Foxp3 expression and nitric oxide production in peripheral blood mononuclear cells of communicants with pulmonary tuberculosis.

The understanding of the mechanisms involved in the immune response is of significant relevance to the control of tuberculosis (TB), especially in individuals living with patients with TB. To characterize the nitric oxide (NO) production and the Foxp3 marker expression in this population, peripheral blood mononuclear cells of intradomiciliary contacts of individuals with pulmonary tuberculosis with (CTb, susceptible) and without (STb, resistant) previous history of active infection were stimulated in vitro with Mycobacterium tuberculosis antigen (TbAg) and with the mitogen Concanavalin A for 24 and 48 h. The groups analysed did not present significant difference in the Foxp3 mRNA expression nor in the NO production. Negative correlation (P = 0.09) between NO and Foxp3 after a 48-h stimulation with TbAg was observed in the STb group. In this group, after a 24-h culture stimulated with TbAg (P = 0.03), this same correlation was observed. In comparison with the cytokines previously studied by our group (Cavalcanti et al., 2009), a positive correlation was observed between IL-10 and Foxp3 after a 48-h culture of cells from communicants susceptible to tuberculosis (STb) stimulated with TbAg (P = 0.04). Evaluating the entire population, a positive correlation was observed between the cytokine TNF-α and the Foxp3 marker in the cultures stimulated for 24 (P = 0.03) and 48 (P = 0.02) hours with TbAg. Therefore, considering the similarity in the exposure and the individual capacity of responding to the contact with M. tuberculosis, the present study contributes to the comprehension of the immune regulation in individuals living with patients with TB.

Antigenic fractions of Leishmania (Viannia) braziliensis: the immune response characterization of patients at the initial phase of disease.

American cutaneous leishmaniasis (ACL) has different clinical manifestations and these manifestations are dependent on the immunological status of the host. As CD4(+) and CD8(+) T cells and their mediators play a fundamental role in the host response to Leishmania and there is also a search for antigenic molecules to be used as future vaccines and tools for prognostic tests, this study characterized ACL patients' immune response after stimulation with soluble and insoluble fractions of L. (V.) braziliensis. We demonstrated a prevailing production of the Th2 cytokines, IL-4 and IL-10 and a specific production of IFN-γ and TNF-α in patients before treatment. There was also a predominance of CD4(+) T cells and a small percentage CD8(+) T cells. The insoluble antigenic fraction primarily stimulated CD4(+) T cells, while the soluble antigenic fraction showed a mixed profile, with CD4(+) T cells being the main responsible for Th2 cytokines and CD8(+) T cells for Th1 cytokines. Therefore, our results showed that a down-modulation of the Th1 type of response occurs in the initial phase of L. braziliensis disease, being the antigenic fractions capable of stimulating a specific immune response.

Metabolic and functional changes in lymphocytes and macrophages as induced by ageing.

Key enzyme activities of glycolysis, pentosephosphate pathway, Krebs cycle, and glutaminolysis were measured in lymphocytes and macrophages of 3- and 15-month-old rats from the control, thioglycollate-injected, and Walker 256 tumor-implanted groups. The percentage of phagocytosis, phagocytic index, and production of H2O2 in macrophages and the rates of [2-14C]-thymidine and [5-3H]-uridine incorporation in cultured lymphocytes were also determined. The results indicate that the percentage of phagocytosis was not affected but the phagocytic index increased by twofold as a consequence of ageing, whereas the production of H2O2 reduced. The rates of both [2-14C]-thymidine and [5-3H]-uridine incorporation in lymphocytes from aged rats were lower as compared to those of mature animals in the three groups. Taken as a whole, the results of enzyme activities suggest that ageing may reduce the capacity for glucose utilization in lymphocytes and macrophages under the three conditions. Lymphocyte and macrophage glutamine metabolism was not markedly affected by ageing. Therefore, an impaired glucose metabolism during ageing may be one important mechanism for the alteration in lymphocyte proliferation and macrophage phagocytosis observed and also for the modification of the response to inflammatory and tumor challenges.

[Echocardiography and Doppler study of congenitally corrected transposition of the great arteries]. / Estudio ecocardiográfico y Doppler en la transposición congénitamente corregida de las grandes arterias.

In order to determine the echocardiographic and Doppler characteristics of patients with congenitally corrected transposition of the great arteries we studied 5 patients with this condition. Mean age was 19 years, ranging from 6 to 57 years. All patients except the oldest were asymptomatic. In all the patients we could observe the typical pattern of ventricular inversion by two-dimensional echocardiography from the apical view. There was dilation of systemic ventricle in 2 patients and dilation of venous ventricle in every patient. The anterograde valvular flows were normal, and also the hepatic vein flow, showing no impediment in the filling of venous atrium and venous ventricle. We observed tricuspid regurgitation in all the patients probably due to valvular inadaptation to the high ventricular pressure. Two-dimensional echocardiography can easily show the alterations of patients with congenitally corrected transposition of the great arteries. The cardiac Doppler gets additional information about the valvular performance.

Thioglycollate stimulus modifies lymphocyte metabolism and proliferation. A comparison with lymphocyte activation by Walker 256 tumour implantation.

Key enzyme activities of glycolysis, the pentose-phosphate pathway, the Krebs' cycle and glutaminolysis were measured in lymphocytes obtained from the control (CC), thioglycollate-injected (TG) and Walker 256 tumour-implanted (WT) groups, non-immune and immune inflammatory stimuli, respectively. The rates of incorporation of [2-14C]-thymidine and [5-3H]-uridine into cultured lymphocytes were also determined. The results indicated that the rates of both [2-14C]-thymidine and [5-3H]-uridine incorporation were enhanced in lymphocytes obtained from thioglycollate-injected (by an average of 80 per cent) and tumour-implanted animals (by 2.4-fold) as compared to control rats. Lymphocyte hexokinase activity diminished both in the TG (23 per cent) and WT (61 per cent) groups, whereas glucose 6-phosphate dehydrogenase activity was not altered due to the non-immune inflammatory stimulus, being reduced (23 per cent) in WT rats as compared to CC. The activity of lymphocyte citrate synthase was lowered by thioglycollate (39 per cent) and tumour-implantation (46 per cent). In contrast, glutaminase activity was augmented in lymphocytes from the TG (41 per cent) and was not modified in the WT groups. Taken as a whole, the presence of the Walker 256 tumour did not affect the capacity for glutamine utilization but depressed glucose metabolism in these cells. On the other hand, the non-immune inflammatory stimulus suppressed the activities of glycolysis and the Krebs' cycle and enhanced that of glutaminolysis in lymphocytes.

Maximal activities of key enzymes of glutaminolysis, glycolysis, Krebs cycle and pentose-phosphate pathway of several tissues in mature and aged rats.

1. The maximum activities of some key enzymes, which provide a quantitative indices of flux through several important pathways have been measured in brain, liver, muscle, white and brown adipose tissue and lymphocytes of mature and aged rats. 2. The results were expressed as mumol/min per g fresh weight and nmol/min per mg protein. 3. On the both basis, as compared to mature rats, hexokinase activity is decreased in brown adipose tissue and increased in soleus muscle. 4. Glucose-6-phosphate dehydrogenase activity is decreased in most tissues and increased in brain. 5. Citrate synthase activity, which provides a qualitative index of the Krebs cycle, is decreased in white adipose tissues and lymphocytes. 6. Glutaminase activity is decreased in brain, white and brown adipose tissues but is increased in lymphocytes.