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[PMID]:29306027
[Au] Autor:Harris AP; Ismail KA; Nunez M; Martopullo I; Lencinas A; Selmin OI; Runyan RB
[Ad] Endereço:Department of Cellular & Molecular Medicine, University of Arizona, Tucson, AZ 85724-5044, United States.
[Ti] Título:Trichloroethylene perturbs HNF4a expression and activity in the developing chick heart.
[So] Source:Toxicol Lett;285:113-120, 2018 Mar 15.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Exposure to trichloroethylene (TCE) is linked to formation of congenital heart defects in humans and animals. Prior interactome analysis identified the transcription factor, Hepatocyte Nuclear Factor 4 alpha (HNF4a), as a potential target of TCE exposure. As a role for HNF4a is unknown in the heart, we examined developing avian hearts for HNF4a expression and for sensitivity to TCE and the HNF4a agonist, Benfluorex. In vitro analysis using a HNF4a reporter construct showed both TCE and HFN4a to be antagonists of HNF4a-mediated transcription at the concentrations tested. HNF4a mRNA is expressed transiently in the embryonic heart during valve formation and cardiac development. Embryos were examined for altered gene expression in the presence of TCE or Benfluorex. TCE altered expression of selected mRNAs including HNF4a, TRAF6 and CYP2C45. There was a transition between inhibition and induction of marker gene expression in embryos as TCE concentration increased. Benfluorex was largely inhibitory to selected markers. Echocardiography of exposed embryos showed reduced cardiac function with both TCE and Benfluorex. Cardiac contraction was reduced by 29% and 23%, respectively at 10 ppb. The effects of TCE and Benfluorex on autocrine regulation of HNF4a, selected markers and cardiac function argue for a functional interaction of TCE and HNF4a. Further, the dose-sensitive shift between inhibition and induction of marker expression may explain the nonmonotonic-like dose response observed with TCE exposure in the heart.
[Mh] Termos MeSH primário: Poluentes Ambientais/toxicidade
Coração/efeitos dos fármacos
Fator 4 Nuclear de Hepatócito/genética
Transcrição Genética/efeitos dos fármacos
Tricloroetileno/toxicidade
[Mh] Termos MeSH secundário: Animais
Embrião de Galinha
Relação Dose-Resposta a Droga
Ecocardiografia
Fenfluramina/análogos & derivados
Fenfluramina/farmacologia
Genes Reporter
Coração/diagnóstico por imagem
Coração/embriologia
Células Hep G2
Fator 4 Nuclear de Hepatócito/agonistas
Seres Humanos
Miocárdio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Environmental Pollutants); 0 (HNF4A protein, human); 0 (Hepatocyte Nuclear Factor 4); 290YE8AR51 (Trichloroethylene); 2DS058H2CF (Fenfluramine); 403FO0NQG3 (benfluorex)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


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[PMID]:28159275
[Au] Autor:Jin R; Li L; Guo L; Li W; Shen Q
[Ad] Endereço:Institute of Seafood, Zhejiang Gongshang University, Hangzhou, China.
[Ti] Título:A graphene tip coupled with liquid chromatography tandem mass spectrometry for the determination of four synthetic adulterants in slimming supplements.
[So] Source:Food Chem;224:329-334, 2017 Jun 01.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Slimming supplements were popularly sold online driven by the increasement of obesity and the development of social networking platform. However, events of drug abuse in slimming supplements were also frequently reported. In this study, a graphene tip solid-phase extraction (Gtip SPE) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established for determining fenfluramine, phenolphthalein, bumetanide, and sibutramine in slimming supplements. It was validated in terms of linearity (0.9985-0.9995), LOD (1.8ngmL ), LOQ (5.6ngmL ), intra-day precision (<5.1%), inter-day precision (<7.3%), and recovery (82.9-95.2%). Sibutramine is the most commonly used drug, which was detected in Bihais, Galong, and Aolist, with content 12.4, 3.6, 20.3mgg , respectively. Phenolphthalein was also found with content lower than 5.2mgg . The successful application of Gtip SPE and UPLC-MS/MS method indicated its advantage in analyzing low level of contaminates resulted from violation of regulation.
[Mh] Termos MeSH primário: Depressores do Apetite/análise
Cromatografia Líquida
Suplementos Nutricionais/análise
Grafite/química
Espectrometria de Massas em Tandem
[Mh] Termos MeSH secundário: Bumetanida/análise
Ciclobutanos/análise
Fenfluramina/análise
Limite de Detecção
Fenolftaleína/análise
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Extração em Fase Sólida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Appetite Depressants); 0 (Cyclobutanes); 0Y2S3XUQ5H (Bumetanide); 2DS058H2CF (Fenfluramine); 6QK969R2IF (Phenolphthalein); 7782-42-5 (Graphite); WV5EC51866 (sibutramine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170205
[St] Status:MEDLINE


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[PMID]:28079786
[Au] Autor:Baufreton C; Bruneval P; Rousselet MC; Ennezat PV; Fouquet O; Giraud R; Banfi C
[Ad] Endereço:aDepartment of Cardiovascular Surgery, Centre Hospitalier Universitaire d'Angers bDepartment of Pathology, Hôpital Européen Georges Pompidou, Paris Descartes University cDepartment of Pathology, Centre Hospitalier Universitaire d'Angers dDepartment of Cardiology, Centre Hospitalier Universitaire de Grenoble, France eIntensive Care Service, Geneva University Hospitals fHemodynamic Research Group Geneva, Faculty of Medicine, University of Geneva gDivision of Cardiovascular Surgery, Geneva University Hospitals, Geneva, Switzerland.
[Ti] Título:Fatal postoperative systemic pulmonary hypertension in benfluorex-induced valvular heart disease surgery: A case report.
[So] Source:Medicine (Baltimore);96(2):e4985, 2017 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Drug-induced valvular heart disease (DI-VHD) remains an under-recognized entity. PATIENT CONCERNS: This report describes a heart valve replacement which was complicated by intractable systemic pulmonary arterial hypertension in a 61-year-old female with severe restrictive mitral and aortic disease. The diagnosis of valvular disease was preceded by a history of unexplained respiratory distress. The patient had been exposed to benfluorex for 6.5 years. DIAGNOSES: The diagnostic procedure documented specific drug-induced valvular fibrosis. INTERVENTIONS: Surgical mitral and aortic valve replacement was performed. OUTCOMES: Heart valve replacement was postoperatively complicated by unanticipated disproportionate pulmonary hypertension. This issue was fatal despite intensive care including prolonged extracorporeal life support. LESSONS: Benfluorex is a fenfluramine derivative which has been marketed between 1976 and 2009. Although norfenfluramine is the common active and toxic metabolite of all fenfluramine derivatives, the valvular and pulmonary arterial toxicity of benfluorex was much less known than that of fenfluramine and dexfenfluramine. The vast majority of benfluorex-induced valvular heart disease remains misdiagnosed as hypothetical rheumatic fever due to similarities between both etiologies. Better recognition of DI-VHD is likely to improve patient outcome.
[Mh] Termos MeSH primário: Depressores do Apetite/efeitos adversos
Fenfluramina/análogos & derivados
Doenças das Valvas Cardíacas/induzido quimicamente
Hipertensão Pulmonar/etiologia
Complicações Pós-Operatórias/etiologia
[Mh] Termos MeSH secundário: Evolução Fatal
Feminino
Fenfluramina/efeitos adversos
Doenças das Valvas Cardíacas/complicações
Doenças das Valvas Cardíacas/cirurgia
Implante de Prótese de Valva Cardíaca
Seres Humanos
Meia-Idade
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Appetite Depressants); 2DS058H2CF (Fenfluramine); 403FO0NQG3 (benfluorex)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170227
[Lr] Data última revisão:
170227
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170113
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000004985


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[PMID]:27696217
[Au] Autor:Negus SS; Banks ML
[Ad] Endereço:Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA. sidney.negus@vcuhealth.org.
[Ti] Título:Decoding the Structure of Abuse Potential for New Psychoactive Substances: Structure-Activity Relationships for Abuse-Related Effects of 4-Substituted Methcathinone Analogs.
[So] Source:Curr Top Behav Neurosci;32:119-131, 2017.
[Is] ISSN:1866-3370
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Many cathinone analogs act as substrates or inhibitors at dopamine, norepinephrine, and serotonin transporters (DAT, NET, SERT, respectively). Drug selectivity at DAT vs. SERT is a key determinant of abuse potential for monoamine transporter substrates and inhibitors, such that potency at DAT > SERT is associated with high abuse potential, whereas potency at DAT < SERT is associated with low abuse potential. Quantitative structure-activity relationship (QSAR) studies with a series of 4-substituted methcathinone analogs identified volume of the 4-position substituent on the methcathinone phenyl ring as one structural determinant of both DAT vs. SERT selectivity and abuse-related behavioral effects in an intracranial self-stimulation procedure in rats. Subsequent modeling studies implicated specific amino acids in DAT and SERT that might interact with 4-substituent volume to determine effects produced by this series of cathinone analogs. These studies illustrate use of QSAR analysis to investigate pharmacology of cathinones and function of monoamine transporters.
[Mh] Termos MeSH primário: Comportamento Animal/efeitos dos fármacos
Proteínas da Membrana Plasmática de Transporte de Dopamina/efeitos dos fármacos
Propiofenonas/farmacologia
Psicotrópicos/farmacologia
Proteínas da Membrana Plasmática de Transporte de Serotonina/efeitos dos fármacos
Transtornos Relacionados ao Uso de Substâncias
[Mh] Termos MeSH secundário: Anfetamina/farmacologia
Animais
Fenfluramina/farmacologia
Seres Humanos
Metanfetamina/análogos & derivados
Metanfetamina/química
Metanfetamina/farmacologia
Metilaminas/química
Metilaminas/farmacologia
N-Metil-3,4-Metilenodioxianfetamina/farmacologia
Proteínas da Membrana Plasmática de Transporte de Norepinefrina/efeitos dos fármacos
Propiofenonas/química
Psicotrópicos/química
Relação Quantitativa Estrutura-Atividade
Ratos
Autoadministração
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (4-fluoromethcathinone); 0 (4-methoxymethcathinone); 0 (Dopamine Plasma Membrane Transport Proteins); 0 (Methylamines); 0 (Norepinephrine Plasma Membrane Transport Proteins); 0 (Propiophenones); 0 (Psychotropic Drugs); 0 (Serotonin Plasma Membrane Transport Proteins); 0 (clephedrone); 2DS058H2CF (Fenfluramine); 386QA522QG (monomethylpropion); 44RAL3456C (Methamphetamine); 8BA8T27317 (mephedrone); CK833KGX7E (Amphetamine); KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161004
[St] Status:MEDLINE
[do] DOI:10.1007/7854_2016_18


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[PMID]:26825776
[Au] Autor:Jørgensen LM; Weikop P; Villadsen J; Visnapuu T; Ettrup A; Hansen HD; Baandrup AO; Andersen FL; Bjarkam CR; Thomsen C; Jespersen B; Knudsen GM
[Ad] Endereço:1 Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark.
[Ti] Título:Cerebral 5-HT release correlates with [ C]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain.
[So] Source:J Cereb Blood Flow Metab;37(2):425-434, 2017 Feb.
[Is] ISSN:1559-7016
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT receptor agonist PET radioligand, [ C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [ C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular 5-HT levels with microdialysis and [ C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram + pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to deplete cerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2-11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5-HT release, and induced a varying degree of decline in [ C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT receptor occupancy indicates that [ C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high.
[Mh] Termos MeSH primário: Benzilaminas/metabolismo
Encéfalo/metabolismo
Fenetilaminas/metabolismo
Tomografia por Emissão de Pósitrons
Receptor 5-HT2A de Serotonina/metabolismo
Agonistas de Receptores 5-HT2 de Serotonina/metabolismo
Serotonina/metabolismo
[Mh] Termos MeSH secundário: Animais
Benzilaminas/análise
Encéfalo/diagnóstico por imagem
Encéfalo/efeitos dos fármacos
Radioisótopos de Carbono/análise
Radioisótopos de Carbono/metabolismo
Feminino
Fenfluramina/farmacologia
Fenetilaminas/análise
Tomografia por Emissão de Pósitrons/métodos
Receptor 5-HT2A de Serotonina/análise
Agonistas de Receptores 5-HT2 de Serotonina/análise
Serotoninérgicos/farmacologia
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzylamines); 0 (Carbon Radioisotopes); 0 (Cimbi-36); 0 (Phenethylamines); 0 (Receptor, Serotonin, 5-HT2A); 0 (Serotonin 5-HT2 Receptor Agonists); 0 (Serotonin Agents); 2DS058H2CF (Fenfluramine); 333DO1RDJY (Serotonin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170424
[Lr] Data última revisão:
170424
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160131
[St] Status:MEDLINE
[do] DOI:10.1177/0271678X16629483


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[PMID]:27487042
[Au] Autor:Le Ven F; Alavi Z; Jobic Y; Etienne Y; Didier R; Porcher R
[Ad] Endereço:Service de Cardiologie, Hôpital de la Cavale Blanche CHRU Brest, France.
[Ti] Título:Drug-Induced- or Rheumatic- Valvular Heart Disease in Patients Exposed to Benfluorex?
[So] Source:PLoS One;11(8):e0160011, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is a risk of misdiagnosis between benfluorex-induced VHD and acute rheumatic fever (ARF)-related VHD due to common characteristics of both etiologies. We aimed at estimating the probability for a patient exposed to benfluorex presenting with VHD to have, at the same time, a history of ARF-related VHD. Such epidemiological approach could help at reducing the risk of misdiagnosis. We used INSEE data and related literature as well as various modeling hypotheses to drive and test a formula for calculating the probability of a patient presenting with VHD and a history of benfluorex intake to have a prior history of ARF-related VHD. Different scenarios were estimated by a Markov model on the life course of people born in France between 1940 and 1960. Sensitivity analyses were performed under these scenarios. According to the different scenarios and gender, the probability that a patient born between 1940 and 1960 presenting with VHD and a history of benfluorex intake would have had a prior history of ARF-related VHD varied from 0.2% to 2.7%. The probabilities by the year of birth were as follows: 0.8%-2.7% for a patient born in 1940, < 0.5% in all scenarios for patients born after 1955, and < 0.2% in all scenarios for patients, born in 1960. Our results indicate that the burden of ARF-related VHD is low in the patient population exposed to benfluorex. The probability of ARF related VHD should not be over-estimated in the diagnostic procedure of VHD.
[Mh] Termos MeSH primário: Depressores do Apetite/efeitos adversos
Fenfluramina/análogos & derivados
Doenças das Valvas Cardíacas/induzido quimicamente
Doenças das Valvas Cardíacas/epidemiologia
Cardiopatia Reumática/induzido quimicamente
Cardiopatia Reumática/epidemiologia
[Mh] Termos MeSH secundário: Idoso
Feminino
Fenfluramina/efeitos adversos
França/epidemiologia
Seres Humanos
Masculino
Cadeias de Markov
Meia-Idade
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Appetite Depressants); 2DS058H2CF (Fenfluramine); 403FO0NQG3 (benfluorex)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160804
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0160011


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[PMID]:27390966
[Au] Autor:Ennezat PV; Bruneval P; Czitrom D; Gueffet JP; Piriou N; Trochu JN; Patra O; Blanchard-Lemoine B; du Fretay XH; Nazeyrollas P; Assoun B; Jobic Y; Brochet E; Bogino E; Roudaut R; Augier C; Greffe L; Petit-Eisenmann H; Dambrin C; Chavanon O; Guillou L; Grisoli D; Morera P; Banfi C; Remadi JP; Fabre O; Vincentelli A; Lantuejoul S; Ikoli JF; Copin MC; Malergue MC; Maréchaux S; Tribouilloy C
[Ad] Endereço:Department of Cardiology and Cardiovascular Surgery, Centre Hospitalier Universitaire de Grenoble, France. Electronic address: ennezat@yahoo.com.
[Ti] Título:Drug-induced aortic valve stenosis: An under recognized entity.
[So] Source:Int J Cardiol;220:429-34, 2016 Oct 01.
[Is] ISSN:1874-1754
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We have been intrigued by the observation that aortic stenosis (AS) may be associated with characteristic features of mitral drug-induced valvular heart disease (DI-VHD) in patients exposed to valvulopathic drugs, thus suggesting that beyond restrictive heart valve regurgitation, valvulopathic drugs may be involved in the pathogenesis of AS. METHODS: Herein are reported echocardiographic features, and pathological findings encountered in a series of patients suffering from both AS (mean gradient >15mmHg) and mitral DI-VHD after valvulopathic drugs exposure. History of rheumatic fever, chest radiation therapy, systemic disease or bicuspid aortic valve disease were exclusion criteria. RESULTS: Twenty-five (19 females, mean age 62years) patients having both AS and typical features of mitral DI-VHD were identified. Mean transaortic pressure gradient was 32+/-13mmHg. Aortic regurgitation was ≥ mild in 24 (96%) but trivial in one. Known history of aortic valve regurgitation following drug initiation prior the development of AS was previously diagnosed in 17 patients (68%). Six patients underwent aortic valve replacement and 3 both aortic and mitral valve replacement. In the 9 patients with pathology analysis, aortic valvular endocardium was markedly thickened by dense non-inflammatory fibrosis, a characteristic feature of DI-VHD. CONCLUSION: The association between AS and typical mitral DI-VHD after valvulopathic drug exposure may not be fortuitous. Aortic regurgitation was usually associated to AS and preceded AS in most cases but may be lacking. Pathology demonstrated the potential role of valvulopathic drugs in the development of AS.
[Mh] Termos MeSH primário: Estenose da Valva Aórtica/induzido quimicamente
Estenose da Valva Aórtica/diagnóstico por imagem
Fenfluramina/efeitos adversos
Metisergida/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Estenose da Valva Aórtica/patologia
Feminino
Fenfluramina/análogos & derivados
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Nm] Nome de substância:
2DS058H2CF (Fenfluramine); 403FO0NQG3 (benfluorex); XZA9HY6Z98 (Methysergide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE


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[PMID]:27364433
[Au] Autor:Ferro Cavalcante TC; Marcelino da Silva AA; Amaral Almeida LC; Tavares GA; de Farias Campina RC; do Nascimento E; Lopes de Souza S
[Ad] Endereço:Postgraduate in Nutrition, Federal University of Pernambuco (UFPE), Recife, PE, Brazil; College of Nutrition, Petrolina Campus, University of Pernambuco, Petrolina, Pernambuco, Brazil.
[Ti] Título:Effects of perinatal protein malnutrition and fenfluramine action on food intake and neuronal activation in the hypothalamus and raphe nuclei of neonate rats.
[So] Source:Physiol Behav;165:35-42, 2016 Oct 15.
[Is] ISSN:1873-507X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In neonatal rats, hunger and satiety responses occur particularly via dehydration and gastric distention, respectively. The control of food intake in newborns is yet to be fully consolidated, particularly with respect to the participation of the hypothalamic nuclei and their relationship with the serotonergic pathway. Moreover, it is unclear how the environmental stressors in early life, like undernutrition, interfere in these events. Therefore, this study examined the serotonin-system's impact on food intake in rat neonates at postnatal day (P) 10 and P18 and the manner in which protein undernutrition during pregnancy and lactation interferes in this behavior. To accomplish this, Wistar rats were used, nutritionally manipulated by a diet having two protein levels, (8% and 17%) during pregnancy and lactation, to form the Control (n=10) and Low protein groups (n=10). At 10 and 18 postnatal days pups received an acute dose of fenfluramine (3mg/kg) or saline (0.9% NaCl) and subjected to milk consumption testing and then perfused to obtain the brains for the analysis of cell activation of the immunoreactive c-Fos in the hypothalamic and raphe nuclei. At 10days a reduction in weight gain was observed in both groups. On comparison of the neuronal activation for the paraventricular nucleus, an increased activation in response to fenfluramine was observed. At 18days, the weight gain percentage differed between the groups according to the nutritional manipulation, in which the control animals had no significant change while the undernourished presented increased weight gain with the use of fenfluramine. The marking of c-Fos in response to fenfluramine in the hypothalamic and raphe nuclei revealed, an especially lower activation of the PVN, MnR and DR compared intra-group. However when evaluating the effect of undernutrition, marking activation was observed to increase in all the nuclei analyzed, in the hypothalamus and raphe. Data from this study indicate that the action of serotonin via food intake in the neonates may have been delayed by early protein undernutrition.
[Mh] Termos MeSH primário: Dieta com Restrição de Proteínas/efeitos adversos
Ingestão de Alimentos/fisiologia
Hipotálamo/fisiologia
Desnutrição/fisiopatologia
Núcleos da Rafe/fisiologia
Serotonina/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Modelos Animais de Doenças
Ingestão de Alimentos/efeitos dos fármacos
Feminino
Fenfluramina/farmacologia
Transtornos da Nutrição Fetal/metabolismo
Transtornos da Nutrição Fetal/fisiopatologia
Hipotálamo/efeitos dos fármacos
Hipotálamo/crescimento & desenvolvimento
Lactação
Masculino
Leite
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Proteínas Proto-Oncogênicas c-fos/metabolismo
Núcleos da Rafe/efeitos dos fármacos
Núcleos da Rafe/crescimento & desenvolvimento
Ratos Wistar
Inibidores da Captação de Serotonina/farmacologia
Ganho de Peso/efeitos dos fármacos
Ganho de Peso/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proto-Oncogene Proteins c-fos); 0 (Serotonin Uptake Inhibitors); 2DS058H2CF (Fenfluramine); 333DO1RDJY (Serotonin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170614
[Lr] Data última revisão:
170614
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160702
[St] Status:MEDLINE


  9 / 2994 MEDLINE  
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[PMID]:27197941
[Au] Autor:Ceulemans B; Schoonjans AS; Marchau F; Paelinck BP; Lagae L
[Ad] Endereço:Department of Neurology-Pediatric Neurology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.
[Ti] Título:Five-year extended follow-up status of 10 patients with Dravet syndrome treated with fenfluramine.
[So] Source:Epilepsia;57(7):e129-34, 2016 Jul.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dravet syndrome (DS) is a rare and therapy-resistant epilepsy syndrome. A retrospective analysis of add-on fenfluramine treatment in 12 patients with DS was published in 2012 and provided evidence of a meaningful long-term response. Herein we present the results of a subsequent 5-year prospective observation of this original cohort. Ten patients with a mean current age of 24 years were followed prospectively from 2010 until 2014. The mean current dose of fenfluramine was 0.27 mg/kg/day, with a mean treatment duration of 16.1 years. Seizure frequency was derived from a seizure diary. Cardiac examinations and assessments of clinical effectiveness and adverse events were performed at least annually. Three patients were seizure-free for the entire 5 years, and an additional four patients experienced seizure-free intervals of at least 2 years. Fenfluramine was generally well-tolerated. Two patients had mild (stable) valve thickening on the last echocardiography that was deemed clinically insignificant. No patient had any clinical or echocardiographic signs of pulmonary hypertension. These findings support the long-term control of convulsive seizures by low-dose fenfluramine while being well tolerated in this cohort of patients with DS. After up to 27 years of treatment, no patient has developed any clinical signs or symptoms of cardiac valvulopathy or pulmonary hypertension.
[Mh] Termos MeSH primário: Epilepsias Mioclônicas/tratamento farmacológico
Fenfluramina/uso terapêutico
Inibidores da Captação de Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Feminino
Seres Humanos
Estudos Longitudinais
Masculino
Estudos Retrospectivos
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Serotonin Uptake Inhibitors); 2DS058H2CF (Fenfluramine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170616
[Lr] Data última revisão:
170616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160521
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13407


  10 / 2994 MEDLINE  
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[PMID]:27189023
[Ti] Título:Serotonergic modulation for Dravet Syndrome treatment.
[So] Source:ACS Chem Neurosci;7(5):519, 2016 05 18.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Encéfalo/diagnóstico por imagem
Transtornos Relacionados ao Uso de Cocaína/prevenção & controle
Marcação por Isótopo
Radioisótopos
Inibidores da Captação de Serotonina/farmacologia
Vacinas/imunologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Epilepsias Mioclônicas/tratamento farmacológico
Fenfluramina/uso terapêutico
Histona Desacetilases
Seres Humanos
Camundongos
Ratos
Peixe-Zebra
[Pt] Tipo de publicação:INTRODUCTORY JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Radioisotopes); 0 (Serotonin Uptake Inhibitors); 0 (Vaccines); 2DS058H2CF (Fenfluramine); EC 3.5.1.98 (Histone Deacetylases)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170130
[Lr] Data última revisão:
170130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160519
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.6b00116



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