RESUMO
Microcystins produced by cyanobacteria are potent inhibitors of some protein phosphatases, but recent evidence also indicates its potential to generate oxidative stress. In the present study, the effects of microcystin raw extracts (Mic; 0.01 and 20microg/L) and purified okadaic acid (OA; 0.01 and 10microg/L) on short- and long-term memory alteration and antioxidant and oxidative damage were investigated in hippocampus of rats. The results showed an amnesic effect with 0.01 and 20microg/L Mic on retrieval and only with 0.01microg/L Mic on spatial learning. Parallel to these effects oxidative damage was observed as evidenced by augmented levels of lipid peroxides and DNA damage and the absence of antioxidant responses in terms of total oxyradical scavenging capacity. Phase II reactions catalyzed by glutathione-S-transferase were not modified after microcystins exposure. Overall this study showed physiological events (retrieval and spatial learning) that can be related to the classical toxic effects of microcystins (i.e., phosphatase inhibition). In addition, evidence of alternative toxicity mechanisms via oxidative stress generation was also obtained. The fact that organic anion transporter polypeptides (OATP) involved in microcystins uptake are expressed not only in liver but also in brain points to the environmental relevance of the observed effects.
Assuntos
Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Memória/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Animais , Hipocampo/metabolismo , Memória/fisiologia , Memória de Curto Prazo/fisiologia , Microcistinas , Ácido Okadáico/farmacologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
PURPOSE: This study analyzed whether combination therapy with hydroxyurea (HU) could be considered as first line treatment for antiretroviral-naive patients. METHOD: The prospective open-label study was carried out from March 1996 to May 2000. The antiretroviral treatments were treatment 1-didanosine 400 mg/day, stavudine 60/80 mg/day, and HU 500 mg/day; treatment 2-two nucleosides plus a protease inhibitor; treatment 3-didanosine, indinavir, and HU (500-1,000 mg/day). The viral load (VL) and CD4 determinations were performed at weeks 24, 48, 72, and 96. RESULTS: The sample comprised 284 patients. The distribution of patients by levels of VL and CD4 were similar in the three treatment groups. At week 24, patients receiving T1 and T3 achieved higher percentages of undetectable VL (89% and 81%, respectively) with no significant differences (p =.127) between them. The T2 group showed a lower proportion (58%) of undetectable VL, which was significantly lower than T1 (p <.0001) and T3 (p <.0007). At week 48, the results were similar to week 24. At week 96, nearly all patients had undetectable viral load (UVL). The analysis of adverse effects showed that the T2 group at week 48 had a greater proportion of adverse effects that was significantly different from T1 (p =.0026); T3 had intermediate values with no significant difference from T2 (p =.45) and from T1 (p =.048). At week 48, T1 showed higher adherence level with significant difference from the other two treatments. CONCLUSION: Patients were followed for some 96 weeks and, with an intention-to-treat analysis, were found to do better virologically and Clinically in treatment groups containing HU. The combination of antiretroviral drugs with HU may be an excellent option as initial therapy because of its strong antiretroviral action, its lower rate of adverse effect, and the smaller cost as compared to other regimens.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hidroxiureia/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Quimioterapia Combinada , HIV-1/fisiologia , Humanos , Hidroxiureia/efeitos adversos , Cooperação do Paciente , Inibidores da Transcriptase Reversa/efeitos adversos , Carga ViralRESUMO
Objetivo: Evaluar el impacto sobre la tasa de complicaciones en la intubación orotraqueal con la implementación de un protocolo de actuación en el manejo de la vía aérea. Materiales y Métodos: Pacientes admitidos al Servicio de Terapia Intensiva polivalente entre agosto de 2012 y marzo de 2014, que requirieron intubación orotraqueal. Se utilizó un protocolo de actuación "Pensar globalmente y Actuar localmente" durante el proceso de preintubación, intubación y posintubación, que incluye valoración de las vías aéreas, planes de seguridad, optimización cardiovascular y pulmonar. Las complicaciones fueron: 1) intubación dificultosa, 2) intubación esofágica, 3) traumatismo de la vía aérea superior, 4) broncoaspiración, 5) arritmias cardíacas, 6) paro cardiocirculatorio. Se compararon las tasas de complicaciones durante dos períodos: Período 1 (P1): de agosto de 2010 a julio de 2012, en el que se realizó la intubación orotraqueal mediante la Secuencia de Intubación Rápida, y Período 2 (P2): de agosto de 2012 a marzo de 2014, en el que se implementó el protocolo "Pensar globalmente y Actuar localmente". Se evaluaron características demográficas, puntajes APACHE II y SOFA, complicaciones de la intubación, estancia en Terapia Intensiva y mortalidad. El análisis estadístico se realizó utilizando la media, la desviación estándar y la prueba de Fisher para las variables cuantitativas y la prueba de χ2 para las variables dicotó- micas. Se consideró significativa una probabilidad de error <5% (p <0,05). Resultados: 374 pacientes requirieron intubación orotraqueal: 180 (48,1%) en el P1 y 194 (51,8%) en el P2; edad: 59 ± 18 años (P1) y 61 ± 18 años (P2); APACHE II: 18 (P1) y 16 (P2); SOFA: 8 ± 2 y 7 ± 3, respectivamente; complicaciones: P1, 24 (13%), P2, 7 (3,6%) (p <0,001); intubación dificultosa: P1, 8 (33,3%), P2, 1 (14,2%) (p <0,005); intubación esofágica: P1, 3 (12,5%), P2, 1 (14,2%); traumatismo de la vía aérea superior: P1, 5 (21,3%), P2, 2 (28,5%); broncoaspiración: P1, 4 (16,6%), P2, 1 (14,2%); arritmias: P1, 3 (12,5%), P2,2 (28,5%), paro cardiocirculatorio: P1, 1 (4,1%), P2: 0. Estancia en Terapia Intensiva: 13.5 ± 3 días (P1) y 12.8 ± 1.2 días (P2). Mortalidad 10% (P1) y 6,2% (P2) (NS). Conclusión: La aplicación de un protocolo para el manejo de la vía aérea redujo, con significación estadística, la tasa de complicaciones, en particular, la intubación dificultosa. (AR)
Objective: To evaluate the impact of a protocol for the management of the airway on the complication rate in tracheal intubation. Materials and Methods: Patients requiring orotracheal intubation admitted to the Intensive Care Unit from August 2012 to March 2014 were included. The "Think globally and Act locally" protocol was used during pre-intubation, intubation and after intubation, including assessment of the airway, safety plans, cardiovascular and pulmonary optimization. Complications: 1) difficult intubation, 2) esophageal intubation, 3) upper airway trauma, 4) aspiration, 5) arrhythmias, 6) cardiac arrest. Rates of complications were compared during two periods: Period 1 (P1): from August 2010 to July 2012 where orotracheal intubation was conducted through rapid sequence intubation, and Period 2 (P2) from August 2012 to March 2014, where "Think globally and Act locally" protocol was implemented. Demographic characteristics, APACHE II and SOFA scores, complications of intubation, length of stay in the Intensive Care Unit, and mortality were evaluated. Statistical analyses were performed using mean, standard deviation, and Fisher test for quantitative variables and chi square test for dichotomous variables; a probability of error <5% (p <0,05) was considered significant. Results: 374 patients required tracheal intubation: 180 (48.1%) during P1 and 194 (51.8%) during P2; mean age: 59 ± 18 years (P1) and 61 ± 18 years (P2); APACHE II score: 18 (P1) and 16 (P2); SOFA score: 8 ± 2 (P1) and 7 ± 3 (P2); complications: P1, 24 (13%); P2, 7 (3.6%) (p <0.001); difficult intubation: P1, 8 (33.3%), P2, 1 (14.2%) (p <0.005); esophageal intubation: P1, 3 (12.5%), P2, 1 (14.2%), upper airway trauma: P1, 5 (21.3%), P2, 2 (28.5%); aspiration: P1, 4 (16.6%), P2, 1 (14.2%); arrhythmias: P1, 3 (12.5%), P2, 2 (28.5%); cardiac arrest: P1, 1 (4.1%), P2, 0; stay in the Intensive Care Unit: 13.5 ± 3 (P1) and 12.8 ± 1.2 days (P2); mortality: 10% (P1) and 6.2% (P2) (NS). Conclusion: Implementation of a protocol for the management of the airway decreased complications with statistical significance, including difficult intubation.(AR)