• 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.79-86
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• 2007

The isolated plantamajoside from Plantago asiatica that is often used as a marker compound in chemotaxonomic studies has various bioactivites such as the inhibitions of cyclic AMP phosphodi-esterase and 5-lipoxygenase, microbial growth and inflammation, and currently demands the generation of toxicity data. The purpose of this study was to examine the toxicities of the single and 14 days repeated dose toxicity in Sprague-Dawley rats orally administrated with plantamajoside at dose levels of 0, 500, 1000, and 2000 mg of dried material/kg body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or relative organ weight among different dose groups. Also we observed no death and abnormal clinical signs were observed during the experimental period. Between the groups orally administered Plantago asiatica and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no gross findings at final sacrifice. There was no evidence of histopathological alteration mediated by 14 days treatment with Plantago asiatica. These results suggest that no observed adverse effect level (NOAEL) of the oral application was considered to be more than 2000 mg/kg in rats under the conditions employed in this study. Another observation was performed to investigate the safety of Plantago asiatica in respect of genotoxicity. This substance was examined that Salmonella typhimurium reversion assay (Ames test) in strain TA98, TA100, TA1535. In the reverse mutation test, Plantago asiatica did not induce mutagenicity in Samonella typhimurium with and without metabolic activation. These results indicated that Plantago asiatica had no genotoxicity.

• Journal of Sericultural and Entomological Science
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• v.27 no.1
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• pp.1-11
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• 1985

In order to clarify the taxanomic position of a new microsporidia K79 which was isolated from the silkworm larvae, Bombyx mori L. in Korea in 1979, the following several experiments such as estimation of pathogenicity in different instar, histopathological examination under light and electronic microscope and examination of fine structure of the sporse were carried out and their result obtained are as follows. In the test of pathogenicity by oral inoculation, the new microsporidia K79 was lower than Nosema bombycis and the susceptibility of the new microsporidia to silkworm was getting lower as the silkworm larvae grew. The lesion of Silkworms' tissue which was infected with the new microsporidia K79 was found in the epithelial cells of trachea, fat body and silk gland cells. The developmental process of the new microsporidia K79 in vivo could be divided into the following five stages: sporoplasm, schizont, sporont, sporoblast, and spore. The process was just the same as the of N. bombycis, but its development was slower than that of N. bombycis. Several differences in the fine structure of the spore under electron microscope, which could be important keys for the classification of microsporidia, were obtained. Anchoring disk and polaroplast lamella of the new microsporidian spore were disclosed to be different from those of N. bombycis. An average number of polar filament coils of the new microporidian spore was 16 at an angle of 75$^{\circ}$. On the basis of various keys for the classification of microsporidia, the results obtained from various experiments proved that the newly isolated microsporidia should be classified into the Genus, "Nosema", nut is further classification for species should be conducted in the future. Therefore, it may be reasonable that the new microsporidia is temperally classified as Nosema sp. K79 considering the fact that it was discovered in Korea in 1979.a in 1979.

• Journal of fish pathology
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• v.4 no.2
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• pp.79-85
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• 1991

In Feb., 1990 an epizootic disease to masu salmon fry, Oncorhynchus masou cultured at the hatchery of rainbow trout in Samchok, Kwangwon-do have broken out and induced high mortality over 70%. Externally, the diseased fish showed dark discoloration, abdominal distension with ascites, slight exophthalmus and fecal casts. Internally, the gill and the liver of diseased fish were edematous and pale, and the stomach of moribund fish contained the milkish fluid. Microscopically there was extensive necrosis of the hematopoietic tissue in kidney and spleen, and scattered necrosis of pancreas, liver and lateral muscle. Especially, the necrosis of lamina propria, muscle layer and tela submucosa in the digestive tract known as the typical signs associated with infectious hematopoietic necrosis virus was seen clearly.

• Journal of Korean Neurosurgical Society
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• v.30 no.1
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• pp.47-53
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• 2001

Objective : This study was undertaken to evaluate operative results and prognosis according to preoperative clinical status and histopathological finding of spinal cord tumor. Methods : We analyzed of clinical feature, tumor location, histopathologic finding, operative results and prognosis in 55 patients with spinal cord tumor during last 10 years. Results : 1) The incidence of spinal cord tumors varies with the age of affected patients who are 2 to 75 years of age. Peak incidences were in the 5th & 7th decade of life, and the ratio of male to female was 1.2:1. 2) The most common histopathologic type was neurinoma(41.9%). 3) The tumors were located most frequently in the thoracic area(22 cases, 40.0%) and in the intradural extramedullary space(30 cases, 54.5%). 4) The most common initial clinical feature was pain in 20 cases(36.4%). For neurologic status on admission, 30 cases(54.5%) showed motor disturbance. 5) In radiologic studies, there were abnormal finding in 21 cases from plain X-rays among 37 cases. The entire 20 cases in when myelography was done showed subarachnoid blockade, either complete or incomplete. The magnetic resonance imaging, regard as the most accurate diagnostic method, revealed the exact location of the tumor and the relationship of the tumor with the adjacent anatomical structure. 6) The total removal was possible in 36 cases(65.5%), subtotal removal in 17 cases(30.9%) and biopsy in 2 cases (3.6%). Nineteen cases(90.5%) among 21 cases with preoperative radiculopathy group showed recovery or improvement, where as only 11 cases(36.7%) among 30 cases with preoperative motor weakness group showed recovery or improvement, with statistically significant difference(p<0.01). Pathologically, 26 cases(83.9%) among 31 cases of neurinoma and meningioma showed postoperative recovery or improved, but only 1 case(6.3%) among 16 cases of metastatic tumor, astrocytoma and ependymoma recovered. Postoperative complication noted in 5 cases(9.1%), and were noted postoperative hematoma, pneumonia, pulmonary edema and spinal cord infarction. Conclusion : Preoperative neurologic status and histopathologic finding are considered important factors of Postoperative outcome in patients with spinal cord tumor.

• The Journal of Internal Korean Medicine
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• v.32 no.3
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• pp.397-410
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• 2011

Objectives : This study was designed to investigate the effect of Injinsammul-tang (IJS) on hepatocellular carcinogenesis in rats. Methods : Sprague Dawley (SD) rats of control and treatment groups received intraperitoneal injection of 50 mg/kg/day diethylnitrosamine (DENA) weekly for 8 weeks. Experimental rats were classified into 3 groups; normal group (Nor), hepatic cancer induced control group (Con), and IJS extract 250 mg/kg administered group (IST) after being injected with DENA. Thereafter the changes of body weight, liver weight and weight of liver/100g body weight, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and superoxide dismutase (SOD) were measured. Gross anatomy and optical microscopy were also observed. Results : The body weight decreased in Con and IST compared with the Nor. The weight of liver and the weight of liver/100g body weight increased significantly in Con and IST compared with the Nor. The activities of AST, ALT, ALP, LDH increased in the Con compared with Nor, but decreased in IST compared with Con. The activities of SOD increased in the Con and IST compared with Nor. Upon naked eye and light microscopic examination, IJS improved the morphological and histopathological changes of liver caused by DENA-induced hepatic neoplasm. The number of hepatic p53 positive cells decreased in the IST compared with Con. Conclusions : Most of the results did not show a significant effect, but some of the results showed a significant effect. It can be estimated that IJS has some effects on hepatocellular carcinogenesis induced by DENA in rats, and further studies will be needed.

• Journal of Yeungnam Medical Science
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• v.3 no.1
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• pp.261-267
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• 1986

Development of supervoltage treatment machine may minimize skin reaction by skin-sparing effect, but skin damage is still one of "the dose limiting factor" in radiation therapy. In spite of these importance, systemic histopathologic studies of skin in similar conditions which used in clinical treatment has not been performed so far. 60mice were irradiated with conventional fraction ($200{\times}5/wk$) and whole abdominal field ($2{\times}3cm$, from symphysis pubis to xyphoid process). Used machine was 250KV, 24mA, orthovoltage x-ray machine. Histopathological changes of acute skin reaction at the level of total irradiation dose were analyzed and the possible mechanism of later chronic changes were investigated. Obtained results are as follows: 1. In 1,000 rad irradiated group, only mild epidermal edema is noted. 2. In 2,000 rad irradiated group, slightly decreased number and size of hair follicles and appendages, dermal edema and scanty infiltration of inflammatory cells are visible. 3. In 3,000 rad irradiated group, marked increased capillary congestion and prominant infiltration of inflammatory cells are observed. 4. In 4,000 rad irradiated group, vascular wall thickening with proliferation of endothelial cells are prominant. Dermal thinning and hyalinization are newly developed. 5. In 5,000 rad irradiated group, complete desquamation of epidermis is not seen, despite of acceleration of all above mentioned changes.

• The Journal of Pediatrics of Korean Medicine
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• v.29 no.3
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• pp.65-79
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• 2015

Objectives : In this study, effects of haepyoijintang (HIJ) on the increase in airway epithelial mucosubstances of rats and ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Methods : Hypersecretion of airway mucus was induced by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered HIJ during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was evaluated using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of HIJ was evaluated by examining the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN and creatinine concentrations of rats and the body weight gain during experiment, after administering HIJ orally. At the same time, the effect of HIJ on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of HIJ and treated with ATP ($200{\mu}M$), PMA (10 ng/ml), EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to evaluate the effect of HIJ both on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results : (1) HIJ decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) HIJ did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. (3) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin gene expression from NCI-H292 cells. Conclusions : The result from the present study suggests that HIJ might control the production and gene expression of airway mucin observed in various respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of HIJ with their diverse components should be further investigated using animal experimental models that can reflect the pathophysiology of airway diseases through future studies.

• Journal of Pharmacopuncture
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• v.19 no.1
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• pp.37-44
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• 2016

Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

• The Korean Journal of Pharmacology
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• v.2 no.2
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• pp.3-22
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• 1966

An experimental study was done on rabbits to observe the effects of several anticlonorchial drugs on the pathology of the liver infested with Clonorchis sinensis. After two months of infestation with Clonorchis sinensis by giving $400{\sim}500$ metacercariae by mouth, hexachlorophene, chloroquine 2,2' methylenebis (3,4,6 trichlorophenoxy acetic acid) and Hetol were administered orally and follow up macro-and microscopic studies of the liver pathology were done in 2 to 3 days, one month, 2 months and 3 months after the completion of medications. The results obtained in this study are as follows: 1. In both groups which were administered hexachlorophene piperazine 20mg/kg for seven days or 8mg/kg for 18 days, the macroscopic findings of the liver after 3 months revealed only minimal changes of the color and consistency The histopathological findings were the reduction of fibrosis, pseudolobulation, proliferation and adenomatous hyperplasia of bile ducts, and regeneration of liver parenchyma. 2. In groups which were administered chloroquine phosphate 20mg/kg for 18 days or 40mg/kg for 5 days, and also in groups which were administered dithiazanine iodide 30mg/kg for 18 days or 60mg/kg for 5 days, no significant findings of recovery were observed either macroscopically or microscopically. 3. In the group which was given 20mg/kg of 2,2' methylenebis(3,4,6 trichlorophenoxy acetic acid) for 5 days, prominent healing of the damaged tissues was observed after 2 months, revealing the decrease of fibrous tissue, caliber of bile ducts and adenomatous hyperplasia of the epitherial cells of the bile ducts, and regenerationof liver parenchyma. 4. In the group which was given Hetol 200mg/kg for 5 days, swelling, congestion and eddish-brown discoloration of the liver were noted macroscopically after 3 days of completion of drug administration. Hemorrhage, congestion, necrosis and degeneration of the parenchyma were observed microscopically After 10 days, liver appeared almost normal macroscopically, but marked fat degeneration was noted microscopically. After 2 months, the liver was almost normal in gross appearence with only slight atrophy and also marked healing was observed microscopically, i. e. decrease of fibrous tissue and reduction of the previously enlarged bile duct and the regeneration of the liver parenchyma.