• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.339-347
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• 1994

This study was carried out to investigate the pathological changes with paraquat(1.1'-dimethyl-4.4'-dipyrildiylium dichloride) administered by intraperitoneally, orally, skin applied in mice, rats and rabbits. Results were obtained as follows; In 2 days after paraquat administration clinical signs anorexia, depression, tachypnea, and tachycardia, respiratory failure, coma and death were observed in mice, rats and rabbits. Compared toxicity of paraquat with mouse were observed toward to paraquat that resistance was strong than rats and rabbits. Also, mortality of skin application were found the low than intraperitoneal and high than oral administration. In the case of gross observation were appear lips moisture in orally administered rats and rabbits by skin application. Lung of all laboratory animals were observed congestion and haemorrhage, swelling or atrophy. In the case of microscopic findings were severe congestion and haemorrhage, interstitial pneumonia of lung. Congestion and haemorrhage of liver, congestion and haemorrhage, renal tubule epithelium necrosis of kidney were observed in mice, rats and rabbits. Skin application group of mice, rats and rabbits showed infiltration of inflammatory cells and folliculitis of epidermis and dermis. Also, in oral administration group showed congestion and haemorrhage, tachment, necrosis of alimentary tract mucosa.

• Environmental Analysis Health and Toxicology
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• v.21 no.1 s.52
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• pp.35-43
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• 2006

Reproduction and organ structure of the pale chub, Zacco platypus in Isa stream were investigated by means of histological methods. The results of the study confirmed reproductive abnormality and histopathological features in the pale chub. The gonadosomatic index (GSI) of the fish showed two peak in April and August. In summer season, GSI of the male was about two times of the female's GSI. Monthly variation of the gonadal development was very irregular. From the histological analysis of the organ structure, epidermal atrophy, necrosis and hyperplasia of pigment cell were observed in the skin. Epithelial layer lifting and clubbing of the lamella and bifurcation of the filament were observed in the gill. Also histological changes as congestion, cytoplasmic degeneration of hepatic cell, degeneration of bile duct, glomerular dilatation, degeneration of renal tubule and pycnosis of interstitial cell were identified in the liver and kidney, respectively.

• Neonatal Medicine
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• v.28 no.2
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• pp.83-88
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• 2021

Treatment guidelines for postnatal cytomegalovirus (pCMV) infection in preterm have not been established yet. Neutropenia, thrombocytopenia, hepatitis, colitis, and sepsis-like disease are among the clinical manifestations, which range from moderate to serious. We present a case of autopsy diagnosed as pCMV infection in a premature infant delivered at gestational age of 24 weeks and 5 days. On the 7th and 14th days of birth, urinary CMV polymerase chain reaction samples were negative, ruling out congenital CMV infection. However, autopsy examination revealed that the patient had disseminated pCMV infection. CMV inclusion bodies were found in the majority of tissues, including the lung, liver, pancreas, breast, kidney, and adrenal gland, but not the placenta. The thymus exhibited significant cortical atrophy and T-cell immunodeficiency, possibly induced by dexamethasone treatment for bronchopulmonary dysplasia or by pCMV infection itself. If dexamethasone treatment is extended or high doses are considered, it may be beneficial to test the CMV infection status to prevent aggravation of infection. This case demonstrates that, despite the low prevalence, pCMV infection should be considered a differential diagnosis in preterm if other conditions or etiology cannot justify clinical deterioration.

• Journal of Nutrition and Health
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• v.12 no.4
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• pp.29-42
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• 1979

In order to observe metabolic effects of an oral conceptive, Norinyle, on female Guinea pig, the changes of ascorbic acid amount and alkaline phosphatase activity in the liver and serum were determined, and histochemical changes of the uterus were observed by microscopic and electronmicroscopic methods by administration of Norinyle with or without ascorbic acid. The results obtained are summerized as follows: 1) The metabolic changes were clearly influenced by the administration of Norinyle alone, but the changes were diminshed by administration of Norinyle with ascorbic acid. 2) The adimnistration of Norinyle influenced to increases the requirment of ascorbic acid in the liver. 3) The uterus weight of the Norinyle administered group was much increased, while the weight was less increased in the group of administered Norinyle with ascorbic acid than the control. 4) The Norinyle administration was brought about an atrophy of endometrium, of uterus especially, functional layer, that the formation of glands were inadequately and the fromation of basal layer and stroma were diminished. 5) An acute infarction on the all layers of the uterus was developed at 9th and 25th days of Norinyle administration and 20th day of Norinyle with ascorbic acid administration. 6) A hypertrophy of stromal and endovascular cells were observed on the groups administered of Norinyle alone(group II ) or Norinyle with ascorbic acid(group IV). 7) It was observed that amount of collagen fiber in the basal and muscular layeres of uterus were diminished under a microscopical observation by the special stained specimen on the Norinyle administered group, but the amount and distribution of reticulin fiber were not changed significantly. 8) The fille structure of outer functional layer of the uterus were significantly changed by administration of Norinyle which were shown irregurarity of nuclear membrane, poor development ana significant expansion of enaoplasmic reticulum, decreases of the amount of ribosome due to slip off, increases of the number of dense bodies, obvious formation of vaccule, an4 decreases the amount of collagen in inner and outer layer of the stroma. 9) The amount of ascorbic acid in the serum did not much changed but the amount in the liver was much decreased by the administration of Norinyle, And the administration of Norinyle with ascorbic acid induced for a significant diminishing on the changes of uterus which might be able to developed by the administration of Norinyle alone.

• Journal of Environmental Health Sciences
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• v.16 no.1
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• pp.29-43
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• 1990

The purpose of this study is to investigate the vairous change in the toxicity of cadmium by the simultaneous administration of selenium and zinc, which have been reported to change -the toxicity of cadmium through the interaction with cadmium, to rat. For the experiment, 42 rats of Sprague-Dawley strain were used. The experimental groups were divided into 6 groups: a control group, a cadmium (100ppm) alone treatment group, a cadmium (100ppm) and zinc (100ppm) combined treatment group, and three cadmium (100ppm), zinc (100ppm) and selenium (1, 4, and 8ppm) combined treatment groups. The rats were allocated seven to each group and observed for seven weeks. The results of experiment are as follows: 1. The food consumptions of each group were reduced, compared with a control group, especially, in a cadmium and zinc combined treatment group and a cadmium $\cdot$ zinc and selenium(1ppm) combined treatment group to the significant level compared with a control group (p < 0.05). The water consumptions of each group were reduced to the very significant level compared with a control group (p < 0.01). The feed efficiencies of each group were lower than a control group, and among them the highest group was cadmium $\cdot$ zinc and selenium (8ppm) combined treatment group as 90% of a control group. 2. In all groups, the weight gains were highest in the second week and the total weight gains were reduced to the very significant level compared with a control group (p < 0.01). 3. In all groups, the relative weights of liver were reduced, compared with a control group, especially, a cadmium alone treatment group was reduced to the significant level (p < 0.05). The relative weight of kidney was high to the significant level in a cadmium alone treatment group (p < 0.05) compared with a control group. In all groups, the relative weights of testis were reduced, compared with a control group, but the levels were not significant. 4. The accumulation of cadmium was highest in the kidney and the order of height was in liver, testis and blood, respectively. In all groups, the amount of cadmium accumulation was high to the very significant level compared with a control group (p < 0.01). In liver, the amount of acdmium accumulation in. a cadmium alone treatment group was high to the significant level compared with a cadmium $\cdot$ zinc and selenium (8ppm) combined treatment group (p < 0.05), and in kidney, the amount of cadmium accumulation in a cadmium alone tretment group was high to the very significant level compared with the cadmium $\cdot$ zinc and selenium (4, 8ppm) combined treatment groups (p < 0.01). However, in testis, among the treatment groups the level was not significant and in blood, a cadmium alone treatment group was low to the significant level compared with the cadmium $\cdot$ zinc and selenium (4, 8ppm) combined treatment groups (p < 0.05). 5. According to the histopathological finding on the testis, some of the seminiferous tubules of a group treated with cadmium alone showed severe necrosis and atrophy. But the testis of cadmium $\cdot$ zinc and selenium (8ppm) combined treatment group was similar to that of a control group. From the results of this study, it can be concluded that the repeated simultaneous oral administration of large doses of selenium with the cadmium produces the partial amelioration of cadmium toxicity, whereas zinc does not.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.39-56
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• 2002

Objective : The aim of this study is to investigate the inhibitory effect of lnjinchunggantang-derivative on acute and sub-acute hepatic fibrosis induced by $CCl_4$, and to compare the efficiency of lnjinchunggantang-derivative, Salviae Radix and Scirpi Tuber.Zeloariae Rhizoma on acute and sub-acute hepatic fibrosis induced by $CCl_4$. Method : Western blotting for collagen type N, quantitative RT-PCR and gross & histological findings on liver tissue (Hematoxylin & Eosin stain, Reticulin stain, Masson-Trichrome stain) were studied. Results : In the study on collagen type N expression, lnjinchunggantangcderivative, Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix showed inhibitory effect in western blotting. In quantitative RT-PCR assay, lnjinchunggantang-derivative showed inhibitory effect on collagen type N expression in acute hepatic fibrosis model, whereas lnjinchunggantang-derivative, Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix showed inhibitory effect on collagen type N expression in sub-acute hepatic fibrosis model. In the gross findings of acute and sub-acute hepatic fibrosis models,lnjinchunggantang-derivative, Salviae Radix and Scirpi Tuber. Zeloariae Rhizoma showed inhibitory effect on hepatic fibrosis in the order. In the histological findings of acute and sub-acute hepatic fibrosis models in Hematoxylin & Eosin, Reticulin and Masson-Trichrome staining, the liver of $CCl_4$-only group showed atrophy and necrotic change with white nodules whereas that of $CCl_4$+ Injinchunggantang-derivative showed no significant histological change with well preservation of the tone of the tissue, and Scirpi Tuber. Zeloariae Rhizoma and Salviae Radix group showed minimal fibrotic changes. In the scoring system of the extent of the inhibition of the hepatic fibrosis, lnjinchunggantang-derivative group showed statistically significant inhibitory effect(p<0.05) whereas Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix group showed no statistically significant effect in the acute hepatic fibrosis model. In the sub-acute hepatic fibrosis model, lnjinchunggantang-derivative, Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix group showed statistically significant effect (p<0.01). Conclusion : These results show that lnjinchunggantang-derivative, Salviae Radix and Scirpi Tuber.Zeloariae Rhizoma have inhibitory effect in the order on hepatic fibrosis induced by $CCl_4$ by suppressing the expression of collagen type N, ultimately preventing liver cirrhosis. To obtain more credible results in this experiment, developement of a new experimental model more similar to human hepatic fibrosis is still needed.

• Molecules and Cells
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• v.42 no.12
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• pp.893-905
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• 2019

Mitochondria are highly dynamic organelles that constantly undergo fission and fusion processes that closely related to their function. Disruption of mitochondrial dynamics has been demonstrated in acute kidney injury (AKI), which could eventually result in cell injury and death. Previously, we reported that augmenter of liver regeneration (ALR) alleviates renal tubular epithelial cell injury. Here, we gained further insights into whether the renoprotective roles of ALR are associated with mitochondrial dynamics. Changes in mitochondrial dynamics were examined in experimental models of renal ischemia-reperfusion (IR). In a model of hypoxia-reoxygenation (HR) injury in vitro, dynamin-related protein 1 (Drp1) and mitochondrial fission process protein 1 (MTFP1), two key proteins of mitochondrial fission, were downregulated in the Lv-ALR + HR group. ALR overexpression additionally had an impact on phosphorylation of Drp1 Ser637 during AKI. The inner membrane fusion protein, Optic Atrophy 1 (OPA1), was significantly increased whereas levels of outer membrane fusion proteins Mitofusin-1 and -2 (Mfn1, Mfn2) were not affected in the Lv-ALR + HR group, compared with the control group. Furthermore, the mTOR/4E-BP1 signaling pathway was highly activated in the Lv-ALR + HR group. ALR overexpression led to suppression of HR-induced apoptosis. Our collective findings indicate that ALR gene transfection alleviates mitochondrial injury, possibly through inhibiting fission and promoting fusion of the mitochondrial inner membrane, both of which contribute to reduction of HK-2 cell apoptosis. Additionally, fission processes are potentially mediated by promoting tubular cell survival through activating the mTOR/4E-BP1 signaling pathway.

• Toxicological Research
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• v.20 no.1
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• pp.83-88
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• 2004

The present study was carried out to investigate the potential adverse effects of CKD-602 by a 5-day repeated intravenous dose in Sprague-Dawley rats. The test article, CKD-602, was administered intravenously to male and female rats at dose levels of 0.07, 0.22, 0.67, 2.0 and 6.0 mg/kg/day for 5 days consecutively. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period after cessation of the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. There were 2 and 5 treatment related deaths in the 0.67 and 2.0 mg/kg/day dose groups of both genders, respectively. Treatment related clinical signs, including hair loss, skin paleness, decreased locomotor activity, emaciation, and changes in stool were observed in a dose-dependent manner from the third day after initiation of the injection. Decrease or suppression of body weight was also observed dose-dependently in males and females of the treated groups. Gross postmortem examinations revealed a dose-dependent increase in the incidence and severity of atrophy or hypertrophy and white membrane formation in the spleen, atrophy of the thymus, diffuse white spots and paleness of the liver, paleness of the lung, kidney and adrenal gland, and dark red discoloration and dark red contents in the alimentary tract. Based on these results, it was concluded that the 5-repeated intravenous injection of CKD-602 to male and female rats resulted in increased incidence of abnormal clinical signs and death, decreased or suppressed body weight, and increased incidence of abnormal gross findings. In the present experimental conditions, the $LD_{50}$ value was 2.07 (95% confidence limit not specified) mg/kg/day in both genders and the $LD_{10}$ value was 1.72 (95% confidence limit not specified) mg/kg/day in both genders.

• Toxicological Research
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• v.18 no.1
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• pp.47-57
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• 2002

The subacute oral toxicity of 1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5) was investigated in Sprague-Dawley (SD) rats. Five groups of 5 males and 5 females were orally administered at doses of 0, 37.5, 75, 150 and 200 mg/kg with CWJ-a-5 for 2 weeks. In clinical signs, Salivation was observed in the 75, 150 and 500 mg/kg male and female groups. Loss of fur was observed in the 500 mg/kg male and female group. Body weight were significantly decreased in the 150 and 500 mg/kg male groups and in the 500 mg/kg female group. Food consumption was significantly decreased in the 300 mg/kg male group. In serum biochemistry, total cholesterol and phospholipid were significantly increased in 500 mg/kg male and female group. Aspartate aminotransferase was significantly increased in the 500 mg/kg female group. In histopathological examination, vacuolar degeneration of renal tubules in the kidney, vacuolar degeneration of hepatocytes in the liver vacuolar degeneration of myocytes in the heart, vacuolar degeneration of histiocytes in the spleen and thymus, atrophy of seminiferous tubule and degeneration of germinal epithelium in the testis, vacuolar degeneration of corpus luteum, granulosa cell and theca cell in the ovary were observed in the 150 and 500 mg/kg male and female groups. Based on these results, the no observed adverse effect level (NOAEL) with CWJ-a-5 was considered to be 75 mg/kg and the absolute toxic dose was considered to be 150 mg/kg in this study

• Applied Microscopy
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• v.14 no.2
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• pp.66-80
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• 1984

The organic phosphorus compounds have been widely used as an insecticide, since toxicity of these compounds is especially drastic to the insects than to men and other mammals. The organic phosphates are rapidly hydrolized and hence have little cumulative and ecologic effects. However, due to their acute toxic effects organophosphate have recorded rather high fatalities in men and domestic animals. The organic phosphorus compounds are powerful inhibitors to the carboxylic esterase enzymes such as acetylcholinesterase and pseudocholinesterase. As a result of firm binding characteristics of phosphate radicals to the active sites of enzyme, the activities of these enzymes are inhibited by the organophosphates. The organophosphates such as diazinon is easily observed from skin, gastrointestinal tract, conjunctivas and respiratory tract, and it is converted to more toxic form during metabolism in the liver The present study was carried out in order to investigate the hepatotoxicity of diazinon by observing the changes in the ultrastructure of cytoplasmic organelles of hepatic cells in albino mice. The animals were killed at 6, 12 and 24 hours after administration of 25mg/kg diazinon. The piece of hepatic tissue obtained from each animal was ultrathinly sectioned. The specimens stained by uranyl acetate and lead citrate double contrast methods were observed with JEM model 100B electron microscope. The results obtained were as follows: 1) A prominent dilatation and sacculation of the cisternae of rough endoplasmic reticulum associated with detachment of membrane bound-ribosomes, and disaggregation of the free ribosomes were recognized. 2) The hypertrophy of the smooth endoplasmic reticulum associated with depletion of the glycogen particles was observed. 3) The atrophy of cisternae of Golgi complex was observed. 4) A large number of secondary lysosomes (autophagic vacuoles and residual bodies) were formed. Consequently it is suggested that diazinon would induce disorganization of the cytoplasmic organelles of hepatocytes in albino mice.