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showing 10 items of 1074 documents

Liver subcellular fractions from rats treated by organosulfur compounds from Allium modulate mutagen activation

2000

The effects of in vivo administration of naturally occurring organosulfur compounds (OSCs) from Allium species were studied on the activation of several mutagens. Male SPF Wistar rats were given p.o. one of either diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) or dipropyl disulfide (DPDS) during 4 consecutive days and the ability of hepatic S9 and microsomes from treated rats to activate benzo[a]pyrene (BaP), cyclophosphamide (CP), dimethylnitrosamine (DMN), N-nitrosopiperidine (N-PiP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was determined in the Ames test. Administration of DAS, DPS and DPDS resulted in a significant increase of the activation of…

MaleNitrosaminesHealth Toxicology and Mutagenesis[SDV]Life Sciences [q-bio]MutagenSulfidesmedicine.disease_causeIsozymeAlliumDimethylnitrosamineAmes testPropane03 medical and health scienceschemistry.chemical_compound0302 clinical medicineCytochrome P-450 Enzyme SystemBenzo(a)pyreneCytochrome P-450 CYP1A1GeneticsmedicineAnimalsDisulfidesRats WistarCyclophosphamideComputingMilieux_MISCELLANEOUS030304 developmental biology0303 health sciencesDose-Response Relationship DrugMutagenicity TestsDiallyl disulfideImidazolesCytochrome P-450 CYP2E1CYP2E1RatsAllyl Compounds[SDV] Life Sciences [q-bio]Dose–response relationshipBiochemistrychemistry030220 oncology & carcinogenesisCytochrome P-450 CYP2B1ToxicityMicrosomes LiverMicrosomeLiver ExtractsOxidoreductasesMutagensSubcellular Fractions
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Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations

2014

Purpose: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment. Methods: Using one of two next-generation sequencing panels containing either 80 or 129 deafness genes, we screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated families) and analyzed 9 normal-hearing controls. Results: Overall, we found an average of 3.7 variants (in 80 genes) with deleterious prediction outcome, including a number of novel variants, in individuals with nonsyndromic h…

MaleProbandUsher syndromeGene DosageDeafnessBioinformaticsmedicine.disease_causesensorineural hearing lossConnexinsCohort Studiestargeted next-generation sequencingOriginal Research Articlemutational loadChildGenetics (clinical)Oligonucleotide Array Sequence AnalysisGeneticsMutationmedicine.diagnostic_testHomozygoteHigh-Throughput Nucleotide SequencingPedigreeConnexin 26Treatment OutcomeChild PreschoolFemalemedicine.symptomAdultAdolescentSequence analysisHearing lossdeafness gene panelMolecular Sequence DataBiologynonsyndromic hearing lossDNA sequencingYoung AdultAudiometryGenetic variationotorhinolaryngologic diseasesmedicineHumansGenetic Predisposition to DiseaseFamily HealthBase SequenceGenetic VariationInfantDNASequence Analysis DNAmedicine.diseaseMutationAudiometryGene DeletionGenetics in Medicine
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Antimutagenic activity of organosulfur compounds from Allium is associated with phase II enzyme induction

2001

In a previous study, we showed that naturally occurring organosulfur compounds (OSCs) from garlic and onion modulated the activation of carcinogen via the alteration of cytochromes P450. The present study was undertaken to determine the incidence of the in vivo induction of phase II enzymes by individual OSCs on the genotoxicity of several carcinogens. Diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered by gavage (1mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects of treatments on phase II enzymes and on the genotoxicity of carcinogens were evaluated with hepatic cytosols and microsomes from OSCs-treated…

MaleSalmonella typhimuriumHealth Toxicology and Mutagenesis[SDV]Life Sciences [q-bio]Allyl compoundAdministration OralSulfidesmedicine.disease_causeAmes testAllium03 medical and health scienceschemistry.chemical_compoundPropane0302 clinical medicineGeneticsmedicineNAD(P)H Dehydrogenase (Quinone)AnimalsDisulfidesRats WistarEpoxide hydrolaseCarcinogenComputingMilieux_MISCELLANEOUS030304 developmental biologyGlutathione TransferaseEpoxide Hydrolases0303 health sciencesDose-Response Relationship DrugChemistryDiallyl disulfideMutagenicity TestsAntimutagenic Agents3. Good healthRatsSpecific Pathogen-Free Organisms[SDV] Life Sciences [q-bio]Allyl CompoundsBiochemistryAntimutagenic AgentsLiver030220 oncology & carcinogenesisEnzyme InductionAntimutagenGenotoxicityMutagensSubcellular Fractions
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Two types of receptors for 5-hydroxytryptamine on the cholinergic nerves of the guinea-pig myenteric plexus

1985

Abstract The effects of 5-hydroxytryptamine (5-HT) on spontaneous and electrically-evoked release of [3H]-acetylcholine (ACh) from guinea-pig myenteric plexus preparations preincubated with [3H]-choline have been investigated in the absence of cholinesterase inhibitors. 5-HT caused a transient increase in spontaneous release and an inhibition of the electrically-evoked release of [3H]-ACh. The 5-HT-induced contractions of the longitudinal muscle were clearly related to the increase in spontaneous release. The inhibitory effect was not due to activation of alpha-adrenoceptors since it was also observed in the presence of tolazoline and on strips from reserpine-pretreated guinea-pigs. After d…

MaleSerotoninmedicine.medical_specialtyKetanserinMetoclopramideMethiothepinGuinea PigsMethysergideMyenteric PlexusBiologyTachyphylaxisInhibitory postsynaptic potentialBinding Competitivechemistry.chemical_compoundCocainePiperidinesInternal medicinemedicineAnimalsReceptorNeurotransmitterMyenteric plexusPharmacologyMethysergideAcetylcholineElectric StimulationEndocrinologychemistryReceptors SerotoninAutoreceptorFemaleKetanserinSerotonin AntagonistsResearch ArticleMuscle ContractionTropanesmedicine.drugBritish Journal of Pharmacology
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Discovery and SAR Evolution of Pyrazole Azabicyclo[3.2.1]octane Sulfonamides as a Novel Class of Non-Covalent N-Acylethanolamine-Hydrolyzing Acid Ami…

2021

Inhibition of intracellular N-acylethanolamine-hydrolyzing acid amidase (NAAA) activity is a promising approach to manage the inflammatory response under disabling conditions. In fact, NAAA inhibition preserves endogenous palmitoylethanolamide (PEA) from degradation, thus increasing and prolonging its anti-inflammatory and analgesic efficacy at the inflamed site. In the present work, we report the identification of a potent, systemically available, novel class of NAAA inhibitors, featuring a pyrazole azabicyclo[3.2.1]octane structural core. After an initial screening campaign, a careful structure–activity relationship study led to the discovery of endo-ethoxymethyl-pyrazinyloxy-8-azabicyclo…

MaleStereochemistryAnti-Inflammatory AgentsPeptides and proteinsPyrazoleArticleAmidohydrolasesAmidaseRats Sprague-DawleyStructure-Activity Relationshipchemistry.chemical_compoundIn vivoN-AcylethanolamineDrug DiscoverymedicineAnimalsHumansSulfonesEnzyme InhibitorsIC50InhibitionInflammationchemistry.chemical_classificationPalmitoylethanolamideMolecular StructureInhibitorsSulfonamideMice Inbred C57BLMolecular Docking SimulationMechanism of actionchemistryMicrosomes LiverInhibitorsInhibitionSulfonesPeptides and proteinsInflammationPyrazolesMolecular Medicinemedicine.symptomProtein BindingTropanesJournal of Medicinal Chemistry
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Vitamin K epoxide reductase activity in the metabolism of epoxides

1985

Abstract The importance of vitamine K epoxide reductase for the metabolism of a range of structurally diverse epoxides has been investigated. Vitamin K 1 epoxide is reduced by rat liver microsomes at a rate of 0.47 nmoles/g liver/min. The rate of menadione oxide reduction is not significantly higher than the non-enzymatic reduction rate. No measurable reduction of benzo[ a ]pyrene 4,5-oxide, benzo[ a ]pyrene 7,8-oxide, phenanthrene 9,10-oxide, styrene 7,8-oxide, and dieldrin has been detected, nor could trichothecene T-2 toxin inhibit reduction of vitamin K 1 epoxide. Thus, vitamin K epoxide reductase is very specific for vitamin K 1 epoxide. Taking into account the range of structurally di…

MaleStereochemistryEpoxideIn Vitro TechniquesReductaseBiochemistryMixed Function Oxygenaseschemistry.chemical_compoundMenadioneEthers CyclicVitamin K Epoxide ReductasesAnimalsEpoxide hydrolaseTrichloroepoxypropaneEpoxide HydrolasesPharmacologyRats Inbred StrainsVitamin K 1MetabolismRatschemistryBiochemistryMicrosomal epoxide hydrolaseMicrosomes LiverMicrosomeEpoxy CompoundsVitamin K epoxide reductaseBiochemical Pharmacology
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Novel Potent Anticonvulsant Agent Containing a Tetrahydroisoquinoline Skeleton

2006

In our studies on the development of new anticonvulsants, we planned the synthesis of N-substituted 1,2,3,4-tetrahydroisoquinolines to explore the structure-activity relationships. All derivatives were evaluated against audiogenic seizures in DBA/2 mice, and the 1-(4'-bromophenyl)-6,7-dimethoxy-2-(piperidin-1-ylacetyl) derivative (26) showed the highest activity with a potency comparable to that of talampanel, the only noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist in clinical trials as an anticonvulsant agent. Electrophysiological experiments indicated that 26 acts as noncompetitive AMPA receptor modulator.

MaleStereochemistrymedicine.medical_treatmentAMPA receptorIn Vitro TechniquesChemical synthesisMiceStructure-Activity Relationshipchemistry.chemical_compoundPiperidinesSeizuresTetrahydroisoquinolinesAMPADrug DiscoverymedicineAnimalsPotencyReceptors AMPARats WistarTalampanelTetrahydroisoquinolineAntagonistAMPA; Isoquinolines; anticonvulsantsOlfactory PathwaysIsoquinolinesRatsAnticonvulsant AgentAnticonvulsantAcoustic StimulationchemistryMice Inbred DBAMolecular MedicineAnticonvulsants
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Activation of propane 2-nitronate to a genotoxicant in V79-derived cell lines engineered for the expression of rat hepatic sulfotransferases

1999

2-Nitropropane (2-NP) is a genotoxic hepatocarcinogen in rats. The genotoxicity of the compound has been attributed to a sulfotransferase-mediated formation of DNA-reactive species from the anionic form of 2-NP, propane 2-nitronate (P2N). Several observations have suggested that sulfotransferases (SULTs) 1A1 and/or 1C1 may be important in the activation of P2N to a genotoxicant in rat liver, but a definite proof is lacking. In order to identify the sulfotransferase(s) of rat liver that are capable of activating P2N, we have investigated the genotoxicity of P2N in various V79-derived cell lines engineered for expression of individual forms of rat hepatic sulfotransferases. Genotoxicity was a…

MaleSulfotransferaseDNA RepairDNA repairHealth Toxicology and MutagenesisHamstermedicine.disease_causeCell LineNitroparaffinsPropanechemistry.chemical_compoundCricetulusCricetinaeGeneticsmedicineAnimalsRats WistarBiotransformationchemistry.chemical_classificationRatsEnzymeLiverBiochemistrychemistryCell culture2-NitropropaneCarcinogensHydroxysteroidSulfotransferasesGenotoxicityMutagensMutation Research/Genetic Toxicology and Environmental Mutagenesis
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Two laboratory-confirmed cases of Japanese encephalitis imported to Germany by travelers returning from Southeast Asia

2011

Japanese encephalitis virus is the leading cause of encephalitis in Asia and parts of the Pacific. Despite the high number of symptomatic infections in endemic countries, clinical disease in travelers is rare. However, an increasing number of imported infections from popular holiday destinations in Southeast Asia have been recorded in the past few years, including serious disease courses in short-term travelers. Here we report two severe, non-fatal cases in tourists, who returned from a long-time stay in Thailand and a short-term trip to Bali, Indonesia, respectively. Recommendations for vaccination and pre-travel advice are discussed.

MaleVeterinary medicineDestinationsAntibodies ViralSoutheast asiaGermanyVirologyHumansMedicineEncephalitis JapaneseSocioeconomicsAgedTravelbiologybusiness.industryMiddle AgedJapanese encephalitisThailandbiology.organism_classificationClinical diseasemedicine.diseaseVaccinationFlavivirusInfectious DiseasesImmunoglobulin MIndonesiaImmunoglobulin GFemalebusinesshuman activitiesEncephalitisJournal of Clinical Virology
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Dietary lycopene decreases the initiation of liver preneoplastic foci by diethylnitrosamine in the rat

1997

To test whether carotenoids can modulate the initiation of liver preneoplasia by diethylnitrosamine (DEN) or by 2-nitropropane (2-NP) in a sequential protocol of hepatocarcinogenesis, male weanling rats were fed for three or four weeks (respectively) diets containing beta-carotene, canthaxanthin, astaxanthin, or lycopene (300 mg/kg diet) or an excess of vitamin A (15,000 retinol equivalents/kg diet) or were treated intraperitoneally with 3-methylcholanthrene. During this period, all rats were injected intraperitoneally with the initiator carcinogen, either 2-NP (6 times at 100 mg/kg body wt) or DEN (once at 100 mg/kg body wt). Three weeks after the termination of carotenoid or vitamin A fee…

MaleVitaminCancer Researchmedicine.medical_specialtySTRUCTURE[SDV]Life Sciences [q-bio]Medicine (miscellaneous)WeanlingBiologyNitroparaffinsPropane03 medical and health scienceschemistry.chemical_compoundLycopene0302 clinical medicinebeta-CaroteneAstaxanthinInternal medicinemedicineAnimalsAnticarcinogenic AgentsDiethylnitrosamineCanthaxanthinRats Wistar030304 developmental biology0303 health sciencesNutrition and DieteticsLiver NeoplasmsRetinolRetinol EquivalentCarotenoidsLycopeneRats3. Good health[SDV] Life Sciences [q-bio]EndocrinologyOncologychemistry030220 oncology & carcinogenesisCarcinogensRATPrecancerous Conditions
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