• Toxicological Research
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• v.14 no.3
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• pp.435-441
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• 1998

Alginase$Alginase^{ⓡ}$ (Arginine esterase) is one of the snake venoms which is mainly consisted of arginine esterase and acts as a thrombus -forming inhibitor/thrombus-lysin. These present studies were performed to investigate of the acute and subacute toxicity of the Alginase$Alginase^{ⓡ}$ in rats. In acute toxicity study, rats were single administered intravenously with dosages of 0.001, 0.01. 0.1, 1 and 10U/kg B.W. and examined the number of death, clinical sign, body weight and pathological change for 7days after administration of Alginase$Alginase^{ⓡ}$. At maximum dose level (10U/kg B.W.), Alginase$Alginase^{ⓡ}$ induced symptoms of shock with cyanosis and dyspnea. But these symptoms dissappeared after 30~50 minutes and we could not find any other toxic effect in rats. Therefore, $LD_{50}$ Value of Alginase was over 10U/kg B.W. in rats. In four-week intravenous toxicity study of Alginase$Alginase^{ⓡ}$, rats were administered intravenously seven days per week for 28 days, with dosages of 0, 0.0125, 0.125 and 1.25U/kg B.W./day, respectively. Alginase$Alginase^{ⓡ}$ did not caused any death and showed any clinical signs in rats. No significant Alginase$Alginase^{ⓡ}$ -related changes were found in feed uptake, water consumption, hematology, serum biochemistry, urinalysis, ocular examination, organ weight and histopathological examination. From the results, Alginase$Alginase^{ⓡ}$ seems not to have any toxic effect in rats when it were given daily intravenous injections below the dosage 1.25U/kg B.W./day for four weeks.

• Toxicological Research
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• v.23 no.1
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• pp.55-63
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• 2007

Diethylnitrosamine (DEN) is a nitrosamine compound that can induce a variety of liver lesions including hepatic carcinoma, forming DNA-carcinogen adducts. In the present study, microarray analyses were performed with Affymetrix Murine Genome 430A Array in order to identify the gene-expression profiles for DEN and to provide valuable information for the evaluation of potential hepatotoxicity. C57BL/6NCrj mice were orally administered once with DEN at doses of 0, 3, 7 and 20 mg/kg. Liver from each animal was removed 2, 4, 8 and 24 hrs after the administration. The histopathological analysis and serum biochemical analysis showed no significant difference in DEN-treated groups compared to control group. Conversely, the principal component analysis (PCA) profiles demonstrated that a specific normal gene expression profile in control groups differed clearly from the expression profiles of DEN-treated groups. Within groups, a little variance was found between individuals. Student's t-test on the results obtained from triplicate hybridizations was performed to identify those genes with statistically significant changes in the expression. Statistical analysis revealed that 11 genes were significantly downregulated and 28 genes were upregulated in all three animals after 2 h treatment at 20 mg/kg. The upregulated group included genes encoding Gdf15, JunD1, and Mdm2, while the genes including Sox6, Shmt2, and SIc6a6 were largely down regulated. Hierarchical clustering of gene expression also allowed the identification of functionally related clusters that encode proteins related to metabolism, and MAPK signaling pathway. Taken together, this study suggests that match with a toxicant signature can assign a putative mechanism of action to the test compound if is established a database containing response patterns to various toxic compounds.

• Toxicological Research
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• v.29 no.2
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• pp.91-98
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• 2013

Armeniacae semen (AS) has been considered a toxic herb in the Korean medicine as it contains hydrogen cyanide and amygdalin, especially in its endocarp. Therefore, prebrewed AS that is devoid of endocarp has been traditionally used. In the present study, amygdalin content of the prebrewed AS was significantly lower ($2.73{\pm}0.32{\mu}g/ml$; p<0.01) than the content in the extract that contained the endocarps ($28.50{\pm}6.71{\mu}g/ml$); amygdalin content corresponded to 10% of the extract in the present study. Because of single oral dose toxicity of prebrewed AS according to the recommendation of Korea Food and Drug Administration Guidelines (2009-116, 2009), which was based on single oral dose toxicity study of prebrewed AS, mortality due to toxic principles was significantly reduced. In this study, 2,000 mg/kg of prebrewed AS led to death of 1 female rat and 1 male rat at the end of 2 hr of administration. Based on these results, the 50% lethal dose in both male and female rats was determined to be 9279.5 mg/kg. Seizure, loss of locomotion, and increases in respiration and heart rate were observed as prebrewed AS treatment-related toxicological signs; these signs were restrictedly manifested in the prebrewed AS (2,000 mg/kg)-treated rats. In addition, no changes were observed in body weight, organ weight, gross features, and histopathological parameters with 2,000 mg/kg of AS in both male and female rats. These findings serve as direct evidence that amygdalin in AS is the toxic principle, which can be reduced by the traditional prebrewing method involving the exclusion of endocarp.

• Journal of Life Science
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• v.21 no.5
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• pp.713-719
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• 2011

In this study, we evaluated whether Lunasin Enriched Soybean (LES) suppressed 1-chloro-2,4-dinitrochlorobenzene (DNCB) induced allergic contact dermatitis in vivo. In the group treated with DNCB alone, erythema and hemorrhage in the skin were observed, while the application of LES after DNCB treatment modulated erythema and hemorrhage similar to the untreated group. In histopathological analysis of the skin, DNCB-treated groups showed increased skin thickness compared to the untreated groups, while the treatment of LES dose-dependently modulated skin thickness. Also, hypertrophy and hyperkeratosis of the epidermis, intracellular edema and infiltration of inflammatory cells were observed in the group treated with DNCB alone, while treatment of LES inhibited these inflammatory changes. DNCB also induced a significant up-regulation of iNOS and COX-2 expression, as compared to the untreated groups. However, the treatment of LES significantly decreased the down-regulation of iNOS and COX-2 expression, as compared to DNCB-treated groups. Also, LES reduced the IgE level in DNCB-stimulated groups. And lunasin from LES translocated the nucleus of the cells in the skin of Sprague-Dawley rats. Taken together, it is thought that LES has the potential to be used as an alternative treatment for allergic contact dermatitis.

• Toxicological Research
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• v.25 no.3
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• pp.140-146
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• 2009

This study was performed to evaluate the toxicity of cadmium selenide for a period of 28 days in Sprague-Dawley rats. Each of 10 healthy male and females rats per group received daily oral administration for 28-day period at dosage levels 30, 300 and 1,000 mg/kg of body weight. Mortality and clinical signs were checked, and body weight, water intake and food consumption were also recorded weekly. There were no dose-related changes in food consumption or urine volume. All animals survived to the end of study with no clinical signs or differences in body weight gain observed when compared with the control group. At the end of study, all animals including control group, were subjected to necropsy. Blood samples were collected for hematology tests including coagulation time and biochemistry analysis. Blood coagulation time and relative organ weight were unaffected by all received doses. White Blood Cell (WBC) counts significantly increased in the 300 mg/kg administered male animal group when compared to the control. Monocyte (MO) value were also increased significantly in both 300 and 1,000 mg/kg male animal group. However, Mean Corpuscular Volume (MCV) were significantly decreased compared with the control in the 1,000 mg/kg dose groups for male and female animals. Mean Corpuscular Hemoglobin (MCH) decreased significantly for female in the 300 and 1,000 mg/kg group compared to the control. Blood biochemical values of Inorganic phosphorus (IP) were significantly increased in both the 300 and 1,000 mg/kg dose groups in male animals when compared to the control. Creatinine (CRE) levels indicated significant increase in kidney function for the female, 30 mg/kg dose group when compared with control. There was a significant decrease in thymus absolute organ weight in the female, 1,000 mg/kg dose group when compared with control. Histopathological findings revealed no evidence of injury related to cadmium selenide except for one case of focal hepatic inflammation in the high dose (1,000 mg/kg) group. One case of lung inflammation was also seen in the control group. Basis on these result, the No Observable Adverse Effect Level (NOAEL) of cadmium selenide was determined to be more than 1,000 mg/kg/day for male and female rats under conditions in this study.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.2
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• pp.160-165
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• 2009

Contact dermatitis is induced by allergy response from a lot of chemical substances brought on by environmental contamination. In this study, we investigated allergy prevention effect of baicalein which is Scutellaria radix extract. Scutellaria radix is the dried roots of Scutellaria baicalensis Georgi (Labiatae). It has been used in oriental traditional medicine for treatment of fever, diarrhea and inflammation. We have induced allergy by PCL after oral administration of 0 mg/kg, 50 mg/kg or 100 mg/kg baicalein dose for 8 times during 8 days in BALB/c mice and measured ear thickness, IgE level, histamine level, mast cell number and histopathological changes. The ear thickness of the 100 mg/kg baicalein group was thinner than that of the 0 mg/kg baicalein group. IgE level and histamine level of the 100 mg/kg baicalein group were lower than those of 0 mg/kg baicalein group. The number of mast cells of 0 mg/kg baicalein group more than that of 100 mg/kg baicalein group in the ear tissue. In addition, intradermal edema with prominent inflammatory cell infiltration was observed at 0 mg/kg baicalein group more than 100 mg/kg baicalein group in the ear tissue. These results suggest that baicalein has allergy prevention effect in BALB/c mice.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2004.11a
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• pp.85-87
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• 2004

We fabricated flexible thermoradiotherapy probes to alternated combination with Interstitial hyperthermia and Brachyradiotherapy thermoradiotherapy probe was coated by gold plate on polyethylene brachytherapy probe. When Agar phantom was heated 15 minute with 30 W radiofrequency power, temperature increased as 5oC for polyethylene probe and 20oC for gold coated polyethylene probe. We observed that the 1 cm square array would heat a volume with a 1.25 cm radius circular field cross section to therapeutic temperatures (90% relative SAR using Tm) and the 2 cm square array with a 1.75 cm radius rectangular field with central inhomogeneity. With 2 cm long electrode implants, we observed that the 1 cm square array would heat a 3 cm long sagittal section to therapeutic temperature (90% relative SAR using Tm). The histopathological changes associated with RF heating of normal canine brains have been correlated with thermal distributions. RF needle electrode heating was applied for 50 min to generate tissue temperatures of 43${\circ}$C. We obtained a quarter of the heated tissue material immediately after heating and sacrificed at intervals from 7${\sim}$30 days. The acute stage was demonstrated by liquefactive necrosis, pyknosis of neuronal element in the gray matter. Mild gliosis occurring around the necrosis was demonstrated in the last sacrificed (days30)canine brain.

• The Korean Journal of Pesticide Science
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• v.7 no.4
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• pp.271-279
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• 2003

To investigate the toxicological effects of technical of IAP-3006, we performed subchronic oral toxicity study in Sprague-Dawley (SD) rats. In the subchronic dietary study, rats of both sexes were fed diets containing technical of IAP-3006 at concentrations of 0, 1000, 10,000, or 15,000 ppm for 90 days. No clinical signs and mortality were observed in animals treated with technical of IAP-3006 throughout the experimental period. There were also no significant changes in body weights, feed consumption, and any gross or histopathological lesions. Although there were statistically significant differences between the control and treated groups in some relative and absolute organ weights, and hematological and biochemical analyses, the data were in biologically normal ranges and did not show a dose-dependent manner. From these results, it is suggested that subchronic oral toxicity NOEL of technical of IAP-3006 in rats may be over 15,000 ppm.

• Journal of Pharmacopuncture
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• v.12 no.3
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• pp.5-24
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• 2009

Injinho-tang(IJ) has been used for the treatment of hepatobiliary diseases. This study was performed to observe the effect of IJ extract on the hepatocellular carcinogenesis and hepatic cirrhosis induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Experimental groups were divided into two ; 8th and 12th week group, and subdivided into four; normal group(Nor), hepatocellular cancer and hepatic cirrhosis inducing control group(Con), and IJ extract 260mg/kg/day(IJA) or 520mg/kg/day(IJB) administered groups to Con. The results obtained are as follows: The body weight was decreased in the Con, IJA and IJB compared with the Nor from the 2nd week to the 12th week. The weight of liver and the weight of liver/100g body weight were decreased significantly in Con, IJA and IJB compared with the Nor. The activities of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were significantly increased in the Con compared with Nor, but decreased in the IJA and IJB compared with Con from the 8th week group. The activities of alkaline phosphatase(ALP), lactacte dehydrogenase (LDH) and alpha fetoprotein(AFP) were increased significantly in the Con compared with Nor, but decreased in the IJA and IJB compared with Con. The activities of superoxide dismutase(SOD) were decreased in the IJA and IJB compared with Con, but the activities of catalase were increased in the IJA and IJB compared with Con. According to the light and electron microscopical observation, IJA and IJB improved the morphological and histopathological changes of the liver injured by DENA and $CCl_4$. The number of hepatic p53 positive cells was decreased in the IJA and IJB compared with Con. These results suggest that administration of IJ extract suppress or retard DENA and $CCl_4$-induced hepatocelluar carcinogenesis and hepatic cirrhosis in rats.

• Journal of Korean Neurosurgical Society
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• v.42 no.1
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• pp.27-34
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• 2007

Objective : On the magnetic resonance image (MRI) of the infiltrating brain tumor, enhancement is usually higher in malignant tumor than in benign tumor, and tumor cells can invade into the peritumoral area without definite enhancement. In various pathological conditions, the blood brain barrier (BBB) becomes changed to pathological condition, allowing various materials extravasating into the interstitial space, and degree of enhancement is depend on the pathology. Authors performed dynamic MRI on enhancing and surrounding edematous area in order to evaluate the degrees of opening of BBB, to differentiate tumor from non-tumorous condition, and to determine its relationship with the recurrence of the tumor. Methods : Dynamic MRI was performed in 25 patients. Dynamic scans were done every 15 seconds after administration of Gd-DTPA on the enhancing and surrounding area for maximum 300 seconds, and the patterns of enhancement were ana lysed. The enhancement curve with initial steep increase followed by slow decrease was defined as "N pattern", those with initial steep increase followed by additional slow increase as "T pattern", and those with initial steep increase followed by plateau as "E pattern". Histopathological findings were compared with the dynamic scan. Results : The graphs taken from enhancing area showed "T pattern" regardless of pathology. In the surrounding area, "T pattern" was noticed in the malignant tumors, but "E pattern" or "N pattern" was noted in low-grade or benign tumors and non-tumorous condition. "T pattern" in the surrounding area was related to the malignant with tumor cell infiltration and recurrence. Conclusion : The results suggest that the malignant tumor infiltration changes the condition of BBB enough to extravasate the Gd-DTPA. Enhancement pattern in the surrounding edematous area may be a useful information to differentiate the malignant glioma with the low-grade and benign tumors or other non-tumorous conditions.