Search results for "Idiosyncrasy"

showing 4 items of 4 documents

Predicting drug-induced cholestasis: preclinical models.

2018

In almost 50% of patients with drug-induced liver injury (DILI), the bile flow from the liver to the duodenum is impaired, a condition known as cholestasis. However, this toxic response only appears in a small percentage of the treated patients (idiosyncrasy). Prediction of drug-induced cholestasis (DIC) is challenging and emerges as a safety issue that requires attention by professionals in clinical practice, regulatory authorities, pharmaceutical companies, and research institutions. Area covered: The current synopsis focuses on the state-of-the-art in preclinical models for cholestatic DILI prediction. These models differ in their goal, complexity, availability, and applicability, and ca…

0301 basic medicineIdiosyncrasymedicine.drug_classDrug Evaluation PreclinicalIn Vitro TechniquesToxicologyBioinformaticsModels BiologicalBile flow03 medical and health sciencesCholestasismedicineAnimalsBileHumansDrug induced cholestasisPharmacologyLiver injuryCholestasisBile acidbusiness.industryReproducibility of ResultsGeneral Medicinemedicine.disease030104 developmental biologymedicine.anatomical_structureHepatocyteDuodenumHepatocytesChemical and Drug Induced Liver InjurybusinessExpert opinion on drug metabolismtoxicology
researchProduct

Metabolic activation and drug-induced liver injury:in vitroapproaches for the safety risk assessment of new drugs

2015

Drug-induced liver injury (DILI) is a significant leading cause of hepatic dysfunction, drug failure during clinical trials and post-market withdrawal of approved drugs. Many cases of DILI are unexpected reactions of an idiosyncratic nature that occur in a small group of susceptible individuals. Intensive research efforts have been made to understand better the idiosyncratic DILI and to identify potential risk factors. Metabolic bioactivation of drugs to form reactive metabolites is considered an initiation mechanism for idiosyncratic DILI. Reactive species may interact irreversibly with cell macromolecules (covalent binding, oxidative damage), and alter their structure and activity. This r…

0301 basic medicineDrugLiver injuryIdiosyncrasyMechanism (biology)media_common.quotation_subjectMetaboliteCellPharmacologyBiologyToxicologymedicine.diseaseIn vitro03 medical and health scienceschemistry.chemical_compound030104 developmental biologymedicine.anatomical_structureDrug developmentchemistrymedicinemedia_commonJournal of Applied Toxicology
researchProduct

Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury

2017

Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…

0301 basic medicineDrugCYP2B6Drug-induced liver injuryHealth Toxicology and Mutagenesismedia_common.quotation_subjectPopulationDrug Evaluation PreclinicalPharmacologyToxicologyHepatotoxicity mechanismsGene Expression Regulation EnzymologicOrgan Toxicity and MechanismsAdenoviridae03 medical and health sciences0302 clinical medicineCYPToxicity TestsHumansCytochrome P450 Family 2educationmedia_commonMembrane Potential Mitochondrialeducation.field_of_studyCYP3A4biologyCytochrome P450IdiosyncrasyHep G2 CellsGeneral MedicineCYP2E1Recombinant ProteinsHigh-Throughput Screening Assays030104 developmental biology030220 oncology & carcinogenesisInactivation MetabolicToxicityCell modelbiology.proteinChemical and Drug Induced Liver InjuryReactive Oxygen SpeciesDrug metabolism
researchProduct

La desheredación del menor de edad

2021

This work aims to answer the eternal question of the disinheritance of the child under legal age. To this end, we will approach the institute of disinheritance, its foundation and its jurisprudential evolution. We will also address the capacity and responsibility of the child under legal age and the emancipated minor. Subsequently, we will carry out the study of the disinheritance of the child under legal age, subject to the whim of the specific disinherited causes, since each of the causes provided for in art. 853 Spanish Civil Code are endowed with their own idiosyncrasy, being very complicated, if not impossible, to deal with the subject of this work apart from the vicissitudes that can …

reconciliaciónits foundation and its jurisprudential evolution. We will also address the capacity and responsibility of the child under legal age and the emancipated minor. SubsequentlyLegitimatedisinheritancewe will carry out the study of the disinheritance of the child under legal agewe will study the problems posed by reconciliation between the ascendant and the disinherited minorif not impossiblereconciliation. 384 465since each of the causes provided for in art. 853 Spanish Civil Code are endowed with their own idiosyncrasysince reconciliationdesheredaciónpresents its own vicissitudes when the heir is a child under legal age. Legítimaand before submitting this study to a reflective recapitulationmaltrato de obrato deal with the subject of this work apart from the vicissitudes that can occur according to the imputed facts. FinallyManuel Ángel This work aims to answer the eternal question of the disinheritance of the child under legal age. To this endinsultspsychological abusemenor emancipadoas a means that allows disinheritance to be rendered ineffective:CIENCIAS JURÍDICAS [UNESCO]maltrato psicológicomistreatment of workinjuriasmenor de edadalimentosfood2070-8157 22082 Revista Boliviana de Derecho 584568 2021 32 8055227 La desheredación del menor de edad Gómez Valenzuelasubject to the whim of the specific disinherited causesemancipated minorwe will approach the institute of disinheritancechild under legal ageUNESCO::CIENCIAS JURÍDICASbeing very complicated
researchProduct