High glycemia and resistin normalized in children with double burden of malnutrition: a cross-sectional study.

The coexistence of stunting and excess weight in the same individual is defined as a double burden of malnutrition (DBM) and is associated with noncommunicable diseases. In this study, we evaluated the impact of DBM on adipokine concentrations and metabolic profiles in children compared with weight excess alone. Children were allocated to the weight excess group (n = 23) (height-for-age (HAZ) > 0.0 and < 2.0 Z-score and body mass index-for-age (BMI/A) > 1.0 Z-score) or DBM (n = 22) group (HAZ < -1.0 Z-score (including mild stunting) and BMI/A > 1.0 Z-score). Lipid, glycemic profile, resistin, plasminogen activator inhibitor-1, leptin, and adiponectin concentrations were analyzed. Glycemia was significantly higher in the DBM group compared to the weight excess group (5.05 (4.76-5.31) mmol/L vs. 4.57 (4.35-4.81) mmol/L), although no differences were found in insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Adipokine concentrations did not differ between the groups. However, the DBM group showed higher resistin concentrations normalized by body fat mass than those of the weight excess group (1.44 (0.98-1.93) ng/mL vs. 0.76 (0.55-1.45) ng/mL). Insulin and HOMA-IR showed a negative correlation with adiponectin (r = -0.590 and -0.624, respectively, both p < 0.01). DBM was associated with increased glucose and resistin concentrations adjusted by fat mass compared to that associated with excess weight alone. Therefore, this association between mild stunting and weight excess has deleterious potential for long-term metabolic function, highlighting an additional precaution against weight gain in children, especially in those with stunting.

Erythrocyte and plasma selenium in children with acute inflammatory response.

OBJECTIVES: Plasma selenium may not reflect selenium status in critically ill patients because it transiently decreases inversely with the magnitude of the systemic inflammatory response. The decision to supplement selenium should ideally be based on laboratory measurements that reliably reflect selenium status. We hypothesized that erythrocyte selenium, unlike plasma selenium, is not affected by the systemic inflammatory response in critically ill children. METHODS: In a prospective study of 109 critically ill children, plasma and erythrocyte selenium concentrations were evaluated on admission, and plasma selenoprotein P was evaluated on days 1, 2, and 3 of the ICU stay. The main outcome was the effect of systemic inflammation on the erythrocyte and plasma selenium concentrations. The magnitude of the systemic inflammatory response was measured using serum C-reactive protein (CRP) and procalcitonin levels. The covariates were age, sex, anthropometric nutritional status, diagnosis of severe sepsis/septic shock, and clinical severity on admission. Multiple linear regression and generalized estimating equations were used for statistical analysis. RESULTS: Erythrocyte selenium levels were not influenced by the magnitude of the inflammatory response or by the patient's clinical severity. Procalcitonin (ß coefficient=-0.99; 95%CI: -1.64; -0.34, p = 0.003) and clinical severity (ß coefficient= -11.13; 95%CI: -21.6; -0.63), p = 0.038) on admission were associated with decreased plasma selenium concentrations. Erythrocyte selenium was associated with selenoprotein P in the first three days of ICU stay (ß coefficient=0.32; 95%CI: 0.20; 0.44, p < 0.001). CONCLUSION: Unlike plasma selenium, erythrocyte selenium does not change in children with an acute systemic inflammatory response and is associated with selenoprotein P concentrations. Erythrocyte selenium is probably a more reliable marker than plasma selenium for evaluating the selenium status in critically ill children.

Topiramate treatment in Wistar rats during childhood induces sex-specific vascular dysfunction in adulthood.

The present study determined whether treatment during childhood with topiramate (TPM), a new generation antiepileptic drug, results in altered aortic reactivity in adult male and female rats. We also sought to understand the role of endothelium-derived contractile factors in TPM-induced vascular dysfunction. Male and female Wistar rats were treated with TPM (41 mg/kg/day) or water (TPM vehicle) by gavage during childhood (postnatal day, 16-28). In adulthood, thoracic aorta reactivity to phenylephrine (phenyl), as well as aortic thickness and expression of cyclooxygenases (COX-1 and COX-2), NOX2, and p47phox were evaluated. The aortic response to phenyl was increased in male and female rats from the TPM group when compared with the control group. In TPM male rats, the hyperreactivity to phenyl was abrogated by the inhibition of NADPH oxidase and COX-2, while in female rats, responses were restored only by inhibition of COX-2. In addition, TPM male rats presented aortic hypertrophy and increased expression of NOX-2 and p47phox, while TPM female rats showed increased COX-2 aortic expression. Taken together, for the first-time, the present study provides evidence that treatment with TPM during childhood causes vascular dysfunction in adulthood, and that the mechanism underlying the vascular effects of TPM is sex-specific.

Mitochondrial DNA: A new driver for sex differences in spontaneous hypertension.

The prevalence of arterial hypertension (AH) is higher in men than in premenopausal women of the same age. AH has been characterized as a chronic inflammatory disease and activation of Toll-like receptors (TLR) by damage-associated molecular patterns (DAMPs) is involved. Mitochondrial DNA (mtDNA) may be released by end-organ damage, which is recognized and activates TLR9. The serum level of mtDNA is increased in AH. The aim of this study was to compare the serum mtDNA levels between male and female spontaneously hypertensive rats (SHR) and to evaluate the sex differences in the effect of mtDNA on the function, inflammation and signaling pathway related to TLR9 in the vasculature. Male and female 15-week-old SHR and Wistar rats were used to evaluate the arterial blood pressure, serum mtDNA, contractile response, inflammatory markers and signaling pathway related to TLR9. Male SHR had higher arterial blood pressure values and serum mtDNA compared to female SHR and to male and female normotensive Wistar rats. In male SHR aorta, mtDNA incubation increased the contractile response to phenylephrine, which was blunted by inhibition of TLR9, and also increased pro-inflammatory molecules IL-6 and TNF-α. However, in female SHR aorta, mtDNA incubation did not change the contractile response, reduced pro-inflammatory molecules and prevented oxidative stress. mtDNA incubation did not change the expression of TLR9, MyD88 and eNOS neither in male nor in female SHR aorta, but it increased the phosphorylation of ERK1/2 in male and reduced in female SHR aorta. The mtDNA differential modulation of vascular response in male and female SHR might contribute to sex differences in AH. This study contributes to the understanding of a need for more personalized therapeutic strategies for men and women with hypertension. Keywords: Sex differences, Arterial hypertension, Mitochondrial DNA, Toll-Like receptor 9.

Detrimental Impact of Low Birth Weight on Circulating Number and Functional Capacity of Endothelial Progenitor Cells in Healthy Children: Role of Angiogenic Factors.

OBJECTIVE: To provide a comprehensive assessment of the relationship of birth weight with both endothelial progenitor cell function and angiogenic factors in children. STUDY DESIGN: Anthropometric measures, biochemical profile, endothelial progenitor cell number, endothelial progenitor cell colony-forming units, vascular endothelial growth factor-A, and nitric oxide plasma levels of 58 children aged 7-11 years were determined. RESULTS: A positive correlation was observed between birth weight and circulating endothelial progenitor cell number (r= 0.461; P= .001), endothelial progenitor cell colony-forming units (r= 0.512; P < .001), vascular endothelial growth factor-A (r= 0.407; P= .002), and nitric oxide (r= 0.547; P < .001) levels, whereas the adjustment for prematurity, family history of cardiovascular disease, and systolic blood pressure levels did not modify these associations. CONCLUSION: Low birth weight was associated with a decrease in the circulating/functional capacity of endothelial progenitor cells among healthy children, independent of traditional cardiovascular risk factors. This detrimental impact was accompanied by lower circulating levels of angiogenic factors.

Beneficial Impact of Moderate to Vigorous Physical Activity Program on Circulating Number and Functional Capacity of Endothelial Progenitor Cells in Children: The Crucial Role of Nitric Oxide and VEGF-A.

PURPOSE: Endothelial progenitor cells (EPCs) appear to interact with physical training. This study aimed to provide a comprehensive assessment of the relationship of moderate to vigorous physical activity (MVPA) with both angiogenic factors and EPC function in healthy children. METHODS: Forty children (22 boys and 18 girls) aged 7 to 11 years participated in a 10-week MVPA program (duration: 45 min; intensity: 75%-85% of heart rate reserve; frequency: 4 sessions/wk). The anthropometric data, biochemical profile, EPCs number, EPCs colony-forming units, and vascular endothelial growth factor-A (VEGF-A) and nitric oxide (NO) plasma levels were evaluated before and after the MVPA program. RESULTS: After a 10-week MVPA program, a significant increase was detected in circulating/functional capacity of EPCs, NO, and VEGF-A levels, associated with improvement of waist circumference and estimated maximum rate of oxygen consumption (VO2max). A strong positive correlation was found between delta of EPCs number and variation of both NO level (r = .677, P < .001) and VEGF-A level (r = .588, P < .001). Furthermore, a significant correlation between NO level variation and delta of VEGF-A level was observed (r = .708, P < .001). CONCLUSION: Our findings suggest that lifestyle intervention implemented by MVPA program can contribute meaningfully to improve circulating/functional capacity of EPCs in healthy children, possibly due to the increase of plasma NO and VEGF-A levels.

Intervenção sobre fatores de risco emcrianças e adolescentes / Risk factor intervention in children and adolescents

As doenças cardiovasculares estão entre as principais causas de mortalidade no mundo e não afligem apenas os adultos. Muitos trabalhos têm demonstrado que elas já podem ser vistas na infância. Entre os fatores de risco para a doença cardiovascular, pode-se destacar a dislipidemia, o baixo peso ao nascer e a obesidade infantil. A detecção de dislipidemia na infância é crucial, por ser considerada a fase estratégica para a implementação de medidas de prevenção da aterosclerose no âmbito populacional. Embora as causas ambientais ou poligênicas sejam as mais frequentes, é importante a identificação de formas genéticas como a hipercolesterolemia familiar e hipertrigliceridemias de base genética, pois medidas relacionadas aos hábitos de vida e terapêutica medicamentosa devem ser iniciadas preco-cemente, evitando-se complicações e mudando a história natural dos desfechos clínicos. Outros estudos têm demonstrado que o baixo peso ao nascer também contribui para o desenvolvimento tardio de hipertensão arterial, doença coronariana e disfunção endotelial. Possivelmente, por conta das agressões ao sistema vascular em desenvolvimento. No en-tanto, os mecanismos ainda são incertos. Evidências sugerem que alguns biomarcadores, tais como os níveis de ácido úrico e homocisteína e a baixa concentração de óxido nítrico observados em crianças com baixo peso ao nascer, podem estar associados a alterações deletérias na vida adulta. Por fim, o terceiro fator que deve ser considerado é a obesidade infantil. Essa desordem tem causa multifatorial e pode favorecer o surgimento das etapas iniciais da aterosclerose, como a disfunção endotelial, já na infância. Porém, é um fator de risco modificável, e as estratégias de prevenção e intervenção baseiam-se, na maioria dos casos, em mudanças do estilo de vida, como alimentação saudável e exercício físico.

Cardiovascular disease is one of the leading causes of mortality in the world and does not affect adults alone. Many papers have shown that it can already be seen in childhood. The most significant risk factors for cardiovascular disease include dyslipidemia, low birth weight and childhood obesity. Screening for dyslipidemia in childhood is crucial as this is considered a strategic phase for the implementation of measures aimed at preventing atherosclerosis in the population setting. Although environment or polygenic causes are the most common, it is important to identify genetic forms such as familial hypercholesterolemia and hypertriglyceridemia, since measures related to lifestyle and pharmacotherapy must be initiated early in life to avoid complications and change the natural history of clinical outcomes. Other studies have shown that low birth weight also contributes to the late development of hypertension, coronary artery disease and endothelial dysfunction, possible due to injury to the developing vascular system. However, the mechanisms are still uncertain, and evidence suggests that some biomarkers, such as uric acid and homocysteine levels, and the low concentration of nitric oxide observed in low birthweight children, may be associated with deleterious changes in adulthood. Finally, the third factor to be considered is childhood obesity. This disorder has a multifactorial etiology and may favor the onset of the first stages of atherosclerosis, such as endothelial dysfunction, in young children. However, it is a modifiable risk factor, and prevention and intervention strategies are largely based on lifestyle changes such as healthy diet and exercise

Estado nutricional e condições ambientais e de saúde de crianças Pataxó, Minas Gerais, Brasil / Nutritional status and environmental and health conditions of Pataxó indigenous children, Minas Gerais State, Brazil / Estado nutricional y condiciones ambientales y de salud de niños Pataxó, Minas Gerais, Brasil

Resumo: Descrever o estado nutricional e as condições ambientais e de saúde das crianças Pataxó de cinco aldeias de Minas Gerais, Brasil. O estado nutricional foi classificado com base no peso e estatura/comprimento, tendo como referência o padrão de crescimento da Organização Mundial da Saúde. Questionários baseados no I Inquérito Nacional de Saúde e Nutrição dos Povos Indígenas foram utilizados para a avaliação das condições ambientais dos domicílios e de saúde dos menores de cinco anos. Dos 70 menores de dez anos avaliados (93,3%), 34 tinham menos de cinco anos. Não se observaram déficits nutricionais e sobrepeso foi registrado para 11,4% das crianças. A maioria das crianças (74,3%) vivia em domicílios com energia elétrica, 95% em domicílios com latrina/sanitário e 52,9% lançavam dejetos em fossa séptica. A realização de seis ou mais consultas de pré-natal foi reportada por 82,4% das mães dos menores de cinco anos, e 91,2% iniciaram o pré-natal no primeiro trimestre de gestação. Dentre as causas de internações hospitalares nos últimos 12 meses (23,5%), somente uma foi devido à diarreia e nenhuma por causa de infecções respiratórias. Foram verificadas coberturas universais para a maioria das vacinas avaliadas. A inexistência de déficits nutricionais entre as crianças Pataxó pode estar associada às melhores condições de habitação, saneamento e cobertura das ações básicas de saúde infantil quando comparadas às condições verificadas no I Inquérito Nacional de Saúde e Nutrição dos Povos Indígenas e de estudos pontuais. Este trabalho pretende subsidiar discussões e ações que visem a melhorias do estado nutricional infantil dos indígenas no Brasil.

Abstract: To describe the nutritional status and the environmental and health conditions of the Pataxó children from five villages of Minas Gerais State, Brazil. Among the under 10 years old, weight and height/length were classified according to the growth references of World Health Organization. Questionnaires evaluating environmental conditions of the households and health conditions of under 5 years old were based in the First National Survey of Indigenous People's Health and Nutrition. Among the 70 children evaluated (93.3%), 34 were under 5 years old. Nutritional deficits were not observed and overweight was registered for 11.4% of the children. Most of the children (74.3%) lived in households with electric energy, 95% in households with toilets and 52.9% in households that threw waste in septic tanks. Six or more antenatal appointments were reported by 82.4% of the mothers of the under five years old and 91.2% started the antenatal appointments within the first trimester of pregnancy. Among the causes of hospitalizations in the previous 12 months (23.5%), only one was due to diarrhea and none to respiratory infection. Universal coverage was observed for the majority of the vaccines. The absence of nutritional deficits among the Pataxó children may be associated to better housing and sanitation conditions and coverage of basic childhood health actions when compared to the conditions reported by the First National Survey of Indigenous People's Health and Nutrition and related studies with other specific indigenous peoples. The current study aims to back discussions and measures to improve the nutritional status of indigenous children in Brazil.

Resumen: El objetivo de este trabajo fue describir el estado nutricional, así como las condiciones ambientales y de salud de niños Pataxó, procedentes de cinco aldeas de Minas Gerais, Brasil. El estado nutricional se clasificó en base al peso y estatura/longitud, teniendo como referencia el patrón de crecimiento de la Organización Mundial de la Salud. Se utilizaron cuestionarios basados en la I Encuesta Nacional de Salud y Nutrición de los Pueblos Indígenas para la evaluación de las condiciones ambientales de los domicilios y de salud de los menores de cinco años. De los 70 menores de 10 años evaluados (93,3%), 34 tenían menos de cinco años. No se observaron déficits nutricionales y se registro sobrepeso en 11,4% de los niños. La mayoría de los niños (74,3%) vivía en domicilios con energía eléctrica, 95% en domicilios con letrina/retrete y un 52,9% efectuaba deposiciones en fosa séptica. La realización de seis o más consultas de carácter prenatal fueron informadas por parte de un 82,4% de las madres de los menores de cinco años, y un 91,2% comenzaron las consultas prenatales durante el primer trimestre de gestación. Entre las causas de internamientos hospitalarios en los últimos 12 meses (23,5%), solamente una se debió a diarrea y ninguna a causa de infecciones respiratorias. Se verificaron coberturas universales para la mayoría de las vacunas evaluadas. La inexistencia de déficits nutricionales entre los niños Pataxó puede estar asociada a las mejores condiciones de vivienda, saneamiento y cobertura de las acciones básicas respecto a salud infantil, cuando se comparan con las condiciones verificadas en la I Encuesta Nacional de Salud y Nutrición de los Pueblos Indígenas y de otros estudios puntuales. Este trabajo pretende servir de apoyo para futuras discusiones y acciones que tengan por objetivo las mejoras en el estado nutricional infantil de los indígenas en Brasil.

Family history of cardiovascular disease and non-HDL cholesterol in prepubescent non-obese children / Importância clínica da história familiar de doença cardiovascular e da dosagem do colesterol não HDL em crianças eutróficas

Summary Objective: To describe the values of non-HDL cholesterol (NHDL-c) and the frequency of a family history of early cardiovascular disease (family HCVD) in healthy prepubescent children. Analyze the association between NHDL-c and family HCVD, and possible associations with other risk factors for cardiovascular disease (CVD). Method: Cross-sectional study including 269 prepubescent (aged 6-10 years) schoolchildren with a normal body mass index (+1SD<BMI>-2SD). Data collected: Family HCVD; weight and height, waist circumference and systemic blood pressure; lipid profile (total cholesterol TC, HDL-c, triglycerides and LDL-c), NHDL-c calculation (CT-HDL-c, cut-off = 145 mg/dL) and insulin resistance (HOMA-IR). Results: High levels were found for NHDL-c in 10 (3.7%) of these schoolchildren, and family early HCVD was found in 46 (17.1%) of them. There was a weak association between family HCVD and NHDL-c (Cramer’s-V-test = 0.120; p=0.050). Among the children with NHDL-c≥145 mg/dL, 4 (40%) have family HCVD. The presence of family HCVD was not associated with the variables being studied. The variables independently associated with NHDL-c ≥ 145 mg/dL were: HOMA-IR (OR=1.7; 95CI 1.1-2.6) and diastolic blood pressure (OR=1.1; 95CI 1.02-1.2). Conclusion: NHDL-c values were associated with blood pressure and insulin resistance. Family HCVD was not associated with other classic risk factors for CVD, even though the frequency found was five times higher than that of high NHDL-c.

Resumo Objetivos: descrever os valores do colesterol não HDL (NHDL-c) e a frequência de história cardiovascular familiar precoce (HDCV familiar) em crianças eutróficas e pré-púberes. Analisar a associação entre o NHDL-c e o HDCV familiar e possíveis associações com outros fatores de risco para doenças cardiovasculares (DCV). Método: estudo transversal com 269 escolares (6-10 anos) pré-púberes e com índice de massa corporal normal (+1DP<IMC>-2DP). Dados coletados: HDCV familiar; peso e estatura, circunferência abdominal e pressão arterial sistêmica; perfil lipídico (colesterol total – CT, HDL-c, triglicérides e LDL-c), cálculo do NHDL-c (CT-HDL-c, ponto de corte 145 mg/dL) e resistência à insulina (HOMA-IR). Resultados: observaram-se valores elevados de NHDL-c em 10 (3,7%) e presença de HDCV familiar precoce em 46 (17,1%) crianças. Houve fraca associação entre HDCV familiar e NHDL-c (Cramer’s-V-test = 0,120; p=0,050). Entre as crianças com NHDL-c ≥145 mg/dL, quatro (40%) tinham HDCV familiar. A presença de HDCV familiar não se associou com as variáveis estudadas. As variáveis que se associaram de forma independente com o NHDL-c ≥145 mg/dL foram HOMA-IR (OR=1,7; IC95% 1,1-2,6) e pressão arterial diastólica (OR=1,1; IC95% 1,02-1,2). Conclusão: os valores de NHDL-c se associaram com pressão arterial e resistência insulínica. HDCV familiar não se associou com outros fatores de risco clássicos para DCV, embora a frequência encontrada tenha sido quase cinco vezes superior à de NHDL-c elevado.

Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension / Treinamento de Força em Ratos Espontaneamente Hipertensos com Hipertensão Arterial Grave

Abstract Background: Resistance training (RT) has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH). Objective: This study examined the effects of two RT protocols (vertical ladder climbing), performed at different overloads of maximal weight carried (MWC), on blood pressure (BP) and muscle strength of spontaneously hypertensive rats (SHR) with SH. Methods: Fifteen male SHR ENT#091;206 ± 10 mmHg of systolic BP (SBP)ENT#093; and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP) were divided into 4 groups: sedentary (SED-WKY) and SHR (SED-SHR); RT1-SHR training relative to body weight (~40% of MWC); and RT2-SHR training relative to MWC test (~70% of MWC). Systolic BP and heart rate (HR) were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. Results: Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05), whereas SBP of the SED-SHR group increased by 19 mmHg (p < 0.05). There was a decrease in HR only for the RT1 group (p < 0.05). There was a higher increase in strength in the RT2 (140%; p < 0.05) group as compared with RT1 (11%; p > 0.05). Conclusions: Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength.

Resumo Fundamentos: O treinamento de força (TF) tem sido recomendado como tratamento não farmacológico para hipertensão arterial moderada. Apesar do papel importante que a intensidade do exercício desempenha sobre a prescrição do treinamento, ainda não há nenhum dado avaliando os efeitos da intensidade do TF sobre a hipertensão arterial grave (HAG). Objetivo: Este estudo analisou os efeitos de dois protocolos do TF(subida em escada vertical), realizados com diferentes sobrecargas do peso máximo carregado (PMC), sobre a pressão arterial (PA) e a força muscular de ratos espontaneamente hipertensos (SHR) com HAG. Métodos: Quinze SHR machos (206 ± 10 mmHg de PA sistólica (PAS)) e cinco ratos Wistar Kyoto (WKY; 119 ± 10 mmHg de PAS) foram divididos em 4grupos:sedentários: (SED-WKY) e SHR (SED-SHR); treinados: TF1-SHR conforme o peso corporal (~40% do PMC); e TF2-SHR conforme o teste de PMC (~70% do PMC). Foram coletadas medidas de PAS e a frequência cardíaca (FC) semanalmente usando o método de pressão arterial caudal. A progressão da força muscular foi determinada a cada 15 dias. O TF consistiu de 3 sessões semanais em dias não consecutivos durante 12 semanas. Resultados: Os dois protocolos de TF preveniram o aumento da PAS(respectivamente, delta - 5 e -7 mmHg; p > 0, 05), enquanto que a PAS do grupo SED-SHR aumentou em 19 mmHg (p < 0, 05). Houve queda na FC apenas para o grupo TF1 (p < 0, 05). Foi observado um aumento mas significativo de força no grupo do protocolo TF2 (140%; p < 0, 05) em comparação com o TF1 (11%; p>0, 05). Conclusões: Nossos dados indicam que ambos os protocolos de TF foram efetivos na prevenção da elevação crônica da PAS na HAG. Além disso, sobrecargas maiores de TF induziram a um maior aumento de força muscular.

Body mass index, adipokines and insulin resistance in asthmatic children and adolescents.

OBJECTIVE: This study aimed to describe the body mass index, insulin resistance, levels of adipokines and inflammatory markers in Brazilian asthmatic children and adolescents and to investigate their possible association with the severity and control of asthma. METHODS: Cross-sectional study (n = 92; age: 3-18 years). Assessed data: Body weight and height, used to calculate the body mass index (BMIZ) and height-for-age (HAZ). Laboratory measurements: Lipid profile; glycemia and insulin for homeostasis model assessment (HOMA); adipokines; tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1); total immunoglobulin E (IgE) and specific IgE against aeroallergens. RESULTS: The median age was 9.6 years (3.0-16.6); most participants were male (n = 52, 56.5%), pre-pubertal (n = 54, 58.6%) and had atopic asthma (n = 85, 92.4%). Overweight/obesity (38%) showed an inverse correlation with age (adjusted odds ratio [OR] = 0.781; 95% confidence interval [CI] 0.66-0.92) and a direct correlation with the leptin concentration (adjusted OR = 1.13; 95% CI 1.04-1.22). Insulin concentration was independently associated with moderated persistent asthma (adjusted OR = 1.31; 95% CI 1.09-1.52). HOMA showed a direct correlation with the leptin (ß = 0.475; 95% CI 0.117-0.268) and total IgE (ß = 0.197; 95% CI 0.002-0.096) levels and an inverse correlation with the TNF-α levels (ß = -0.255; 95% CI;-0.366-0.055). CONCLUSIONS: Asthma was associated with insulin resistance and a systemic inflammatory response possibly mediated by adipokines, with leptin levels standing out among the participants with excess weight.

Leukemia, non-Hodgkin's lymphoma, and Wilms tumor in childhood: the role of birth weight.

There is emerging evidence that higher birth weight is associated with increased risk of cancer, in particular childhood leukemia. The purpose of this paper is to study whether this correlation is also significant with other childhood cancer. For this, we conducted a case-control study including 410 childhood cancer patients and 1,575 matched controls to investigate birth weight as a risk factor for leukemia, Wilms tumor, and non-Hodgkin's lymphoma. The estimated risk for all cancers has been found to be statistically and significantly higher in birth weight of more than 4,000 g (odds ratio, 2.50 and 95% confidence intervals (CI), 1.72-3.63). For leukemia, the estimated risk was 1.86 (95% CI, 1.04-3.30), for non-Hodgkin lymphoma, 1.99 (95% CI, 1.08-3.69), and being more remarkable for Wilms tumor, 4.76 (95% CI, 2.73-8.28). Moreover, moderate increased risk of both leukemia and non-Hodgkin lymphoma was also associated with birth weight between 3,000 and 3,999 g. High birth weight was associated with all cancers also when adjusted by gestational age, length at birth, and gender (odds ratio, 6.10 and 95% CI, 1.15-32.57). No associations were found for maternal alcohol consumption during pregnancy, maternal smoking, or smoking by other people at home or presence of obstetric variables (e.g., gestational diabetes, preeclampsia, and abruptio placentae). The present study supports the hypothesis that high birth weight is an independent risk factor for childhood Wilms tumor, leukemia, and non-Hodgkin lymphoma. Further studies should explore biological reasons to explain this relationship and, ultimately, to expand our knowledge about prenatal influences on the occurrence of this disease.

Intrauterine undernutrition in rats interferes with leukocyte migration, decreasing adhesion molecule expression in leukocytes and endothelial cells.

Experimental and epidemiologic data have shown that malnutrition predisposes individuals to infections. Immune responses are compromised, particularly in undernourished children. Therefore, we investigated the migratory capacity of leukocytes, using the intravital microscopy technique, in male Wistar rats (8-9 wk of age) that were undernourished in utero after their dams were fed 50% less food than the amount consumed by control dams. The number of leukocytes rolling along the venular endothelium, sticking after stimulation with leukotriene B4, tumor necrosis factor-alpha (TNF-alpha) or zymosan-activated plasma, or migrating after TNF-alpha stimulation was significantly reduced in the undernourished rat offspring. Compared with nourished rat offspring, undernourished offspring had significantly reduced numbers of circulating leukocytes, higher blood pressure, and higher leukocyte rolling velocity (V(WBC)), as well as a higher ratio between V(WBC) and RBC velocity (V(RBC)). Endothelial P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression, analyzed by immunohistochemistry, and basal leukocyte L-selectin expression, analyzed by flow cytometry, were significantly reduced in the undernourished rat offspring. Because the groups did not differ in leukocyte CD11/18 expression, endothelial expression of platelet-endothelial cell adhesion molecule-1, or venular blood flow velocity and, consequently, venular shear rate, we conclude that intrauterine undernutrition in rats reduces leukocyte migration, downregulates endothelial expression of P-selectin and ICAM-1, as well as leukocyte expression of L-selectin, while reducing leukocyte counts. The higher V(WBC) and V(WBC)/V(RBC) ratio may also play a role in this reduced leukocyte migration. Our data suggest that this phenomenon is involved in the increased predisposition to infections in undernourished subjects.

Relative contribution of estrogen withdrawal and gonadotropins increase secondary to ovariectomy on prostaglandin generation in mesenteric microvessels.

Recent studies have established that ovariectomy impairs endothelial function, partially by increasing vasoconstrictor prostaglandins generation. Because ovariectomy causes concomitant lack of estrogen and increase of gonadotropins (ie, LH and FSH), in this study we explored the relative role of estrogen and LH/FSH in modulating vasoconstrictor prostaglandins generation in mesenteric arteriolar bed of SHR. Endothelium-dependent relaxation to acetylcholine (ACh) and bradykinin (Bk) was markedly reduced in ovariectomized (OVX) compared with SHR in physiological estrus (OE). Estrogen replacement (OVX + E), but not the decrease in LH/FSH levels with leuprolide (OVX + Leu), corrected the altered vasorelaxation response in OVX. Treatment of mesenteries with diclofenac, prostaglandin-H synthase (PGHS) inhibitor, significantly enhanced the relaxing response in arteries from OVX and OVX + Leu, but not those from OE, indicating that a PGHS-derived vasoconstrictor has modified the endothelium-dependent response during estrogen but not LH/FSH deprivation. Confirming these data, in response to exogenous arachidonic acid, whereas arteries from OVX and OVX + Leu exhibited a marked and similar vasoconstrictor response, the arteries from OE and OVX + E rats exhibited a slight vasodilation. We also demonstrated by RT-PCR that ovariectomy significantly increased PGHS-2 but not PGHS-1 mRNA expression in comparison to OE. The PGHS-2 overexpression in OVX was corrected by estrogen replacement, but not by the reduction of LH/FSH levels. Altogether these data strongly support a role for hypoestrogenism rather than LH/FSH enhancement, associated with the removal of ovaries, in the increase of vasoconstrictor prostaglandins, possibly by a mechanism involving PGHS-2 overexpression.

Intrauterine undernutrition: expression and activity of the endothelial nitric oxide synthase in male and female adult offspring.

OBJECTIVE: Epidemiological studies suggest that intrauterine undernutrition plays an important role in the development of arterial hypertension in adulthood. In an attempt to define the mechanisms whereby blood pressure may be raised, we have hypothesized that arteries from offspring of nutritionally restricted dams exhibit abnormalities in the endothelial function and in nitric oxide synthesis. In order to investigate the existence of potential gender differences on the effects of intrauterine undernutrition, both male and female offspring of pregnant Wistar rats on normal and restricted diets were studied in adulthood. METHODS: Female pregnant Wistar rats were fed either normal or 50% of the normal intake diets, during the whole gestational period. At 14 weeks of age, the rats were used for the study of vascular reactivity, eNOS and iNOS gene expression, eNOS activity and, in the case of females, estrogen levels. RESULTS: Intrauterine undernutrition induced hypertension in both male and female offspring, but hypertension was more severe in male rats. Endothelium-intact aortic rings from male and female rats in the restricted diet group exhibited increased responses to norepinephrine, decreased vasodilation to acetylcholine and unaltered responses to sodium nitroprusside in comparison to aortic rings from control rats. No gender-related differences were observed in the vascular reactivity studies. Intrauterine undernutrition promoted decreased gene expression for eNOS in aorta isolated from male, but not female, offspring, reduction in eNOS activity in both male and female offspring and impairment in synthesis of estrogen in female offspring. CONCLUSION: Our data show that intrauterine undernutrition: (1) induces hypertension both in the male and female offspring, hypertension being more severe in male than in female rats; (2) alters endothelium-dependent responses in aortas from the resulting offspring. The endothelial dysfunction is associated with a decrease in activity/expression of eNOS in aortas from male offspring. The mechanism involved in altered response to ACh in female offspring might be a consequence of reduction in estrogen levels leading to reduced eNOS activity.