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Escitalopram-induced hepatitis:A case report

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World Journal of Clinical Cases 2022年第8期10卷 2468-2473页

作者： Guillaume Wabont Laurie Ferret Nicolas Houdre Antoine Lepied Johana Bene etienne Cousein Department of Pharmacy Valenciennes HospitalValenciennes 59300France Department of Emergency Medicine Valenciennes HospitalValenciennes 59300France Department of Psychiatry Valenciennes HospitalValenciennes 59300France Department of Pharmacology Lille University HospitalLille 59000France

BACKGROUND The antidepressant escitalopram is widely prescribed for the treatment of *** is generally well-tolerated,and cholestasis is not mentioned in its summary of product characteristics(Sm PC).We present a case of cholestatic and cytolysis liver injury due to escitalopram and a Vigi Base?*** SUMMARY A 68-year-old man was admitted to our emergency unit due to clinical jaundice associated with hepatitis,pruritus and dark *** tested the patient for the most common etiologies of jaundice,including hemolysis,viral hepatitis,cirrhosis,carcinoma,cholangitis,cholelithiasis and intrahepatic or extrahepatic *** etiological study was negative,and an adverse drug reaction was the sole possible *** patient was receiving treatment with *** days after its withdrawal,pruritus was *** days after withdrawal,clinical jaundice *** took a month and three weeks after withdrawal for the patient to have normalized liver function *** our knowledge,this is the first reported case of cholestasis where treatment with escitalopram was the only possible cause,with a highly probable *** addition,we determined whether escitalopram is associated with hepatotoxicity and cholestasis by performing a disproportionality *** cases of hepatobiliary disorders induced by escitalopram and reported in the World Health Organization pharmacovigilance database(Vigi Base?)were analyzed to characterize this *** found that patients treated with escitalopram had an increased risk of hepatitis[odds ratio(OR)=1.938(1.186-3.166)]and cholestasis[OR=1.866(1.279-2.724)][OR(95%confidence interval)].The median duration between the introduction of escitalopram and the occurrence of acute hepatitis and/or cholestasis was ten days+/-seven *** Although extremely rare,this case report,the review of the literature and the pharmacovigilance update confirm that escitalopram can cause drug-induced hepatotox

关键词： Escitalopram Hepatitis Cholestasis Pharmacovigilance Case report

Silibinin induces hepatic stellate cell cycle arrest via enhancing p53/p27 and inhibiting Akt downstream signaling protein expression

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Hepatobiliary & Pancreatic Diseases International 2017年第1期16卷 80-87页

作者： Devaraj Ezhilarasan Jonathan Evraerts Brice Sid Pedro Buc Calderon Sivanesan Karthikeyan etienne Sokal Mustapha Najimi institut de recherche expérimentale et clinique (irec) laboratory of pediatric hepatology and cell therapyuniversité catholique de louvain，1200，Brussels，Belgium louvain drug research institute toxicology and cancer biology research group pmnt unituniversité catholique de louvain，1200，Brussels，Belgium facultad de ciencias de la salud universidad arturo prat，Iquique，Chil department of pharmacology and environmental toxicology food and hepatotoxicology laboratory dr. alm post graduate institute of basic medical sciences university of madrastaramani campus，Chennai-600 l13，India

BACKGROUND： Proliferation of hepatic stellate cells （HSCs） plays a pivotal role in the progression of liver fibrosis conse- quent to chronic liver injury. Silibinin, a flavonoid compound, has been shown to possess anti-fibrogenic effects in animal models of liver fibrosis. This was attributed to an inhibition of cell proliferation of activated HSCs. The present study was to gain insight into the molecular pathways involved in silibinin anti-fibrogenic effect. METHODS： The study was conducted on LX-2 human stellate cells treated with three concentrations of silibinin （10, 50 and 100 μmol/L） for 24 and 96 hours. At the end of the treatment cell viability and proliferation were evaluated. Protein expression of p27, p21, p53, Akt and phosphorylated-Akt was evaluated by Western blotting analysis and Ki-67 protein expression was by immunocytochemistry. Sirtuin activity was evaluated by chemiluminescence based assay. RESULTS： Silibinin inhibits LX-2 cell proliferation in doseand time-dependent manner; we showed that silibinin upregulated the protein expressions of p27 and p53. Such regulation was correlated to an inhibition of both downstream Akt and phosphorylated-Akt protein signaling and Ki-67 protein expression. Sirtuin activity also was correlated to silibinin- inhibited proliferation of LX-2 cells. CONCLUSION： The anti-proliferative effect of silibinin on LX-2 human steUate cells is via the inhibition of the expres- sions of various cell cycle targets including p27, Akt and sir- tuin signaling.

关键词： silibinin hepatic stellate cells in vitro cell cycle arrest proliferation

大别山碰撞后火山岩的锆石U-Pb年龄和氧同位素组成

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高校地质学报 2003年第2期9卷 163-171页

作者：夏群科郑永飞 E.deloule 中国科技大学地球和空间科学学院合肥230026 法国国家科研中心岩石学和地球化学研究中心

利用阴极发光技术 (CL)观察了大别山碰撞后玄武岩和安山岩的锆石内部结构 ,并通过离子探针技术 (SIMS)测定了其U Pb年龄和氧同位素组成。玄武岩中锆石都是直接从玄武质岩浆中结晶的岩浆锆石 ,其年龄为 130± 2Ma(1σ) ;安山岩中有两种锆... 详细信息

利用阴极发光技术 (CL)观察了大别山碰撞后玄武岩和安山岩的锆石内部结构 ,并通过离子探针技术 (SIMS)测定了其U Pb年龄和氧同位素组成。玄武岩中锆石都是直接从玄武质岩浆中结晶的岩浆锆石 ,其年龄为 130± 2Ma(1σ) ;安山岩中有两种锆石 ,绝大多数是直接从安山质岩浆中结晶出来的岩浆锆石 ,年龄为 133± 3Ma(1σ) ,少数是残留的原岩锆石 ,其年龄有两组 :76 8～80 5Ma和 182 7～ 1873Ma。玄武岩和安山岩的岩浆锆石年龄表明 ,大别山碰撞后火山岩的主体应形成于 130Ma左右 ,属早白垩世。结合文献资料来看 ,大别山碰撞后火山岩和侵入岩无论是化学组成、微量元素配分、Sr Nd同位素比值还是年龄 ,都是基本一致的 ,说明火山岩和侵入岩的源区以及成因可能是相同的。玄武岩和安山岩的岩浆结晶年龄一致 ,暗示着它们之间的可能的成因联系。玄武岩锆石相对于正常地幔亏损18O(δ18O =(4 .1± 0 .6 )‰ ) ,说明其岩浆源区可能含有一定数量的俯冲板块断离后进入该区地幔的大别山榴辉岩原岩组分。安山岩中残留的原岩锆石既有扬子板块的年龄信息 ,又有华北板块的年龄信息。

关键词：大别山火山岩锆石U—Pb年龄氧同位素离子探针

女山单斜辉石巨晶锂同位素组成的离子探针分析

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矿物学报 2003年第4期23卷 359-363页

作者：杨晓志夏群科 E.deloule 中国科学技术大学地球与空间科学学院化学地球动力学研究实验室安徽合肥230026 法国国家科研中心岩石学和地球化学研究中心

应用离子探针技术测定了一组女山单斜辉石巨晶的锂同位素组成。结果表明,无论是不同样品之间还是同一样品内部,锂同位素组成都是均一的,δ7Li=(+8.0±2.7)‰,明显高于MORB值(+1.5‰～+5.1‰)。巨晶的锂同位素组成直接继承自地幔源区,高... 详细信息

应用离子探针技术测定了一组女山单斜辉石巨晶的锂同位素组成。结果表明,无论是不同样品之间还是同一样品内部,锂同位素组成都是均一的,δ7Li=(+8.0±2.7)‰,明显高于MORB值(+1.5‰～+5.1‰)。巨晶的锂同位素组成直接继承自地幔源区,高δ7Li的特征暗示源区受到过俯冲海洋板块析出流体的交代作用。结合Sr Nd同位素的资料来看,交代流体可能来自于蚀变洋壳而不是海洋沉积物。

关键词：单斜辉石巨晶锂同位素离子探针

Liver cell transplantation for Crigler-Najjar syndrome type Ⅰ: Update and perspectives

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World Journal of Gastroenterology 2008年第22期14卷 3464-3470页

作者： Philippe A Lysy Mustapha Najimi Xavier Stéphenne Annick Bourgois Franoise Smets etienne M Sokal Université Catholique de Louvain Cliniques Universitaires Saint Luc HPED Department PEDI Unit Laboratory of Pediatric Hepatology and Cell Therapy Brussels B-1200 Belgium

Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic control of various diseases. Crigler-Najjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma. The patient is at permanent risk for irreversible brain damage. The goal of liver cell transplantation is to reduce serum bilirubin levels within safe limits and to alleviate phototherapy requirements to improve quality of life. Preliminary data on Gunn rats, the rodent model of the disease, were encouraging and have led to successful clinical trials. Herein we report on two additional patients and describe the current limits of the technique in terms of durability of the response as compared to alternative therapeutic procedures. We discuss the future developments of the technique and new emerging perspectives.

关键词： Hepatocyte transplantation Cell therapy Inborn error of metabolism Crigler-Najjar Liver regeneration Animal models

Hepato-biliary profile of potential candidate liver progenitor cells from healthy rat liver

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World Journal of Gastroenterology 2012年第27期18卷 3511-3519页

作者： Cédric Maerckx Isabelle Scheers Tatiana Tondreau David Campard Omar Nyabi Mustapha Najimi etienne Sokal Laboratory of Pediatric Hepatology and Cell Therapy Université Catholique de Louvain1200 BrusselsBelgium

AIM： To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS： Rat fibroblastic-like liver derived cells （rFLDC） were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry, immunocyto- chemistry, reverse transcription polymerase chain reac- tion and functional assays. RESULTS： rFLDC exhibit fibroblastoid morphology, ex- press mesenchymal （CD73, CD90, vimentin, m-smooth muscle actin）, hepatocyte （UGTIA1, CK8） and biliary （CK19） markers. Moreover, these cells are able to store glycogen, and have glucose 6 phosphatase activity, but not UGTIA1 activity. Under the hepatogenic differentia- tion protocol, rFLDC display an up-regulation of hepatocyte markers expression （albumin, tryptophan 2,3-di- oxygenase, G6Pase） correlated to a down-regulation of the expression of the biliary marker CK19. CONCLUSION： Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC. However, we demonstrated the presence of an original rodent hepato-biliary cell type.

关键词： Hepato biliary profile Hepatogenic differentiation Liver Progenitor cell Rat

Does “Latent Tuberculosis Infection” (LTBI)” Really Exist? Genealogy of a Medical Nosology

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Journal of Tuberculosis Research 2021年第3期9卷 197-204页

作者： Patricia etienne University Hospital of Guadeloupe Pointe-à-Pitre France

Introduction: The diagnosis of latent tuberculosis infection (LTBI) is based on secular ways: chest radiography and tuberculin skin test (TST). In front of a recent enthusiasm for LTBI, this paper reports a historical perspective of this concept. Method: Bibliometric analysis and literature review from medical databases, using the terms “latent tuberculosis infection (“LTBI”), “primary tuberculosis”, “tuberculin skin test”, “tuberculosis”, and from reference books on tuberculosis. Results: In the PubMED/MEDLINE search for LTBI, a total of 7787 articles were found between 1901 and 2020, 95% from 2000 to 2020. In the first part of the 20th century, LTBI term was used for sub-clinical tuberculosis disease, the latency being also called “primary tuberculosis” or “abortive tuberculosis infection”. From 1960, randomized prospective therapeutic studies mentioned “tuberculosis chemoprophylaxis”

关键词： Tuberculin Skin Test Latent Tuberculosis Infection IGRA Tests Medical History

Nanovolcano microelectrode arrays: toward long- term on-demand registration of transmembrane action potentials by controlled electroporation

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Microsystems & Nanoengineering 2020年第1期6卷 578-589页

作者： Benoit X.E.Desbiolles etienne de Coulon Nicolas Maino Arnaud Bertsch Stephan Rohr Philippe Renaud Laboratory of Microsystems LMIS4 Ecole Polytechnique Federale de LausanneLausanneSwitzerland Department of Physiology Laboratory of Cellular Optics IIUniversity of BernBernSwitzerland

Volcano-shaped microelectrodes(nanovolcanoes)functionalized with nanopatterned self-assembled monolayers have recently been demonstrated to report cardiomyocyte action potentials after gaining spontaneous intracellular *** nanovolcanoes exhibit recording characteristics similar to those of state-of-the-art micro-nanoelectrode arrays that use electroporation as an insertion *** this study,we investigated whether the use of electroporation improves the performance of nanovolcano arrays in terms of action potential amplitudes,recording durations,and *** with neonatal rat cardiomyocyte monolayers grown on nanovolcano arrays demonstrated that electroporation pulses with characteristics derived from analytical models increased the efficiency of nanovolcano recordings,as they enabled multiple on-demand registration of intracellular action potentials with amplitudes as high as 62 mV and parallel recordings in up to~76%of the available *** performance of nanovolcanoes showed no dependence on the presence of functionalized nanopatterns,indicating that the tip geometry itself is instrumental for establishing a tight seal at the cell–electrode interface,which ultimately determines the quality of ***,the use of electroporation permitted the recording of attenuated cardiomyocyte action potentials during consecutive days at identical sites,indicating that nanovolcano recordings are nondestructive and permit long-term on-demand recordings from excitable cardiac *** from demonstrating that less complex manufacturing processes can be used for next-generation nanovolcano arrays,the finding that the devices are suitable for performing on-demand recordings of electrical activity from multiple sites of excitable cardiac tissues over extended periods of time opens the possibility of using the devices not only in basic research but also in the context of comprehensive drug testing.

关键词： arrays recording action

南大别黄镇低温榴辉岩多同位素体系年代学研究

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中国科学（D辑） 2003年第9期33卷 828-840页

作者：陈道公 E.deloule 程昊夏群科吴元保中国科学技术大学地球与空间科学系合肥230026 CRPG-CNRS Nancy France

首次对南大别黄镇低温榴辉岩和围岩花岗片麻岩进行了锆石U/Pb热电离质谱(TIMS)和二次离子质谱(SIMS)定年、云母和角闪石^(40)Ar-^(39)Ar定年和矿物内部Sm-Nd同位素体系研究。一个榴辉岩样品锆石U-Pb SIMS权平均年龄为231.6±9.7Ma,云母... 详细信息

首次对南大别黄镇低温榴辉岩和围岩花岗片麻岩进行了锆石U/Pb热电离质谱(TIMS)和二次离子质谱(SIMS)定年、云母和角闪石^(40)Ar-^(39)Ar定年和矿物内部Sm-Nd同位素体系研究。一个榴辉岩样品锆石U-Pb SIMS权平均年龄为231.6±9.7Ma,云母的^(40)Ar-^(39)Ar等时年龄为232.6±2.1Ma,最低坪年龄为221.7±2.4Ma;另一榴辉岩锆石U-Pb TIMS一致年龄为221.3±1.4～222.5±2.3Ma,围岩花岗片麻岩锆石SIMS下交点年龄为221±35Ma。退变质角闪岩中角闪石^(40)Ar-^(39)Ar等时年龄为205.9±1.0Ma.除云母可能含有过剩氩外,上述各年龄代表了低温榴辉岩峰期变质作用和退变质作用时间。南大别黄镇低温榴辉岩变质时代不同于北大别北部熊店低温榴辉岩,它和南大别高温榴辉岩同属统一的南大别高压-超高压地体,高温榴辉岩和低温榴辉岩的区别可能在于它们不同的俯冲深度或折返时不同的冷却速率。

关键词：大别山低温榴辉岩多同位素体系年代学高压-超高压变质作用退变质作用变质岩