RESUMO
BACKGROUND AND PURPOSE: This study investigated whether isoflurane ameliorates neurological sequelae after germinal matrix hemorrhage (GMH) through activation of the cytoprotective sphingosine kinase/sphingosine-1-phosphate receptor/Akt pathway. METHODS: GMH was induced in P7 rat pups by intraparenchymal infusion of bacterial collagenase (0.3 U) into the right hemispheric germinal matrix. GMH animals received 2% isoflurane either once 1 hour after surgery or every 12 hours for 3 days. Isoflurane treatment was then combined with sphingosine-1-phosphate receptor-1/2 antagonist VPC23019 or sphingosine kinase 1/2 antagonist N,N-dimethylsphingosine. RESULTS: Brain protein expression of sphingosine kinase-1 and phosphorylated Akt were significantly increased after isoflurane post-treatment, and cleaved caspase-3 was decreased at 24 hours after surgery, which was reversed by the antagonists. Isoflurane significantly reduced posthemorrhagic ventricular dilation and improved motor, but not cognitive, functions in GMH animals 3 weeks after surgery; no improvements were observed after VPC23019 administration. CONCLUSIONS: Isoflurane post-treatment improved the neurological sequelae after GMH possibly by activation of the sphingosine kinase/Akt pathway.
Assuntos
Encéfalo/efeitos dos fármacos , Hemorragias Intracranianas/tratamento farmacológico , Isoflurano/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Modelos Animais de Doenças , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/metabolismo , Isoflurano/farmacologia , Fármacos Neuroprotetores/farmacologia , Fosforilação/efeitos dos fármacos , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptores de Lisoesfingolipídeo/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Esfingosina/uso terapêuticoRESUMO
PurposeThe purpose of this study was to compare the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression, to that of treatment as usual (TAU) alone. MethodsIn this study, 302 depressed adult Family Medicine outpatients were randomized to receive either TAU or additional access to Thrive, a fully automated iCBT program with three video-based modules, each containing 10 lessons using behavioral activation, cognitive restructuring, and social skills training. The primary outcome was the change in the score on an online patient health questionnaire (PHQ-9), measured at 0, 8, and 24 weeks. ResultsThe intervention group saw a relative improvement of 2.5 points in PHQ-9 scores at 8 weeks (p = 0.002, d = -0.48), was 6.0 times (p < 0.001) more likely to respond (defined as a ≥ 50% reduction in PHQ-9 score), and was 5.2 times (p = 0.04) more likely to have achieved remission (defined as a PHQ-9 score of < 5) at 8 weeks, but by 24 weeks, the control group had improved to a similar extent as the intervention group (d = -0.14). The intervention group improved in productivity at 8 weeks (p = 0.03), but by 24 weeks, the TAU group had also improved to a similar extent. No significant differences in anxiety, quality of life, or suicidal ideation were found. Patients reported high satisfaction with this iCBT tool, including ease of use, tailoring, and perceived helpfulness. However, only 43% of the intervention group and 58% of the TAU group had outcome measures at every time point. ConclusionsiCBT was associated with greater depression response and remission at 8 weeks, compared with the control group. Depression scores in the intervention group remained similar at 24 weeks, at which time the control group also showed similar rate of response and remission.
Assuntos
Terapia Cognitivo-Comportamental , Depressão , Adulto , Depressão/terapia , Humanos , Internet , Atenção Primária à Saúde , Qualidade de Vida , Resultado do TratamentoRESUMO
This review evaluates the mechanism of volatile anesthetics as cardioprotective agents in both clinical and laboratory research and furthermore assesses possible cardiac side effects upon usage. Cardiac as well as non-cardiac surgery may evoke perioperative adverse events including: ischemia, diverse arrhythmias and reperfusion injury. As volatile anesthetics have cardiovascular effects that can lead to hypotension, clinicians may choose to administer alternative anesthetics to patients with coronary artery disease, particularly if the patient has severe preoperative ischemia or cardiovascular instability. Increasing preclinical evidence demonstrated that administration of inhaled anesthetics - before and during surgery - reduces the degree of ischemia and reperfusion injury to the heart. Recently, this preclinical data has been implemented clinically, and beneficial effects have been found in some studies of patients undergoing coronary artery bypass graft surgery. Administration of volatile anesthetic gases was protective for patients undergoing cardiac surgery through manipulation of the potassium ATP (KATP) channel, mitochondrial permeability transition pore (mPTP), reactive oxygen species (ROS) production, as well as through cytoprotective Akt and extracellular-signal kinases (ERK) pathways. However, as not all studies have demonstrated improved outcomes, the risks for undesirable hemodynamic effects must be weighed against the possible benefits of using volatile anesthetics as a means to provide cardiac protection in patients with coronary artery disease who are undergoing surgery.