Expression of estrogen receptor subtypes and neuronal nitric oxide synthase in neutrophils from women and men: regulation by estrogen.
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OBJECTIVES: (a) To identify the subtype of estrogen receptor (ER) expressed in neutrophils from premenopausal women and in neutrophils from men under different estrogen conditions and (b) to analyze the association between the modifications in the expression of ER subtypes and neuronal nitric oxide synthase (nNOS) expression induced by estrogen. METHODS: Neutrophils were isolated from pre-menopausal women during different stages of the menstrual cycle and from ten men for in vitro estrogen incubations. RESULTS: Neutrophils from premenopausal women expressed both ERalpha and ERbeta subtypes which were increased in the ovulatory phase of the menstrual cycle. Neutrophils derived from men also expressed ERalpha and ERbeta but only ERalpha expression was enhanced by in vitro incubation with 17beta-estradiol (10(-8) mol/l). In vitro incubation of neutrophils from women with 17beta-estradiol enhanced expression of both ER-alpha and ER-beta subtypes. nNOS protein was overexpressed in neutrophils from premenopausal women during the ovulatory phase. 17beta-Estradiol (10(-8) mol/l) also increased nNOS protein expression in neutrophils derived from men. Mithramycin A (10(-6) mol/l) and curcumin (10(-6) mol/l), prevented the upregulation of nNOS and ERalpha in neutrophils derived from men, suggesting the involvement of AP-1 and Sp-1 transcription factors. CONCLUSIONS: Although the in vivo levels of circulating estrogen concentrations seem to be associated with overexpression of both ERalpha and ERbeta in neutrophils from premenopausal women, which was further confirmed by the in vitro experiments with neutrophils from women, in vitro incubation of neutrophils from men with 17beta-estradiol only increased ERalpha protein expression which was associated with enhanced expression of nNOS protein. (+info)
Intrauterine undernutrition: expression and activity of the endothelial nitric oxide synthase in male and female adult offspring.
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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. (+info)
Parasexual genetic analysis of the cellular slime mold Dictyostelium discoideum A3.
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Haploid strain A3 of the cellular slime mold Dictyostelium discoideum is valuable for biochemical studies because it is capable of axenic growth. Mutants of A3 temperature-sensitive for growth and resistant to the drugs cycloheximide, acriflavin, or methanol were isolated.--Heterozygous diploid recombinants, formed at low frequency by cell and nuclear fusion, were isolated by selecting temperature-resistant progeny of mixed cultures of two nonallelic temperature-sensitive haploids (LOOMIS 1969). Each drug-resistant mutation was found to be recessive. Two independently isolated methanol-resistant mutants were in one complementation group.--Diploids of A3 heterozygous for drug resistance formed drug-resistant segregants with a frequency of approximately 10(-4). Segregants selected for resistance to a single drug were either haploid or diploid; the fraction which was haploid varied from 0.11 to 0.86, depending on the selected marker. Segregants selected for resistance to two or three drugs were almost all haploid.--Using this parasexual cycle of diploid formation and haploidization, linkage of these temperature-sensitive and drug-resistance mutations to each other and to mutations studied by KATZ and SUSSMAN (1972) and by WILLIAMS, KESSIN and Newell (1974b) was analyzed. The methanol-resistant mutants were found to be partially resistant to acriflavin, and unlinked to the mutant selected for acriflavin resistance, which was methanol-sensitive. Of the expected seven linkage groups in D. discoideum, five, and a possible sixth, have been marked.--Linkage analysis of a mutant abnormal in morphogenesis showed that its phenotype results from two unlinked chromosomal mutations. (+info)
Incidence of morphological and lipid abnormalities: gender and treatment differentials after initiation of first antiretroviral therapy.
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OBJECTIVE: To provide population-based incidence estimates for constituent symptoms of human immundeficiency virus (HIV)-related lipodystrophy syndrome and to identify possible independent predictors of accrued cases. DESIGN: Prospective population-based cohort. Methods Study subjects were antiretroviral-naive individuals who initiated treatment between October 1998 and May 2001 and provided completed self-reported data regarding the occurrence of lipoatrophy, lipohypertrophy and increased triglyceride and cholesterol levels. Possible predictors of incident lipoatrophy, lipohypertrophy, dyslipidaemia and mixed lipodystrophy (symptoms of both lipoatrophy and lipohypertrophy) were identified using logistic regression modelling. A sub-analysis restricted to subjects retaining original treatment at study completion was conducted using similar methods. RESULTS: Among the 366 study subjects, cumulative incidence was 29% for lipoatrophy, 23% for lipohypertrophy, 9% for dyslipidaemia, and 13% for mixed lipodystrophy after a median duration of 12 months of antiretroviral therapy. In an intentto-treat analysis incident lipoatrophy and lipohypertrophy were independently associated with initiation of protease inhibitor (PI)-containing regimens, (adjusted odds ratio [AOR] = 1.94; 95% CI: 1.25-3.03 and AOR = 1.76; 95% CI: 1.09-2.85, respectively) and female gender (AOR = 2.06; 95% CI: 1.03-4.12 and AOR = 2.36; 95% CI: 1.17-4.74, respectively). Both mixed lipodystrophy and reported dyslipidaemia were associated only with PI inclusion in the initial regimen (AOR = 2.27; 95% CI: 1.14-4.53 and AOR = 2.14; 95% CI: 1.26-3.65, respectively). Similar results were obtained in analysis of individuals retained in initial treatment groups throughout follow-up. CONCLUSION: Incident morphological and lipid abnormalities are common among individuals initiating first-time antiretroviral therapy. Use of PI was consistently associated with all lipodystrophy-related abnormalities after adjustment for a broad range of patient personal, clinical and treatment characteristics. (+info)
Sex preference and contraceptive behaviour among men in Mbeya region, Tanzania.
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While recent studies confirm parental child sex preference in less developed countries, its pattern varies. Son preference is especially prevalent in Bangladesh, China, India, and Pakistan. Sex preference in sub-Saharan Africa is a neglected area of enquiry. Completed research focuses on women's views to the neglect of men, despite the latter's importance as primary decision-makers. This study identifies factors influencing contraceptive behaviour among men in Mbeya region, Tanzania, demonstrating how it is affected by their preferred family sex composition. Data used were collected from a cross-sectional survey of 600 men aged 16-50 and six focus groups conducted in the region's rural and urban areas. Using single statements and Coombs' Scales, sex preference was found to be prevalent in the study area, with sons strongly preferred to daughters. Sex preference is significantly associated with the number of existing daughters a man has, his marital status, residence and occupation. Findings suggest programmes should be initiated to challenge men's attitudes towards one-sex family composition. Men should be educated about the advantages of small family sizes and persuaded that both children's sexes are equally important. Such measures can assist men in reconsidering their desired family sizes, reduce biases towards one sex, minimise marital problems and improve women's status. Efforts to increase contraceptive use in Tanzania will be hampered, however, if men maintain their preference for sons over daughters. (+info)
Gender-specific programming of insulin secretion and action.
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Insulin secretion and glucose tolerance were studied in 20-week-old male and female offspring of rat dams maintained on an isocaloric 20% or 8% protein diet during pregnancy and lactation after transfer to the same diet at weaning. Protein-restricted male and female offspring were also weaned onto a 20% protein diet. In males, post-absorptive insulin concentrations were suppressed by protein restriction from conception to adulthood (by 41%; P<0.001); however, basal insulin levels were 2.6-fold higher (P<0.001) if protein restriction was limited to gestation and lactation. Post-absorptive insulinaemia in females was unaffected by early or sustained protein restriction, but was lower than for males in the control group and the group exposed to protein restriction during early life alone (by 40% (P<0.001) and 52% (P<0.001) respectively). Plasma insulin/blood glucose ratios were higher in males compared with females in both control and early protein-restricted groups (1.6-fold (P<0.05) and 2.3-fold (P<0.001) respectively). A positive linear relationship existed between mean ambient insulin and glucose concentrations in males (r=1.0) and females (r=0.9), but the gradient was 12.4-fold greater (P<0.01) in males. beta-Cell function was evaluated after intravenous glucose challenge. In males, the acute insulin response and the suprabasal 30-min area under the insulin curve were dramatically higher in rats exposed to protein restriction during gestation and lactation alone (2.6- and 2.8-fold respectively; P<0.001). In contrast, these parameters were lowered by extending the exposure to protein restriction to adulthood in males, and by either early or prolonged exposure to protein restriction in females. The insulin resistance index was increased (2.5-fold; P<0.001) in male, but not female, rats exposed to protein restriction during gestation and lactation alone, and was not increased by extending the period of protein restriction to adulthood in either sex. Thus the data have demonstrated gender-specific lowering of insulin sensitivity due to protein restriction during early life only. The insulinogenic index (insulin response in relation to prevailing glycaemia) was increased in male, but not female, rats exposed to protein restriction during gestation and lactation alone (3.0-fold; P<0.001). A modest decline in insulin secretion in the female groups exposed to protein restriction until either the end of lactation or adulthood was compensated by increased insulin sensitivity, as demonstrated by significant decreases in the insulin resistance index in both groups (by 48% and 52% respectively; P<0.05). Glucose disappearance rates did not differ between the male and female control or early protein-restricted groups but were higher in both male (31%; P<0.05) and female groups (46%; P<0.001) exposed to protein restriction from conception to adulthood. Marked gender differences in glucose-stimulated insulin secretion were not associated with gender differences with respect to glucose tolerance. Our data therefore demonstrated that exposure to protein restriction during early life alone leads to relative insulin resistance and hyperinsulinaemia in adulthood, but this relationship is gender specific, observed only in males, and glucose tolerance is maintained. (+info)
Postnatal depression and infant growth and development in low income countries: a cohort study from Goa, India.
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BACKGROUND: Postnatal depression is a recognised cause of delayed cognitive development in infants in developed countries. Being underweight is common in South Asia. AIMS: To determine whether postnatal depression contributes to poor growth and development outcomes in Goa, India. METHODS: Cohort study for growth outcomes with nested case-control study for developmental outcomes. A total of 171 babies were weighed and measured at 6-8 weeks following birth. The following measures were used: Edinburgh Postnatal Depression Scale for maternal mood, and sociodemographic and infant health variables. Outcome measures were: weight (<5th centile), length (<5th centile), and Developmental Assessment Scale for Indian Infants scores at six months. RESULTS: Postnatal depression was a strong, and independent, predictor of low weight and length and was significantly associated with adverse mental development quotient scores. CONCLUSIONS: This study provides evidence for the first time that postnatal depression, a potentially treatable disorder, is a cause of poor growth and development in South Asia. (+info)
The melanocortin system.
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The melanocortin system consists of melanocortin peptides derived from the proopiomelanocortin gene, five melanocortin receptors, two endogenous antagonists, and two ancillary proteins. This review provides an abbreviated account of the basic biochemistry, pharmacology, and physiology of the melanocortin system and highlights progress made in four areas. In particular, recent pharmacological and genetic studies have affirmed the role of melanocortins in pigmentation, inflammation, energy homeostasis, and sexual function. Development of selective agonists and antagonists is expected to further facilitate the investigation of these complex physiological functions and provide an experimental basis for new pharmacotherapies. (+info)