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showing 10 items of 10542 documents

Anti- Toxoplasma Activities of 24 Quinolones and Fluoroquinolones In Vitro: Prediction of Activity by Molecular Topology and Virtual Computational Te…

2000

ABSTRACT The apicoplast, a plastid-like organelle of Toxoplasma gondii , is thought to be a unique drug target for quinolones. In this study, we assessed the in vitro activity of quinolones against T. gondii and developed new quantitative structure-activity relationship models able to predict this activity. The anti- Toxoplasma activities of 24 quinolones were examined by means of linear discriminant analysis (LDA) using topological indices as structural descriptors. In parallel, in vitro 50% inhibitory concentrations (IC 50 s) were determined in tissue culture. A multilinear regression (MLR) analysis was then performed to establish a model capable of classifying quinolones by in vitro acti…

medicine.drug_classStereochemistryMolecular ConformationBiologyModels BiologicalStructure-Activity RelationshipAnti-Infective AgentsPredictive Value of TestsMoxifloxacinparasitic diseasesmedicineAnimalsStructure–activity relationshipComputer SimulationPharmacology (medical)Mechanisms of Action: Physiological EffectsAntibacterial agentPharmacology4-QuinolonesBiological activityQuinoloneGatifloxacinGrepafloxacinTrovafloxacinInfectious DiseasesRegression AnalysisToxoplasmaFluoroquinolonesmedicine.drugAntimicrobial Agents and Chemotherapy
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Development and biological investigations of hypoxia-sensitive prodrugs of the tyrosine kinase inhibitor crizotinib

2019

Despite the huge success of tyrosine kinase inhibitors as anticancer agents, severe side effects are a major problem. In order to overcome this drawback, the first hypoxia-activatable 2-nitroimidazole-based prodrugs of the clinically approved ALK and c-MET inhibitor crizotinib were developed. The 2-aminopyridine functionality of crizotinib (essential for target kinase binding) was considered as ideal position for prodrug derivatization. Consequently, two different prodrugs were synthesized with the nitroimidazole unit attached to crizotinib either via carbamoylation (A) or alkylation (B) of the 2-aminopyridine moiety. The successful prodrug design could be proven by docking studies and a dr…

medicine.drug_classTyrosine kinase inhibitorAntineoplastic Agents01 natural sciencesBiochemistryArticleTyrosine-kinase inhibitorStructure-Activity Relationshipchemistry.chemical_compoundDrug DevelopmentCrizotinibIn vivoDrug DiscoverymedicineHumansAnaplastic Lymphoma KinaseProdrugsHypoxiaProdrugProtein Kinase InhibitorsMolecular BiologyCells CulturedCell ProliferationNitroimidazoleDose-Response Relationship DrugMolecular StructureCrizotinib010405 organic chemistryChemistryNitroimidazoleOrganic ChemistryProto-Oncogene Proteins c-metProdrugCell Hypoxia0104 chemical sciences010404 medicinal & biomolecular chemistrySettore CHIM/03 - Chimica Generale E InorganicaDocking (molecular)Cancer researchDrug Screening Assays AntitumorKinase bindingTyrosine kinasemedicine.drugBioorganic Chemistry
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EndothelinA receptor antagonist BSF-208075 causes immune modulation and neuroprotection after stroke in gerbils.

2005

Leukocytes contribute to the ischemia-reperfusion injury. Recent studies suggested endothelins could be important mediators for leukocyte activation in stroke. We tested if the endothelinA receptor antagonist BSF-208075 (ambrisentan) could reduce an ischemic lesion by modulation of leukocyte-endothelium interactions. Twenty-four gerbils underwent either a sham operation (n=6) or 15 min of bilateral carotid artery occlusion resulting in global cerebral ischemia. Ischemic animals received normal saline (n=6), 5 mg/kg BSF-208075 (n=6) or 30 mg/kg (n=6) administered intravenously at 10 min of reperfusion. Leukocytes rolling or adhering to endothelium were counted by intravital microscopy in par…

medicine.hormoneMaleAmbrisentanmedicine.drug_classEndothelin A Receptor AntagonistsIschemiaPharmacologyBrain IschemiaEndothelinsLeukocytesMedicineAnimalsImmunologic FactorsMolecular BiologyStrokeDose-Response Relationship DrugPhenylpropionatesbusiness.industryGeneral NeuroscienceEndothelinsAntagonistBrainmedicine.diseaseReceptor antagonistReceptor Endothelin APyridazinesStrokeChemotaxis LeukocyteNeuroprotective AgentsTreatment OutcomeAnesthesiaCerebrovascular CirculationReperfusion InjuryNerve DegenerationEncephalitisNeurology (clinical)businessEndothelin receptorGerbillinaeIntravital microscopyDevelopmental Biologymedicine.drugBrain research
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Comparison of the contractile effects of endothelin-1 and sarafotoxin S6b in goat isolated cerebral arteries

1992

1. The effects of endothelium-derived endothelin-1 and snake venom-derived sarafotoxin S6b, peptides with striking structural and functional similarities, were examined and compared in isolated middle cerebral arteries of goats. 2. Endothelin-1 and sarafotoxin S6b contracted cerebral arteries in a concentration-dependent manner. The potency of endothelin-1 (EC50 = 4.9 (3.9-6.2) x 10(-10) M) was about ten times higher than that of sarafotoxin S6b (EC50 = 5.5 (4.4-6.9) x 10(-9) M). The tension returned to basal values after repeated washings and contraction with endothelin-1 could be reproduced. Endothelin-1 and sarafotoxin S6b induced further contraction in arteries precontracted with prosta…

medicine.hormonemedicine.medical_specialtyContraction (grammar)IndomethacinCerebral arteriesProstacyclinViper Venomscomplex mixturesEndothelinsNicardipinechemistry.chemical_compoundInternal medicinemedicineAnimalsVasoconstrictor AgentsPharmacologyDose-Response Relationship DrugEndothelinsGoats3-Pyridinecarboxylic acid 14-dihydro-26-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)- Methyl esterCerebral ArteriesEndothelin 1EGTAEndocrinologychemistryVasoconstrictioncardiovascular systemFemaleEndothelium Vascularmedicine.symptomVasoconstrictionResearch Articlecirculatory and respiratory physiologymedicine.drugMuscle contractionBritish Journal of Pharmacology
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Electrocardiographic Indices of Left Ventricular Hypertrophy and Repolarization Phase Share the Same Genetic Influences: A Twin Study

2009

Background: Both left ventricular hypertrophy (LVH) and repolarization phase (RP) are known to be attributable to genetic influences, but less is known whether they share same genetic influences. The aim of this study was to investigate to what extent individual differences in electrocardiographic (ECG) LVH and RP are explained by genetic and environmental influences and whether these influences are shared between these two traits. Methods: Resting ECG recordings were obtained from 186 monozygotic and 203 dizygotic female twin individuals, aged 63 to 76 years. Latent factors, called LVH and RP, were formed to condense the information obtained from LVH indices (Cornell voltage and Cornell pr…

medicine.medical_specialty030204 cardiovascular system & hematologyLeft ventricular hypertrophyGenetic correlationCorrelationElectrocardiography03 medical and health sciences0302 clinical medicinePhysiology (medical)Internal medicineGenetic modelingHumansRepolarizationMedicineGenetic Predisposition to Diseasecardiovascular diseases030212 general & internal medicineAgedbusiness.industryOriginal ArticlesGeneral MedicineMiddle AgedHeritabilitymedicine.diseaseTwin studyEndocrinologyCardiologyFemaleHypertrophy Left VentricularCardiology and Cardiovascular MedicinebusinessAnnals of Noninvasive Electrocardiology
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Verbesserte Auswertbarkeit transitorisch evozierter otoakustischer Emissionen durch Korrelationsfilterung

1993

Hearing screening as well as evaluation of cochlear function under therapy with ototoxic agents or patients with various diseases is increasingly done by registration of transient evoked otoacoustic emissions (TEOAE). Usually the standard system ILO 88 Otodynamic Analyser is used, where until now emissions were analyzed subjectively. However, evaluation of signals may be difficult mainly in the hearing threshold area. In this article we describe a method to mathematically analyze registered emissions by correlation-filtering. This allows to better identify small specific responses, to further increase the sensitivity of TEOAE, and offers a more objective means for audiologic diagnoses.

medicine.medical_specialtyAbsolute threshold of hearingElectrodiagnosismedicine.diagnostic_testbusiness.industryOtoacoustic emissionAudiologyHearing screeningCochlear functionStandard systemCorrelationOtorhinolaryngologyReference valuesmedicinebusinessLaryngo-Rhino-Otologie
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Surgical research and clinical routine in the new century.

2002

The German Research Foundation (DFG) has recentlydenounced the poor state of clinical research in Germany[2]. It is therefore worthwhile to contemplate the currentstate of surgical research with special focus on the futurepossibilities to combine research and clinical routine inuniversity hospitals.Current StateReading the daily newspaper one may get the impres-sion that German universities and clinical research in par-ticular are in a deep crisis, and that German professors areto be blamed for it. In medicine, additional insufficienciesof the system are obvious, with corruption cases broughtup against clinicians and conflicts of interest due to thefact that clinical professors in addition …

medicine.medical_specialtyAcademic Medical Centersbusiness.industryInstitutionalisationCorruptionPublic healthMemorandummedia_common.quotation_subjectResearchPublic relationslanguage.human_languageNewspaperGermanIncentiveClinical researchGeneral SurgeryGermanymedicinelanguageHumansSurgerybusinessmedia_commonEuropean surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes
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Parameters for coronary plaque vulnerability assessed with multidetector computed tomography and intracoronary ultrasound correlation

2009

In the absence of a fixed relationship between plaque vulnerability and flow-limiting stenosis, alternative morphological expressions exist that could predict the liability of coronary lesions to rapidly progress or rupture, causing acute coronary syndromes. Modern multidetector computed tomography technology is capable of noninvasively detecting lesion location, attenuation, remodeling and calcification pattern, which may be considered as surrogate morphological markers of vulnerability and could contribute to increase the prognostic value of individual coronary plaque burden. J Cardiovasc Med 10:821 -826 (C) 2009 Italian Federation of Cardiology.

medicine.medical_specialtyAcute coronary syndromeVulnerabilityCoronary Angiographymedicine.disease_causeRisk AssessmentSeverity of Illness IndexLesionCorrelationPredictive Value of TestsRisk FactorsInternal medicineIntravascular ultrasoundHumansMedicineAcute Coronary SyndromeUltrasonography InterventionalRupturemedicine.diagnostic_testbusiness.industryCoronary StenosisGeneral MedicinePrognosismedicine.diseaseVulnerable plaqueStenosisCardiologyRadiologymedicine.symptomTomography X-Ray ComputedCardiology and Cardiovascular MedicinebusinessSettore MED/36 - Diagnostica Per Immagini E Radioterapiacomputed tomography intravascular ultrasound plaque remodeling vulnerable plaqueCalcification
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Dynamic Force Production Capacities Between Coronary Artery Disease Patients vs. Healthy Participants on a Cycle Ergometer

2020

Background: The force-velocity-power (FVP) profile is used to describe dynamic force production capacities, which is of great interest in training high performance athletes. However, FVP may serve a new additional tool for cardiac rehabilitation (CR) of coronary artery disease (CAD) patients. The aim of this study was to compare the FVP profile between two populations: CAD patients vs. healthy participants (HP). Methods: Twenty-four CAD patients (55.8 ± 7.1 y) and 24 HP (52.4 ± 14.8 y) performed two sprints of 8 s on a Monark cycle ergometer with a resistance corresponding to 0.4 N/kg × body mass for men and 0.3 N/kg × body mass for women. The theoretical maximal force (F 0) and velocity (V…

medicine.medical_specialtyAcute coronary syndromecycle sprintPhysiologyPhysical activityphysical activitykuntotestitforce-velocity-power relationship030204 cardiovascular system & hematologylcsh:Physiologyacute coronary syndromeCoronary artery disease03 medical and health sciences0302 clinical medicinePhysiology (medical)Internal medicinemedicineCycle ergometervoimantuotto (fysiologia)Exercise physiologykuntoutujatOriginal Researchexercise physiologySedentary timelcsh:QP1-981business.industrySignificant differenceliikuntafysiologiahealth030229 sport sciencesmedicine.diseasecardiac rehabilitationsydän- ja verisuonitauditCardiologykuntoutusbusinessFrontiers in Physiology
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Contribution of parental and school personnel smoking to health risk behaviours among Finnish adolescents.

2009

Abstract Background This study compared parental smoking with school personnel smoking in relation to adolescents' smoking behaviours, alcohol use, and illicit drug use. Methods A cross-sectional survey for 24,379 adolescents was linked to a survey for 1946 school employees in 136 Finnish schools in 2004-2005. Surveys included smoking prevalence reported by school staff, adolescents' reports of school staff and parental smoking, adolescents' own smoking behaviours, alcohol use, and illicit drug use. Multilevel analyses were adjusted for individual and school-level confounding factors. Results Parental smoking was associated with all health risk behaviours among both sexes (risk range 1.39 t…

medicine.medical_specialtyAdolescentCross-sectional studySubstance-Related Disordersmedicine.medical_treatmenteducationHealth BehaviorBinge drinkingIn Vitro Techniques03 medical and health sciences0302 clinical medicineRisk-TakingEnvironmental healthEpidemiologymedicineOdds RatioPrevalenceIllicit drugHumans030212 general & internal medicineParent-Child RelationsPsychiatryLife StyleFinland030505 public healthSchoolsbusiness.industryPublic healthlcsh:Public aspects of medicineData CollectionSmokingPublic Health Environmental and Occupational Healthlcsh:RA1-1270Odds ratioFacultyAlcoholismCross-Sectional StudiesAdolescent BehaviorSmoking cessationFemaleBiostatistics0305 other medical sciencebusinessResearch ArticleBMC public health
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