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Mechanisms and significance of liver steatosis in hepatitis C virus infection

World Journal of Gastroenterology 2006年第42期12卷 6756-6765页

作者： francesco Negro services de Gastroentérologie et d'Hépatolo- gie et de pathologie clinique H?pitaux Universitaires Genève 1205 Switzerland

The pathogenesis of liver damage associated with chronic hepatitis C virus （HCV） infection is thought to be largely immunomediated. However, some frequent histoo pathological features, such as steatosis, suggest a direct cytopathic effect of HCV. The direct responsibility of HCV in the pathogenesis of steatosis is shown by：（1） the association with HCV genotype 3 infection, suggesting that some viral sequences are involved in the intracellular aco cumulation of lipids; （2） the correlation between severity of steatosis and HCV replication levels; （3） association between response to treatment and disappearance of steatosis. Experimental studies have shown that the nuo cleocapsid protein of HCV （core protein） is capable and sufficient to induce lipid accumulation in hepatocytes. Moreover, the observation that chronic hepatitis C pao tients have reduced serum levels of ApoB suggests an interference with the very-low density lipoprotein （VLDL） assembly, although other mechanisms are possible. In patients with sustained virological response induced by antiviral therapy, such levels are normalized. Other obo servations suggest that the pathogenesis of steatosis in chronic hepatitis C is not solely due to HCV. The origin of the mild steatosis observed in most patients may be metabolic, since its severity correlates with body mass index and insulin resistance. Most studies have shown a correlation between presence and/or severity of steatosis and fibrosis stage, but it is unclear whether this effect is direct or mediated by the associated insulin resistance, increased susceptibility to apoptosis, or by inflammao tory cytokines. Finally, steatosis negatively influences the rate of response to antiviral treatment, as confirmed by large clinical trials. Management of steatosis in chronic hepatitis C requires knowledge of its pathogenesis and may involve both life-style changes and pharmacological interventions, although the latter remain largely experio mental.

关键词： Hepatitis C Fibrosis Insulin Resistance Insulin signaling

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Virtual brain twins: from basic neuroscience to clinical use

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National Science Review 2024年第5期11卷 72-86页

作者： Huifang E.Wang Paul Triebkorn Martin Breyton Borana Dollomaja Jean-Didier Lemarechal Spase Petkoski Pierpaolo Sorrentino Damien depannemaecker Meysam Hashemi Viktor K.Jirsa Aix Marseille Université Institut National de la Santéet de la Recherche Médicale Institut de Neurosciences des Systèmes(INS) UMR1106 service de Pharmacologie clinique et Pharmacosurveillance AP–HM

Virtual brain twins are personalized, generative and adaptive brain models based on data from an individual's brain for scientific and clinical use. After a description of the key elements of virtual brain twins,we present the standard model for personalized whole-brain network models. The personalization is accomplished using a subject's brain imaging data by three means:(1) assemble cortical and subcortical areas in the subject-specific brain space;(2) directly map connectivity into the brain models, which can be generalized to other parameters; and(3) estimate relevant parameters through model inversion, typically using probabilistic machine learning. We present the use of personalized whole-brain network models in healthy ageing and five clinical diseases: epilepsy, Alzheimer's disease, multiple sclerosis, Parkinson's disease and psychiatric disorders. Specifically, we introduce spatial masks for relevant parameters and demonstrate their use based on the physiological and pathophysiological hypotheses. Finally, we pinpoint the key challenges and future directions.

关键词： virtual brain twin personalized modeling inference neuroscience brain disorder

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Acute liver failure is frequent during heat stroke

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World Journal of Gastroenterology 2008年第1期14卷 158-159页

作者： JM Garcin JA Bronstein S Cremades P Courbin F Cointet clinique médicale hpital d'instruction des armées Bégin F 94163 Saint Mandé France service de pathologie digestive hpital d'instruction des armées Clermont Tonnerre F 29200 Brest France

Acute liver failure （ALF） is relatively frequent during heat stroke （HS）. This risk must be emphasized, because its inddence is higher than is usually thought. In a recent study by Weigand et al, two cases were reported in which liver failure was the leading symptom. We have confirmed their conclusion in a study of 25 cases of HS with ALF, compared with 25 other cases without ALE Moreover, we observed that hypophosphatemia on admission could predict occurrence of ALF during HS. As for clinical and other biological parameters, phosphatemia should be monitored for at least 3 d in all cases of HS, even when it is thought to be mild.

关键词： Heat stroke, Hypophosphatemia Liver failure

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VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues

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World Journal of Gastroenterology 2006年第5期12卷 830-831页

作者： Muriel Mathonnet Bernard descottes denis Valleix Francois Labrousse Yves denizot service de Chimrgie DigestiveEndocrinienne et GénéraleCHU DupuytrenLimogesFrance service de Chirurgie Viscérale et TransplantationCHU DupuytrenLimogesFrance service d'Anatomo-pathologie CHU DupuytrenLimogesFrance UMR CNRS 6101Faculté de MédecineLimogesFrance

We read with a great interest the recent work of deli and colleagues. in the World Journal of Gastroenterology reporting vascular endothelial growth factor （VEGF） expression in hepatocellular carcinoma （HCC） and cirrhotic liver tissues. This well-documented work shows that VEGF was significantly higher in surrounding cirrhotic liver tissues than in HCC. Authors assessed VEGF expression using immunohistochemistry. The immunohistochemical staining is an efficient tool to assess the percentage of cells stained positively for VEGF but is not really efficient to estimate their true VEGF content. Evaluation of the VEGF protein by an enzyme-linked immunosorbent assay 0ELISA） has been reported, by us and others, to be an efficient tool in order to assess tissue VEGF expression. We have, thus, tested whether the ELISA method might be an efficient tool in order to confirm data reporting higher amounts of VEGF in surrounding cirrhotic liver tissues than in HCC. deli and colleagues. also correctly pointed out that basic fibroblast growth factor （bFGF） has been reported to act cooperatively on VEGF expression. We have, thus, also assessed bFGF tissue levels in order to search for a putative link between VEGF and bFGF levels in cirrhotic tissues.

关键词： Vascular endothelial growth factor Hepatocellular carcinoma, Cirrhotic liver tissues

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Insights in living-donor liver transplantation associated with two-stage total hepatectomy:First case in neuroendocrine tumor metastases and functional assessment techniques

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Hepatobiliary & Pancreatic Diseases International 2022年第4期21卷 392-395页

作者： Laurent Coubeau Samuele Iesari Paulina Henry Philippe D’Abadie Aude Vanbuggenhout Raymond Reding aTransplantation Abdominale Cliniques Universitaires Saint-LucUniversite catholique de LouvainBrusselsBelgium Pole de Chirurgie Experimentale et Transplantation Institut de Recherche Experimentale et CliniqueUniversite catholique de LouvainBrusselsBelgium department of Biotechnological and Applied Clinical Sciences University of L’AquilaL’AquilaItaly service d’anatomo-pathologie Cliniques Universitaires Saint-LucUniversite catholique de LouvainBrusselsBelgium service de medecine nucleaire Cliniques Universitaires Saint-LucUniversite catholique de LouvainBrusselsBelgium

To the Editor:While organ shortage commonly dooms patients on waiting list,alternative options as living-donor liver transplantation(LDLT)are assiduously *** principles of liver surgery rule LDLT:there must be suffici... 详细信息

关键词： donor liver surgery

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Pazopanib-induced posterior reversible encephalopathy syndrome with possible syndrome of inappropriate secretion of antidiuretic hormone: an incidental or pathophysiological association?

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Neural Regeneration Research 2020年第6期15卷 1166-1168页

作者： Jonathan Wong So Bérenger Largeau Frédérique Beau-Salinas Stephan Ehrmann Christophe Magni Jérome Meunier CHR d’Orléans Service d’Oncologie MédicaleOrléansFrance CHRU de Tours Centre d’Investigation Clinique-CIC INSERM 1415ToursFrance CHRU de Tours Service de PharmacosurveillanceCentre Régional de Pharmacovigilance Centre-Val de LoireToursFrance Universitéde Tours INSERMCentre d’étude des pathologies respiratoires(CEPR)-UMR 1100CHRU de ToursService de Médecine Intensive RéanimationCIC INSERM 1415réseau CRICS-TRIGGERSEPToursFrance CHR d’Orléans Service de NeuroradiologieOrléansFrance

Introduction:Pazopanib is an oral protein kinase inhibitor(PKI)that targets vascular endothelial growth factor(VEGF)receptors,fibroblastic growth factor receptors,platelet-derived growth factor receptors,and stem cell factor that inhibits VEGF-induced cellular *** is approved for use in advanced renal cell carcinoma and subtypes of advanced soft-tissue sarcoma(deguchi et al.,2018).Major adverse drug reactions of pazopanib include hypertension,high-grade hyponatremia and posterior reversible encephalopathy syndrome(PRES)(Berardi et al.,2016;deguchi et al.,2018).In clinical trials,few investigations have been conducted to determine the aetiology of PKI-associated hyponatremia,the mechanism remains therefore *** rare cases of PKI-induced syndrome of inappropriate secretion of antidiuretic hormone(SIADH)(Largeau et al.,2019),and none with pazopanib,have been *** is a clinical and radiological entity where a bilateral white matter oedema,occurring predominantly in the posterior occipital and parietal lobes,is associated with several neurologic ***,a recent review suggests that SIADH could be a symptom of PRES(Largeau et al.,2019).To our knowledge,this is the first case published where pazopanib-induced PRES occurs contemporaneously with possible SIADH.

关键词： al. SIADH antidiuretic

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Improving the prognosis before and after liver transplantation:Is muscle a game changer?

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World Journal of Gastroenterology 2022年第40期28卷 5807-5817页

作者： Alexis Goffaux Alicia delorme Géraldine Dahlqvist Nicolas Lanthier Laboratory of Hepato-Gastroenterology Institut de Recherche Expérimentale et CliniqueUniversitécatholique de LouvainBrussels 1200Belgium service d’Hépato-Gastroentérologie Cliniques universitaires Saint-LucUniversitécatholique de LouvainBrussels 1200Belgium

Liver transplantation(LT)is currently the only curative treatment option for selected patients with end stage liver disease or hepatocellular *** waiting list-mortality,post-transplant morbidity and mortality and refining the selection of the patients remain our current central *** this field,different concepts dealing with nutrition and the muscle such as sarcopenia,malnutrition,frailty or myosteatosis have emerged as possible game *** more than a decade,many prospective studies have demonstrated that sarcopenia and frailty are major predictive factors of mortality in the waiting list but also after *** is also a well-known risk factor for morbidity and *** composition is a newer concept giving insight on muscle quality which has also been shown to be linked to poorer *** of these terms has a precise definition as well as pathophysiological *** bidirectional liver-muscle axis makes sense in this *** the best,easy to use in clinical practice tools to assess muscle quality,quantity,and function in this specific population and developing quality prospective studies to identify interventional strategies that could improve these parameters as well as evaluate the effect on mortality are among the important challenges of today.

关键词： Muscle Liver Transplantation Sarcopenia Myosteatosis Frailty

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Transient and etiology-related transcription regulation in cirrhosis prior to hepatocellular carcinoma occurrence

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World Journal of Gastroenterology 2009年第3期15卷 300-309页

作者： Frédérique Caillot Céline derambure Paulette Bioulac-Sage Arnaud Franois Michel Scotte Odile Goria Martine Hiron Maryvonne Daveau Jean-Philippe Salier Inserm Unité 905 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides Faculté de Médecine-Pharmacie76183 RouenFrance service d'Anatomie Pathologique Centre Hospitalier Universitaireand Inserm U88933000 BordeauxFrance Département pathologie Centre Hospitalier Universitaire76183 RouenFrance service de Chirurgie Générale et Digestive Centre Hospitalier Universitaire76183 RouenFrance service d'Hépato-gastro-entérologie Centre Hospitalier Universitaire76183 RouenFrance

AIM： To search for transcription dysregulation that could （1） differentiate hepatocellular carcinoma （HCC）-free from HCC-related cirrhosis （2） differentiate HCC-free cirrhosis related to HCV from that related to alcohol intake. METHODS： Using microarray analysis, we compared transcript levels in HCC-free cirrhosis （alcoholism： 7; hepatitis C： 7）, HCC-associated cirrhosis （alcoholism： 10; hepatitis C： 10） and eight control livers. The identified transcripts were validated by qRT-PCR in an independent cohort of 45 samples （20 HCC-free cirrhosis; 15 HCC-associated cirrhosis and 10 control livers）. We also confirmed our results by ***： In HCC-free livers, we identified 70transcripts which differentiated between alcoholicrelated-cirrhosis, HCV-related cirrhosis and control livers. They mainly corresponded to down-regulation. Dysregulation of Signal Transduction and Activator of Transcription-3 （STAT-3） was found along with related changes in STAT-3 targets which occurred in an etiology-dependent fashion in HCC-free cirrhosis. In contrast, in HCC, such transcription dysregulations were not observed. CONCLUSION： We report that transcriptional dysregulations exist in HCC-free cirrhosis, are transiently observed prior to detectable HCC onset and may be appear like markers from cirrhosis to HCC transition.

关键词： Liver Pathology Alcoholism Hepatitis Cvirus Gene expression Carcinogenesis

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Long-term stability of gentamicin sulfate-ethylenediaminetetraacetic acid disodium salt (EDTA-Na_2) solution for catheter locks

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Journal of Pharmaceutical Analysis 2018年第6期8卷 386-393页

作者： Anne-Sophie Fiolet Elise Jandot Pauline Doucey Coralie Crétet Célia Brunel Christine Pivot Jean-Marc Ghigo Christophe Beloin David Lebeaux Fabrice Pirot service Pharmaceutique Plateforme FRIPHARM Groupe Hospitalier Centre Edouard Herriot Hospices Civils de Lyon Unité de Génétique des Biofilms Département de Microbiologie Institut Pasteur service de Microbiologie Unité Mobile de Microbiologie Clinique Assistance Publique-H?pitaux de Paris H?pital Européen Georges Pompidou Université Paris descartes 12 rue de l'Ecole de Médecine Laboratoire de Recherche et Développement de Pharmacie Galénique Industrielle UMR 5305 Plateforme FRIPHARMF-69373 Faculté de Pharmacie Université Claude Bernard Lyon 1 8 avenue Rockefeller

A lock solution composed of gentamicin sulfate(5 mg/mL) and ethylenediaminetetraacetic acid disodium salt(EDTA-Na2, 30 mg/mL) could fully eradicate in vivo bacterial biofilms in totally implantable venous access ports(TIVAP). In this study, fabrication, conditioning and sterilization processes of antimicrobial lock solution(ALS) were detailed and completed by a stability study. Stability of ALS was conducted for12 months in vial(25 °C 7 2 °C, 60% 7 5% relative humidity(RH), and at 40 °C 7 2 °C, RH 75% 7 5%)and for 24 h and 72 h in TIVAP(40 °C 7 2 °C, RH 75% 7 5%). A stability indicating HPLC assay with UV detection for simultaneous quantification of gentamicin sulfate and EDTA-Na2 was developed. ALS was assayed by ion-pairing high performance liquid chromatography(HPLC) needing gentamicin derivatization, EDTA-Na2 metallocomplexation of samples and gradient mobile phase. HPLC methods to separate four gentamicin components and EDTA-Na2 were validated. Efficiency of sterility procedure and conditioning of ALS was confirmed by bacterial endotoxins and sterility tests. Physicochemical stability of ALS was determined by visual inspection, osmolality, pH, and sub-visible particle counting. Results confirmed that the stability of ALS in vials was maintained for 12 months and 24 h and 72 h in TIVAP.

关键词： Gentamicin-EDTA-Na2 loaded antimicrobial lock solution Pharmaceutical compounding Stability indicating HPLC assay method Totally implantable venous access ports

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Quantitative analysis using ELISA of vascular endothelial growth factor and basic fibroblast growth factor in human colorectal cancer,liver metastasis of colorectal cancer and hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第23期12卷 3782-3783页

作者： Muriel Mathonnet Bernard descottes denis Valleix Francois Labrousse Véronique Truffinet Yves denizot service de Chirurgie Digestive Endocrinienne et GénéraleCHU Dupuytren2 avenue Luther KingLimoges 87045France service de Chirurgie Viscérale et Transplantation CHU Dupuytren2 avenue Luther King87045 LimogesFrance service d'Anatomo-pathologie CHU Dupuytren2 avenue Luther King87045 LimogesFrance UMR CNRS 6101 Faculté de Médecine2 rue Docteur Marcland87025 LimogesFrance

Angiogenesis consists of the sprouting of capillaries from pre-existing vessels. It is well-known that tumor growth is angiogenesis-dependent. Vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （bFGF） stimulated vascular endothelial cell proliferation and are involved in the neoplastic angiogenesis of several types of tumors including those of the intestinal tract. Authors usually investigated VEGF and using immunohistochemistry bFGF protein expressions or Western blotting and VEGF and bFGF transcripts using reverse transcriptase Dolymerase chain reaction （RT-PCR）.

关键词： Vascular endothelial growth factor Basicfibroblast growth factor Colorectal cancer Hepatocellularcarcinomas

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