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| 1 | 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 |
| 2 | Granuloeyte colonystimulating factor(G-CSF)andG-CSF receptor expression in humanischemie stroke显示文摘 | Hasselblatt M Jeibmann A Riesmeier B | 2007 | Acta Neuropathol2007，113，1： | 1 |
| 3 | Granuloeyte colony stimulating factor (G - CSF) and G - CSF receptor expression in hu- man ischemie stroke 显示文摘 | Hasselblatt hi Jeibmann A Riesmeier B | 2007 | Acta Neuropathol2007，113，1： | 1 |
| 4 | 筛状神经上皮肿瘤(CRINET):非横纹肌样脑室肿瘤伴INI1缺失预后较好显示文摘AT/RT是一个恶性胚胎性肿瘤,其特征是具有横纹肌样细胞、SMARCB1基因(Hsnfs5/INI1)改变且预后不良。本文报道2例幼儿颅内非横纹肌样神经上皮瘤,它们分别位于第三和第四脑室。瘤组织内主要是筛状结构。作者建议命名为筛状神经上皮肿瘤。病理组织学上,这2例肿瘤的结构十分相似,瘤细胞密集,为小细胞型未分化的瘤细胞, | 徐庆中 Hasselblatt M | 2010 | 诊断病理学杂志2010，17，3： | 1 |
| 5 | Erythropoietin therapy for acute stroke is both safe and beneficial显示文摘 | Ehrenreich H Hasselblatt M Dembowski C | 2002 | Mol Med2002，8，8： | 1 |
| 6 | Nonsence mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression显示文摘 | Hasselblatt M Gesk S Oyen F | | 0，，06： | 1 |
| 7 | Erythropoietin therapy for acute stroke is both safe and beneficial 显示文摘 | Ehrenreieh H Hasselblatt M Dembowski C | 2002 | Mol Med2002，8，： | 1 |
| 8 | The brain erythropoietin system and its potential for therapeutic exploitation in brain disease显示文摘 | Hasselblatt M Ehrenreich H Siren AL | 2006 | J Neuro surg Anesthesiol2006，18，2： | 1 |
| 9 | Angiomatous meningioma: a clinicopathologic study of 38 cases显示文摘 | Hasselblatt M Nolte KW Paulus W | 2004 | Am I Surg Pathol2004，28，： | 1 |
| 10 | Erythropoietin therapy for acute stroke is both safe and beneficial显示文摘 | Ehrenreich H Hasselblatt M Dembowski C | 2002 | Mol Med2002，8，8： | 1 |
| 11 | Erythropoietin therapy for acute stroke is both safe and beneficial显示文摘 | Hannelore Ehrenreich Martin Hasselblatt Christoph Dembowski | 2002 | Molecular Medicine2002，，8： | 1 |
| 12 | Erythropoietin therapy for acute stroke is both safe and beneficial 显示文摘 | Ehrenreich H Hasselblatt M Dembowski C | 2002 | Mol Med2002，8，8： | 1 |
| 13 | Erythropoietin therapy for acute stroke is both safe and beneficial显示文摘 | Ehrenreich H Hasselblatt M Dembowski C | 2002 | Molec Med2002，8，8： | 1 |
| 14 | Prognostic implications of atypical histologic features in choroid plexus papilloma 显示文摘 | Jeibmann A Hasselblatt M Gerss J | 2006 | J Neuropathol Exp Neurol2006，65，11： | 1 |
| 15 | Angiomatous menin- gioma: a clinicopathologic study of 38 cases 显示文摘 | Hasselblatt M Nolt KW Paulus W | 2004 | Am J Surg Pathol2004，28，3： | 1 |
| 16 | Erythropoietin therapy for acute stroke is both safe and beneficial 显示文摘 | Ehrenreich H Hasselblatt M Dembowski C | 2002 | Mol Med2002，8，： | 1 |
| 17 | The brain erythropoietin system and its potential for therapeutic exploitation in brain dis- ease显示文摘 | Hasselblatt M Ehrenreich H Siren AL | 2006 | J Neurosurg Anesthesiol2006，18，2： | 1 |
| 18 | Casein kinaseⅠepsilon interacts with mitochondrial proteins for the growth and survival of human ovarian cancer cells显示文摘 | Rodriguez N Yang JZ Hasselblatt K | 2012 | EMBO Mol Med2012，4，9： | 1 |
| 19 | Erythropoietin therapy for acute stroke is both safe and beneficial显示文摘 | Ehrenreich H Hasselblatt M Dembowski M | 2002 | Mol Med2002，8，8： | 1 |
| 20 | Ependymal tumors 显示文摘 | Hasselblatt M | 2009 | Recent Results Cancer Res2009，171，： | 1 |
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