Genome wide association study on early puberty in Bos indicus.

The aim of this study was to evaluate a genome wide association study (GWAS) approach to identify single nucleotide polymorphisms (SNPs) associated with fertility traits (early puberty) in Nellore cattle (Bos indicus). Fifty-five Nellore cows were selected from a herd monitored for early puberty onset (positive pregnancy at 18 months of age). Extremes of this phenotype were selected; 30 and 25 individuals were pregnant and non-pregnant, respectively, at that age. DNA samples were genotyped using a high-density SNP chip (>777.000 SNP). GWAS using a case-control strategy highlighted a number of significant markers based on their proximity with the Bonferroni correction line. Results indicated that chromosomes 5, 6, 9, 10, and 22 were associated with the traits of interest. The most significant SNPs on these chromosomes were rs133039577, rs110013280, rs134702839, rs109551605, and rs41639155. Candidate genes, as well as quantitative trait loci (QTL) previously reported in the Ensembl and Cattle QTLdb databases, were further investigated. Analysis of the regions close to the SNP on chromosomes 9 and 10 revealed that four QTL had been previously classified under the reproduction category. In conclusion, we have identified SNPs in close proximity to genes associated with reproductive traits. Moreover, U6 spliceosomal RNA was present on three different chromosomes, which is possibly associated with age at first calving, suggesting that it might be a strong candidate for future studies.

Involvement of cerebral nervous system areas and cytokines on antihyperalgesic and anti-inflammatory activities of Kielmeyera rugosa Choisy (Calophyllaceae) in rodents.

Kielmeyera rugosa is a medicinal plant known in Northeastern Brazil as 'pau-santo', and it is used in the treatment of several tropical diseases such as malaria, schistosomiasis, and leishmaniasis. We evaluated antihyperalgesic and anti-inflammatory activities of methanol stem extract of K. rugosa (MEKR) in mice. The mechanical hyperalgesia induced by carrageenan and tumor necrosis factor-alpha (TNF-α), prostaglandin E2 , and dopamine were assessed. We also investigated the anti-inflammatory effect of MEKR on carrageenan-induced pleurisy and paw edema. Ninety minutes after the treatment, the animals were submitted to an imunofluorescence for Fos protein. MEKR (100, 200, and 400 mg/kg; p.o.) inhibited the development of mechanical hypernociception and edema. MEKR significantly decreased TNF-α and interleukin 1ß levels in pleural lavage and suppressed the recruitment of leukocytes. MEKR (1, 10, and 100 mg/mL) did not produce cytotoxicity, determined using the methyl-thiazolyl-tetrazolium assay in vitro. The locomotor activity was not affected. MEKR activated significantly the bulb olfactory, piriform cortex, and periaqueductal gray of the central nervous system. Our results provide first time evidence to propose that MEKR attenuates mechanical hyperalgesia and inflammation, in part, through an activation of central nervous system areas, mainly the periaqueductal gray and piriform cortex areas.

Socioeconomic position, macroeconomic environment and overweight among adolescents in 35 countries.

OBJECTIVE: It is important to understand levels and social inequalities in childhood overweight within and between countries. This study examined prevalence and social inequality in adolescent overweight in 35 countries, and associations with macroeconomic factors. DESIGN: International cross-sectional survey in national samples of schools. SUBJECTS: A total of 11-, 13- and 15-year-olds from 35 countries in Europe and North America in 2001-2002 (N=162 305). MEASUREMENTS: The main outcome measure was overweight based on self-reported height and weight (body mass index cut-points corresponding to body mass index of 25 kg/m(2) at the age of 18 years). Measures included family and school affluence (within countries), and average country income and economic inequality (between countries). RESULTS: There were large variations in adolescent overweight, from 3.5% in Lithuanian girls to 31.7% in boys from Malta. Prevalence of overweight was higher among children from less affluent families in 21 of 24 Western and 5 of 10 Central European countries. However, children from more affluent families were at higher risk of overweight in Croatia, Estonia and Latvia. In Poland, Lithuania, Macedonia and Finland, girls from less affluent families were more overweight whereas the opposite was found for boys. Average country income was associated with prevalence and inequality in overweight when considering all countries together. However, economic inequality as measured by the Gini coefficient was differentially associated with prevalence and socioeconomic inequality in overweight among the 23-high income and 10-middle income countries, with a positive relationship among the high income countries and a negative association among the middle income countries. CONCLUSION: The direction and magnitude of social inequality in adolescent overweight shows large international variation, with negative social gradients in most countries, but positive social gradients, especially for boys, in some Central European countries. Macroeconomic factors are associated with the heterogeneity in prevalence and social inequality of adolescent overweight.

Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?

Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe), triglyceride-reducing (fibrates), or lipid antioxidant (thioctic acid) therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated.

Comparison of plasma pigment epithelium-derived factor (PEDF), retinol binding protein 4 (RBP-4), chitinase-3-like protein 1 (YKL-40) and brain-derived neurotrophic factor (BDNF) for the identification of insulin resistance.

AIMS: To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. METHODS: We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). RESULTS: PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend=0.029; for RBP-4 p-trend=0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. CONCLUSIONS: Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes.

Waist circumference and waist-to-hip ratio are related to gestational glucose tolerance.

OBJECTIVE: To evaluate the relationship of central fat distribution with gestational glucose tolerance during the usual time for screening gestational diabetes. RESEARCH DESIGN AND METHODS: This cross-sectional study investigated 1,113 consecutive women, > or = 20 years old, pregnant for approximately 21 to 28 weeks, without history of previous diabetes outside pregnancy, who attended two general prenatal care units in Porto Alegre, Brazil, from 1991 to 1993. Weight, height, waist and hip circumferences, and skinfolds were measured, and a 2-h, 75-g glucose tolerance test was performed. Data were analyzed using multiple linear regression models. RESULTS: Waist-to-hip ratio (WHR) and waist circumference were independently associated with higher 2-h glycemia. Glycemic level was 0.11 and 0.13 mmol/l greater for each standard deviation increase in WHR (0.06) and waist circumference (8.0 cm), respectively (P < 0.02). Restricting analyses to the subset of women with uterine height < or = 26 cm improved the association (0.13 and 0.19 mmol/l, respectively, P < 0.02); differences of 0.22 and 0.19 mmol/l were observed for 1 SD changes in the sum of skinfold thicknesses (24.7 mm) and in age (5.5 years), respectively. CONCLUSIONS: Central fat distribution measured in pregnancy is an independent predictor of gestational glucose intolerance. This finding supports the concept that NIDDM and gestational diabetes are parts of the same disease, differing basically in their moment of detection. The usefulness of these anthropometric measurements in identifying pregnant women at high risk of having gestational glucose intolerance merits further investigation.

Gestational diabetes mellitus diagnosed with a 2-h 75-g oral glucose tolerance test and adverse pregnancy outcomes.

OBJECTIVE: To evaluate American Diabetes Association (ADA) and World Health Organization (WHO) diagnostic criteria for gestational diabetes mellitus (GDM) against pregnancy outcomes. RESEARCH DESIGN AND METHODS: This cohort study consecutively enrolled Brazilian adult women attending general prenatal clinics. All women were requested to undertake a standardized 2-h 75-g oral glucose tolerance test (OGTT) between their estimated 24th and 28th gestational weeks and were then followed to delivery. New ADA criteria for GDM require two plasma glucose values > or = 5.3 mmol/l (fasting), > or = 10 mmol/l (1 h), and > or = 8.6 mmol/l (2 h). WHO criteria require a plasma glucose > or = 7.0 mmol/l (fasting) or > or = 7.8 mmol/l (2 h). Individuals with hyperglycemia indicative of diabetes outside of pregnancy were excluded. RESULTS: Among the 4,977 women studied, 2.4% (95% CI 2.0-2.9) presented with GDM by ADA criteria and 7.2% (6.5-7.9) by WHO criteria. After adjustment for the effects of age, obesity, and other risk factors, GDM by ADA criteria predicted an increased risk of macrosomia (RR 1.29, 95% CI 0.73-2.18), preeclampsia (2.28, 1.22-4.16), and perinatal death (3.10, 1.42-6.47). Similarly, GDM by WHO criteria predicted increased risk for macrosomia (1.45, 1.06-1.95), preeclampsia (1.94, 1.22-3.03), and perinatal death (1.59, 0.86-2.90). Of women positive by WHO criteria, 260 (73%) were negative by ADA criteria. Conversely, 22 (18%) women positive by ADA criteria were negative by WHO criteria. CONCLUSIONS: GDM based on a 2-h 75-g OGTT defined by either WHO or ADA criteria predicts adverse pregnancy outcomes.

Hypertensive disorders in pregnancy: frequency and associated factors in a cohort of Brazilian women.

OBJECTIVE: To evaluate the frequency of and risk factors associated with hypertensive disorders in general antenatal care in five distinct areas of Brazil. METHODS: We performed a cohort study of 4892 women enrolled in midpregnancy from 1991 to 1995. Patients were queried at enrollment about hypertension prior to pregnancy. Medical diagnoses of hypertensive disorders in pregnancy were abstracted from patient records. Hypertensive disorders in pregnancy were classified according to recommendations of the American College of Obstetrics and Gynecology (ACOG). RESULTS: Of 4892 women studied, 367 (7.5%) presented hypertensive disorders, 113 (2.3%) being preeclampsia/eclampsia and 198 (4.0%) chronic hypertension. Frequencies of superimposed preeclampsia/eclampsia and transitory hypertension were 0.5% and 0.7%, respectively. Greater brachial arm circumference was strongly associated both with preeclampsia/eclampsia and with chronic hypertension (threefold difference across extreme quartiles, p < or =0.001). In adjusted analyses, being older, black, and obese were important and statistically significant risk factors for chronic hypertension. Similarly, nulliparity was a statistically significant risk factor for preeclampsia/eclampsia, and tendencies toward increased risk were seen for older, black, and obese women in adjusted analyses. Preeclampsia/eclampsia and chronic hypertension were notably less frequent in Manaus, although regional differences were statistically significant only for chronic hypertension. CONCLUSIONS: Hypertensive disorders commonly complicate pregnancy in Brazilian women. Risk factors for these disorders appear similar to those reported in other countries. Use of an inappropriately sized cuff to measure blood pressure may result in many false-positive diagnoses in more obese women. The considerably lower frequency of hypertensive disorders found in Manaus, in the Amazon region, warrants further study.

Prevalence of gestational diabetes mellitus--do the new WHO criteria make a difference? Brazilian Gestational Diabetes Study Group.

AIMS: To describe the prevalence of gestational diabetes mellitus (GDM) according to the 1998 WHO provisional recommendations and compare it to that found with previous 1985 WHO criteria. METHODS: A total of 5564 consecutive women aged 20 years or more without diagnosis of diabetes mellitus outside of pregnancy in general prenatal care clinics of the National Health Service in 6 state capitals of Brazil, between their 20th and 28th gestational weeks were enrolled. RESULTS: Of the 5004 women who completed a 75-g oral glucose tolerance test, 379 (7.6%, 95% confidence interval (CI) 6.9% to 8.4%) had GDM by the 1998 criteria (fasting glucose > or = 7.0 mmol/l or 2 h glucose > or = 7.8 mmol/l). Of these 379 cases, only 21 (5.5%) had hyperglycaemia in the range considered diabetes mellitus outside pregnancy (fasting glucose > or = 7.0 mmol/l or 2 h glucose > or = 11.1 mmol/l); the remaining 358 (94.5%) had hyperglycaemia in the impaired glucose tolerance range (fasting glucose < 7.0 and 2 h glucose > or = 7.8 mmol/l and < 11.1 mmol/l). Using the 1985 criteria (fasting or 2 h glucose > or = 7.8 mmol/l), 378 cases of GDM were found, 15 in the diabetes range and 363 in the impaired glucose tolerance range. CONCLUSIONS: Prevalence of GDM is minimally altered by the new WHO definition. Although GDM is a common condition, the vast majority of the cases have hyperglycaemia in the range considered impaired glucose tolerance outside pregnancy.

Short stature and gestational diabetes in Brazil. Brazilian Gestational Diabetes Study Group.

AIMS/HYPOTHESIS: To examine the association between maternal stature and gestational diabetes mellitus. METHODS: We studied a sample of 5564 consecutive Brazilian women 20 or more years old, who were pregnant for approximately 21-28 weeks, had no history of diabetes outside pregnancy and were attending general prenatal care units in six state capitals in Brazil from 1991 to 1995. We did a 2-h, 75-g oral glucose tolerance test, defining gestational diabetes by World Health Organisation criteria. RESULTS: Those in the shortest quartile of height (< or = 151 cm) had a 60% increase in the odds of having gestational diabetes, independently of prenatal clinic, age, global obesity, family history of diabetes, skin colour, referral pattern, waist circumference, parity, previous gestational diabetes, education, ambient temperature and gestational age compared with the tallest quartile [odds ratio (OR) = 1.60, p = 0.005]. This association was observed for those with above median values of skinfold thickness (OR = 1.74, p = 0.006) but not for those with below median values (OR = 1.22, p = 0.51). Associations of short stature with high 2-h glycaemia (> or = 7.8 mmol/l) (OR = 1.61, p = 0.005) were essentially the same as those for gestational diabetes. There was, however, no association between short stature and gestational hyperglycaemia when the latter was defined exclusively by fasting values (OR = 0.97, p = 0.90). CONCLUSION/INTERPRETATION: In Brazil short stature associates with gestational diabetes, principally in women with greater fat mass. This difference in glycaemic levels is present postprandially but not in the fasting state.

Variation in glucose tolerance with ambient temperature.

Ambient temperature may affect venous glucose concentration after glucose tolerance tests. We analysed 1030 standardised 75 g tests. Although mean fasting values did not differ, post-load values did: adjusted mean 2 h glucose concentration was 1.03 mmol/L lower at lower (5-14 degrees C) than at higher (25-31 degrees C) temperatures (p < 0.001). The occurrence of abnormal glucose tolerance doubled on warmer days. The diagnostic accuracy of the glucose tolerance test showed clinically significant temperature-associated variation. These variations, if confirmed, call for temperature standardisation during glucose tolerance testing and/or alternative strategies for use when standardisation is not feasible.