RESUMO
Otolaryngologists are in a good position to advocate for our patients and our specialty. We can do it as a volunteer or as a full-time job running for political office at the state or federal level. To be taken seriously, we need to offer solutions besides citing the problems. We encourage otolaryngologists to work with our Academy and its ENT-PAC (Ear, Nose, Throat Political Action Committee). Medicine is a great profession and Otolaryngology-Head and Neck Surgery is an even better specialty.
Assuntos
Reforma dos Serviços de Saúde , Liderança , Otorrinolaringologistas/organização & administração , Otolaringologia , Humanos , Guias de Prática Clínica como Assunto , Reembolso de Incentivo , Sociedades Médicas , Estados UnidosRESUMO
Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood-brain barrier and directly activates orexigenic AgRP+ neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight. In humans, a genetic deficiency in asprosin causes a syndrome characterized by low appetite and extreme leanness; this is phenocopied by mice carrying similar mutations and can be fully rescued by asprosin. Furthermore, we found that obese humans and mice had pathologically elevated concentrations of circulating asprosin, and neutralization of asprosin in the blood with a monoclonal antibody reduced appetite and body weight in obese mice, in addition to improving their glycemic profile. Thus, in addition to performing a glucogenic function, asprosin is a centrally acting orexigenic hormone that is a potential therapeutic target in the treatment of both obesity and diabetes.
Assuntos
Regulação do Apetite/genética , Hipotálamo/metabolismo , Proteínas dos Microfilamentos/fisiologia , Fragmentos de Peptídeos/fisiologia , Hormônios Peptídicos/fisiologia , Adolescente , Adulto , Animais , Depressores do Apetite/metabolismo , Feminino , Fibrilina-1 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/genética , Neurônios/metabolismo , Fragmentos de Peptídeos/genética , Hormônios Peptídicos/genética , Ratos , Transdução de Sinais , Adulto JovemRESUMO
Here, we attempt to reveal how 2-aminofluorene (AF), benzo(alpha)pyrene (BP) and their major metabolites affect T-cell responses to antigenic and mitogenic stimuli. P-450-related metabolism of these parent compounds to metabolites seems to precede the observed immunosuppression; therefore, we investigated the influence of alpha-naphthoflavone (P-450 inhibitor) and beta-naphthoflavone (P-450 inducer) on BP and AF immunosuppression. We used proliferative responses to concanavalin A and the allogeneic mixed lymphocyte response as correlates of immunosuppression. We also attempted to correlate DNA-adduction to the extent of observed immunosuppression for AF and BP metabolites. These data show that the pathway to the strongest immunosuppressive agents for polycyclic aromatic hydrocarbons and arylamines are divergent and related to metabolism by P450 enzymes.