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Alcohol-induced hepatic fibrosis in pig

  • Lee, Chang-Woo;Jyeong, Jong-Sik;Lee, Cha-Soo;Jeong, Kyu-Shik
    • Korean Journal of Veterinary Service
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    • v.26 no.4
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    • pp.345-359
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    • 2003
  • A number of toxicants have been incriminated as a causing hepatic disease. Among many detrimental injury, alcohol has been noted for hepatitis, fatty liver, fibrosis, and hepatic cirrhosis. The purpose of this study was to develop animal model for hepatic fibrosis in pigs fed ethanol, and to search for a new anti-fibrogenic agent via this model. Twelve male Landrace pigs were divided into 3 groups of 4 animals each. Group 1, 2 and 3 were fed with active ceramic water only, ceramic water + liquid diet containing 15% ethanol and normal tap water + liquid diet containing 15% ethanol for 12 weeks, respectively. At week 12, all pigs were immediately sacrificed for collection each tissue and blood. Serologically, serum ALT and AST levels were significantly reversed in group 2, as compared to group 3. They were normal range in pigs of group 1. Microscopically, macrovesicular lipid droplets and moderate hepatocellular necrosis were evident in the tap water + ethanol fed group 3. However, the active ceramic water treated group 1 showed normal architecture. Moreover, in group 2, mild fatty changes and necrosis were observed in hepatocytes. Collagen fibers were increased in spaces surrounding periportal and interlobular connective tissues in the group 3 of tap water + ethanol, but collagen synthesis and its thickness of fibrotic septa connecting portal tracts were markedly reduced in the group 2 of ceramic water + ethanol. Myofibroblasts were detected mainly in the interlobular connective tissues of pig liver of group 3 treated ethanol and tap water. Few to no myofibroblasts were observed in groups 1 and 2. CYP2E1 was not or rarely detected in group 1 fed ceramic water. However, group 2 showed slightly activation of CYP2E1 in the area of pericentral vein, while CYP2E1 was significantly activated in group 3 fed tap water and ethanol. Based on the above data, we believe that we have developed a unique alcohol induced fibrosis model in pig, which will be useful in developing anti-fibrotic agents and drugs. Furthermore, the active ceramic water used in our study had an inhibitory and may be protective against ethanol induced hepatic toxicity and fibrosis.

Toxic effects of methylcellulose solution on the liver, spleen and kidney in the Sprague-Dawley(SD) rats following repeated oral or intravenous administration (Methylcellulose의 경구 및 정맥내 반복 투여가 SD랫드의 간장, 비장 및 신장에 미치는 독성학적인 영향)

  • Song, Si-whan;Kang, Boo-hyun;Han, Sang-seop;Roh, Jung-koo;Lee, Chang-eup
    • Korean Journal of Veterinary Research
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    • v.36 no.1
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    • pp.221-233
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    • 1996
  • This experiment was carried out to study the toxic effect of solublized methylcellulose (MC). Sprague-Dawley rats were dosed with 1%(w/v) MC in 0.9% saline by gavage at a dose of 10ml/kg b.w/day or by intravenous injection at a dose of 5ml/kg b.w/day for 28 days. Clinical signs were observed once a day. Body weights, water and food consumptions were measured and urinalysis was performed several times during the experiment. Rats were sacrificed on days 3, 7, 15 and 28 for hematology, blood chemistry, organ weights and histopathology. The relative weight of the spleen and foamy cells of the spleen were increased in the gavage group. Body weight gain, food consumptions, the values of RBC, Hb, MCH, Hct, serum proteins, glucose, bilirubin, AST, and ALP were decreased in I.V. treatment group. On the other hand, water consumptions, the values of serum cholesterol, creatinine, and BUN were increased. Microscopic findings were granulomas, distended sinusoids, and hypertrophy of Kupffer cells with vacuoles in the liver. Spleen exhibited granuloma, increased extramedullary hematopoiesis, and congestion. Kidney exhibited foamy cells in the glomeruli, distension of the tubules. The findings appeared more severe when the treatment was extended. In conclusion, MC solution is not a safe vehicle for intravenous administration because of the toxic effects on the liver, kidney and spleen. In addition, a long-term and large dosage of oral administration of MC appears to be unsafe also and needs to be investigated further.

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Atypical Aortic Coarctation at the Level of Aortic Hiatus: Report of a case treated by bypass graft (대동맥 열공부에 발생한 비전형적 대동맥 협착증: 외과적 수술을 가한 1례)

  • 남민우;유회성;지정희
    • Journal of Chest Surgery
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    • v.5 no.1
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    • pp.13-18
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    • 1972
  • In 1835,Schlesinger first described a case of subisthmlc lower thoracic aortic coarctation. Since Olim`s unsuccessful reconstructive surgery in 1949 and Beattie`s first successful resection with homograft replacement on such a lesion in 1951 were reported,about 20 cases of atypical aortic coarctation had been treated by definitive surgery until 1964. In Korea, only 2 cases of atypical aortic coarctation treated by bypass graft were reported until now. This is the third case-report treated by reconstructive surgery. The patient,11 year old girl who had 2 year history of headache, visual weakness, intermittent claudlcation, and general weakness, was first diagnosed of having the hypertension due to atypical coarctation by the findings of high blood pressure[170/110mmHg] at the upper extremity and weak pulsation on both femoral artery,murmur on the epigastrium, absence of aortic knob, and aorto graphy. Aortography demonstrated the isolated segmental narrowing[length 5cm, diameter 0.4cm] at the level of aortic hiatus 2cm above celiac arterial origin, the dilated right 9th, 10th, 11th intercostal arteries with multiple dimunitive collaterals and no associated abnormalities in the other arteries. Preoperatlve positive findings were strong positive mantoux test, high AST[720 units]. transient mild cardiomegaly with right lung infiltration on chest X-ray and suggestive left ventricular hypertrophy on ECG. On December 1970, through separate left thoracotomy and abdominal approach, bypass graft between descending thoracic aorta and abdominal aorta below renal artery was performed. The operation was first successful with satisfactory reduction of hypertension on the upper trunk[postoperatlve 130/80mmHg] and strong pulsation on the lower extremities[postop. O, postop. 140/100mmHg]. However,6 weeks after surgery, she expired of sudden hemoptysis and shock due to anastomotic leak within the thorax. Operative finding disclosed that the affected aorta was firm, with rich periaortic fibrosis and the outer diameter of stenotic site was not attenuated. Histopathology of the resected specimen was also compatible with primary arteritis.

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Analytical trend of perfluorinated compounds in environmental and biota samples (환경 및 생체시료 중 과불화 화합물의 분석 동향)

  • Lee, Won-Woong;Chang, Won-Hee;Pyo, Hee-Soo;Kang, Tae-Seok;Hong, Jong-Ki
    • Analytical Science and Technology
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    • v.23 no.4
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    • pp.331-346
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    • 2010
  • Perfluorinated compounds have characteristics of resistance to heat, acidic, basic conditions and also resist water, oil, grease, pollutant. Futhermore they are used by various industrial material, nowadays, they produced in large scale for indutrial and commercial areas. However, they also resist metabolizing and degrading in environmental system (plant, animal, even human body). Moreover, in animal's bodies, PFCs can be accumulated in organ (eg; liver) and lead to liver cell necrosis even oncogenesis. Perfluorinated compounds are newly registered as new persistent organic pollutants (POPs) on Stockholm convention in 2009. Therefore necessity for analytical methodology for determination of PFCs in various environmental samples is even more increased. This study discussed sample preparation and instrumental conditions for the analysis of PFCs in environmental and biota samples.

Effects of low-level exposure to manganese and lead on immune function (저 농도의 망간과 납 노출이 면역기능에 미치는 영향)

  • Kim, Ki-Woong;Park, SangHwoi;Won, Yong Lim;Lee, Sung Kwang
    • Analytical Science and Technology
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    • v.27 no.5
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    • pp.248-253
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    • 2014
  • This study aimed to evaluate the effects of exposure to manganese (Mn) and lead (Pb) on immune system. The subjects were 42 male workers, among whom 13 office workers (Group I) had never been occupationally exposed to heavy metals, 21 were worked in manufacturing factories (Group II) and 8 were welders (Group III). The mean blood Mn and Pb level by groups were significantly different. The numbers of CD19+ and total lymphocytes in Group I were significantly higher than those in other groups, but no significant differences were found in other T lymphocytes subpopulation. Mn and Pb concentrations showed negative correlation with T lymphocytes subpopulation, but Mn concentrations were statistical significances with T lymphocytes subpoplation except CD4+CD45RO+ and natural killer cell. Pb concentration was only statistical significance with total lymphocytes. Our results suggest that occupationally exposed to Mn and Pb can affect the cellular immune response.

Studies on the effects of PUERARIAE RADIX(葛根) and ARTEMISIAE HERBA(茵蔯) on experimental liver damages induced by alcohol, d-galactosamine and $CCl_4$ (인진(茵蔯)과 갈근(葛根)이 d-galactosamine, 급성(急性) alcohol중독(中毒) 및 $CCl_4$중독(中毒) 백서(白鼠)의 간손상(肝損傷)에 미치는 영향(影響))

  • Woo, Hong-Jung;Lee, Jang-Hoon;Kim, Young-Chul
    • The Journal of Korean Medicine
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    • v.18 no.1
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    • pp.411-429
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    • 1997
  • Recent survey shows that chronic liver disease such as chronic hepatitis, liver cirrhosis and hepatoma is the third leading causes for death in Korea. In oriental medicine, viral hepatitis is related to Hwangdal(黃疸) and alcoholic liver disease is related to Joosang(酒傷). ARTEMISIAE HERBA and PUERARIAE RADIX have long been used in treating those symptoms. This study was done to evaluate the effect of AR1EMISIAE HERBA and PUERARIAE RADIX on viral and alcoholic hepatitis. ARTEMISIAE HERBA and PUERARIAE RADIX were decocted respectively with water and followed by vaccum evaporation. The solution was diluted to adequate concentration. Sprague-Dawley rats were used in this experiment. Each group was given PUERARIAE RADIX or ARTEMISIAE HERBA solution orally and CCl4, d-galactosamine or alcohol was given orally 30 minutes later. After 24 hours of starvation, blood samples were taken to check serum GOT, GPT, LDH and ALP activities, TC, TG, glucose and BUN levels. These results show that ARTEMISIAE HERBA has better effect on liver injury induced by d-Galactosamine than PUERARIAE RADIX and that both ARTEMISIAE HERBA and PUERARlAE RADIX have good effect on acute alcoholic liver disease while in the liver injury induced by $CCl_{4}$, PUERARIAE RADIX has better inhibitory effect on serum AST, ALT and ALP levels and ARTEMISIAE HERBA has better inhibitory effect on serum total cholesterol and triglyceride. And the result that high concentration group has better effect shows these effects are concentration-dependent. Further study on the mechanism of these herbs is still required.

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The Effect of Bee Venom Pharmacopuncture Therapy on the Condition of Different Concentration in Rheumatoid Arthritis Rat Model (흰쥐의 류마티스 관절염 모델에서 봉약침의 농도별 처리 조건에 따른 치료 효과)

  • You, Deok-Seon;Yeom, Seung-Ryong;Lee, Su-Kyung;Kwon, Young-Dal;Song, Yung-Sun
    • Journal of Korean Medicine Rehabilitation
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    • v.21 no.2
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    • pp.101-123
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    • 2011
  • Objectives : The aim was to study the effect of bee venom pharmacopuncture therapy with different concentration on rheumatoid arthritis rat model. Methods : We enforced a bee venom pharmacopuncture therapy with different concentration on rheumatoid arthritis rat model by the intradermal injection of chicken type II collagen emulsified. 14 days after the onset of the rheumatoid arthritis rat model, a fixed volume of bee venom was daily injected to ST-35 acupoint in the rat's knee joint for 2-3 weeks. The hind paw volume, arthritic index, arthritic flexion pain test, pain threshold, and serum analysis (CRP, $PGE_2$, ALT, AST) were analyzed, and the expression profiles of COX-2, c-fos, and substance-P at the dorsal horn region of the spinal cord and subchondral bone of the knee joint were also analyzed by using the immunohistochemistry. Results : After the treatment of rheumatoid arthritis rats with bee venom pharmacopuncture, the paw volume of edema of arthritic rats were almost restored to the level of normal group, and behavior tests were very effective. Also the evaluation on the blood serum analysis was remarkable. COX-2, c-fos, and substance-P positive cells in the immunohistological section of dorsal horn region of the spinal cord and subchondral bone of the knee joints were significantly decreased. also the bee venom pharmacopuncture was effective to alleviate their rheumatoid arthritic inflammation cytokine inhibition as regards to the behavior tests and joint histological appearance. Conclusions : Based on the results in this study, bee venom pharmacopuncture with concentrated treatment condition was very effective in low fixed quantity and progressive low increased quantity.

Enzyme hydrolysate of silk protein suppresses tert-butyl hydroperoxide-induced hepatotoxicity by enhancing antioxidant activity in rats

  • Suh, Hyung Joo;Kang, Bobin;Kim, Chae-Young;Choi, Hyeon-Son
    • Food Science and Preservation
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    • v.24 no.4
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    • pp.550-558
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    • 2017
  • The purpose of current study is to investigate the beneficial effect of enzyme (Alcalase) hydrolysates of silk protein in rat. Alcalase-treated silk protein hydrolysate (ATSH) itself did not show any cytotoxicity on the hepatic tissues and blood biochemistry, similar to the normal condition. ATSH played a protective role in tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity and liver damage. The values of AST (aspartate aminotransferase) and ALT (alanine aminotransferase), which are the indicators of the liver function, were effectively alleviated with the ATSH treatment in a dose dependent manner. The level of Lactate dehydrogenase (LDH) and Malondialdehyde (MDA), which were increased with t-BHP treatment, were significantly reduced by ATSH. High dose of ATSH (2 g/kg) reduced the t-BHP-induced LDH release by 48%. Antioxidant and antioxidant enzymes in liver cells were significantly increased by ATSH treatment in their level and activities. ATSH (2 g/kg) increased glutathione (GSH), an intracelluar antioxidant, by 2.5-fold compared with the t-BHP treated group. The activities of glutathione-s-transferase (GST), superoxide dismutase (SOD), and catalase were also elevated by 38%, 60%, and 45%, respectively, with ATSH (2 g/kg) treatment. The antioxidative effect of ATSH was recapitulated to the protection from t-BHP induced liver damages in hematoxylin and eosin (H&E) staining. Thus, ATSH might be used as a hepatoprotective agent.

Effects of Supplementing Jeju Native Chicken Meat Fed a Tangerine By-product on Lipid Metabolism, Protein Levels and Enzyme Activities in White Rats (감귤 부산물을 급여한 제주도 토종 닭고기가 흰쥐의 지질대사, 단백질 농도 및 효소 활성에 미치는 영향)

  • Moon, Yoon-Hee;Yang, Seung-Ju;Jung, In-Chul
    • Journal of the East Asian Society of Dietary Life
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    • v.19 no.3
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    • pp.363-368
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    • 2009
  • In this experiment, three different diets were produced to investigate the effects of Jeju native chicken meat, from chickens that were fed a tangerine by-product, on physiological activities in rats. The first diet did not contain any chicken (TS), the second diet contained 10% chicken that had not been fed the tangerine by-product (T0), and the third diet contained 10% that had been fed the by-products (T1). These diets were provided to 11-week-old male rats for four weeks. Weight gain, feed intake, feed efficiency, liver, kidney, and epididymis fat weights were not significantly different among the TS, T0, and T1 groups. Total lipid, triglycerides, and cholesterol levels in the liver were significantly lower in T0 and T1 than in TS (p<0.05). And total lipid, phospholipid, triglycerides, total cholesterol, HDL-cholesterol, DL+VLDL-cholesterol, HDL-cholesterol/total cholesterol, and atherogenic index levels in the blood serum were similar between T0 and T1, which did not present any significant differences. The feed containing the tangerine by-product did not cause any statistically significant differences in serum protein, glucose, or hemoglobin. Finally, T0 and T1 showed similar trends in terms of $\gamma$-GTP, ALT, AST, and ALP activities, which again did not present any statistically significant differences.

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Atypical Clinical Course of after Glyphosate Herbicide Intoxication (Glyphosate 음독의 임상양상)

  • Kim, Yong-Won;Kim, Hyun;Cha, Kyoung-Chul;Shin, Hyung-Jin;Cha, Yong-Sung;Lee, Kang-Hyun;Hwang, Sung-Oh
    • Journal of The Korean Society of Clinical Toxicology
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    • v.9 no.1
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    • pp.8-13
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    • 2011
  • Purpose: Although glyphosate-surfactant herbicide intoxication is relatively mild toxic in humans, we encountered an atypical clinical presentation. We performed this study to understand the atypical clinical course and factors associated with severe intoxication after glyphosate ingestion. Methods: We conducted a retrospective study of 61 patients (male 43, mean age $54{\pm}18.8$ years) who were presented with glyphosate ingestion between March 1997 and March 2011. The severe intoxication group was defined as patients with systolic blood pressure less than 90 mmHg, respiratory distress needing intubation, or altered mental state. Results: Of the 61 patients, 22 patients (36.1%) had a severe clinical course, 1 patient (1.6%) had died and 1 patient (1.6%) had moribund discharge. The most common symptoms were nausea with or without vomiting which occurred in 30 patients (49.2%). Twenty-seven patients had metabolic acidosis that was the second most common medical complication. Advanced age, pH, base excess, $HCO_3$, Sat, creatinine, X-ray abnormalities and ECG abnormalities were significant factors. Hemoglobin, platelet, $pO_2$, $pCO_2$, BUN, sodium, potassium and AST levels were not different comparing the laboratory characteristics between the severe and mild intoxication groups. Conclusion: The results of this study showed that severe intoxication occurred in 22 patients (36.1%) after glyphosate intoxication. Advanced age, pH, base excess, $HCO_3$, Sat, creatinine, X-ray abnormality and ECG abnormalities were significant predictive factors for severe intoxication in patients with glyphosate surfactant herbicide poisoning.

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