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Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation

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World Journal of Gastroenterology 2020年第34期26卷 5101-5117页

作者： David Fernández-Ramos Fernando Lopitz-Otsoa laura Delacruz-Villar Jon Bilbao Martina Pagano laura mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato Precision Medicine and Metabolism Laboratory Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160BizkaiaSpain CIBERehd-Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas Madrid 28029Spain Department of Precision Medicine University of Campania"Luigi Vanvitelli"Naples 80138Italy Liver Disease Laboratory Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160Spain Proteomics Platform Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160Spain OWL Metabolomics Derio 48160Spain Instituto Biofisika(UPV/EHU CSIC)Leioa 48940SpainDepartamento de Bioquímica y Biología MolecularUniversidad del País VascoLeioa 48940Spain Pre-clinical and Chemistry Manufacturing and ControlsGalmed PharmaceuticalsTel Aviv 6578317Israel Metabolomics Platform Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160Spain Division of Digestive and Liver Diseases Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of *** a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic *** To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with *** Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 ***,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled *** the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 *** metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related *** Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in *** translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA ***,liver metabolomic analysis showed

关键词： Nonalcoholic fatty liver disease Steatohepatitis Methionine and choline deficient diet Tricarboxylic acid cycle Hemoglobin A1c Stearoyl-CoA desaturase 1

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Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study

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World Journal of Gastroenterology 2017年第39期23卷 7139-7149页

作者： Michele Maria Luchetti Devis Benfaremo Francesco Ciccia laura Bolognini Monia Ciferri Alessia Farinelli Matteo Rossini Piergiorgio mosca Giovanni Triolo Armando Gabrielli Dipartimento Scienze Cliniche e Molecolari Clinica MedicaUniversità Politecnica delle Marche Dipartimento Biomedico di Medicina Interna e Specialistica Sezione di Reumatologia Università degli Studi di Palermo Dipartimento Gastro-enterologico e dei Trapianti Polo Ospedaliero--Universitario 'Umberto I-G.M. Lancisi- G. Salesi'

AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis Disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel Disease Questionnaire(IBDQ), Crohn's Disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo *** Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earli

关键词： Clinimetric assessment Patient reported outcomes Inflammatory bowel diseases Enteropathic spondyloarthritis Tumor necrosis factor-inhibitors Multidisciplinary evaluation

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Biological Control of <i>Ceratitis capitata</i>(Diptera: Tephritidae) in Argentina: Releases of <i>Diachasmimorpha longicaudata</i>(Hymenoptera: Braconidae) in Fruit-Producing Semi-Arid Areas of San Juan

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Natural Science 2014年第9期6卷 664-675页

作者： Lorena Suarez Fernando Murua Natalia Lara Jorge Escobar Gustavo Taret José Luis Rubio Guido Van Nieuwenhove laura Bezdjian Pablo Schliserman Sergio Marcelo Ovruski Laboratorio de Investigaciones Ecoetológicas de moscas de la Fruta y sus Enemigos Naturales (LIEMEN) División Control Biológico de Plagas Planta Piloto de Procesos Industriales Microbiológicos y Biotecnología (PROIMI)—CCT Tucumán—CONICET Tucumán Argentina Programa de Control y Erradicación de mosca de los Frutos de San Juan (ProCEM)—Dirección de Sanidad Vegetal Animal y Alimentos San Juan Argentina Programa de Control y Erradicación de mosca de los Frutos de San Juan (ProCEM)—Dirección de Sanidad Vegetal Animal y Alimentos San Juan Argentina IMCN-Diversidad de Invertebrados Departamento de Biología San Juan Argentina

The Mediterranean fruit fly (Medfly), Ceratitis capitata (Wiedemann) is one of the major pests of fruit crops in Argentina and it is a phytosanitary barrier to the export of fresh fruits. In the Province of San Juan, located in the central-eastern region of Argentina known as Cuyo, control strategies against Medfly in fruit-producing irrigated-valleys have been implemented by the National Fruit Fly Control and Eradication Program (ProCEM) jointly with the provincial government and the producers. This program uses an area-wide integrated pest management approach that includes the use of environment-friendly strategies to suppress or eradicate Medfly, such as the use of the sterile insect technique and the application of new-generation bait sprays, and more recently the release of the Indo-Pacific parasitoid Diachasmimorpha longicaudata (Ashmead). This exotic larval-prepupal endoparasitoid is being mass-reared on larvae of Vienna 8 TSL C. capitata strain at the BioPlanta San Juan facility. In this respect, the objective of this study was to assess the effectiveness of laboratory-reared D. longicaudata females in order to find and successfully parasitize Medfly larvae in different host fruit species once released under semi-arid environmental conditions in ecologically isolated fruit-growing valleys of San Juan. Ground releases were used to disperse parasitoids in 6 fruit-producing valleys. In total, 40,000 adult parasitoids were released at places with various Medfly host plants bearing fruits and in which no insecticides were regularly applied, such as backyards and small orchards. 119 D. longicaudata adults were recovered from 6 Medfly-infested fruit species that were collected in 5 release sites (Pocito, Zonda, Santa Lucía, Caucete, and Rivadavia). The highest number of parasitoids was recovered from fig, followed by grape, rose, orange, tangerine, and persimmon. Data provided from this study open up the possibility of implementing a parasitoid mass-release program

关键词： Environment-Friendly Strategies Medfly Parasitoid Release Irrigated Valleys

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The Neurologist in the Emergency Room: Prospective Study of the Neurological Emergency Group in Lombardia

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Journal of Health Science 2019年第4期7卷 254-261页

作者： MariaLuisa Delodovici Marco Mauri Megi Meneri Marco Gallazzi Elena Ballabio Giuseppina Borutti Maria Vittoria Calloni Elisa Candeloro Bruno Censori Claudio De Piazza laura Fusi Franca Mazzucchelli Ignazio Santilli Elisabetta Forapani Chiara Scaccabarozzi Maria Sessa Lucia Tancredi Massimiliano Braga Dept. of Neurology and Stroke Unit Ospedale di Circolo e Fondazione MacchiUniversità dell’InsubriaASST-Settelaghile Luigi Borri 57 21100 VareseItaly Dept. of Neurology Ospedale di Desio (MB) Director G. Mazzini 1 20832 Desio (MB)Italy Dept. of Neurology ASST Lecco-Ospedale A. Manzonidell’Eremo 9/11 23900 LeccoItaly Dept. of Neurology Ospedale di Cremona ASST Cremona Directorle Concordia 1 26100 CremonaItaly Dept. of Neurology Ospedale Sant’Anna ComoRavona 20 22042 SFermo della BattagliaComoItaly Dept. of Neurology Ospedale di Vimercate (MB) Santi Cosma e Damiano 10 20871 Vimercate (MB)Italy Dept. of Neurology Ospedale S. Carlo BorromeoA. Mosca 12 20152 MilanoItaly Dept. of Neurology Director Ospedale Civile di VogheraVolturno 14 Voghera 27058 (PV)Italy Dept. of Neurology Ospedale di Legnano ASST Ovest MilanesePapa Giovanni Paolo II20025 Legnano (MI)Italy Dept. of Neurology Fondazione IRCCS C. Mondino Mondino 2Pavia 27100Italy Dept. of Neurology ASST Papa Giovanni XXIII Piazza OMS 1 24127 BergamoItaly Dept. of Neurology Ospedale Valduce ComoDante Alighieri 11 22100 ComoItaly Dept. of Neurology Ospedale di Saronno ASST Valle olonaPiazzale Borella 1 Saronno 21047 (VA)Italy Dept. of Neurology Ospedale S. Antonio Abate Gallarate. Pastori 4 21013 Gallarate VareseItaly

Purpose of the work was to quantify the workloads and the neurologist’s commitment in ER, to verify the management of urgencies and appropriateness of neurological counseling requests. Neurologic emergencies are frequent in elderly patients and are associated with high morbidity and mortality. Due to the aging population, neurologic pathologies in emergency room (ER) are widely expected to increase. The role of the neurologist in this context is controversial. Methods: in 14 operative units of neurology a prospective collection of neurological evaluations in ER was carried out using boards of detection of the most frequent neurological clinical pictures seen in the course of a week. Data were collected from 738 cases. Attention was focused on cerebrovascular diseases (CVD), impairment of consciousness, epilepsy, headache, dizziness, head trauma and disorders of the peripheral nervous system (PNS). Achievements: neurological consultations were on average 5% of total accesses to ER. The most common pathology seen was ischemic stroke. After counseling most patients were discharged home. The CVD required the greatest commitment to the specialist. The usefulness of the specialized neurological “filter” has been confirmed in a non-simple operative context, aimed at optimizing the appropriateness of the hospitalization and the economy of the diagnostic path.

关键词： Emergency room neurological diseases neurology workload

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