RESUMO
Light is recognized as an accurate and noninvasive tool for stimulating excitable cells. Here, we report on a non-genetic approach based on organic molecular phototransducers that allows wiring- and electrode-free tissue modulation. As a proof of concept, we show photostimulation of an in vitro cardiac microphysiological model mediated by an amphiphilic azobenzene compound that preferentially dwells in the cell membrane. Exploiting this optical based stimulation technology could be a disruptive approach for highly resolved cardiac tissue stimulation.
Assuntos
Fortalecimento Institucional , Currículo , Países em Desenvolvimento , Acessibilidade aos Serviços de Saúde , Transtornos Mentais/terapia , Serviços de Saúde Mental , Médicos de Atenção Primária/educação , Psiquiatria/educação , Guatemala , Humanos , Saúde Mental , Organizações , População Rural , Transtornos Relacionados ao Uso de Substâncias/terapiaRESUMO
Tobacco addiction is a chronic disorder that is characterized by a negative affective state upon smoking cessation and relapse after periods of abstinence. Previous research has shown that an increased central release of corticotropin-releasing factor (CRF) at least partly mediates the deficit in brain reward function associated with nicotine withdrawal in rats. The aim of these studies was to investigate the role of CRF in the central nucleus of the amygdala (CeA), the lateral bed nucleus of the stria terminalis (BNST), and the nucleus accumbens shell (Nacc shell) in the deficit in brain reward function associated with precipitated nicotine withdrawal. The intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. In all experiments, the nicotinic receptor antagonist mecamylamine (3 mg/kg) elevated the brain reward thresholds of the nicotine-dependent rats (9 mg/kg per day of nicotine salt) and did not affect the brain reward thresholds of the saline-treated control rats. The administration of the nonspecific CRF1/2 receptor antagonist D-Phe CRF((12-41)) into the CeA and the Nacc shell prevented the mecamylamine-induced elevations in brain reward thresholds in the nicotine-dependent rats. Blockade of CRF1/2 receptors in the lateral BNST did not prevent the mecamylamine-induced elevations in brain reward thresholds in the nicotine-dependent rats. These studies indicate that the negative emotional state associated with precipitated nicotine withdrawal is at least partly mediated by an increased release of CRF in the CeA and the Nacc shell.
Assuntos
Tonsila do Cerebelo/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Transtornos do Humor/induzido quimicamente , Transtornos do Humor/patologia , Nicotina/efeitos adversos , Agonistas Nicotínicos/efeitos adversos , Núcleo Accumbens/metabolismo , Síndrome de Abstinência a Substâncias , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Hormônio Liberador da Corticotropina/administração & dosagem , Hormônio Liberador da Corticotropina/análogos & derivados , Hormônio Liberador da Corticotropina/antagonistas & inibidores , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Mecamilamina/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Antagonistas Nicotínicos/uso terapêutico , Núcleo Accumbens/efeitos dos fármacos , Ratos , Ratos Wistar , Autoadministração/métodos , Síndrome de Abstinência a Substâncias/patologiaRESUMO
BACKGROUND/PURPOSE: Complete androgen insensitivity syndrome (CAIS) is a rare disorder; however, surgeons have noted a higher rate in girls with inguinal hernias. A few retrospective studies have estimated the incidence of CAIS to be 0.8% to 2.4% in girls with inguinal hernias. An inexpensive, quick screening method for this population has not been established. Because CAIS is associated with a short vagina, measuring vaginal length could serve this purpose if normal standards were known. The authors endeavored to (1) prospectively confirm the incidence of CAIS, (2) identify normal standards of vaginal length, and (3) assess the usefulness of measuring vaginal length to screen for CAIS in girls with inguinal hernias. METHODS: Vaginal lengths were measured in 270 girls with inguinal hernias at a university hospital from 1991 to 2003. A fallopian tube was identified to exclude CAIS. If CAIS was suspected, gonadal tissue was sampled and karyotyping was performed. Linear regression analysis was performed, and 95% confidence intervals were calculated for individual values. RESULTS: Normal vaginal length for age was established. Three patients were found to have significantly short vaginas: 2 were confirmed to have CAIS, 1 did not (false-positive). One other infant was proved to have CAIS despite having a normal vaginal length (false-negative). The incidence of CAIS in our study was 1.1% (3/270). CONCLUSIONS: This is the largest prospective study of the incidence of CAIS in girls with hernias. The authors found that 1.1% of premenstrual girls with inguinal hernias have this syndrome. The authors also provide standards for normal vaginal length in the pediatric population. Vaginal length increases predictably with age, and some patients with CAIS have significantly shorter vaginas. Vaginal length is not a perfect predictor of this disorder, but can be a useful adjunctive screening tool.
Assuntos
Síndrome de Resistência a Andrógenos/diagnóstico , Síndrome de Resistência a Andrógenos/epidemiologia , Hérnia Inguinal/complicações , Programas de Rastreamento/métodos , Vagina/anormalidades , Síndrome de Resistência a Andrógenos/complicações , Pesos e Medidas Corporais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Valores de ReferênciaRESUMO
The purpose of this study was to investigate the clinical safety of sodium valproate and total and unbound valproic acid plasma concentrations after rapid infusion in hospitalized, acutely ill children. Four children (5-15 years) completed the study. Sodium valproate doses (8.3-15.4 mg/kg) were administered in Assuntos
Anticonvulsivantes/administração & dosagem
, Epilepsia Parcial Complexa/tratamento farmacológico
, Epilepsia Generalizada/tratamento farmacológico
, Epilepsia Tônico-Clônica/tratamento farmacológico
, Ácido Valproico/administração & dosagem
, Doença Aguda
, Adolescente
, Anticonvulsivantes/efeitos adversos
, Anticonvulsivantes/farmacocinética
, Criança
, Pré-Escolar
, Relação Dose-Resposta a Droga
, Esquema de Medicação
, Quimioterapia Combinada
, Epilepsia Parcial Complexa/sangue
, Epilepsia Parcial Complexa/diagnóstico
, Epilepsia Generalizada/sangue
, Epilepsia Generalizada/diagnóstico
, Epilepsia Tônico-Clônica/sangue
, Epilepsia Tônico-Clônica/diagnóstico
, Feminino
, Meia-Vida
, Humanos
, Infusões Intravenosas
, Masculino
, Taxa de Depuração Metabólica/fisiologia
, Resultado do Tratamento
, Ácido Valproico/efeitos adversos
, Ácido Valproico/farmacocinética