• The korean journal of orthodontics
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• v.20 no.1
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• pp.23-45
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• 1990

It is the aim of this study to determine the effects of facial denervation on physiological properties of facial muscles and facial bones in growing rabbits. Experimental animals of fifty two Oryctolagus cuniculus rabbits were employed. Unilateral dissection of facial nerve was carried out on twelve rabbits, bilateral dissection of facial nerve was made on another twelve rabbits and the other twenty rabbits were on unilateral dissection of facial nerve for the histochemical analyses. Six rabbits on the bilateral surgical sham operations and six rabbits of non-intervention served the control groups. EMG records of the orbicularis oris, buccinator and masseter muscles as well as lateral and dorsoventral cephalometric films were taken and analyzed at 0, 1, 2, 5 and 8 weeks respectively. The orbicularis oris, buccinator and masseter muscles of both sides were removed from the animals of the histochemistry group and muscle fibers were classified on the basis of histochemical staining for $\alpha$-GPD, NADH-D and myosin ATPase. EMG activities of orbicularis oris and buccinator muscles were vanished immediately after denervation. Recovery of activities were detected one week after denervation in buccinator and five weeks in orbicularis oris muscles. Histochemical properties of masseter muscles remained as fast glycolytic through the experimental period. Orbicularis oris muscle fibers showed the gradual diminution of size and ratio of the slow oxidative fibers accompanied with atrophy, phagocytosis and vacuolation as well as the augmentation of fast oxidative glycolytic fibers. The buccinator muscle manifested the augmentation of fast oxidative glycolytic fibers at five weeks of experiment. Visual changes in morphology of craniofacial area were not evident, however it variety of subtle changes were apparent from statistical analysis of cephalometric measurements. It is concluded facial nerve regulates the physiological properties of facial muscles and interrelation between the function of the facial muscles and changes of facial bones would be in some degrees.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.599-607
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• 2018

Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration-(>$50{\mu}M$) and time-dependent manners, both of which corresponded with ROS generation. An antioxidant, N-acetylcysteine, attenuated TAK-875-mediated hepatotoxicity, which confirmed the role of ROS generation. Of note, knockdown of GPR40 using siRNA abolished the hepatotoxicity of TAK-875 and attenuated ROS generation. In contrast, TAK-875 induced no cytotoxicity in fibroblasts up to $500{\mu}M$. Supporting the hepatotoxic potential of TAK-875, exposure to TAK-875 resulted in increased mortality of zebrafish larvae at$25{\mu}M$. Histopathological examination of zebrafish exposed to TAK-875 revealed severe hepatotoxicity as manifested by degenerated hypertrophic hepatocytes with cytoplasmic vacuolation and acentric nuclei, confirming that TAK-875 may induce direct hepatotoxicity and that ROS generation may be involved in a GPR40-dependent manner.

• The Korean Journal of Pain
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• v.29 no.3
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• pp.158-163
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• 2016

Background: Phenol and alcohol have been used to ablate nerves to treat pain but are not specific for nerves and can damage surrounding soft tissue. Lidocaine at concentrations > 8% injected intrathecal in the animal model has been shown to be neurotoxic. Tests the hypothesis that 10% lidocaine is neurolytic after a peri-neural blockade in an ex vivo experiment on the canine sciatic nerve. Methods: Under ultrasound, one canine sciatic nerve was injected peri-neurally with 10 cc saline and another with 10 cc of 10% lidocaine. After 20 minutes, the sciatic nerve was dissected with gross inspection. A 3 cm segment was excised and preserved in 10% buffered formalin fixative solution. Both samples underwent progressive dehydration and infusion of paraffin after which they were placed on paraffin blocks. The sections were cut at $4{\mu}m$ and stained with hemoxylin and eosin. Microscopic review was performed by a pathologist from Henry Ford Hospital who was blinded to which experimental group each sample was in. Results: The lidocaine injected nerve demonstrated loss of gross architecture on visual inspection while the saline injected nerve did not. No gross changes were seen in the surrounding soft tissue seen in either group. The lidocaine injected sample showed basophilic degeneration with marked cytoplasmic vacuolation in the nerve fibers with separation of individual fibers and endoneurial edema. The saline injected sample showed normal neural tissue. Conclusions: Ten percent lidocaine causes rapid neurolytic changes with ultrasound guided peri-neural injection. The study was limited by only a single nerve being tested with acute exposure.

• Asian-Australasian Journal of Animal Sciences
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• v.8 no.1
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• pp.1-6
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• 1995

This study represented an endeavor to observe clinical signs and pathological lesions in broiler chicks suffering from experimental Infectious stunting syndrome(ISS). One hundred and twenty day old broiler chicks were divide randomly into two equal groups i.e. control (A) and inoculated (B). At day one of age each chick of the groups (A and B) was dosed with one ml of either tryptose phosphate broth or prepared inoculum respectively. Chicks of both the groups were housed separately under similar standard management. Inoculation induced characteristic clinical changes in birds of treatment group like of brownish diarrhea, lameness, feather developing problems and paleness of combs, wattles and shanks. By day-29 of the experiment all the stunted birds from group-B and an equal number of birds from group-A were slaughtered. These birds were examined thoroughly to record the gross changes in various structures and then the severely affected organs were processed for histopathological examination. The skeletons of affected birds were brittle, keel bones showed quite prominence while the muscles and subcutaneous tissues were almost devoid of fat. Grossly it was observed that pancreas, spleen and bursa of Fabricius were severely atrophied while the intestines were ballooned with undigested feed and gases. Histopathological examination of pancreas and spleen revealed a classical picture necessary for understanding the pathogenesis of the syndrome. The acivar cells of pancreas were atrophied and underwent vacuolation, degeneration and vecrosis. The zymogen granules were almost absent from the acinar cells. A characteristic change was an inflammatory reaction in one or more pancreatic ducts where the epithelium and fibrous tissues occluded the lumen of the ducts and led to the obstruction in pancreatic drainage.

• Environmental Analysis Health and Toxicology
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• v.22 no.2 s.57
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• pp.119-128
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• 2007

The present study was conducted to find out effect of PFOS on survival, activity, growth and organ structure of the melania snail, Semisulcospira gottschei. Experimental groups were composed of one control condition and four PFOS exposure condition (0.1, 0.5, 1.0 and 5.0 mg/L). After 16 week exposure, survival rate and activity were not significantly influenced at the two lower exposure groups, 0.1 and 0.5 mg/L, but they were significantly reduced in 1.0 and 5.0 mg/L groups. Total weight and meat weight rate (MWR) were reduced in PFOS exposure group in comparison to control group. Also, histological degenerations such as acidification of mucous, necrosis and split of muscular fiber bundle, atrophy of anterior pedal gland were recognized in the foot. Hepatopancreas showed the atrophy and degeneration of the digestive cell, vacuolation of digestive gland and closure of lumen in digestive gland.

• The Journal of Dong Guk Oriental Medicine
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• v.2 no.2
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• pp.1-15
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• 1993

The purpose of this study is to observe the effect of Woogyuyem on serum reaction and hepatic tissue in Cyclosporin A treated rats. In this study, the experimental rats divided two group(Control group and Sample group). Under the same condition, both control group and sample group were injected to abdomen with Cyclosporin A for 7days. And then, control group were administered water, sample group were administered Woogy-uyeum for 300days. The change of transaminase and bile acid and SOD activity in blood serum, hepatic tissue were measured at 3rd, 7th, 15th, 30th day. The obtained results are summarised as follows : 1. In the change of SGOT contents, as compared with control group, sample group was significantly decreased at 7th and 15th day. 2. In the. change of SGPT contents, as compared with control group, sample group was significantly decreased at 15th day. 3. In the change of serum bile acid contents, as compared with control group, sample group was significantly decreased at 7th and 15th day. 4. In the change of serum SOD activity, as compared with control group, sample group was significantly increased at 15th and 30th day. 5. In the change of hepatic tissue, as compared with control group, the vacuolation of hepatocytes in the sample group was reduced, the liver plates were reconstructed, and the epitheriai cell wasn't destructed.

• Biomolecules & Therapeutics
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• v.8 no.1
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• pp.84-92
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• 2000

This Study was conducted to assess the single dose toxicity of DA-125, a new anthracycline anti-cancer agent, in rats and mice. The Drug was administered once intravenously to both sexes of rats and mice. Then followed a 14-day period of observation. The $LD_{50}$ Values (95% confidence limit) were estimated to be 60.9 mg/kg (57.5~64.3 mg/kg) for male rats and 60.2 mg/kg (56.2~64.5 mg/kg) for female rats, and 85.8 mg/kg (81.0~90.9 mg/kg) for male mice and 84.5 mg/kg (78.2~91.9 mg/kg) for female mice. Both sexes of rats and mice given the drug revealed the clinical sign of decreased locomotor activity, emaciation, hair loss, red-dish brown urine, salivation, and watery diarrhea. In addition, body weight from the next day to the 7th day tended to be decreased slightly in rats and mice treated with DA-125. Death occurred from the next day after administration to the 12th day. Macroscopically, congestion of gastrointestinal organ, lung, and adrenal glands were found in both sexes on the dead rats and mice. Histopathological examination of dead rats manifested atrophy of spleen, hypoplasia of bone marrow, hypcplasia and necrosis of lymphocyte in thymus, atrophy of villi in small intestine (duodenum, jejunum, and ileum), hyperplasia of granular epithelium in small intestine, degeneration of germinal epithelium in testis, defer oration of tubular epithelium in kidney, and vacuolation and myolysis of myocardium in heart. Histopathological examination of dead mice revealed hypoplasia of spleen and mesenteric lymph node, local necrosis of liver, atrophy of villi in small intestine, hyperplasia of glandular epithelium in small and large intestine, degeneration of tubular in kidney, degeneration of germinal cells in testis, and slight vacuolar degeneration of myocardium in heart.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.9-19
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• 1993

DA-125, a new anthracycline antibiotic, showed antitumor activity against animal tumors and human tumors. Therefore we studied the cardiotoxic potential of DA-125 in hamsters and rats as a part of safety research, and compared it with that of doxorubicin(DXR). In acute cardiotoxicity test model used hamsters DA-125 was administered intravenously at a dose of 6, 9, 12 mg/kg, and DXR at 3 mg/kg was given. The electrocardiogram(ECG) of hamsters was recorded for 30 minutes after administration. The DA-125 caused slight ECG alterations at a dose of 6 mg/kg. At a dose of 12 mg/kg DA-125 induced moderate to remarkable changes in ECG like decrease of heart rate, widening of PR interval and 07 interval, and A-V block in 3 out of 5 animals. The severity of ECG alteration at 12 mg/kg of DA-125 was similar to that at 3mg/kg of DXR and these changes caused by DA-125 and DXR recovered within 10 minutes after injection. In chronic cardiotoxicity test model used rats, DA-125 was administered intravenously once a week for three weeks at a dose of 6, 9mg/kg and DXR was given at a dose of 6mg/kg. Electrocardiogram was recorded every week from the start of administration to 2 weeks after the last administration and the animals were sacrificed for histological heart examination at 1 week or 2 weeks after the last administration. DA-125 did not cause any abnormal changes in ECG and in histological heart examination due to administration, but DXR caused widening of ST segment, QRS complex, and QT interval from 1 week after administration and these changes were continued to necropsy. These alterations in ECG were accompanied by cardiac histological lesions such as vacuolation in myocardiac cells, interstitial edema and necrosis of myocytes. These results suggest that DA-125 is less cardiotoxic than DXR.

• Korean Journal of Veterinary Pathology
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• v.7 no.1
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• pp.43-54
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• 2003

The purpose of this study was to investigate protective effects against transmissible gastroenteritis virus (TGEV) infection in piglets by administration of the TGEV antiserum orally at 2hrs, 24hrs and 36hrs after birth. Five piglets administered with the TGEV antiserum were experimentally challenged with TGEV at four-day-old. Control group was four piglets challenged with TGEV only. Clinical signs and gross, histopathological and immunohistochemical findings were examined. In clinical signs, piglets of the control group appeared the typical signs such as severe watery diarrhea, depression and anorexia but piglets of the TGEV antiserum adminstered group recovered progressively. In clinical signs, piglets of the control group appeared the typical signs such as severe watery diarrhea, depression and anorexia but piglets of the TGEV antiserum adminstered group recovered progressively. In mortality, control group showed 75%, but TGEV antiserum adminstered group showed 20.0 %, respectively. In gross findings, piglets of the control group appeared the typical findings of congestion, distension of lumen, contaning curdes of undigested milk in stomach. But gross findings of piglets of the TGEV antiserum adminstered group appeared milder than them of control group. In histopathological findings, piglets of the control group appeared the typical findings of villous atrophy and fusion, congesion, exfoliation, vacuolation, squamation, loss of cilia and proliferation of crypt. But histopathological findings of piglets of the TGEV antiserum adminstered group appeared milder than them of control group. In immunohistochemical findings, piglets of the TGEV antiserum adminstered group showed more intensive in reaction for IgA and IgG than them of control group. The recation for IgA was stronger than that of IgG. It was concluded that oral administration of TGEV antiserum to piglets was effective to prevent TGEV infection and reduce their mortality.

• Biomedical Science Letters
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• v.9 no.1
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• pp.51-58
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• 2003

This study was carried out to investigate the preventive and therapeutic effect of Panax ginseng water extract (PG-WE) on the toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), one of the most notorious toxic environmental pollutants belonging to the group of polyhalogenated aromatic hydrocarbons. Normal control (NC) group guinea pigs (180~200 g) received vehicle and saline, and TCDD-treated (TT) group was given TCDD and saline. P100 and P200 group animals received PG-WE for 28 days since 1 week before TCDD exposure at daily doses of 100 mg/kg b.w. and/or 200 mg/kg b.w., respectively. C100 and C200 group received PG-WE for 14 days starting 1 week after TCDD-exposure. Toxicity was induced by a single intraperitoneal injection of TCDD (1 $\mu\textrm{g}$/kg b.w.). Abnormal increase in AST and ALT activities in TT group was significantly improved by the administration of PC-WE. Microscopically, there were mild to moderate swelling of hepatocytes, hyperchromatism of individual cells, acidophilic cytoplasm and cytoplasm vacuolation of some hepatocytes, slight to moderate variations of staining density, occasional single cell necrosis, variable size and shape of some hepatocytes, small groups of degenerating hepatocytes surrounded by mononuclear cells, dilated sinusoids of centrilobular zone and some loss of lobular architecture in TT group liver. From these results, we could find the protective and therapeutic role of PG-WE in TCDD-induced liver toxicity by examining the blood chemical parameters and histopathological observation.