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Lyon遗传性高血压大鼠:一种低肾素性高血压动物模型(英文)

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Acta Pharmacologica Sinica 2003年第1期24卷 3-8页

作者： Jean SASSARD 69373 Lyon Cedex 08 8 avenue Rockefeller CNRS UMR 5014 Département de Physiologie et pharmacologie clinique Facultéde Pharmacie France.

This paper reviews the data which demonstrate that Lyon genetically hypertensive (LH) rats exhibit a low renin form of hypertension. Since when compared to normotensive controls, LH rats exhibit a low renin release and are salt-sensitive. Despite this, the blockade of the renin-angiotensin system normalizes the blood pressure level and the regional blood flows in LH rats. Such a discrepancy between the compulsory presence of angiotensin Ⅱ for the hypertension to develop and the low level of renin release seen in LH rats led to two hypotheses: 1) the existence of an early, short lasting increase of renin release which would be sufficient for the occurrence of a stable hypertension; 2) an hypersensitivity to the effects of angiotensin Ⅱ. The study of the long-term effects of early short lasting blockades of the renin-angiotensin system allowed to exclude the first hypothesis. Concerning a hypersensitivity to the effects of angiotensin Ⅱ, it was found to exist in the preglomerular vessels of LH rats. Th

关键词：高血压肾素血管紧张素Ⅱ 肾素-血管紧张素系统遗传学大鼠

Antioxidant Activity and Hepatoprotective Effect of an Aqueous Extract of <i>Alchornea cordifolia</i>Leaves

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Pharmacology & Pharmacy 2017年第11期8卷 369-380页

作者： Kouakou Etienne Effo Sylvain Landry Kouakou Geneviève Irié-N’Guessan N’Doua Gisèle Kouakou-Siransy Département de pharmacologie Pharmacie clinique et Thérapeutique UFR Sciences Pharmaceutiques et Biologiques Université Félix Houphouet Boigny Abidjan C&#212 te d’Ivoire

Alchornea cordifolia is a medicinal plant, whose ethanolic and methanolic extracts have shown antioxidant activity which could confer hepatoprotective effect, knowing that liver cells are attacked by free radicals. The hepatoprotective effect of these extracts has been demonstrated in models of hepatotoxicity induced by paracetamol high doses in animals. However, anti-tubercular drugs at the usual dose present hepatotoxicity risk. Could Alchornea cordifolia help to limit hepatotoxicity induced by anti-tubercular drugs? This work aimed to evaluate the antioxidant activity and the hepatoprotective effect of an aqueous extract of A. cordifolia leaves (AEAC). The antioxidant activity of A. cordifolia leaves was studied in vitro by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals scavenging assay and by the iron reduction ability. A phytochemical screening was carried out to identify the chemical groups that could be responsible for this activity. The hepatoprotective effect was demonstrated in a model of hepatotoxicity induced by isoniazid and rifampicin in rats. Two hours after induction of hepatotoxicity, the animals were orally administered the AEAC at 200 mg/kg, 400 mg/kg, 800 mg/kg for 10 consecutive days. A blood sample was taken on the 11th day for the evaluation of transaminases, markers of hepatic cytolysis. A totally of 96 rats were used in this study. AEAC showed dose-dependent antioxidant activity. Phytochemical screening revealed the presence of flavonoids, tannins and alkaloids. Administrated alone, aqueous extract of A. cordifolia leaves didn’t modificate the transaminases, isoniazid and the isoniazid + rifampicin combination resulted in increasing transaminases (ALT and AST) by more than 48%. AEAC at 800 mg/kg reduced AST and ALT levels by more than 45%. AEAC at 200 mg/kg and 400 mg/kg decreased ALT more than 40%. Knowing that antioxidant activity protects liver, the AEAC may by its antioxidant activity, contribute to protect against the hepatotoxicity

关键词： Antioxidant Hepatoprotective Aqueous Extract Alchornea cordifolia

Hypofractionated Radiation Therapy for the Treatment of Breast Cancer: Experience of National Institute of Oncology, Rabat, Morocco

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Journal of Cancer Therapy 2016年第10期7卷 773-783页

作者： A. S. Koné A. Diakité S. Ahid I. M. Diarra K. Diabaté R. Abouqal Y. Cherrah N. Benjaafar Service de Radiothérapie Institut National d’Oncologie de Rabat Rabat Morocco Laboratoire de pharmacologie & Toxicologie Faculté de Médecine et de pharmacie de Rabat Rabat Morocco Laboratoire de Biostatistique de Recherche Clinique et d’Epidémiologie Faculté de Médecine et de pharmacie de Rabat Rabat Morocco

Hypofractionated radiation therapy has proven effective on locoregional control and tolerance in the adjuvant treatment of breast cancer. The aim of this study is to compare the results of hypofractionated radiation therapy versus conventional radiation therapy in terms of local control and tolerance. It was a retrospective study of patients observations collected from January 2007 to December 2008 in Department of Radiation Therapy in Institut National d’Oncologie de Rabat. The treatment results were evaluated by the rate of locoregional recurrence, distant recurrence and research of late toxicities. Radiotherapy was delivered using the same technique in both groups, by gamma photons of cobalt 60 with an energy of 1.25 MeV. They were 2 groups: the first group treated with standard dose rate and the second group treated by hypofractionated radiation therapy. The mean age of the patients was 42.8 ± 6.9 years old in the standard group and 43.22 ± 7.2 years old in the hypofractionation group. We noted a predominance of infiltrating ductal carcinoma. The majority of patients were pT2, pN0 and pN1. The majority of patients had radical surgery and chemotherapy with anthracyclines in both groups. We noted a statistically significant difference in the irradiation of chest wall between the standard (89.2%) and hypofractionated group (70.3%), with p = 0.043. The median duration of radiation therapy was statistically different in both groups: 39 days in the standard and 23 days in the hypofractionated group (p 0.001). The local recurrences were statistically identical to 12 and 24 months (p = 0.999). Concerning toxicities, the frequency of adverse event was similar in both groups. Hypofractionated radiation therapy with a total dose of 42 Gy at 2.8 Gy per fraction in 5 fractions weekly is comparable to standard radiotherapy in terms of local control and tolerance and is therefore a very good alternative to standard treatment.

关键词： Hypofractionated Radiation Therapy Breast Cancer Local Control Tolerance

RIP140 regulates POLK gene expression and the response to alkylating drugs in colon cancer cells

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Cancer Drug Resistance 2022年第2期5卷 401-414页

作者： Pascale Palassin Marion Lapierre Sandrine Bonnet Marie-Jeanne Pillaire Balázs Győrffy Catherine Teyssier Stéphan Jalaguier Jean-Sébastien Hoffmann Vincent Cavaillès Audrey Castet-Nicolas IRCM Institut de Recherche en Cancérologie de MontpellierINSERMU1194Institut Régional du Cancer de MontpellierUniversitéde MontpellierMontpellier 34298France Institut de pharmacologie et de Biologie Structurale IPBSUniversitéde ToulouseCNRSUPSToulouse 31077France. Department of Bioinformatics Semmelweis University and TTK Lendület Cancer Biomarker Research GroupBudapest H-1117Hungary Laboratoire de pathologie Laboratoire d’excellence Toulouse CancerInstitut Universitaire du Cancer-ToulouseOncopoleToulouse 31059France Département de Pharmacie clinique Centre Hospitalo-Universitaire MontpellierMontpellier 34295France. Unitéde Formation et de Recherche des Sciences Pharmaceutiques et Biologiques Montpellier 34090France.

Aim:The transcription factor RIP140(receptor interacting protein of 140 kDa)is involved in intestinal *** plays a role in the control of microsatellite instability(MSI),through the regulation of MSH2 and MSH6 gene *** aim of this study was to explore its effect on the expression of POLK,the gene encoding the specialized translesion synthesis(TLS)DNA polymeraseκknown to perform accurate DNA synthesis at ***:Different mouse models and engineered human colorectal cancer(CRC)cell lines were used to analyze by RT-qPCR,while Western blotting and luciferase assays were used to elucidate the role of RIP140 on POLK gene *** DNA microarray datasets were *** in vitro sensitivity of CRC cells to methyl methane sulfonate and cisplatin was ***:RIP140 positively regulates,at the transcriptional level,the expression of the POLK gene,and this effect involves,at least partly,the p53 tumor *** different cohorts of CRC biopsies(with or without MSI),a strong positive correlation was observed between RIP140 and POLK gene *** connection with its effect on POLK levels and the TLS function of this polymerase,the cellular response to methyl methane sulfonate was increased in cells lacking the Rip140 ***,the association of RIP140 expression with better overall survival of CRC patients was observed only when the corresponding tumors exhibited low levels of POLK,thus strengthening the functional link between the two genes in human ***:The regulation of POLK gene expression by RIP140 could thus contribute to the maintenance of microsatellite stability,and more generally to the control of genome integrity.

关键词： Colorectal cancer genome stability translesion DNA synthesis polymerase Pol Kappa RIP140

Respiratory Symptoms Associated with Workplaces Located along a Road with High-Traffic at Cotonou, Benin

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Open Journal of Respiratory Diseases 2020年第2期10卷 32-42页

作者： Parfait Houngbégnon Hervé Lawin Marius Kêdoté Affoussatou Amadou Eloic Atindegla Benjamin Fayomi Simplice Dossou-Gbété Victoire Agueh Institut Régional de Santé Publique University of Abomey-CalaviOuidahBenin EcoHealth Chair Faculty of Health SciencesUniversity of Abomey-CalaviCotonouBenin Institut de Recherche clinique du Bénin Abomey-CalaviBenin Unitéde Recherche en Microbiologie Appliquée et pharmacologie des substances naturelles University of Abomey-CalaviAbomey-CalaviBenin Laboratoire de Mathématiques et leurs Applications de Pau(LMAP)UMR CNRS Universitéde Pau et des pays de l’AdourPauFrance

Objective: Air pollution is becoming one of the public concerns requiring urgent feasible response per local context. Defining accurately the level of exposure of outdoor air pollution effect on health of venders working along main roads and roundabouts with high traffic is important. This study was conducted to assess respiratory health risks on venders associated with different geographical positions in Cotonou. Methods: A cross-sectional study was conducted along the main road with high traffic including three roundabouts in Cotonou. The 194 study participants from all shops, one respondent per shop, were given a unique GPS data associated to indicate the shop’s geographical position. The study employed validated questionnaire on respiratory symptoms. Results: Study participants had mean age of 36.26 (±11.65) years with sex ratio of (M/F) 1.8. Majority (72.7%) of study participates reported to have at least one respiratory symptom and 69% of them were working in non-ventilated rooms. The proportion of having at least one respiratory symptom was significantly different (p Conclusion: Working in roundabout is associated with more respiratory symptoms than working in shops along main road. Air pollution mitigation efforts should focus in such settings, taking into account the sub-population of workers in resource limited countries.

关键词： Air Pollution High Traffic Roundabouts Vendors Health Risk Symptom

Use of Antipsychotics: A Study from the French National Insurance Healthcare System Database

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Pharmacology & Pharmacy 2015年第8期6卷 411-419页

作者： Gaelle Desamericq Franck Schurhoff Isabelle Macquin-Mavier Anne-Catherine Bachoud-Levi Patrick Maison Departement d’Etudes Cognitives Ecole Normale SuperieureParisFrance Inserm U955Equipe 01CreteilFrance Facultede medecine UniversiteParis EstCreteilFrance Centre de Reference Maladie de Huntington AP-HPHopital H.Mondor—A.ChenevierCreteilFrance Inserm U955Equipe 15CreteilFrance Pole de Psychiatrie AP-HPHopital H.Mondor—A.ChenevierCreteilFrance pharmacologie clinique AP-HPHopital H.Mondor—A.ChenevierCreteilFrance Ansm Surveillance DivisionSaint DenisFrance

A marked increase in antipsychotic prescriptions has been observed in most countries since the introduction of second-generation antipsychotics. Misuse could partly explain this rise. We described the use of antipsychotic medication in France. This retrospective analysis was conducted on the sample “Echantillon généraliste de beneficiaries” from the French National Insurance Healthcare System. All reimbursements for antipsychotic medications in 2010 were identified. Antipsychotics use was described in terms of patient’s profiles and condition of use. In 2010, we identified 11,729 single patients with at least one reimbursement for antipsychotic medication (2.23% of French health insurance beneficiaries). The mean age in the population was 54 (sd 20) years. Forty-one percent had declared psychiatric disorder and 15% had a psychiatric follow-up for unknown diseases. Schizophrenia, others psychosis and personality disorders were the three main diagnoses of psychiatric disease. Patients without declared psychiatric disorders and without psychiatric follow-up accounted for 23% (aged between 15 and 65) and 20% (aged 65 years and over) of the population using antipsychotics. Forty-five percent of patients aged between 15 and 65 had more than 3 months of treatment refunded. Patients aged 65 years and over were 69% without dementia and 47% had more than three months of treatment of antipsychotics refunded during the year. These results suggested that antipsychotic treatments were used in France at long term in particular for patients without declared psychiatric disorder or psychiatric follow-up.

关键词： Antipsychotics Outpatients Pharmaco-Epidemiology Database France Use

Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients

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World Journal of Hepatology 2018年第11期10卷 856-866页

作者： Dominique Salmon Pascale Trimoulet Camille Gilbert Caroline Solas Eva Lafourcade Julie Chas Lionel Piroth Karine Lacombe Christine Katlama Gilles Peytavin Hugues Aumaitre Laurent Alric Franoois Boué Philippe Morlat Isabelle Poizot-Martin Eric Billaud Eric Rosenthal Alissa Naqvi Patrick Miailhes Firouzé Bani-Sadr Laure Esterle Patrizia Carrieri Franoois Dabis Philippe Sogni Linda Wittkop 无 Assistance Publique des Hopitaux de Paris Hopitaux Universitaires Paris CentreHopital Hotel DieuUnitédes Maladies infectieuses et tropicalesParis 75004France Université Paris Descartes Sorbonne Paris CitéParis 75006France Trimoulet CHU de BordeauxHopital PellegrinLaboratoire de VirologieBordeaux 33000France Trimoulet CNRS-UMR 5234Microbiologie fondamentale et PathogénicitéUniversitéde BordeauxBordeaux 3000France Philippe Morlat Laure EsterleFrancois DabisLinda WittkopUniv.BordeauxISPEDInsermBordeaux Population Health Research Centerteam MORPH3EUSUMR 1219CIC-EC 1401Bordeaux F-33000France APHM Hopital La TimoneLaboratoire de Pharmacocinétique et ToxicologieMarseille 13005France Centre Hospitalier Universitaire de Dijon Département d'InfectiologieDijon cedex 21079France INSERM-CIC 1342 Universitéde Bourgogne Dijon 21000France Assistance Publique des Hopitaux de Paris GHUEP site Saint-AntoineServices Maladies infectieuses et tropicalesParis 75011France UniversitéPierre et Marie Curie UMR S1136Institut Pierre Louis d' Epidémiologie et de SantéPubliqueParis 75646France UniversitéParis-Sorbonne Paris 75005France Assistance Publique des Hopitaux de Paris Hopital PitiéSalpêtrière Services Maladies infectieuses et tropicalesParis 75013France Assistance Publique des Hopitaux de Paris Hopital Bichat-Claude BernardLaboratoire de PharmacologieParis 75877France IAME UMR 1137Sorbonne Paris CitéINSERMUniversitéParis DiderotParis 75890France Centre Hospitalier de Perpignan Service Maladies infectieuses et tropicalesPerpignan 66000Franc Centre Hospitalier Universitaire de Toulouse Hopital PurpanService Médecine interne-Pole DigestifToulouse 31300France UMR 152 IRD UniversitéToulouseⅢ Paul SabatierToulouse 31330France Hopital Antoine-Béclère Assistance Publique des Hopitaux de ParisUniversitéParis SudService Médecine interne et immunologieClamart 92140France Centre Hospitalier Universitaire de Bordeaux Service de médecine interneHopital Saint-AndréBordeaux 33000France Uni

AIMTo describe factors associated with treatment failure and frequency of resistance-associated substitutions （RAS）.METHODSHuman immunodefciency virus （HIV）/hepatitis C virus （HCV） coinfected patients starting a first direct-acting antiviral （DAA） regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defned as：（1） non-response [HCV-RNA remained detectable during treatment, at end of treatment （EOT）]; and （2） relapse （HCV-RNA suppressed at EOT but detectable thereafter）. Sequencing analysis was performed to describe prevalence of drug class-specifc RAS. Factors associated with failure were determined using logistic regression *** 559 patients, 77% had suppressed plasmaHIV-RNA 〈 50 copies/mL at DAA treatment initiation41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in22 patients and were mainly relapses （17, 77%） thenundefined failures （3, 14%） and non-responses （29%）. Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5A or NS5B RAS were detected in10/14 patients with samples available for sequencinganalysis. After adjustment for age, sex, ribavirin useHCV genotype and treatment duration, low platelecount was the only factor signifcantly associated with ahigher risk of failure （OR： 6.5; 95%CI： 1.8-22.6）. CONCLUSIONOnly 3.9% HIV-HCV coinfected patients failed DAAregimens and RAS were found in 70% of those failingLow platelet count was independently associated withvirological failure.

关键词： Human immunodeficiency virus Hepatitis C virus Direct-acting antiviral Treatment virological failure Resistant associated mutations