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Journal of Renewable materials 2019年第1期7卷 73-87页

作者： Ingrid Souza Vieira da Silva Natália Soares Prado Patrícia Gontijo de melo Danilo Campion Arantes m.ra zeni andrade Harumi Otaguro Daniel Pasquini Instituto de Química Universidade Federal de UberlândiaCampus Santa MônicaAv.João Naves deÁvila2121Uberlândia-MG38400-902Brazil Instituto Federal do Triângulo mineiro Campus Uberaba Rua João Batista Ribeiro4000Uberaba-MG38064-790Brazil Departamento de Ciências Naturais(DCNAT) Universidade Federal de São João Del-ReiPraça D.Helvécio74São João Del-Rei-MG36301-160Brazil Universidade de Caxias do Sul Rua Francisco Getúlio Vargas1130Caxias do Sul-RS95070-970Brazil

In this work,nine different types of edible coating based on pectin,cellulose nanocrystals,glycerol,and essential oil of lemongrass were prepared and used to coat strawberries with a film formed directly on the surface of the coated *** effects of the different edible coatings on refrigerated fruits in terms of weight loss,titratable acidity,total soluble solids,pH,and anthocyanin content was evaluated after 2 days,4 days,6 days,and 8 days of *** of the edible coatings reduced the weight loss of the coated strawberries and the anthocyanin *** total soluble solids content of or uncoated fruit increase more markedly than that of coated *** contrast,pH was maintained for both coated and uncoated *** edible coatings were effective in minimizing of the weight loss,without worsening the physical chemistry *** treatments T5 and T9 presented the best results.

关键词： Strawberry edible coating cellulose nanocrystals pectin shelf life

Adverse hepatic reactions associated with calcium carbimide and disulfiram therapy: Is there still a role for these drugs?

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World Journal of Gastroenterology 2006年第31期12卷 5078-5080页

作者： Carmen Verge m Isabel Lucena Enrique López-Torres m José Puche-García Enrique Fraga manuel Romero-Gomez raúl J andrade Clinical Pharmacology ServiceVirgen de la Victoria University Hospital School of MedicineMálagaSpain Gastroenterology ServiceUniversity Hospital Reina Sofia CórdobaSpain Gastroenterology ServiceUniversity Hospital Virgen de Valme SevillaSpain Liver UnitDepartment of Gastroenterology University HospitalMálagaSpain

Disulfiram and calcium carbimide are two alcohol deterrants widely used in alcoholism treatment, however, there exist great concerns over their safety. Reports on hepatotoxicity, mainly related to disulfiram therapy, have been published. The hepatotoxic potential of calcium carbimide is less well characterized. Here, we describe four cases of liver damage related to this therapeutic group that were submitted to a Registry of hepatotoxicity and point out the limitations that we face when prescribing these compounds. A reassessment of the role of these compounds in the management of alcohol dependence is clearly needed.

关键词： Calcium carbimide Disulfiram Hepatotoxicity

Prolonged cholestasis after raloxifene and fenofibrate interaction: A case report

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World Journal of Gastroenterology 2006年第32期12卷 5244-5246页

作者： m Isabel Lucena raúl J andrade Luis Vicioso F Jesús González Ketevan Pachkoria Beatriz García-mu(n|~)oz Clinical Pharmacology Service Virgen de la Victoria University Hospital School of MedicineMalagaSpain Liver Unit Gastroenterology Service Virgen de la Victoria University HospitalSchool of MedicineMálagaSpain Department of Pathology Virgen de la Victoria University Hospital School of MedicineMálagaSpain Institute of Biopathology and Regenerative medicine University of Granada Spain Clinical Pharmacology Service Virgen de la Victoria University Hospital School of MedicineMálagaSpain

Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistance of toxic cholestasis.

关键词： raloxifene Fenofibrate Drug-drug interactions Hepatotoxicity Causality assessment

Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

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World Journal of Gastroenterology 2007年第3期13卷 329-340页

作者： raúl J andrade mercedes Robles Alejandra Fernández-Castaer Susana López-Ortega m Carmen López-Vega m Isabel Lucena Liver Unit Gastroenterology Service "Virgen de la Victoria" University Hospital and School of Medicine Mlaga Spain Clinical Pharmacology Service "Virgen de la Victoria" University Hospital and School of Medicine Mlaga Spain

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.

关键词： Drug-induced hepatotoxicity Causality assessment Diagnostic algorithms Clinical scales

AASLD practice guidance on drug,herbal,and dietary supplement-induced liver injury:also useful for hepatobiliary surgeons

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Hepatobiliary Surgery and Nutrition 2023年第5期12卷 746-751页

作者： Jose maría Pinazo-Bandera miren García-Cortés raúl J.andrade Service of Gastroenterology and Hepatology University Hospital Virgen de la VictoriaInstituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BionandUniversidad de MálagaMálagaSpain Centro de Investigación Biomédico en Red Enfermedades Hepáticas y Digestivas(CIBERehd) MadridSpain

Drug-induced liver injury(DILI)is a term used to describe an unexpected liver reaction to drugs,but also to herbal products and dietary supplements(HDS).In the current therapeutic armamentarium,only a small number of available drugs are still capable of causing liver damage in *** include,in addition to paracetamol-the prototypical example of this group-niacin(now rarely used to treat hypercholesterolaemia),intravenous methotrexate and probably ketamine(an intravenous hypnotic used in critically ill patients for rapid sequence induction)(1).

关键词： Drug-induced liver injury(DILI) hepatotoxicity causality assessment Revised Electronic Causality Assessment method(RECAm)

Preclinical models of idiosyncratic drug-induced liver injury(iDILI):moving towards prediction

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3685-3726页

作者： Antonio Segovia-Zafra Daniel E.Di Zeo-Sanchez Carlos Lopez-Gomez Zeus Perez-Valdes Eduardo Garcıa-Fuentes raul J.andrade m.Isabel Lucena marina Villanueva-Paz Unidad de Gestio´n Clı´nica de Gastroenterologı´a Servicio de Farmacologıa ClınicaInstituto de Investigacio´n Biomedica de Malaga-IBIMAHospital Universitario Virgen de la VictoriaUniversidad de MalagaMalaga 29071Spain Centro de Investigacion Biomedica en Red en el Area Tematica de Enfermedades Hepaticas y Digestivas(CIBERehd) Madrid 28029Spain Platform ISCIII de Ensayos Clınicos UICEC-IBIMAMalaga 29071Spain Unidad de Gestion Clınica de Aparato Digestivo Instituto de Investigacion Biomedica de Malaga(IBIMA)Hospital Universitario Virgen de la VictoriaMalaga 29010Spai

Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the *** remains a major public health problem and a major cause of drug *** the lack of biomarkers for iDILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of iDILI is *** of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant ***,major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI ***,there are many gaps for explaining all the complexity of iDILI susceptibility and ***,there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug ***,the current experimental models and the future directions in iDILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI *** also comment about in silico approaches and the increasing relevance of patient-derived cellular models.

关键词： Drug-induced liver injury Preclinical models mechanisms Oxidative stress mitochondrial damage Immune response Personalized medicine

drug-induced autoimmune liver disease:a diagnostic dilemma of an increasingly reported disease

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World Journal of Hepatology 2014年第4期6卷 160-168页

作者： Agustin Castiella Eva Zapata m Isabel Lucena raúl J andrade Gastroenterology Service Mendaro Hospital Clinical Pharmacology Universidad de Mál-agaInstituto de Investigación Biomédica de MálagaUniversity Hospital Virgen de la Victoria Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Liver Unit Universidad de MálagaInstituto de Investigación Biomédica de MálagaUniversity Hospital Virgen de la Victoria

The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or *** usually develops in individuals with a genetic back-ground mainly consisting of some risk alleles of the major histocompatibility complex(HLA).many drugs have been linked to AIH phenotypes,which sometimes persist after drug discontinuation,suggesting that they awaken latent *** least three clini-cal scenarios have been proposed that refers to drug- induced autoimmune liver disease(DIAILD):AIH with drug-induced liver injury(DILI); drug induced-AIH(DI-AIH); and immune mediated DILI(Im-DILI).In addi-tion,there are instances showing mixed features of DI-AIH and Im-DILI,as well as DILI cases with positive *** distinguishing DILI from AIH remains a *** more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however,a detailed standard-ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag-nosis between both *** information on the relationship of drugs and AIH is being available,being drugs like statins and biologic agents more fre-quently involved in cases of *** addition,there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of *** collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of

关键词： Drug-induced liver injury Autoimmune hepatitis Drugs Drug-induced autoimmune hepatitis Drug-induced autoimmune liver disease

HER2 therapies and gastric cancer:A step forward

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World Journal of Gastroenterology 2013年第37期19卷 6165-6169页

作者： ramon andrade de mello Andrea marin marques António Araújo Department of medical Oncology Gastrointestinal UnitPortuguese Oncology Institute Department of medicine FMUP-Faculty of MedicineUniversity of Porto Centro Hospitalar médio Ave Unidade Santo Tirso

Gastric cancer usually is diagnosed in advanced stages and thus current medical practice affords limited therapeutic ***,recent studies established the role of human epidermal growth factor receptor 2(HER2)in clinical ***,an antiHER2 monoclonal antibody,acquired a main role in advanced gastric cancer harboring HER2 overexpression and/or amplification improving survival to 17.1 mo according to trastuzumab for gastric cancer phaseⅢtrial ***,new promising drugs,such as c-met inhibitors,are in development and assessment for this ***,novel drugs will emerge in the next feel years for help oncologists improve clinical management of advanced gastric cancer providing higher survival and quality of *** this mini-review we will discuss some issues in this regard and provide an actual overview of this setting.

关键词： Gastric cancer Trastuzumab c-met Human epidermal growth factor receptor 2 Lapatinib Pertuzumab