• Title/Summary/Keyword: Chronic liver injury

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Manipulation of Hepatitis B Viral DNA for Generating Transgenic Mice

  • Kim, Seung-Hee;Park, Sang-Ho;Kim, Tae-Gyun;Lee, Song-Deuk;Aree Moon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.178-178
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    • 1996
  • Hepatitis B virus (HBV) infection is one of the serious problems in Southeast Asia including Korea because it causes chronic hepatitis, which can easily be transformed In fatal conditions such as cirrhosis and hepatoma. Even though lots of informations on structural characteristics and gene expression mechanisms have been accumulated, the mechanism for HBV-induced hepatocellular injury which is believed to be the consequences of the immunological response is not well understood. In order tn perform immunopathological studies for prevention and treatment of HBV infection, we designed transgenic mice as a disease model which can mimic HBV infection, In this study, a promoter-HBV DNA fragment for the preparation of HBV transgenic mice has been constructed. To add a proper enzyme site on 5' end of HBV gene, total HBV (subtype adr) gene was inserted into BamHI site of pBluescript SK vector and reextracted by PstI-SacI treatment A liver-specific promoter, rat ${\alpha}$ 2u globulin gene promoter, was insrted to pBluescript SK vector and reextracted by BamHI-PstI treatment, Promoter-HBV DNA was constructed by ligation of two fragments using identical PstI sites. For large scale production of promoter-HBV DNA, it was inserted to BamHI-SacI site of pBluescript SK vector.

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Expression of Hepatitis B Virus Antigen by Recombinant Vaccinia Virus VV-$\textrm{HBV}_{L}$

  • Lee, Yun-Kyung;Yu, Jung-An;Ahn, Byung-Yoon;Aree Moon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.82-82
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    • 1997
  • The hepatitis B virus(HBV) is a small, enveloped virus with a circular, double-stranded DNA genome. HBV causes active and chronic hepatitis worldwide, including Korea, and is considered to be a major factor for liver cirrhosis and hepatocellular carcinoma. In contrast to the wealth of knowledge on the gene structure and expressional regulation, immunological and pathological mechanisms for HBV-induced hepatocellular injury are not well known. In the present study, vaccinia virus which has been demonstrated to be a useful eukaryotic expression vector was used to clone the gene for HBV surface antigen, L(S+preS2+preS1). The recombinant vaccinia virus vector, pMJ-L, which contains L surface antigen gene of adr-type HBV was constructed, and subseouently used for making recombinant vaccinia virus VV-$\textrm{HBV}_{L}$. Expression of the HBV antigen was examined by immunofluorescent antibody (IFA) test using mouse monoclonal anti-hepatitis B surface antigen. HBsAg was detected in the recombinant virus indicating that the VV-$\textrm{HBV}_{L}$ expressed S antigen successfully. The HBV-Vaccinia Virus recombinant obtained in this study is currently being used for studying the immunological aspects of HBV infection.

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Protective Effects of the Phenolic Compounds from the Leaves of Hedera rhombea on Hepatic Injury (송악의 페놀성 물질의 간 보호효과)

  • 김경숙;송지영;이인란
    • YAKHAK HOEJI
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    • v.43 no.4
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    • pp.516-525
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    • 1999
  • Hedera rhombea (HR) has been used for treatments of hemorrage, chronic catarrh, jaundice, lithisis and convulsion. This study was done to isolate active compounds that have protective effect on liver damage. BuOH and EtOAc fractions of HR recovered serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) and ${\gamma}-glutamyltranspeptidase$ (${\gamma}-GTP$) activities in CCl4 treated rats. We isolated 7 phenolic compounds from BuOH and EtOAc fractions, which were identified as 3-caffeoyl quinic acid, 3,4-di-O-caffeoyl quinic acid, 3,5-di-O-caffeoyl quinic acid, 4,5-di-O-caffeoyl quinic acid, caffeic acid, methyl 3,4-di-O-caffeoyl quinic acid and methyl 3,5-di-O-caffeoyl quinic acid by chemical and spectral analysis. These compounds reduced significantly serum GOT and GPT elevated by CCl4 treatment in rats, and 3-caffeoyl quinic acid, 3,5-di-O-caffeoyl quinic acid and caffeic acid also showed mild inhibitory activity against human immunodeficiency virus.

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Effects of Cadmium on Heat Shock Protein Induction and on Clinical Indices in Rats (카드뮴이 랫드의 Heat Shock Protein 발현에 미치는 영향과 독성학적 변화에 관한 연구)

  • 김판기
    • Journal of Environmental Health Sciences
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    • v.22 no.4
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    • pp.91-101
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    • 1996
  • Exposure indices are important tools which enable scientists to reliably predict and detect exposures to xenobiotics and resultant cell injury. Since the de novo synthesis of stress proteins can be detected early after exposure to some agents, analysis of toxicant-induced changes in gene expression, i.e. alterations in patterns of protein synthesis, may be useful to develop as biomarkers of exposure and toxicity. The acute and chronic effects of cadmium(Cd, $CdCl_2$ 20 mg/kg) on Wistar male rats were evaluated concerning cadmium contents, tissues enzyme activity, HSP expression. The results of the study were as follows: 1. Less cadmium was absorbed through the digestive tracts, but the ratio of contents in renal to hepatic cadmium was higher at 8 weeks after treatment. 2. ALT(alanine aminotransferase), AST(aspartate aminotransferase), glucose, BUN(blood urea nitrogen), creatinine, the key indices of the clinical changes in hepatic and renal function were significantly changed by the cadmium treatment after 1 week in liver, after 4 weeks in kidney. 3. Enhanced synthesis of 70 KDa relative molecular mass proteins were detected in 2 hours after cadmium exposure, with maximum activity occurring at 8~48 hours. Induction of $HSP_{70}$ was evident at proximal tubules and glomeruli in kidney. Testicular cells produced enough HSP to be detected normally. From the above results, it could be concluded that $HSP_{70}$ induction by the cadmium treatment was a rapid reaction to indicate the exposure of xenobiotics.

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Life-Threatening Necrotizing Fasciitis of the Posterior Neck

  • Choi, Ji-An;Kwak, Jung-Ha;Yoon, Chung-Min
    • Journal of Trauma and Injury
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    • v.33 no.4
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    • pp.260-263
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    • 2020
  • Necrotizing fasciitis is an infection of the subcutaneous tissue that results in destruction of the fascia and is disproportionately common in patients with chronic liver disease or diabetes. Necrotizing fasciitis of the head and neck is rare, but has a high fatality rate. A 50-year-old man with a past medical history of diabetes reported a chief complaint of a wound in the posterior neck due to trauma. The wound had grown and was accompanied by pus and redness, and the patient had a fever. When the patient was referred to department of plastic & reconstructive surgery, the sternocleidomastoid muscle, semispinalis capitis muscle, splenius capitis muscle, and trapezius muscles were exposed, and the size of the defect was about 25×20 cm. Dead tissue resection was performed before negative-pressure wound therapy, followed by a split-thickness skin graft (STSG). After a 2-week course of aseptic dressing post-STSG, the patient recovered completely. No postoperative complications were observed for 1 year. Necrotizing fasciitis is a life-threatening, rapidly spreading infection, requiring early diagnosis and active surgical treatment. In addition, broad-spectrum antibiotics are required due to the variety of types of causative bacteria. Broad necrotizing fasciitis of the posterior neck is rare, but can quickly progress into a life-threatening stage.

Protective Effect of Mixed Extract including Hovenia dulcis Thunberg against Chronic Ethanol Treatment-induced Cytotoxicity in a Brain and Liver Tissue (만성 알코올 섭취로부터 유도되는 뇌 및 간 조직 독성에 대한 지구자 혼합 추출물의 보호 효과)

  • Kim, Jong-Min;Park, Seon-Kyeong;Guoa, Tian-Jiao;Kang, Jin-Yong;Ha, Jeong-Su;Lee, Du-Sang;Kwon, O-Jun;Lee, Uk;Heo, Ho Jin
    • Journal of agriculture & life science
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    • v.50 no.2
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    • pp.125-138
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    • 2016
  • To assess the industrial possibility of mixed-extracts containing Hovenia dulcis Thunberg and 12 different botanical ingredients, a protective effect was confirmed in the chronic ethanol-induced the liver, brain, and blood injury in mouse. Blood glucose levels of the normal control group(NG) and ethanol administration group(EG) were respectively 119.43mg/dL and 305.25mg/dL, and the mixed-extracts administration group(100, 200mg/kg body weight + 25% ethanol 5g/kg body weight respectively; ME100 & ME200) were decreased to 272.76mg/dL and 234.60mg/dL. Blood ethanol contents were decreased in ME100 and ME200(3.85mg/dL, 3.08mg/dL) compared to EG(4.08mg/dL), and blood acetaldehyde contents were also decreased in ME(15.76mg/dL, 15.16mg/dL) compared to EG(18.72mg/dL). The contents of hepatotoxic indicators such as glutamine pyruvic transaminase(GPT) and glutamic oxaloacetic transaminase (GOT), nephrotoxic indicators such as blood urea nitrogen(BUN), and creatine(CRE), and total cholestero(TCHO), and triglyceride(TG) in mouse blood serum were significantly decreased in the ME compared to EG. The acetylcholinesterase(AChE) activity of ME(109.00% and 108.47%, respectively) in mouse brain tissues was decreased in ME compared to EG(116.10%). Finally, ME was remarkable in vivo antioxidant activities in the mouse liver and brain tissues by superoxide dismutase(SOD), oxidized glutathione(GSH)/total GSH ratio and the malondialdehyde (MDA) assay. Therefore, the mixed-extracts was considered to be effective a high value food with protective effect against chronic ethanol traetment-induced cytotoxicity in liver and brain tissues.

A Case of Successful Endoscopic and Conservative Treatment for Intentional Ingestion of Sharp Foreign Bodies in the Alimentary Tract (고의로 섭취한 커터칼날의 내시경 및 보존적 치료 증례 보고)

  • Park, Jong-Min;Kim, Seong Yup;Chung, Il Yong;Kim, Woo-Shik;Shin, Yong-Chul;Kim, Yeong Cheol;Park, Sei Hyeog
    • Journal of Trauma and Injury
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    • v.26 no.4
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    • pp.304-307
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    • 2013
  • Food bolus impaction is the most common cause of esophageal foreign body obstruction in adults. Other causes include intentional ingestion in psychiatric patients or prison inmates. We experienced successful treatment of a patient with intentional ingestion of multiple sharp foreign bodies(25 cutter and razor fragments). A 47-year-old male patient who was suffering from chronic alcoholism was admitted, via the emergency room, with dysphagia and neck pain. He was suffering from alcoholic liver cirrhosis and psychiatric problems, such as chronic alcoholism, anxiety disorder and insomnia. The patient had intended to leave the hospital after having swallowed the sharp objects. Plain radiographs and computed tomography (CT) scan showed multiple, scattered metal fragments in the esophagus, stomach, and small bowel. We performed emergent endoscopy and successfully removed one impacted blade in the upper esophagus using by a snare with an overtube. The rest of the fragments had already passed through the pylorus, so we could not find them with endoscopy. We checked the patient with simple abdominal radiographs and careful physical examinations every day. All remaining fragments were uneventfully excreted through stool during the patient's 6 day hospital stay. Finally, we were able to confirm the presence of the objects in the stool, and radiographs were negative. The patient was discharged without complications after 14 days hospital stay and then was followed by the Department of Psychiatry.

The Effect of Injinchunggantang-derivative on Proliferation of Hepatocyte (인진청간탕가미방(茵蔯淸肝湯加味方)이 간세포(肝細胞)의 증식능력(增殖能力)에 미치는 영향(影響))

  • Park, Yong-Jin;Kim, Young-Chul;Lee, Jang-Hoon;Woo, Hong-Jung
    • The Journal of Korean Medicine
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    • v.19 no.1
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    • pp.145-164
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    • 1998
  • The purpose of this study is to evaluate the effect of Injinchunggantang-derivative on proliferation of hepatocyte in rats. Cell viability is studied by MTI assay. The gene related to cell replication such as p53, waf1, bcl-2 and $bcl-_{X_L}$ is quantitized by quantitative RT-PCR and the proteins coded by these genes are studied by Western blotting. The results are as follows. 1. The hepatocytes cultured in medium with lnjinchunggantang-derivative showed better viability compared with control grroup in MTI assay, and the hepatocytes cultured in medium with the Injinchunggantang-derivative-and-ethanol-mixed group showed better viability than the hepatocytes cultrued in 10% ethanol culture medium(control group), noting that Injinchunggantang-derivative has protective effect on hepatocyte injury. There was no dose- and time-dependence. 2. In quantitative RT-PCR, i) Bel-2 gene increased significantly both in Injinchunggantang-derivative group and in Injinchunggantang-derivative-and-ethanol-mixed group, while it showed no significant increase or decrease in other group. ii) $Bcl-_{X_L}$ gene increased significantly in Injinchunggantang-derivative group as well as in Injinchunggantang-deri vative-and-ethanol -mixed group. iii) P53 gene showed no significant increase or decrease in hepatocytes cultured in medium with 10% ethanol and in hepatocytes cultured in medium with Injinchunggantang-derivative-and-ethanol-mixed group, suggesting that 10% ethanol induced cell toxicity, thus increased p53 gene expression. iv) Wafl gene showed no significant increase or decrease in hepatocytes cutured in medium with Injinchtrnggantang-derivative, while increased in hepatocytes cultured in medium with 10% ethanol and in hepatocytes cultured in medium with Injinchtrnggantang-derivative-andethanol-mixed group, suggesting that 10% ethanol induced cell toxicity increased wafl gene expression. 3. In the study on protein by western blotting, the band of bcl-2 and $bcl-_{X_L}$ were widened in Injinchtrnggantang-derivative group. Especially the amount of $bcl-_{X_L}$ increased significantly compared with other groups. But in the study on p53 and wafl, there was no significant difference among those groups. Above study shows that Injinchunggantang-derivative has good effect on cell viability and that the genes resistant to cell death such as bcl-2 and $bcl-_{X_L}$ are induced by Injinchunggantang-derivative to resist to cell death by toxic agent And this is reconfirmed in protein study using' western blotting: These results suggest that Injinchunggantang-derivative has inhibitory effect on cell death as well as protective effect on hepatocyte. Therefore this prescription is recommended in various liver diseases such as chronic liver disease and-induced hepatic injury.

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Fermented ginseng, GBCK25, ameliorates steatosis and inflammation in nonalcoholic steatohepatitis model

  • Choi, Naeun;Kim, Jong Won;Jeong, Hyeneui;Shin, Dong Gue;Seo, Jeong Hun;Kim, Jong Hoon;Lim, Chae Woong;Han, Kang Min;Kim, Bumseok
    • Journal of Ginseng Research
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    • v.43 no.2
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    • pp.196-208
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    • 2019
  • Background: Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Methods: Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Results: Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Conclusion: Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.

Early Surgical Stabilization of Ribs for Severe Multiple Rib Fractures (중증 다발성 늑골골절에 대한 조기 수술적 늑골고정술)

  • Hwang, Jung-Joo;Kim, Young-Jin;Ryu, Han-Young;Cho, Hyun-Min
    • Journal of Trauma and Injury
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    • v.24 no.1
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    • pp.12-17
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    • 2011
  • Purpose: A rib fracture secondary to blunt thoracic trauma continues to be an important injury with significant complications. Unfortunately, there are no definite treatment guidelines for severe multiple rib fractures. The purpose of this study was to evaluate the result of early operative stabilization and to find the risk factors of surgical fixation in patients with bilateral multiple rib fractures or flail segments. Methods: From December 2005 to December 2008, the medical records of all patients who underwent operative stabilization of ribs for severe multiple rib fractures were reviewed. We investigated patients' demographics, preoperative comorbidities, underlying lung disease, chest trauma, other associated injuries, number of surgical rib fixation, combined operations, perioperative ventilator support, and postoperative complications to find the factors affecting the mortality after surgical treatment. Results: The mean age of the 96 patients who underwent surgical stabilization for bilateral multiple rib fractures or flail segments was 56.7 years (range: 22 to 82 years), and the male-to-female ratio was 3.6:1. Among the 96 patients, 16 patients (16.7%) underwent reoperation under general or epidural anesthesia due to remaining fracture with severe displacement. The surgical mortality of severe multiple rib fractures was 8.3% (8/96), 7 of those 8 patients (87.5%) dying from acute respiratory distress syndrome or sepsis. And the other one patient expired from acute myocardial infarction. The risk factors affecting mortality were liver cirrhosis, chronic obstructive pulmonary disease, concomitant severe head or abdominal injuries, perioperative ventilator care, postoperative bleeding or pneumonia, and tracheostomy. However, age, number of fractured ribs, lung parenchymal injury, pulmonary contusion and combined operations were not significantly related to mortality. Conclusion: In the present study, surgical fixation of ribs could be carried out as a first-line therapeutic option for bilateral rib fractures or flail segments without significant complications if the risk factors associated with mortality were carefully considered. Furthermore, with a view of restoring pulmonary function, as well as chest wall configuration, early operative stabilization of the ribs is more helpful than conventional treatment for patients with severe multiple rib fractures.