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| 1 | Comprehensive lifestyle intervention vs soy protein-based meal regimen in non-alcoholic steatohepatitis显示文摘BACKGROUND Non-alcoholic steatohepatitis(NASH) has become one of the leading causes of liver disease in the western world. In obese patients weight reduction is recommended. Up to now there are no specific guidelines for weight loss in order to reduce hepatic fat content.AIM To investigate the effects of a 24-wk guided lifestyle intervention program compared to a meal replacement regimen based on soy protein.METHODS Twenty-six subjects with NASH participated in a randomized single-center study. They were randomly assigned to either meal replacement group(MR-G)with soy-yogurt-honey preparation or to guided lifestyle change group(LC-G)with endurance activity and nutrition counselling. Serum alanine transaminase(ALT), aspartate transaminase(AST), lipid parameters, and adipokines were measured. Liver fat content and lipid composition were determined by magnetic resonance imaging and magnetic resonance spectroscopy. Body fat mass and lean body mass were assessed using Bod Pod? device. Pre-and post-intervention monitoring of parameters was performed. Statistical analyses were conducted with SPSS software, results were expressed as median(interquartile range).RESULTS Twenty-two subjects(MR-G, n = 11 and LC-G, n = 11) completed the study(9 women, 13 men; age 52.1(15.0) years, body mass index(BMI) 32.3(3.3) kg/m^2).In both groups a significant weight loss was achieved(MR-G:-6.4(3.6) kg, P <0.01; LC-G:-9.1(10.4) kg, P < 0.01). BMI dropped in both groups(MR-G:-2.3(1.5)kg/m^2, P = 0.003; LC-G:-3.0(3.4) kg/m^2, P = 0.006). Internal fat and hepatic lipid content were markedly reduced in both groups in comparable amount. There was a strong correlation between reduction in liver fat and decrease in ALT.Likewise, both groups showed an improvement in glycemic control and lipid profile. Changes in adipokines, particularly in adiponectin and leptin were closely related to intrahepatic lipid changes.CONCLUSION Comprehensive lifestyle intervention and meal replacement regimen have comparable effects on body and liver fat, as well as decrease in markers of hepatic inflammation among NASH patients. | Peter Deibert Adhara Lazaro Denise Schaffner Aloys Berg Daniel Koenig Wolfgang Kreisel Manfred W Baumstark Daniel Steinmann Martin Buechert Thomas Lange | 2019 | World Journal of Gastroenterology2019，25，9： | 3 |
| 2 | Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension显示文摘AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver cirrhosis.METHODS In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure transducers.RESULTS Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpression and abrogated zonation of PDE-5 likely contribute to the pathogenesis of cirrhotic portal hypertension. PDE-5 inhibition may therefore be a reasonable therapeutic approach for portal hypertension. | Denise Schaffner Adhara Lazaro Peter Deibert Peter Hasselblatt Patrick Stoll Lisa Fauth Manfred W Baumstark Irmgard Merfort Annette Schmitt-Graeff Wolfgang Kreisel | 2018 | World Journal of Gastroenterology2018，24，38： | 2 |
| 3 | Oligosaccharide reprocessing and recycling of a cell surface glycoprotein in cultured rat hepatocytes 显示文摘 | Kreisel W Hildebrand H Mossner W | 1993 | Biol Chem Hoppe-Seyler1993，374，： | 1 |
| 4 | A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients显示文摘 | Schurmann D Kreisel W | 2001 | Clin Infect Dis2001，33，： | 1 |
| 5 | Complete remission of Crohn's disease after high - dose eyclophosphamide and autologous stem cell transplantation显示文摘 | Kreisel W Potthoff K Bertz H | 2003 | Bone Marrow Transplan12003，32，： | 1 |
| 6 | Innate immune cells in transplantation 显示文摘 | Spahn JH Li W Kreisel D | 2014 | Current Opinion Organ Transplantation2014，19，1： | 1 |
| 7 | A randomized,doubleblind,double-dummy,muhicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients显示文摘 | Ally R Schurmann D Kreisel W | | 0，，09： | 1 |
| 8 | Budes- onide induces remission more effectively than prednisone in a controlled thai of patients with autoimmune hepatitis 显示文摘 | MANNS MP WOYNAROWSKI M KREISEL W | 2010 | Gas- troenterology2010，139，： | 1 |
| 9 | Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis显示文摘 | Manns MP Woynarowski M Kreisel W | 2010 | Gastroenterology2010，139，4： | 1 |
| 10 | Innate immune cells in transplantation 显示文摘 | Spahn JH Li W Kreisel D | 2014 | Curt Opin Organ Transplant2014，19，1： | 1 |
| 11 | Budes- onide induces remission more effectively than pred- nisone in a controlled trial of patients with autoimmune hepatitis显示文摘 | Manns MP Woynarowski M Kreisel W | 2010 | Gastroenterology2010，139，4： | 1 |
| 12 | Differentiation of perianal fistulas with digital subtraction magnetic resonance fistulography显示文摘 | Schaefer O Lohrmann C Kreisel W | 2005 | Inflamm Bowel Dis2005，11，4： | 1 |
| 13 | In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation显示文摘 | Kreisel D Nava RG Li W | | 0，，： | 1 |
| 14 | In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation 显示文摘 | Kreisel D Nava RG Li W | 2010 | Proceedings National Academy of Sciences2010，107，18： | 1 |
| 15 | Differentiation of perianal fistulas with digital subtraction magnetic resonance fistulography显示文摘 | Schaefer O Lohrmann C Kreisel W | 2005 | Inflamm Rowel Dis2005，11，4： | 1 |
| 16 | Muhiparameter flow cy- tometric approach fi)r simultaneous evaluation of T lymphccyte-endo- lhelial cell interactions显示文摘 | Krupnick A S Kreisel D Szeto W Y | 2001 | Cytometry2001，46，5： | 1 |
| 17 | Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis显示文摘 | Mamas MP Woynarowski M Kreisel W | 2010 | Gastroenterology2010，139，4： | 1 |
| 18 | In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation 显示文摘 | Kreisel D Nava RG Li W | 2010 | Proc Natl Acad Sci2010，107，18： | 1 |
| 19 | Complete remission of Crohn's disease after high-dose cyclophosphamide and autologous stem cell transplantation 显示文摘 | Kreisel W Potthoff K Bertz H | 2003 | Bone Marrow Transplant2003，32，3： | 1 |
| 20 | Multiparameter flow cytometric approach for simultaneous evaluation of T lympho-cyte-endothelial cell interactions显示文摘 | Krupnick A S Kreisel D Szeto W Y | 2001 | Cytometry2001，46，5： | 1 |
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