Maternal forced swimming reduces cell proliferation in the postnatal dentate gyrus of mouse offspring

Physical exercise positively affects the metabolism and induces proliferation of precursor cells in the adult brain. Maternal exercise likewise provokes adaptations early in the offspring. Using a high-intensity swimming protocol that comprises forced swim training before and during pregnancy, we determined the effect of maternal swimming on the mouse offspring's neurogenesis. Our data demonstrate decreased proliferation in sublayers of the postnatal dentate gyrus in offspring of swimming mother at postnatal day (P) 8 accompanied with decreased survival of newly generated cells 4 weeks later. The reduction in cell numbers was predominantly seen in the hilus and molecular layer. At P35, the reduced amount of cells was also reflected by a decrease in the population of newly generated immature and mature neurons of the granule cell layer. Our data suggest that forced maternal swimming at high-intensity has a negative effect on the neurogenic niche development in postnatal offspring

Leucurogin, a new recombinant disintegrin cloned from Bothrops leucurus (white-tailed-jararaca) with potent activity upon platelet aggregation and tumor growth

Disintegrins and disintegrins-like proteins are able to inhibit platelet aggregation and integrin-mediated cell adhesion. the aim of this study was to produce one disintegrin-like cloned from Bothrops leucurus venom gland and to characterize it regarding biological activity. the recombinant protein was purified by one step procedure involving anion-exchange chromatography (DEAE-cellulose) and presented a molecular mass of 10.4 kDa. the purified protein was able to inhibit platelet aggregation induced by collagen (IC(50) = 0.65 mu M) and to inhibit growth of Ehrlich tumor implanted in mice by more than 50% after 7 days administration of 10 mu g/day. No effects were observed upon adenosine 5'diphosphate (ADP)-and arachidonic acid (AA)-induced platelet aggregation. the recombinant protein was recognized by an antibody specific for jararhagin one metalloproteinase isolated from Bothrops jararaca venom, and therefore it was named leucurogin. Anti-angiogenesis effect of leucurogin was evaluated by the sponge implant model. After 7 days administration leucurogin inhibited, in a dose dependent way, the vascularization process in the sponge. Leucurogin represents a new biotechnological tool to understand biological processes where disintegrins-like are involved and may help to characterize integrins that can be involved in development and progression of malignant cells. (C) 2011 Elsevier B.V. All rights reserved.FAEPFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Minas Gerais, Inst Ciencias Biol, BR-31270901 Belo Horizonte, MG, BrazilUniv Mogi das Cruzes, Ctr Civ, BR-08780911 São Paulo, BrazilProteobras Desenvolvimento Biotecnol Ltda, BR-13069310 São Paulo, BrazilFundacao Ezequiel Dias, BR-30510010 Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilWeb of Scienc

Caloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activation

The antineoplastic drug cisplatin promotes renal injury, which limits its use. Protocols that reduce renal cisplatin toxicity will allow higher doses to be used in cisplatin treatment. Here, we compare physical exercise and caloric restriction (CR) as protocols to reduce cisplatin renal injury in mice. Male C57BL/6 were divided into four groups: Control, cisplatin, exercise + cisplatin, and 30% CR + cisplatin. Animals were injected with a single dose of cisplatin (20 mg/kg i.p.) and sacrificed 96 h after injection. Quantitative real time PCR, histological analyses, immunohistochemistry, and biochemical measurements were performed to investigate renal injury, necrosis, apoptosis, and inflammatory mechanisms. Both protocols protected against cisplatin renal injury, but CR was more effective in reducing uraemia and renal necrosis. The CR + Cisplatin group exhibited reduced serum IL-1 beta and INF-alpha levels. No differences were noted in the renal mRNA expression of cytokines. Both interventions reduced apoptosis, but only the CR + Cisplatin group decreased TNFR2 protein expression. PPAR-ci was activated in mice after CR. An antagonist of PPAR-alpha blocked the protective effect of CR. Both interventions attenuated the nephrotoxicity caused by cisplatin injection, but CR + Cisplatin showed a better response by modulating TNFR2. Moreover, part of the CR benefit depends on PPAR-alpha activation.FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)CAPES/DAADUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Med, Disciplina Nefrol, Sao Paulo, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Immunol, Sao Paulo, BrazilUniv Sao Paulo, Dept Clin Med, Sao Paulo, BrazilUniv Fed Pelotas, Escola Nutr, Dept Nutr, Pelotas, BrazilMax Delbruck Ctr Mol Med, Berlin, GermanyUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Med, Disciplina Nefrol, Sao Paulo, BrazilFAPESP: 2013/06207-6FAPESP: 2015/20082-7CAPES/DAAD: 427/15Web of Scienc

Exercise and Caloric Restriction Alter the Immune System of Mice Submitted to a High-Fat Diet

As the size of adipocytes increases during obesity, the establishment of resident immune cells in adipose tissue becomes an important source of proinflammatory mediators. Exercise and caloric restriction are two important, nonpharmacological tools against body mass increase. To date, their effects on the immune cells of adipose tissue in obese organisms, specifically when a high-fat diet is consumed, have been poorly investigated. Thus, after consuming a high-fat diet, mice were submitted to chronic swimming training or a 30% caloric restriction in order to investigate the effects of both interventions on resident immune cells in adipose tissue. These strategies were able to reduce body mass and resulted in changes in the number of resident immune cells in the adipose tissue and levels of cytokines/chemokines in serum. While exercise increased the number of NK cells in adipose tissue and serum levels of IL-6 and RANTES, caloric restriction increased the CD4+/CD8+ cell ratio and MCP-1 levels. Together, these data demonstrated that exercise and caloric restriction modulate resident immune cells in adipose tissues differently in spite of an equivalent body weight reduction. Additionally, the results also reinforce the idea that a combination of both strategies is better than either individually for combating obesity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniv São Paulo, Sch Arts Sci & Humanities, BR-03828000 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Lab Transplantat Immunobiol, Dept Immunol, BR-05508900 São Paulo, BrazilUniv Fed Pelotas, Sch Nutr, Dept Nutr, BR-96010610 Pelotas, RS, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilFAPESP: 2011/03528-0Web of Scienc

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 +/- 1.11) to UIP (23.45 +/- 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.CNPqCNPqFAPESP [07/52785-0, 08/53022-3, 08/57130-5]FAPESPLaboratorio Diagnostika, Hospital das Clinicas and Faculdade de Medicina, Universidade de Sao PauloLaboratorio Diagnostika, Hospital das Clinicas and Faculdade de Medicina, Universidade de Sao Paul

On the Implications of a Sex Difference in the Reaction Times of Sprinters at the Beijing Olympics

Elite sprinters offer insights into the fastest whole body auditory reaction times. When, however, is a reaction so fast that it represents a false start? Currently, a false start is awarded if an athlete increases the force on their starting block above a given threshold before 100 ms has elapsed after the starting gun. To test the hypothesis that the fastest valid reaction times of sprinters really is 100 ms and that no sex difference exists in that time, we analyzed the fastest reaction times achieved by each of the 425 male and female sprinters who competed at the 2008 Beijing Olympics. After power transformation of the skewed data, a fixed effects ANOVA was used to analyze the effects of sex, race, round and lane position. The lower bounds of the 95, 99 and 99.9% confidence intervals were then calculated and back transformed. The mean fastest reaction time recorded by men was significantly faster than women (p<0.001). At the 99.9% confidence level, neither men nor women can react in 100 ms, but they can react in as little as 109 ms and 121 ms, respectively. However, that sex difference in reaction time is likely an artifact caused by using the same force threshold in women as men, and it permits a woman to false start by up to 21 ms without penalty. We estimate that female sprinters would have similar reaction times to male sprinters if the force threshold used at Beijing was lowered by 22% in order to account for their lesser muscle strength

Kinin B(1) receptor deficiency leads to leptin hypersensitivity and resistance to obesity

OBJECTIVE-Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown.RESEARCH DESIGN and METHODS-Using genetic and pharmacological strategies to abrogate the kinin B(1) receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity.RESULTS-Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet.CONCLUSIONS-Our data suggest that kinin B(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.Universidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniv Mogi das Cruzes, Mogi Das Cruzes, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, BrazilSanofi Aventis, Montpellier, FranceUniversidade Federal de São Paulo, Dept Med, BR-04023062 São Paulo, BrazilInst Natl Sante & Rech Med, Dept Renal & Cardiac Remodeling, U858 I2MR, Toulouse, FranceUniv Toulouse 3, Inst Med Mol Rangueil, F-31062 Toulouse, FranceInst Natl Rech Agron AgroParisTech, UMR914 Nutr Physiol & Ingest Behav, Paris, FranceMax Delbruck Ctr Mol Med, Berlin, GermanyUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, BR-04023062 São Paulo, BrazilWeb of Scienc

Balance between the two kinin receptors in the progression of experimental focal and segmental glomerulosclerosis in mice

Focal and segmental glomerulosclerosis (FSGS) is one of the most important renal diseases related to end-stage renal failure. Bradykinin has been implicated in the pathogenesis of renal inflammation, whereas the role of its receptor 2 (B2RBK; also known as BDKRB2) in FSGS has not been studied. FSGS was induced in wild-type and B2RBK-knockout mice by a single intravenous injection of Adriamycin (ADM). in order to further modulate the kinin receptors, the animals were also treated with the B2RBK antagonist HOE-140 and the B1RBK antagonist DALBK. Here, we show that the blockage of B2RBK with HOE-140 protects mice from the development of FSGS, including podocyte foot process effacement and the re-establishment of slit-diaphragm-related proteins. However, B2RBK-knockout mice were not protected from FSGS. These opposite results were due to B1RBK expression. B1RBK was upregulated after the injection of ADM and this upregulation was exacerbated in B2RBK-knockout animals. Furthermore, treatment with HOE-140 downregulated the B1RBK receptor. the blockage of B1RBK in B2RBK-knockout animals promoted FSGS regression, with a less-inflammatory phenotype. These results indicate a deleterious role of both kinin receptors in an FSGS model and suggest a possible cross-talk between them in the progression of disease.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Clin & Expt Immunol Lab, Div Nephrol, BR-04023900 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, BR-05508000 São Paulo, BrazilUniversidade Federal de São Paulo, Translat Med Div, Clin & Expt Immunol Lab, BR-04039002 São Paulo, BrazilInst Butantan, Lab Cellular Biol, BR-05503900 São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Biophys, BR-04023062 São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, BrazilINSERM, Unite Mixte Rech 699, F-75870 Paris, FranceAlbert Einstein Hosp, Inst Israelita Ensino & Pesquisa Albert Einst, Renal Transplantat Unit, BR-05521000 São Paulo, BrazilUniversidade Federal de São Paulo, Clin & Expt Immunol Lab, Div Nephrol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Translat Med Div, Clin & Expt Immunol Lab, BR-04039002 São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Biophys, BR-04023062 São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, BrazilFAPESP: 2012/05605-5FAPESP: 07/07139-3FAPESP: 12/02270-2CNPq: 140739/2008-4Web of Scienc