RESUMEN
Although lymphomas account for almost half of blood-derived cancers that are diagnosed each year, the causes of new cases are poorly understood, as reflected by the relatively few risk factors established. Galectin-1, an immunoregulatory ß-galactoside-binding protein, has been widely associated with tumor-immune escape. The aim of the present work was to study the relationship between tumor growth rate, aggressiveness, and response to cyclophosphamide (Cy) therapy with regard to Gal-1 expression in murine T-cell lymphoma models. By means of a disruptive selection process for tumor growth rate, we generated two lymphoma variants from a parental T-cell lymphoma, which have unique characteristics in terms of tumor growth rate, spontaneous regression, metastatic capacity, Gal-1 expression and sensitivity to Cy therapy. Here, we show that Gal-1 expression strongly correlates with tumor growth rate, metastatic capacity and response to single-dose Cy therapy in T-cell lymphoma models; this association might have important consequences for evaluating prognosis and treatments of this type of tumors.
Asunto(s)
Galectina 1/metabolismo , Linfoma de Células T/patología , Linfocitos T Reguladores/metabolismo , Animales , Antígenos CD4/metabolismo , Proliferación Celular/efectos de los fármacos , Ciclofosfamida/administración & dosificación , Femenino , Factores de Transcripción Forkhead/metabolismo , Galectina 1/genética , Galectina 1/inmunología , Regulación Neoplásica de la Expresión Génica , Humanos , Terapia de Inmunosupresión , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/inmunología , Ratones , Metástasis de la Neoplasia , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patologíaRESUMEN
OBJECTIVE: This prospective study aimed to characterize the changes in blood lactate concentration and blood oxygen saturation in patients during the immediate postoperative period of cardiac surgery with extracorporeal circulation. METHODS: Blood samples were collected from 35 patients in a rapid and random order from the arterial line and from the proximal and distal port of a pulmonary artery catheter. RESULTS: The results showed no statistically significant differences between the blood oxygen saturation in the right atrium (72% ± 0.11%) and the blood oxygen saturation in the pulmonary artery (71% ± 0.08%). The blood lactate concentration in the right atrium was 1.7mmol/L ± 0.5mmol/L, and the blood lactate concentration in the pulmonary artery was 1.6mmol/L ± 0.5mmol/L (p < 0.0005). CONCLUSION: The difference between the blood lactate concentration in the right atrium and the blood lactate concentration in the pulmonary artery might be a consequence of the low blood lactate concentration in the blood from the coronary sinus, as it constitutes an important substrate for the myocardium during this period. The lack of differences between the blood oxygen saturation in the right atrium and the percentage of blood oxygen saturation in the pulmonary artery suggests a lower oxygen extraction by the myocardium given a lower oxygen consumption.
OBJETIVO: Caracterizar as modificações na concentração sanguínea do lactato e da saturação de oxigênio em pacientes no pós-operatório imediato de cirurgia cardíaca com circulação extracorpórea. MÉTODOS: Foram coletadas amostras de sangue de 35 pacientes, de forma rápida e aleatória, do acesso arterial e das portas proximal e distal de um cateter pulmonar. RESULTADOS: Não foram verificadas diferenças estatisticamente significantes entre saturação de oxigênio no átrio direito (72% ± 0,11%) e na artéria pulmonar (71% ± 0,08%). A concentração sanguínea de lactato no átrio direito foi de 1,7mmol/L ± 0,5mmol/L, enquanto na artéria pulmonar esta concentração foi de 1,6mmol/L ± 0,5mmol/L (p < 0,0005). CONCLUSÃO: A diferença entre as concentrações sanguíneas de lactato no átrio direito e na artéria pulmonar pode ser consequência da baixa concentração de lactato no sangue do seio coronário, já que o lactato é um importante substrato para o miocárdio durante este período. A ausência de diferenças entre saturação sanguínea de oxigênio no átrio direito e na artéria pulmonar sugere extração de oxigênio mais baixa pelo miocárdio, em razão do menor consumo de oxigênio.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Circulación Extracorporea/métodos , Ácido Láctico/sangre , Oxígeno/sangre , Anciano , Femenino , Atrios Cardíacos , Humanos , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Periodo Posoperatorio , Estudios Prospectivos , Arteria PulmonarRESUMEN
Risky decision-making seems to be markedly disrupted in patients with chronic pain, probably due to the high cost that impose pain and negative mood on executive control functions. Patients' behavioral performance on decision-making tasks such as the Iowa Gambling Task (IGT) is characterized by selecting cards more frequently from disadvantageous than from advantageous decks, and by switching often between competing responses in comparison with healthy controls (HCs). In the present study, we developed a simple heuristic model to simulate individuals' choice behavior by varying the level of decision randomness and the importance given to gains and losses. The findings revealed that the model was able to differentiate the behavioral performance of patients with chronic pain and HCs at the group, as well as at the individual level. The best fit of the model in patients with chronic pain was yielded when decisions were not based on previous choices and when gains were considered more relevant than losses. By contrast, the best account of the available data in HCs was obtained when decisions were based on previous experiences and losses loomed larger than gains. In conclusion, our model seems to provide useful information to measure each individual participant extensively, and to deal with the data on a participant-by-participant basis.
RESUMEN
Chlorpyrifos (CPF) is an organophosphorus cholinesterase inhibitor widely used as an insecticide. Neuro and genotoxicity of this agent were evaluated following daily subcutaneous injections at 0.1, 1 and 10mg/kg or its vehicle to laboratory rats during one week, at the end of which somatosensory evoked potentials (SEP) and power spectrum of the electroencephalogram (EEGp) were recorded under urethane anesthesia. In another group of conscious animals, auditory startle reflex (ASR) was evaluated followed, after euthanasia, with measurements of plasma B-esterases, and genotoxicity with the alkaline comet assay (ACA) at the same CPF doses. The results indicated a CPF dose related inhibition of B-esterases. Enhanced inhibition of the ASR by a subthreshold pre-pulse was observed at all doses and ACA showed a significant higher DNA damage than vehicle controls in animals exposed to 10mg/kg CPF. A trend to higher frequencies of EEGp and an increase in amplitude of the first negative wave of the SEP were found at all doses. The first positive wave of the SEP decreased at the CPF dose of 10mg/kg. In summary, a shift to higher EEG frequencies and alterations of somatosensory and auditory input to the central nervous system were sensitive manifestations of CPF toxicity, associated with depression of B-esterases. The changes in electrical activity of the cerebral cortex and DNA damage observed at doses that do not elicit overt toxicity may be useful in the detection of CPF exposure before clinical signs appear.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiopatología , Cloropirifos/toxicidad , Inhibidores de la Colinesterasa/toxicidad , Daño del ADN/efectos de los fármacos , Reflejo de Sobresalto/efectos de los fármacos , Acetilcolinesterasa/sangre , Estimulación Acústica , Animales , Temperatura Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Butirilcolinesterasa/sangre , Carboxilesterasa/sangre , Relación Dosis-Respuesta a Droga , Electroencefalografía , Esterasas/sangre , Esterasas/efectos de los fármacos , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Masculino , Pruebas de Mutagenicidad , Inhibición Prepulso/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
RESUMO Objetivo: Caracterizar as modificações na concentração sanguínea do lactato e da saturação de oxigênio em pacientes no pós-operatório imediato de cirurgia cardíaca com circulação extracorpórea. Métodos: Foram coletadas amostras de sangue de 35 pacientes, de forma rápida e aleatória, do acesso arterial e das portas proximal e distal de um cateter pulmonar. Resultados: Não foram verificadas diferenças estatisticamente significantes entre saturação de oxigênio no átrio direito (72% ± 0,11%) e na artéria pulmonar (71% ± 0,08%). A concentração sanguínea de lactato no átrio direito foi de 1,7mmol/L ± 0,5mmol/L, enquanto na artéria pulmonar esta concentração foi de 1,6mmol/L ± 0,5mmol/L (p < 0,0005). Conclusão: A diferença entre as concentrações sanguíneas de lactato no átrio direito e na artéria pulmonar pode ser consequência da baixa concentração de lactato no sangue do seio coronário, já que o lactato é um importante substrato para o miocárdio durante este período. A ausência de diferenças entre saturação sanguínea de oxigênio no átrio direito e na artéria pulmonar sugere extração de oxigênio mais baixa pelo miocárdio, em razão do menor consumo de oxigênio.
ABSTRACT Objective: This prospective study aimed to characterize the changes in blood lactate concentration and blood oxygen saturation in patients during the immediate postoperative period of cardiac surgery with extracorporeal circulation. Methods: Blood samples were collected from 35 patients in a rapid and random order from the arterial line and from the proximal and distal port of a pulmonary artery catheter. Results: The results showed no statistically significant differences between the blood oxygen saturation in the right atrium (72% ± 0.11%) and the blood oxygen saturation in the pulmonary artery (71% ± 0.08%). The blood lactate concentration in the right atrium was 1.7mmol/L ± 0.5mmol/L, and the blood lactate concentration in the pulmonary artery was 1.6mmol/L ± 0.5mmol/L (p < 0.0005). Conclusion: The difference between the blood lactate concentration in the right atrium and the blood lactate concentration in the pulmonary artery might be a consequence of the low blood lactate concentration in the blood from the coronary sinus, as it constitutes an important substrate for the myocardium during this period. The lack of differences between the blood oxygen saturation in the right atrium and the percentage of blood oxygen saturation in the pulmonary artery suggests a lower oxygen extraction by the myocardium given a lower oxygen consumption.