RESUMO
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients with intractable epilepsy. However, the pathogenesis of SUDEP seems to be poorly understood. Our previous findings showed that the incidence of seizure-induced respiratory arrest (S-IRA) was markedly reduced by atomoxetine in a murine SUDEP model. Because the central norepinephrine α-1 receptor (NEα-1R) plays a vital role in regulating respiratory function, we hypothesized that the suppression of S-IRA by atomoxetine was mediated by NE/NEα-1R interactions that can be reversed by NEα-1R antagonism. We examined whether atomoxetine-mediated suppression of S-IRA evoked by either acoustic stimulation or pentylenetetrazole (PTZ) in DBA/1 mice can be reversed by intraperitoneal (IP) and intracerebroventricular (ICV) administration of prazosin, a selective antagonist of NEα-1R. The content and activity of tyrosine hydroxylase (TH), a rate-limiting enzyme for NE synthesis, in the lower brainstem was measured by ELISA. Electroencephalograms (EEG) were obtained from using the PTZ-evoked SUDEP model. In our models, atomoxetine-mediated suppression of S-IRA evoked by either acoustic stimulation or PTZ was significantly reversed by low doses of IP and ICV prazosin. Neither repetitive acoustic stimulation nor S-IRA reduced TH levels in lower brainstem. However, the enzyme activity of TH levels in lower brainstem was significantly increased by mechanical ventilation with DBA/1 mice, which makes the dying DBA/1 mice suffering from S-IRA and SUDEP recover. EEG data showed that although the protective effect of atomoxetine was reversed by prazosin, neither drug suppressed EEG activity. These data suggest that deficient synthesis of NE and norepinephrinergic neurotransmission contributed to S-IRA and that the NEα-1R is a potential therapeutic target for the prevention of SUDEP.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/toxicidade , Tronco Encefálico/efeitos dos fármacos , Ondas Encefálicas/efeitos dos fármacos , Norepinefrina/deficiência , Prazosina/toxicidade , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Respiração/efeitos dos fármacos , Insuficiência Respiratória/metabolismo , Convulsões/metabolismo , Estimulação Acústica , Inibidores da Captação Adrenérgica/farmacologia , Animais , Cloridrato de Atomoxetina/farmacologia , Tronco Encefálico/metabolismo , Tronco Encefálico/fisiopatologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos Endogâmicos DBA , Pentilenotetrazol , Receptores Adrenérgicos alfa 1/metabolismo , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/prevenção & controle , Convulsões/tratamento farmacológico , Convulsões/etiologia , Convulsões/fisiopatologia , Transdução de Sinais , Morte Súbita Inesperada na Epilepsia/etiologia , Morte Súbita Inesperada na Epilepsia/prevenção & controle , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The sorption behavior of phosphorus onto sediment was investigated with the addition of BC derived from incomplete biomass combustion (PC). The sorption kinetic curves of phosphorus onto PC and sediment could be described by a two-compartment first order equation, and the sorption isotherms fit the Freundlich model well. With increasing amounts of PC added, the sorption capacity increased while the HI did not change much. The distribution of phosphorus forms showed that CaP (ACa-P plus DAP) constituted the highest fraction in the sediment samples. Throughout the sorption process, CaP and OP changed very little, but the Ex-P and FeP increased obviously, and the presence of PC made this increase more significantly. The high specific area and the presence of iron and aluminum, as well as the modification of the sediments surface properties, make the addition of PC be favorable for the sorption of phosphorus onto sediments.
Assuntos
Sedimentos Geológicos/química , Fósforo/química , Fuligem/química , Adsorção , Cinética , Propriedades de Superfície , Poluentes Químicos da Água/químicaRESUMO
OBJECTIVE: To observe the effects of S-adenosylmethionine (SAMe) in the treatment of cholestasis after total parenteral nutrition (TPN). METHODS: Thirty SD rats were randomly divided into control group, hypercalorie group, hypercalorie+SAMe group, sepsis group and sepsis+SAMe group to compare their states of cholestasis. Sixteen patients received SAMe because of cholestasis after prolonged TPN, and the therapeutic efficacy was observed. RESULTS: Bile flow was obviously decreased and the serum levels of total bile acid and gamma-glutamyl transpeptidase (gamma-G T) were markedly increased in the hypercalorie and sepsis groups. Meanwhile, hepatocyte fatty degeneration, dilatation of cholangioles, and bile sludge could be seen microscopically. SAMe administration in the hypercalorie+SAMe and sepsis+ SAMe groups could increase the bile flow, decrease the serum levels of total bile acid and gamma-G T, reduce the pathological damage to the liver, and clear the bile sludge in the cholangioles. Cholestasis and abnormal liver function were the main manifestations of the 16 patients before SAMe administration. After SAMe treatment for 3 weeks, serum levels of total bilirubin, alkaline phosphatase (AKP), gamma-G T, alanine amino transferase (ALT), and aspartate amino transferase (AST) were obviously decreased, and normalized in the 4th week. CONCLUSION: SAMe could prevent and treat cholestasis without discontinuation of TPN.