RESUMO
Although the predominant role of tryptophan hydroxylase 2 (TPH2) in the CNS and its influence on the vulnerability to psychiatric disorders have clearly been demonstrated in several studies, the role of TPH1 on neuronal mechanisms, respectively on behavioral traits is still poorly understood. In a previous study of tryptophan hydroxylase 1 (TPH1) and TPH2 mRNA expression in different human brain regions we observed significantly higher TPH1 than TPH2 mRNA concentrations in the pituitary (unpublished observations). Considering the importance of the pituitary in the functional circuits between brain and body, we investigated the TPH1 and TPH2 mRNA expression in more detail, using human postmortem samples of the posterior and anterior pituitary compared to cortex, hippocampus and raphe nuclei. Specimens were available from different psychiatric patients (drug abusers, n=12; suicide victims, n=11; schizophrenics, n=9) and controls (n=15). Additionally we performed immunohistochemical analysis applying monospecific antibodies for both TPH isoforms to verify that the mRNA is of cellular and not just vascular or other origin. Highest TPH2 mRNA levels were observed in the raphe nuclei in patients and controls. By contrast, in the anterior and posterior pituitary TPH1 was found to be the predominantly expressed isoform in all subgroups. TPH1 and TPH2 mRNA expression in the further brain regions was only marginal and nearly identical except in the hypothalamus where higher TPH1 than TPH2 mRNA levels could be measured. Interindividual differences between the subgroups were not detectable. The results of the present study extended our previous findings by the additional immunohistochemical determination of the neuronal TPH1 and TPH2 protein expression in the anterior pituitary and provide evidence against a strictly separated duality of the serotonergic system. It seems that TPH1 might also have an impact on neuronal mechanisms via hypothalamic-pituitary-adrenal axis regulation by its predominant localization in the pituitary. These observations may open up new research strategies not only for several psychiatric disorders, but also for the relationship between psychiatric and somatic diseases.
Assuntos
Encéfalo/metabolismo , Neurônios/metabolismo , Hipófise/metabolismo , Triptofano Hidroxilase/metabolismo , Adolescente , Adulto , Idoso , Córtex Cerebral/metabolismo , Feminino , Humanos , Hipotálamo/metabolismo , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Núcleos da Rafe/metabolismo , Esquizofrenia/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Suicídio , Triptofano Hidroxilase/genética , Adulto JovemAssuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Neuropeptídeos/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Suicídio , Adulto , Tonsila do Cerebelo/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Feminino , Humanos , Hipotálamo/metabolismo , Masculino , Pessoa de Meia-Idade , Neuropeptídeos/genética , RNA Mensageiro/análise , Assunção de RiscosAssuntos
Neoplasias da Mama/cirurgia , Mastectomia Segmentar/métodos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
For testing the efficiency of Bonnecor in intravenous administration (0.3 mg/kg) 36 patients were examined electrophysiologically (31 with paroxysmal supraventricular tachycardias, 5 with ventricular tachycardias). In other 6 patients haemodynamic investigations were performed by means of right-heart catheterization and thermodilution. The supraventricular tachycardias induced by programmed electrostimulation could be interrupted by administration of Bonnecor in 45% of the cases. After the administration of Bonnecor the inducibility of supraventricular tachycardias was suppressed in 11 of the 31 patients. In 2 of the 5 patients with ventricular tachycardia an evocation of ventricular tachycardias was no more possible after an intravenous application of Bonnecor; a medicamentous termination of the ventricular tachycardias had been tried only in one case. Clinically relevant negatively inotropic effects could not be proved. Apart from insignificant malaises in few cases, no side-effects occurred.