RESUMO
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.
Assuntos
Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Técnicas de Diagnóstico Endócrino , Proteínas do Olho/sangue , Resistência à Insulina , Fatores de Crescimento Neural/sangue , Proteínas Plasmáticas de Ligação ao Retinol/análise , Serpinas/sangue , Adulto , Idoso , Feminino , Técnica Clamp de Glucose , Intolerância à Glucose/sangue , Intolerância à Glucose/complicações , Intolerância à Glucose/diagnóstico , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/metabolismo , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Proteínas Plasmáticas de Ligação ao Retinol/metabolismoRESUMO
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.
Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Animais , Neuropatias Diabéticas/metabolismo , Humanos , Hipolipemiantes/farmacologiaRESUMO
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.
Assuntos
Fertilidade/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Característica Quantitativa Herdável , Reprodução/genética , Maturidade Sexual/genética , Animais , Cruzamento , Bovinos , Cromossomos de Mamíferos/química , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Masculino , Fenótipo , Gravidez , RNA Nuclear Pequeno/genética , Spliceossomos/genéticaRESUMO
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.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Sistema Nervoso Central/efeitos dos fármacos , Citocinas/metabolismo , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Carragenina/efeitos adversos , Dinoprostona/metabolismo , Dopamina/metabolismo , Edema/tratamento farmacológico , Interleucina-1beta/metabolismo , Magnoliopsida/química , Masculino , Camundongos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Córtex Piriforme/efeitos dos fármacos , Caules de Planta/química , Pleurisia/tratamento farmacológico , Proteínas Proto-Oncogênicas c-fos/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A criopreservação de tecido ovariano é uma biotécnica alternativa potencialmente útil na formação de bancos de células germinativas para a estocagem de DNA de espécies de alto valor zootécnico, raras ou em extinção. Além disso, gera grandes perspectivas na preservação da fertilidade de pacientes com câncer ou com problemas de infertilidade que possam provocar falha ovariana prematura. A criopreservação aliada ao processo de xenotransplante é um campo vasto para pesquisas, abrangendo desde métodos e protocolos mais efetivos de preservação até aspectos fundamentais da foliculogênese.
Cryopreservation of ovarian tissue is an alternative biotechnology potentially useful to implement gene DNA banks of livestock animals, rare and endangered species. Furthermore, it generates great prospects to save the fertility of patients with cancer or infertility problems that can cause premature ovarian failure. The cryopreservation combined with xenotransplantation is an ample field for research, rangingfrom more effective methods and protocols, including fundamental aspects of folliculogenesis.
Assuntos
Feminino , Animais , Criopreservação/tendências , Criopreservação/veterinária , Preservação do Sêmen/métodos , Preservação do Sêmen/tendências , Preservação do Sêmen/veterinária , Transplante Heterólogo/tendências , Transplante Heterólogo/veterinária , Ovário , Preservação da FertilidadeRESUMO
A criopreservação de tecido ovariano é uma biotécnica alternativa potencialmente útil na formação de bancos de células germinativas para a estocagem de DNA de espécies de alto valor zootécnico, raras ou em extinção. Além disso, gera grandes perspectivas na preservação da fertilidade de pacientes com câncer ou com problemas de infertilidade que possam provocar falha ovariana prematura. A criopreservação aliada ao processo de xenotransplante é um campo vasto para pesquisas, abrangendo desde métodos e protocolos mais efetivos de preservação até aspectos fundamentais da foliculogênese.(AU)
Cryopreservation of ovarian tissue is an alternative biotechnology potentially useful to implement gene DNA banks of livestock animals, rare and endangered species. Furthermore, it generates great prospects to save the fertility of patients with cancer or infertility problems that can cause premature ovarian failure. The cryopreservation combined with xenotransplantation is an ample field for research, rangingfrom more effective methods and protocols, including fundamental aspects of folliculogenesis.(AU)
Assuntos
Animais , Feminino , Criopreservação/tendências , Criopreservação/veterinária , Transplante Heterólogo/tendências , Transplante Heterólogo/veterinária , Preservação do Sêmen/métodos , Preservação do Sêmen/tendências , Preservação do Sêmen/veterinária , Ovário , Preservação da FertilidadeRESUMO
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.
Assuntos
Glicemia/metabolismo , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/fisiopatologia , Macrossomia Fetal/epidemiologia , Teste de Tolerância a Glucose , Pré-Eclâmpsia/epidemiologia , Resultado da Gravidez , Adulto , Fatores Etários , Peso Corporal , Brasil , Estudos de Coortes , Parto Obstétrico , Diabetes Gestacional/classificação , Escolaridade , Etnicidade , Feminino , Morte Fetal/epidemiologia , Teste de Tolerância a Glucose/métodos , Humanos , Recém-Nascido , Paridade , Valor Preditivo dos Testes , Gravidez , Segundo Trimestre da Gravidez , Cuidado Pré-Natal , Fatores de Risco , Fatores de TempoRESUMO
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.
Assuntos
Eclampsia/epidemiologia , Hipertensão/epidemiologia , Complicações Cardiovasculares na Gravidez/epidemiologia , Adulto , Brasil/epidemiologia , Estudos de Coortes , Feminino , Humanos , GravidezRESUMO
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.
Assuntos
Estatura , Diabetes Gestacional/epidemiologia , Adulto , Índice de Massa Corporal , Peso Corporal , Brasil/epidemiologia , Feminino , Teste de Tolerância a Glucose , Humanos , Incidência , Razão de Chances , Gravidez , Cuidado Pré-Natal , Grupos Raciais , Pigmentação da PeleRESUMO
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.