Intrauterine Undernourishment Alters TH1/TH2 Cytokine Balance and Attenuates Lung Allergic Inflammation in Wistar Rats

IL-4 produced by Th2 cells can block cytokine production by Th1 cells, and Th1 IFN-gamma is known to counterregulate Th2 immune response, inhibiting allergic eosinophilia. As intrauterine undernutrition can attenuate lung inflammation, we investigated the influence of intrauterine undernourishment on the Th1/Th2 cytokine balance and allergic lung inflammation. Intrauterine undernourished offspring were obtained from dams fed 50% of the nourished diet of their counterparts and were immunized at 9 weeks of age. We evaluated the cell counts and cytokine protein expression in the bronchoalveolar lavage, mucus production and collagen deposition, and cytokine gene expression and transcription factors in lung tissue 21 days after ovalbumin immunization. Intrauterine undernourishment significantly reduced inflammatory cell airway infiltration, mucus secretion and collagen deposition, in rats immunized and challenged. Intrauterine undernourished rats also exhibited an altered cytokine expression profile, including higher TNF-alpha and IL-1 beta expression and lower IL-6 expression than well-nourished rats following immunization and challenge. Furthermore, the intrauterine undernourished group showed reduced ratios of the IL-4/IFN-gamma and the transcription factors GATA-3/T-Bet after immunization and challenge. We suggest that the attenuated allergic lung inflammation observed in intrauterine undernourished rats is related to an altered Th1/Th2 cytokine balance resulting from a reduced GATA-3/T-bet ratio. Copyright (C) 2012 S. Karger AG, BaselConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundo de Auxilio aos Docentes e Alunos (FADA-UNIFESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunol Transplantes, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nefrol, Lab Imunol Clin & Expt, BR-09972270 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nefrol, Lab Imunol Clin & Expt, BR-09972270 São Paulo, BrazilFAPESP: 07/07139-3FAPESP: 09/09849-3FAPESP: 09/52119-6FAPESP: 10/01404-0FAPESP: 12/02270-2Web of Scienc

O Aluno com Paralisia Cerebral em Contexto Educativo: Diferenciação de metodologias e estratégias

O modelo de Educação Inclusiva, atualmente implementado e defendido pelas organizações internacionais, pressupõe um único sistema educacional para TODOS os alunos, partindo da aceitação das diferenças individuais e da valorização da diversidade humana, como potenciadores de capacidades num mesmo processo educacional. A Educação Inclusiva não abrange somente crianças/jovens com deficiências, mas alarga a sua intervenção a todos os que, temporária ou permanentemente, apresentem necessidades especiais. Os alunos com Necessidades Educativas Especiais de carácter motor, especialmente Paralisia Cerebral, inseridos no ensino regular, pela especificidade das manifestações apresentadas e das significativas limitações ao nível da atividade e da participação, beneficiarão com a implementação de medidas educativas que diminuam a sua situação de desvantagem e promovam o desenvolvimento das suas potencialidades, recorrendo a metodologias e estratégias facilitadoras do seu desenvolvimento global, que abordaremos numa breve revisão da literatura

Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

Background/Aims: We investigated the effects of leptin in the development of lipopolysaccharide (LPS)-induced acute lung inflammation (ALI) in lean mice. Methods: Mice were administered leptin (1.0 mu g/g) or leptin (1.0 mu g/g) followed by LPS (1.5 mu g/g) intranasally. Additionally, some animals were given LPS (1.5 mu g/g) or saline intranasally alone, as a control. Tissue samples and fluids were collected six hours after instillation. Results: We demonstrated that leptin alone did not induce any injury. Local LPS exposure resulted in significant acute lung inflammation, characterized by a substantial increase in total cells, mainly neutrophils, in bronchoalveolar lavages (BAL). We also observed a significant lymphocyte influx into the lungs associated with enhanced lung expression of chemokines and cytokines (KC, RANTES, TNF-alpha, IFN-beta, GM-CSF and VEGF). LPS-induced ALI was characterized by the enhanced expression of ICAM-1 and iNOS in the lungs. Mice that received LPS showed an increase in insulin levels. Leptin, when administered prior to LPS instillation, abolished all of these effects. LPS induced an increase in corticosterone levels, and leptin potentiated this event. Conclusion: These data suggest that exogenous leptin may promote protection during sepsis, and downregulation of the insulin levels and upregulation of corticosterone may be important mechanisms in the amelioration of LPS-induced ALI.Copyright (c) 2014 S. Karger AG, BaselConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Complex Fluids INCTFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Inst Biomed Sci 1, Dept Pharmacol, Lab Hypertens, BR-1524 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Immunol, Lab Transplantat Immunobiol, BR-1524 São Paulo, BrazilUniv São Paulo, Lab Inflammat & Vasc Pharmacol, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Lab Clin & Expt Immunobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Lab Clin & Expt Immunobiol, São Paulo, BrazilFAPESP: 12/51104-8FAPESP: 10/01404-0FAPESP: 12/02270-2FAPESP: 12/10512-6Web of Scienc

Acute Kidney Injury Reduces Phagocytic and Microbicidal Capacities of Alveolar Macrophages

Background/Aims: Renal ischaemia-reperfusion injury (IRI) is a systemic inflammatory process in which Th1 responses predominate affecting other organs including the lungs. the present study explored the phagocytic and microbicidal capacity of macrophages in rats with lung inflammation that underwent IRI. Methods: the alveolar macrophages of rats sensitised to OVA were evaluated for phagocytosis and bacterial killing 24h after antigen challenge in animals with or without prior submission to 60 min of renal ischaemia. Results: Bronchoalveolar lavage had a high level of cellular infiltrate in immunised animals (420%) compared with control animals; IRI significantly reduced this infiltration (52%). Macrophages from animals immunised and challenged with OVA presented a 10x increase in phagocytic capacity compared to the control group, whereas immunised animals subjected to IRI showed a reduction in the phagocytic index of 68%. the killing of Klebsiella pneumoniae by macrophages from immunised animals was higher (56%) compared with the control group but reduced in animals submitted to IRI (45%). Immunised and challenged group showed an increase in gene expression levels of IL-10(450%), HO-1 (259%), INF-gamma (460%) and MCP-1 (370%) compared to the immunised group subjected to IRI. Conclusions: Renal ischaemia and reperfusion injury apparently alters the phagocytic and microbicidal capacity of macrophages, reducing lung inflammation to OVA. Copyright (C) 2013 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)INCT Complex FluidsFADA-UNIFESPUniversidade Federal de São Paulo, Disciplina Nefrol, Lab Imunol Clin & Expt, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Lab Inflamacao & Farmacol Vasc, BR-04023900 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunobiol Transplante, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Lab Imunol Clin & Expt, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Lab Inflamacao & Farmacol Vasc, BR-04023900 São Paulo, BrazilFAPESP: 07/07139-3FAPESP: 10/52180-4FAPESP: 10/01404-0FAPESP: 12/02270-0FAPESP: 12/51104-8Web of Scienc

Intrauterine food restriction impairs the lipogenesis process in the mesenteric adipocytes from low-birth-weight rats into adulthood

BackgroundIntrauterine food restriction (IFR) during pregnancy is associated with low birth weight (LBW) and obesity in adulthood. It is known that white adipose tissue (WAT) plays critical metabolic and endocrine functions; however, this tissue’s behavior before weight gain and obesity into adulthood is poorly studied. Thus, we evaluated the repercussions of IFR on the lipogenesis and lipolysis processes in the offspring and described the effects on WAT inflammatory cytokine production and secretion.MethodsWe induced IFR by providing gestating rats with 50% of the necessary chow daily amount during all gestational periods. After birth, we monitored the offspring for 12 weeks. The capacity of isolated fat cells from mesenteric white adipose tissue (meWAT) to perform lipogenesis (14C-labeled glucose incorporation into lipids) and lipolysis (with or without isoproterenol) was assessed. The expression levels of genes linked to these processes were measured by real-time PCR. In parallel, Multiplex assays were conducted to analyze pro-inflammatory markers, such as IL-1, IL-6, and TNF-α, in the meWAT.ResultsTwelve-week-old LBW rats presented elevated serum triacylglycerol (TAG) content and attenuated lipogenesis and lipolysis compared to control animals. Inflammatory cytokine levels were increased in the meWAT of LBW rats, evidenced by augmented secretion by adipocytes and upregulated gene and protein expression by the tissue. However, there were no significant alterations in the serum cytokines content from the LBW group. Additionally, liver weight, TAG content in the hepatocytes and serum glucocorticoid levels were increased in the LBW group.ConclusionThe results demonstrate that IFR throughout pregnancy yields LBW offspring characterized by inhibited lipogenesis and lipolysis and reduced meWAT lipid storage at 12 weeks. The increased serum TAG content may contribute to the augmented synthesis and secretion of pro-inflammatory markers detected in the LBW group

Inflammatory milieu as an early marker of kidney injury in offspring rats from diabetic mothers

The present study investigated the early presence of inflammatory response in renal tissue of young offspring from diabetic mothers. The effect of L-arginine (L-arg) supplementation was also investigated. The offspring was divided into four groups: group CO (controls); group DO (diabetic offspring); group CA (CO receiving 2% L-arg solution) and group DA (DO receiving the 2% L-arg solution). Glycemia, arterial pressure and renal function were evaluated; gene and protein expression of pro-inflammatory cytokines were also measured. Blood pressure levels were significantly increased in 2 and 6 month-old DO rats, whereas L-arg administration caused a significant decrease in the DA group, at both ages. DO rats showed a significantly blunted glycemic response to exogenous insulin. In 2 month-old DO animals, renal protein expression of pro-inflammatory molecules was significantly increased. At six months of age, we also observed an increase in gene expression of pro-inflammatory molecules, whereas L-arg supplementation prevented this increase at both ages. Our data suggest that activation of inflammatory pathways is present early in the kidney of DO rats, and that L-arg can attenuate the expression of these markers of tissue inflammation. Our results also reinforce the concept that intrauterine environmental factors are a fundamental determinant in the development of metabolic and vascular diseases later in life. (C) 2012 Elsevier B.V. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de So Paulo [2007/07139-3, 2010/17782-3, 2012/02270-2, 2010/52180-4]Fundacao de Amparo a Pesquisa do Estado de So PauloConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Instituto Nacional de Ciencia e Tecnologia de Fluidos Complexos (INCT Complex Fluids)Instituto Nacional de Ciencia e Tecnologia de Fluidos Complexos (INCT Complex Fluids