one hundred six dogs. The dogs were toy poodle, Yorkshire Terrier, Pekingese and Chihuahua. Scaling and polishing time, possible treatment time after the first injection of anesthetics, the number of anethesia added, presence of tongue movement during anesthesia, the presence of swaying sign during recovery and respiration were evaluated. The possible treatment time after the first Injection of anesthetic in toy poodle were 26.3${\pm}$3.0 minutes with intravenous(IM) treatment of ketamine 10mg/kg, and 21.4${\pm}$6.6 minutes with intramuscula(IM) treatment of zoletil 8mg/kg, In Yorkshire Terrier were 19.51: 1.7 minutes with IV treatment of ketamine 10mg/kg. 19.0${\pm}$5.2 minutes IM and 20.8${\pm}$6.1 minutes with IM treatment of zoletil 5mg/kg,24.8${\pm}$3,5 minutes with IM treatment of zoletil 8mg/kg. In pekingese were 27.5${\pm}$2.1 minutes with IM treatment of ketamine 10mg/kg,28.0${\pm}$4.2 minutes with IM treatment of zoletil 8mg/kg. In Chihuahua were 19.5${\pm}$1.9 minutes with IV treatment of ketamine 7mg/kg, 17.5${\pm}$1.7 minutes with IM treatment of ketamine 10mg/kg and 20.3${\pm}$3.8 minutes with IM treatment of zoletil 5mg/kg, 21.2${\pm}$5.5 minutes with IM treatment of zoletil 8mg/kg. Swaying sign was observed in all group during recovery time, espically, in toy poodle and Yorkshire Terrier which administered zoletil 8mg/kg IM showed more severe swaying sign. The present results suggested that injection of zoletil 8mg/kg IM might be relatively effective for scaling in Chihuahua Within 20 minutes treatment for scaling in Yorkshire Terrier and Chihuahua, IM treatment of ketamine 7 to 10mg/kg is recommended.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.2
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• pp.214-222
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• 2011

To examine the new practical utilization of mucilages in Opuntia humifusa, polysaccharides were isolated from O. humifusa and their anti-metastatic activity and structural analysis were carried out. In experimental lung metastasis of B16BL6 melanoma cells, prophylactically intravenous (i.v.) administration of the crude polysaccharide (CNC-0) from O. humifusa significantly inhibited lung metastasis in a dose-dependant manner. The main polysaccharide, CNC-Ia was purified to homogeneity from CNC-0 by two successive column chromatographies using DEAE-Sepharose FF and Sephadex G-100 and its structure was characterized. Molecular mass of CNC-Ia was estimated to be 700 kDa and it mainly consisted of arabinose, galactose and xylose in addition to two minor sugars such as rhamnose and fucose. Methylation analysis indicated that CNC-Ia comprised at least 18 different glycosyl linkages such as terminal Araf, 5-linked Araf, 4-linked Galp and terminal Xylp in addition to three characteristic linkages such as full branched Araf, 3,4,6-branched Galp and full branched Galp. To analyze the fine structure of CNC-Ia, it was sequentially digested by exo-${\alpha}$-L-arabinofuranosidase and endo-${\beta}$-1,4-D-galactanase. These analyses suggested that CNC-Ia belongs to be a highly branched Type I arabinogalactan which has a ($1{\rightarrow}4$)-${\beta}$-galactan backbone with arabinosyl oligosaccharide side chains.

• The Journal of Internal Korean Medicine
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• v.31 no.4
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• pp.763-774
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• 2010

Objectives : In condition of brain infarction, irreversible axon damage occurs in central nerve system(CNS), because gliosis becomes physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. The current study is to examine the effect of the Uncariae Ramulus et Uncus on CD81 and GFAP expression in the rat brain following middle cerebral artery occlusion. Methods : In order to study ischemic injuries on brain, infarction was induced by middle cerebral artery occlusion(MCAO) using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Results : The following results were obtained 1. Measuring the size of cerebral infartion induced by MCAO in the rat after injection of Uncariae Ramulus et Uncus showed the size was decreased. 2. Intravenous injection of Uncariae Ramulus et Uncus showed pyramidal cell death protection in the hippocampus in the MCAO rat. 3. Water extract injection of Uncariae Ramulus et Uncus decreased GFAP expression significantly in the MCAO rat. 4. Uncariae Ramulus et Uncus water extract decreased CD81 expression in the MCAO rat. 5. The administration of water extract of Uncariae Ramulus et Uncus induced up-regulation of c-Fos expression significantly compared with MCAO. 6. The admistration of water extract of Uncariae Ramulus et Uncus increased ERK expression significantly compared with MCAO. Conclusion : We observed that Uncariae Ramulus et Uncus could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of the rat with cerebral infaction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the up-regulation of c-Fos and ERK. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

• Korean Journal of Veterinary Service
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• v.31 no.4
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• pp.533-546
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• 2008

The efficacy of bovine immune sera to correct the calves with failure of passive transfer(FPT) was evaluated. Immune sera were produced from 14 one-year-old Holstein cattle which were inoculated commercial combined viral vaccine, administered by the challenge of some main enteric or respiratory viruses, aseptically filtered and stored at $4^{\circ}C$ before used. After the treatment of bovine immune sera, Mean transfer factor($mg/d{\ell}$, of IgG administered/kg of body weight) was $5.46{\pm}2.74,\;11.17{\pm}1.27,\;1.40{\pm}0.21$ in K-IP, H-IP and K-IV group, respectively. The corrective effect of bovine immune sera to FPT calf without any clinical signs showed that intravenous route was more effective than intraperitoneal administration(P<0.01). FPT calves with severe signs were not effective response to the immunotherapy used and consequently died within 10 days after the treatment. Ten percentage of controls appeared the clinical signs including diarrhea. On the contrary, there were not any clinical signs in K-IP and H-IV group. There was significant increase of the neutralizing titer against bovine viral diarrhea virus and bovine coronavirus as well as of cell population including CD2, CD4, and monocyte in K-IP and H-IV group after the immunotherapy(P<0.05). Also, K-IP and H-IV group showed the successful correction to FPT within one week after the immunotherapy, but controls had kept the FPT two-four weeks even after the same treatment. Consequently, the results were suggesting that the bovine immune sera could be used the corrective tool to young calves with FPT.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.27-40
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• 1992

The purpose of the present study is an attempt to investigate the effect of intraventricular taurine, which is a naturally occuring amino acid containing sulfur and has inhibitory action in brain, on heart rate and blood pressure in the urethane anesthetized rabbits and also to elucidate the mechanism of its cardiovascular actions. Taurine $(0.15{\sim}1.5\;mg)$ injected into the lateral ventricle of anesthetized normontensive rabbits produced a dose-related fall in arterial blood pressure and heart rate, which were marked and long-lasting along with considerable respiratory depression. However, the intravenous administration of taurine at the same dose with intraventricular injection did not induce any changes in blood pressure as well as heart rate. Depressor responses induced by taurine were inhibited significantly by pretreatment with chlorisondamine, clonidine, strychnine and bicuculline but not by atropine, vagotomy, propranolol and metoclopramide. Moreover, taurine did not affect the pressor responses of norepinephrine. Taurine-induced bradycardic effects were blocked clearly by pretreatment with chlorisondamine, propranolol, clonidine, strychnine and bicuculline, while they were not influenced by atropine, vagotomy and metoclopramide. These experimental results suggest that intraventricular taurine causes long-lasting hypotensive and bradycardic actions, and that these cardiovascular effects may be exerted through taurinergic (glycinergic) and GABAergic receptors which are associated with catecholaminergic neurons in brain.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.413-417
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• 2002

Gitelman's syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria that has recently been reported to be linked to thiazide- sensitive Na-Cl cotransporter gene mutation. In this study, we performed renal clearance studies to differentiate Gitelman's from Bartter's syndrome and to confirm the diagnosis in two patients clinically diagnosed with Gitelman's syndrome. Each patient was hydrated by 20 mL/kg body weight of oral water within 30 minutes, which was followed by intravenous half saline. When urinary flow reached 10 mL/min, samples of urine and serum were obtained to calculate the osmolar clearance, free water clearance, chloride clearance, and distal fractional chloride reabsorption. Subsequently, furosemide or hydrochlorothiazide was administered. Samples were collected and the same parameters were calculated. In our patients, chloride clearance was increased more than 10 times after furosemide administration(2.1 : 25.7 and 2.2 : 27.4 mL/min/100 mL GFR), but not increased after hydrochlorothiazide treatment(2.1 : 1.6 and 2.2 : 2.6 mL/min/100 mL GFR). And the distal fractional chloride reabsorption was significantly decreased by furosemide injection (73% : 15% and 75% : 4.6%), whereas hydrochlorothiazide had no effect on it(73% : 63% and 75% : 78%). These findings indicate that our patients have a defect in thiazide-sensitive Na-Cl cotransporter in the distal tubule, which is compatible with the pathophysiology of Gitelman's syndrome.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.197-205
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• 1991

Local extravasation during intravenous administration of adriamycin (doxorubicin HCl) can cause severe skin ulceration and necrosis. To investigate the mechanism of adriamycin-induced skin toxicity, effects of adriamycin on reactive oxygen radical metabolism using cultured skin cells of fetal rat. Adriamycin produced significant release of lactic dehydrogenase from cultured skin cell preparations dose- and time-dependently. The production of superoxide anion in sonicated suspensions of cultured skin cells was significantly increased by adriamycin under the presence of NADPH and NADH. The drug also stimulated malondialdehyde (MDA) production, an index of lipid peroxidation, in NADPH- and NADH-supported cell preparations. The increased production of MDA was significantly inhibited by oxygen radical scavengers (superoxide dismutase, catalase, thiourea) and antioxidants (butylated hydroxytoluene, ${\alpha}-tocopherol$). Treatment of cultured skin cells with 1, 3,-bis (2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase, enhanced the lipid peroxidation induced by adriamycin. The present study suggests that lipid peroxidation which is resulted from the stimulated production of reactive oxygen radical causes cellular damage in adriamycin-treated skin cells of rat.