Exercise partially reverses the inhibitory effect of caffeine on liver gluconeogenesis in type 1 diabetic rats with hypoglycemia

The purpose was to determine the possible effects of exercise and/or caffeine on hypoglycemia and liver gluconeogenesis in diabetic rats. These were divided into four subgroups: (a) intraperitoneal insulin only, (b) exercise bout before insulin, (c) caffeine after insulin, and (d) exercise bout before and caffeine after insulin. The marked glycemic drop 45 min after insulin (0 min = 229.00, 45 min = 75.75) was considerably reduced (p  0.05) when they were combined (45 min: exercise + caffeine = 65.44) (Mean, in mg·dL−1). Caffeine alone strongly inhibited liver glucose production from 2 mM lactate 45 min after insulin (without caffeine = 3.05, with caffeine = 0.27; p −1). The improved hypoglycemia with caffeine or exercise cannot be explained by their actions on liver gluconeogenesis. As their beneficial effect disappeared when they were combined, such association in diabetic patients should be avoided during the period of hyperinsulinemia due to the risk of severe hypoglycemia

Partial chemical and functional characterization of milk whey products obtained by different processes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Whey protein samples (S-1 to S-5) were tested in vivo and in vitro for nutritional properties and selected bioactivities. Weanling male Wistar rats fed modified AIN-93G (12 g protein. 100 g(-1)) diets for 21 days were used the in vivo studies. The nutritional parameters did not differ among the protein diets tested. Erythrocyte glutathione content was considered high and was higher for S-3, but liver glutathione was the same for all dietary groups. For S-3, cytokine secretion (IL-10 and TNF-alpha) by human peripheral blood mononuclear cells (in RPMI-1640 medium) was higher in the absence of antigen than in the presence of BCG antigen. Interleukin-4 secretion was repressed in all treatments. The IC50, whey protein concentration required to inhibit 50% of the melanoma cell proliferation, was 2.68 mg.mL(-1) of culture medium for the S-3 sample and 3.66 mg.mL(-1) for the S-2 sample. Based on these results, it was concluded that S-3 (whey protein concentrate enriched with TGF-beta and lactoferrin) produced better nutritional and immunological responses than the other products tested.3215664Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CIPED (Pediatrics Investigation Center of the University of Campinas)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Autoimmune lymphoproliferative syndrome presenting with glomerulonephritis

Autoimmune lymphoproliferative syndrome (ALPS) is characterized clinically by chronic non-malignant lymphoproliferation and autoimmunity and is caused by a genetic defect in programmed cell death (apoptosis). Most patients with ALPS have heterozygous mutations in the Fas gene. We describe an 11-year-old Brazilian boy with hepatosplenomegaly, lymphadenopathy, hemolytic anemia, and hypergammaglobulinemia since early infancy. T cell lines from the patient were defective in Fas-mediated apoptosis. He was diagnosed as having ALPS and found to have a novel Fas gene mutation (IVS4+1G>A). In addition, he presented with glomerulonephritis in infancy. An aunt and uncle who had the same Fas mutations also had histories of glomerulonephritis. Although glomerulonephritis is common in Fas-deficient mice, it is infrequent in human ALPS. Corticosteroid therapy ameliorated the glomerulonephritis in our patient, as well as his lymphoproliferation, anemia, and hypergammaglobulinemia. This study suggests that glomerulonephritis is one of the characteristic features of ALPS.18545445

Genetic and environmental influences on atopic immune response in early life

The purpose of our study was to carry out a prospective follow-up of 114 newborns at term (including three pairs of twins), regarding clinical manifestations for atopy during the first year of life. Their IgE levels in cord blood samples, at 3, 6, 9 and 12 months of age were measured and the influence of race, sex, breast-feeding maternal smoking, family income, month of birth, family history and personal manifestations of atopic disease were evaluated. Total serum immunoglobulin E was quantified by microparticle enzyme immunoassay (MEIA). The study group consisted of 60 (53%) male neonates. 67 (59%) Caucasians and 47(41%) blacks. in the clinical follow-up, 32 (28.1%) infants developed obvious atopic disease: 29 infants presented recurrent wheezing, two had cow's milk allergy and one had atopic dermatitis. Probable atopic disease developed in 12 (10.5%) infants, whereas 70 (61.4%) infants showed no manifestations. Cord blood IgE levels in infants with obvious atopic disease was higher when compared to those without (p = 0.024), with 70.97% sensitivity and 46.2% specificity IgE levels were also significantly different up to 12 months in these groups (p = 0.0001), when the sensitivity was 82.1% and the specificity 54.1%. At this age, the IgE levels were higher in infants with obvious atopy than nonatopic disease in relation to male sex (p = 0.015), black race (p = 0.009), breast-feeding for less than 6 months (p = 0.011) and when the family income was less than three times the minimum wage (about US $300) (p = 0.006). There was no association between IgE levels and family history of atopy. We concluded that immune response for atopy was in a large degree influenced by environmental factors and serum IgE at 12 months was a good marker for identifying infants with risk of atopic disease in early life.9639239

Are immunoglobulin E levels associated with early wheezing? A prospective study in Brazilian infants

The relationship between wheezing or asthma and serum immunoglobulin (Ig)E levels in early life is unclear. The aim of this study was to follow-up the IgE immune response in infants that did, or did not, develop recurrent wheezing during their first year of life. One-hundred and two randomised term neonates were included, in which IgE levels were quantified in cord blood samples, at 3, 6, 9 and 12 months of age. Specific IgE levels for food and inhalant allergens and the skin-prick test for inhalant allergens were also assessed at 6 and 12 months. During clinical follow-up, 32 (31%) infants presented with two or more wheezing episodes, while 70 (69%) had no wheezing. Total IgE levels were significantly higher up to 12 months in wheezing infants when compared to nonwheezing group. At 12 months, the specific IgE levels to cow's milk, egg white and mites were higher in infants with recurrent wheezing. There was no influence of family history for atopy on IgE levels. The skin-prick tests were positive in 14% and 23% in wheezing infants at 6 and 12 months, respectively. These results indicate an early allergic sensitisation in wheezing infants, suggesting an altered immunoregulatory T-cell role in immunoglobulin E production.20364064

Abnormalities in body composition and nutritional status in HIV-infected children and adolescents on antiretroviral therapy

This cross-sectional study aimed to compare growth, nutritional status and body composition outcomes between a group of 94 HIV-infected children and adolescents on antiretroviral therapy (ART) and 364 healthy controls, and to evaluate their association with clinical and lifestyle variables within the HIV-infected group. When compared with the control group, HIV patients had higher risk of stunting (odds ratio [OR] 5.33, 95% confidence interval [CI]: 2.83-10.04) and thinness (OR 4.7, 95% CI: 2.44-9.06), higher waist-to-hip ratios (medians 0.89 versus 0.82 for boys and 0.90 versus 0.77 for girls, P < 0.001), and lower prevalence of overweight or obesity (OR 0.33, 95% CI: 0.14-0.78). Protease inhibitor usage was associated with thinness (OR 3.51, 95% CI 1.07-11.44) and lipoatrophy (OR 3.5, 95% CI 1.37-8.95). HIV-infected children on ART showed significant nutritional status and body composition abnormalities, consistent with the severity of vertical HIV infection and the consequences of prolonged ART.22845345

Heterofucans from Dictyota menstrualis have anticoagulant activity

Fucan is a term used to denote a family of sulfated L-fucose-rich polysaccharides which are present in the extracellular matrix of brown seaweed and in the egg jelly coat of sea urchins. Plant fucans have several biological activities, including anticoagulant and antithrombotic, related to the structural and chemical composition of polysaccharides. We have extracted sulfated polysaccharides from the brown seaweed Dictyota menstrualis by proteolytic digestion, followed by separation into 5 fractions by sequential acetone precipitation. Gel electrophoresis using 0.05 M 1,3-diaminopropane-acetate buffer, pH 9.0, stained with 0.1% toluidine blue, showed the presence of sulfated polysaccharides in all fractions. The chemical analyses demonstrated that all fractions are composed mainly of fucose, xylose, galactose, uronic acid, and sulfate. The anticoagulant activity of these heterofucans was determined by activated partial thromboplastin time (APTT) using citrate normal human plasma. Only the fucans F1.0v and F1.5v showed anticoagulant activity. To prolong the coagulation time to double the baseline value in the APTT, the required concentration of fucan F1.0v (20 µg/ml) was only 4.88-fold higher than that of the low molecular weight heparin Clexane® (4.1 µg/ml), whereas 80 µg/ml fucan 1.5 was needed to obtain the same effect. For both fucans this effect was abolished by desulfation. These polymers are composed of fucose, xylose, uronic acid, galactose, and sulfate at molar ratios of 1.0:0.8:0.7:0.8:0.4 and 1.0:0.3:0.4:1.5:1.3, respectively. This is the fist report indicating the presence of a heterofucan with higher anticoagulant activity from brown seaweed

First Report of the Hyper-IgM Syndrome Registry of the Latin American Society for Immunodeficiencies: Novel Mutations, Unique Infections, and Outcomes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry with the clinical phenotype of HIGM syndrome, molecular defects were identified in 37 patients thus far. We retrospectively analyzed the clinical, immunological and molecular data from these 37 patients. CD40 ligand (CD40L) deficiency was found in 35 patients from 25 families and activation-induced cytidine deaminase (AID) deficiency in 2 unrelated patients. Five previously unreported mutations were identified in the CD40L gene (CD40LG). Respiratory tract infections, mainly pneumonia, were the most frequent clinical manifestation. Previously undescribed fungal and opportunistic infections were observed in CD40L-deficient patients but not in the two patients with AID deficiency. These include the first cases of pneumonia caused by Mycoplasma pneumoniae, Serratia marcescens or Aspergillus sp. and diarrhea caused by Microsporidium sp. or Isospora belli. Except for four CD40L-deficient patients who died from complications of presumptive central nervous system infections or sepsis, all patients reported in this study are alive. Four CD40L-deficient patients underwent successful bone marrow transplantation. This report characterizes the clinical and genetic spectrum of HIGM syndrome in Latin America and expands the understanding of the genotype and phenotype of this syndrome in tropical areas.342146156Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Jeffrey Modell FoundationLatin American Advisory Board on Primary Immunodeficiencies initiativeFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2012/50515-4, 2006/57643-7, 2012/51745-3