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Ursodeoxycholic acid treatment improves hepatocyte ultrastructure in rat liver fibrosis

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World Journal of Gastroenterology 2008年第7期14卷 1108-1111页

作者： nuket mas Ilker Tasci Bilgin Comert Ramazan Ocal Mehmet Refik mas epartment of Anatomy Kocatepe UniversitySchool of MedicineAfyonTurkey Department of Internal Medicine Gulhane School of MedicineAnkaraTurkey

AIM: To examine the ultrastructural changes after ursodeoxycholic acid (UDCA) treatment in hepatocytes from experimentally induced fibrotic ***: Liver fibrosis was induced in male Sprague-Dawley rats with CCl4 for 12 wk, and the rats were divided into two groups. Group I was treated with saline and group Ⅱ with UDCA (25 mg/kg per day) for 4 wk. All the rats were killed at wk 16. Mitochondria, nuclei, rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER) of hepatocytes were evaluated according to a scoring ***: Mitochondria, nuclei, RER and SER injury scores in group Ⅱ were significantly lower than those in groupⅠ(P < 0.001). CONCLUSION: UDCA alleviates hepatocyte organelle injury in CCl4-induced liver fibrosis.

关键词： Rat liver fibrosis Rat liver cirrhosis Ursodeoxycholic acid Electron microscopy Hepatocyte ultrastructure

Effects of long term hydrophilic bile acid therapy on in vitro contraction of gallbladder muscle strips in patients with cholesterol gallstones

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World Journal of Gastroenterology 2007年第32期13卷 4336-4339页

作者： Mehmet Refik mas Bilgin Comert nuket mas Levent Yamanel Haluk Ozotuk Ilker Tasci Riadh P Jazrawi Department of Internal Medicine Glhane School of MedicineAnkara 06018Turkey Department of Anatomy Baskent UniversityAnkaraTurkey Charterhouse Clinical Research Unit Ravenscourt Park HospitalRavenscourt ParkLondon W6 0TNUnited Kingdom

AIM:To evaluate ursodeoxycholic acid (UDCA) therapy on the in vitro contraction of gallbladder smooth muscle strips from cholesterol gallstone patients. METHODS:The contraction forces of gallbladder smooth muscle strips from 28 patients with cholesterol gallstones treated with UDCA were compared with contraction forces from 14 untreated patients. The strips were stimulated with increasing concentrations of cholecystokinin-8 (CCK-8). RESULTS:Although the contraction forces that developed in response to CCK-8 were higher in strips from specimens of UDCA treated patients compared to untreated patients,longer treatment periods (6-wk) caused more contraction responses than the short treatment period of 3-wk (F = 19.297,1.85 ± 0.22 g vs 1.70 ± 0.10 g,P < 0.01). Contraction forces developed with maximal stimulation with KCl in the 6-wk treatment group were also higher than contraction forces in the untreated group (F = 4.274,3.77 ± 0.45 g vs 3.30 ± 0.30 g,P < 0.05). CONCLUSION:Six-week UDCA treatment caused an increase in contractions of muscle strips from patients with cholesterol gallstones when compared to shorter treatment administration or controls. We suggest that extending UDCA treatment periods may cause more effective contractions in the gallbladder,and thereby increase the rate of response to treatment.

关键词： Ursodeoxycholic acid Hydrophilic bile acid Gallbladder Cholesterol gallstone

Combination of allopurinol and hyperbaric oxygen therapy:A new treatment in experimental acute necrotizing pancreatitis?

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World Journal of Gastroenterology 2007年第46期13卷 6203-6207页

作者： Bilgin Comert Ahmet Turan Isik Sezai Aydin Ergun Bozoglu Bulent Unal Salih Deveci nuket mas Esref Cinar Mehmet Refik mas Division of Intensive Care Departments of Internal MedicineGulhane School of MedicineAnkara 06018Turkey Division of Geriatric Medicine Department of Internal MedicineGulhane School of MedicineAnkara 06018Turkey Department of Surgery Guven HospitalA.AyranciAnkara 06018Turkey Department of Surgery Numune Training HospitalSihhiyeAnkara 06018Turkey Department of Pathology Gulhane School of MedicineAnkara 06018Turkey Department of Anatomy Medical FacultyBaskent UniversityAnkara 06018Turkey Department of Infection Disease Gulhane School of MedicineAnkara 06018Turkey Department of Internal Medicine Gulhane School of MedicineAnkara 06018Turkey

AIM： To investigate the individual and combined effects of allopurinol and hyperbaric oxygen （HBO） therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation （BT） in the experimental rat acute pancreatitis （AP）. METHODS： Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls （sham, Group I ）. AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group H received saline, Group m allopurinol, Group IV allopurinol plus HBO and Group v HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS： Serum amylase levels were lower in Groups Ⅲ, Ⅳ and v compared to Group H （974 ± 110, 384 ± 40, 851 ＋ 56, and 1664 Ⅳ 234 U/L, respectively, P 〈 0.05, for all）. Combining the two treatment optionsrevealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations （13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P 〈 0.01）. Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups m, iV and v compared to Group H （54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P 〈 0.05 for all）. CONCLUSION： The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.

关键词： Experimental pancreatitis AIIopurinol Hyperbaric oxygen

Pegylated interferon-alpha plus taurine in treatment of rat liver fibrosis

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World Journal of Gastroenterology 2007年第23期13卷 3237-3244页

作者： Ilker Tasci Mehmet Refik mas Sevil Atalay Vural Salih Deveci Bilgin Comert Gunay Alcigir nuket mas Cemal Akay Mithat Bozdayi Cihan Yurdaydin Hakan Bozkaya Ozden Uzunalimoglu Ahmet Turan Isik Harun M Said Department of Internal Medicine Gulhane School of Medicine Ankara 06018 Turkey Department of Pathology Veterinarian Faculty Ankara University Ankara Turkey Department of Pathology Gulhane School of Medicine Ankara 06018 Turkey Department of Anatomy Baskent University Ankara Turkey Institute for Hepatology Ankara University Ankara Turkey Department of Radiation Oncology Medical Faculty University of Würzburg Wiürzburg Germany 不详

AIM: To investigate the antif ibrotic effects of peginterferon- alpha 2b and taurine on oxidative stress markers and hepatocellular apoptosis. METHODS: Sixty rats with CCl4-induced liver fibrosis were divided into 4 groups (n = 15). Group 1 was left for spontaneous recovery (SR). Groups 2-4 received peginterferon-alpha 2b, taurine, and their combination, respectively, for four weeks. Histological f ibrosis scores, histomorphometric analysis, tissue hydroxyproline, tissue MDA, GPx and SOD activities were determined. Activated stellate cells and hepatocellular apoptosis were also evaluated. RESULTS: The degree of f ibrosis decreased in all treatment groups compared to spontaneous recovery group. Taurine alone and in combination with peginterferon-alpha 2b reduced oxidative stress markers, but peginterferon-alpha 2b alone did not. Apoptotic hepatocytes and activated stellate cells were higher in groups 2-4 than in group 1. Combined taurine and peginterferon-alpha 2b further reduced fibrosis and increased activated stellate cell apoptosis, but could not improve oxidative stress more than taurine ***: Peginterferon-alpha 2b exerts anti- f ibrotic effects on rat liver fibrosis. It seems ineffective against oxidative stress in vivo. Peginterferon-alpha 2b in combination with taurine seems to be an antif ibrotic strategy.

关键词： Liver fibrosis Liver cirrhosis Pegylated interferons Taurine Oxidative stress Hepatic stelate cells Apoptosis Malondialdehyde Glutathione peroxidase Superoxide dismutase