Availability of a rich source of sodium during the perinatal period programs the fluid balance restoration pattern in adult offspring

Osmoregulatory mechanisms can be vulnerable to electrolyte and/or endocrine environmental changes during the perinatal period, differentially programming the developing offspring and affecting them even in adulthood. The aim of this study was to evaluate whether availability of hypertonic sodium solution during the perinatal period may induce a differential programming in adult offspring osmoregulatory mechanisms. With this aim, we studied water and sodium intake after Furosemide-sodium depletion in adult offspring exposed to hypertonic sodium solution from 1 week before mating until postnatal day 28 of the offspring, used as a perinatal manipulation model [PM-Na group]. In these animals, we also identified the cell population groups in brain nuclei activated by Furosemide-sodium depletion treatment, analyzing the spatial patterns of Fos and Fos-vasopressin immunoreactivity. In sodium depleted rats, sodium and water intake were significantly lower in the PM-Na group vs. animals without access to hypertonic sodium solution [PM-Ctrol group]. Interestingly, when comparing the volumes consumed of both solutions in each PM group, our data show the expected significant differences between both solutions ingested in the PM-Ctrol group, which makes an isotonic cocktail: however, in the PM-Na group there were no significant differences in the volumes of both solutions consumed after Furosemide-sodium depletion, and therefore the sodium concentration of total fluid ingested by this group was significantly higher than that in the PM-Ctrol group. With regard to brain Fos immunoreactivity, we observed that Furosemide-sodium depletion in the PM-Na group induced a higher number of activated cells in the subfornical organ, ventral subdivision of the paraventricular nucleus and vasopressinergic neurons of the supraoptic nucleus than in the PM-Ctrol animals. Moreover, along the brainstem, we found a decreased number of sodium depletion-activated cells within the nucleus of the solitary tract of the PM-Na group. Our data indicate that early sodium availability induces a long-term effect on fluid drinking and on the cell activity of brain nuclei involved in the control of hydromineral balance. These results also suggest that availability of a rich source of sodium during the perinatal period may provoke a larger anticipatory response in the offspring, activating the vasopressinergic system and reducing thirst after water and sodium depletion, as a result of central osmosensitive mechanism alterations. (C) 2011 Elsevier Inc. All rights reserved.

Prion potency in stem cells biology

Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

N-glycome profiling of Bothrops jararaca newborn and adult venoms

Glycosylation is an important post-translational modification of snake venom proteins and contributes to venom proteome complexity. Many snake venom components are known to be glycosylated, however, very little is known about the carbohydrate structures present in venom glycoproteins. Previous studies showed that the ontogenetic shift in diet, from ectothermic prey in early life to endothermic prey in adulthood, and shift in animal size are associated with changes in the venom proteome of the snake Bothrops jararaca. In this study we explored the composition of the N-glycome released from newborn and adult B. jararaca venom proteins. We used an ion trap mass spectrometer (IT-MS) to disassemble glycan structures based on the use of several pathways of MS (MSn) and demonstrate the presence of some structural isomers in both newborn and adult venom B. jararaca N-glycans. The main N-glycans identified in both venoms are of the hybrid/complex type however some mannose-rich type structures were also detected. The N-glycan composition of newborn and adult venoms did not vary indicating that differences in the utilization of the N-glycosylation motif could be the explanation for the differences in the glycosylation levels indicated by the differential electrophoretic profiles previously reported for B. jararaca newborn and adult venoms. (C) 2011 Elsevier B.V. All rights reserved.

Maternal immune activation in late gestation enhances locomotor response to acute but not chronic amphetamine treatment in male mice offspring: Role of the D1 receptor

Exposure to elevated levels of maternal cytokines can lead to functional abnormalities of the dopaminergic system in the adult offspring, including enhanced amphetamine (AMPH)-induced locomotion. Therefore, it seems reasonable to consider that offspring of challenged mothers would behave differently in models of addictive behavior, such as behavioral sensitization. Thus, we sought to evaluate the effects of prenatal exposure to lipopolysaccharide (LPS) on the locomotor response to acute and chronic AMPH treatment in male mice offspring. For this purpose, LPS (Escherichia coli 0127:B8; 120 mu g/kg) was administered intraperitoneally to pregnant Swiss mice on gestational day 17. At adulthood, male offspring were studied under one of the following conditions: (1) locomotor response to acute AMPH treatment (2.5 or 5.0 mg/kg) in an open field test; (2) behavioral sensitization paradigm, which consists of a daily injection of AMPH (1.0 mg/kg) for 10 days and observation of locomotion in the open field on days 1, 5, 10 (development phase), 15 and 17 (expression phase). The LPS stimulated offspring showed enhancement of the locomotor-stimulant effect after an acute AMPH challenge in comparison to baseline and saline pre-treated mice. They also showed development of behavioral sensitization earlier than the saline pre-treated group, although no changes between saline and LPS pre-treated groups were observed on development or expression of locomotor behavioral sensitization to AMPH. Furthermore, there was up-regulation of D1 receptor protein level within striatum in the LPS-stimulated offspring which was strongly correlated with increased grooming behavior. Taken together, our results indicate that motor and dopaminergic alterations caused by maternal immune activation are restricted to the acute AMPH challenge, mostly due to up-regulation of the D1 receptor within the mesolimbic and nigrostriatal pathways, but no locomotor differences were observed for behavioral sensitization to AMPH. (C) 2012 Elsevier B.V. All rights reserved.

Potential Effects of Alendronate on Fibroblast Growth Factor 23 Levels and Effective Control of Hypercalciuria in an Adult with Jansen's Metaphyseal Chondrodysplasia

Context: Jansen's metaphyseal chondrodysplasia (JMC) is a rare autosomal dominant disorder caused by activating mutations in the PTH 1 receptor (PTH1R; PTH/PTHrP receptor), leading to chronic hypercalcemia and hypercalciuria. Hypophosphatemia is also a hallmark of JMC, and recently, increased fibroblast growth factor 23 (FGF23) levels have been reported in this syndrome. Hypercalcemia has been associated with increased cardiovascular risk; however, cardiovascular disease has not been extensively investigated in JMC patients. Objective: The aim of the study was to describe the long-term follow-up of a JMC patient with regard to the management of hypercalciuria, the evaluation of FGF23 levels under bisphosphonate treatment, and the investigation of cardiovascular repercussion of chronic hypercalcemia. Results: The diagnosis of JCM was confirmed by molecular analysis (p.H223R mutation in PTH1R). The patient was followed from 5 to 27 yr of age. Asymptomatic nephrolithiasis was diagnosed at 18 yr of age, prompting pharmacological management of hypercalciuria. Treatment with alendronate reduced hypercalciuria; however, normocalciuria was only obtained with the association of thiazide diuretic. Serum FGF23 levels, measured under alendronate treatment, were repeatedly within the normal range. Subclinical cardiovascular disease was investigated when the patient was 26 yr old, after 19 yr of sustained mild hypercalcemia; carotid and vertebral artery ultrasonography was normal, as well as coronary computed tomography angiography (calcium score = 0). Conclusion: The long-term follow-up of our JMC patient has provided insight on therapeutic strategies to control hypercalciuria, on the potential effects of alendronate on FGF23 levels, and on the lack of detectable cardiovascular disease at young adulthood after prolonged exposure to hypercalcemia. (J Clin Endocrinol Metab 97: 1098-1103, 2012)

Impairment on sperm quality and fertility of adult rats after antiandrogen exposure during prepuberty

This study evaluated the effects of antiandrogen exposure during the prepubertal period on reproductive development and reproductive competence in adults. Male rats were divided into two groups: flutamide, receiving 25 mg/kg/day of flutamide by oral gavage and control, receiving vehicle daily. Dosing continued from PND 21 to 44, and animals were killed on PND 50 or PND 75-80. The epididymis, prostate, vas deferens and seminal vesicle weights were lower in Flutamide group on PND 50, while on PND 80 only seminal vesicle weight was reduced. Fertility assessed by IUI revealed a decrease in the fertility potential in the flutamide-treated adults. Flutamide accelerated sperm transit time through the epididymis, impairing sperm motility and storage. A quantitative analysis of the cauda sperm membrane proteome revealed a few significant changes in protein expression. Thus, exposure to flutamide during the prepubertal period compromises the function of the epididymis along with epididymal sperm quality at adulthood. (C) 2011 Elsevier Inc. All rights reserved.

Construction and validation of an instrument that breaks the silence: the impact of domestic and/or sexual violence on women's health, as shown during climacterium

Objective: The aim of this study was to construct and to validate a measure of the consequences of domestic violence on women's health during climacterium. Methods: A questionnaire was administered at the Outpatient Climacterium Clinic to 124 women aged 40 to 65 years who were the victims of domestic and/or sexual violence (experimental group). They were divided into three groups: (1) those who were victims of violence exclusively during childhood/adolescence, (2) those who were victims of violence exclusively during adulthood, and (3) those who were victims of violence throughout their lives. The instrument included 34 items evaluating the beginning, frequency, and type of violence; the search for health assistance and reporting of the violence; the violence and the number of comorbidities; and violence and the Kupperman Menopausal Index. We also included a control group composed of perimenopausal and postmenopausal women who did not experience any violence (n = 120). Results: The instrument presented a Cronbach alpha = 0.82, good reliability among the examiners (+0.80), and a good possibility of reproducibility. The mean age of menopause was 45.4 years, and the mean age in the control group was 48.1 years. Group 1 showed a mean of 5.1 comorbidities, Group 2 had 4.6, and Group 3 had 4.4. Sexual violence (43.5%) and other types of violence both presented average comorbidities (4.60) but represented a significant impairment in the victim's sexual life. There were significant associations in group 3 and a high Kupperman Menopausal Index score. In the experimental group, 80.6% did not seek health services for the violence they experienced. Conclusions: The questionnaire presented good internal consistency and a validated construction. It can be easily reproduced and is indicated to evaluate the consequences of domestic and/or sexual violence on women's health during climacterium.

Random regression analyses using B-spline functions to model growth of Nellore cattle

The objective of this study was to estimate (co)variance components using random regression on B-spline functions to weight records obtained from birth to adulthood. A total of 82 064 weight records of 8145 females obtained from the data bank of the Nellore Breeding Program (PMGRN/Nellore Brazil) which started in 1987, were used. The models included direct additive and maternal genetic effects and animal and maternal permanent environmental effects as random. Contemporary group and dam age at calving (linear and quadratic effect) were included as fixed effects, and orthogonal Legendre polynomials of age (cubic regression) were considered as random covariate. The random effects were modeled using B-spline functions considering linear, quadratic and cubic polynomials for each individual segment. Residual variances were grouped in five age classes. Direct additive genetic and animal permanent environmental effects were modeled using up to seven knots (six segments). A single segment with two knots at the end points of the curve was used for the estimation of maternal genetic and maternal permanent environmental effects. A total of 15 models were studied, with the number of parameters ranging from 17 to 81. The models that used B-splines were compared with multi-trait analyses with nine weight traits and to a random regression model that used orthogonal Legendre polynomials. A model fitting quadratic B-splines, with four knots or three segments for direct additive genetic effect and animal permanent environmental effect and two knots for maternal additive genetic effect and maternal permanent environmental effect, was the most appropriate and parsimonious model to describe the covariance structure of the data. Selection for higher weight, such as at young ages, should be performed taking into account an increase in mature cow weight. Particularly, this is important in most of Nellore beef cattle production systems, where the cow herd is maintained on range conditions. There is limited modification of the growth curve of Nellore cattle with respect to the aim of selecting them for rapid growth at young ages while maintaining constant adult weight.

Impact of maternal mild hyperglycemia on maternal care and offspring development and behavior of Wistar rats

The aim of the present study was to evaluate the effect of maternal mild hyperglycemia on maternal behavior, as well as the development, behavior, reproductive function, and glucose tolerance of the offspring. At birth, litters were assigned either to Control (subcutaneous (sc)-citrate buffer) or STZ groups (streptozotocin (STZ)-100 mg/kg-sc.). On PND 90 both STZ-treated and Control female rats were mated. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed during pregnancy. Pregnancy duration, litter size and sex ratio were assessed. Newborns were classified according to birth weight as small (SPA), adequate (APA), or large for pregnancy age (LPA). Maternal behavior was analyzed on PND 5 and 10. Offspring body weight, length, and anogenital distance were measured and general activity was assessed in the open field. Sexual behavior was tested in both male and female offspring. Levels of reproductive hormones and estrous cycle duration were evaluated in female offspring. Female offspring were mated and both a GTT and ITT performed during pregnancy. Neonatal STZ administration caused mild hyperglycemia during pregnancy and changed some aspects of maternal care. The hyperglycemic intrauterine milieu impaired physical development and increased immobility in the open field in the offspring although the latter effect appeared at different ages for males (adulthood) and females (infancy). There was no impairment in the sexual behavior of either male or female offspring. As adults, female offspring of STZ-treated mothers did not show glucose intolerance during pregnancy. Thus, offspring of female rats that show mild hyperglycemia in pregnancy have fewer behavioral and developmental impairments than previously reported in the offspring of severely diabetic dams suggesting that the degree of impairment is directly related to the mother glycemic intensity. (C) 2012 Elsevier Inc. All rights reserved.

Variations in maternal care alter corticosterone and 17beta-estradiol levels, estrous cycle and folliculogenesis and stimulate the expression of estrogen receptors alpha and beta in the ovaries of UCh rats

Background: Variations in maternal care are associated with neonatal stress, hormonal disturbances and reproductive injuries during adulthood. However, the effects of these variations on sex hormones and steroid receptors during ovary development remain undetermined. This study aimed to investigate whether variations in maternal care are able to influence the hormonal profile, follicular dynamics and expression of AR, ER-alpha and ER-beta in the ovaries of UCh rat offspring. Methods: Twenty-four adult UCh rats, aged 120 days, were randomly divided into two groups (UChA and UChB) and mated. Maternal care was assessed from birth (day 0) to the 10th postnatal day (PND). In adulthood, twenty adult female rats (UChA and UChB offspring; n = 10/group), aged 120 days, were euthanized by decapitation during the morning estrus. Results: UChA females (providing high maternal care) more frequently displayed the behaviors of carrying pups, as well as licking/grooming and arched back nursing cares. Also, mothers providing high care had elevated corticosterone levels. Additionally, offspring receiving low maternal care showed the highest estrous cycle duration, increased corticosterone and 17beta-estradiol levels, overexpression of receptors ER-alpha and ER-beta, increased numbers of primordial, antral and mature follicles and accentuated granulosa cell proliferation. Conclusions: Our study suggests that low maternal care alters corticosterone and 17beta-estradiol levels, disrupting the estrous cycle and folliculogenesis and differentially regulating the expression of ER-alpha and ER-beta in the ovaries of adult rats.

Buphthalmos development in adult: case report

To report a case of extensive globe enlargement due to secondary glaucoma in a young adult suffering from ocular surface disorders related to hypohidrotic ectodermal dysplasia. To the best of our knowledge, this is the first report of buphthalmos in the adulthood.

A baixa estatura leve está associada ao aumento da pressão arterial em adolescentes com sobrepeso

FUNDAMENTO: Estudos têm demonstrado que a desnutrição pré/pós-natal leva a um maior risco de doenças não transmissíveis, como diabetes, hipertensão e obesidade na idade adulta. OBJETIVO: Determinar se os adolescentes com sobrepeso e desnutrição leve [escores-Z altura/idade (HAZ) na faixa de <-1 a > -2] têm pressão arterial mais elevada do que os indivíduos com sobrepeso e com estatura normal (HAZ > -1). MÉTODOS: Os participantes foram classificados como de baixa estatura leve ou de estatura normal, e estratificados de acordo com os percentis de massa corporal para a idade, como sobrepeso, peso normal ou abaixo do peso. As pressões arteriais sistólica (PAS) e diastólica (PAD) foram determinadas de acordo com as diretrizes e a gordura abdominal foi analisada por absorciometria de dupla emissão de raios-X. RESULTADOS: Indivíduos com baixa estatura leve e sobrepeso apresentaram valores mais elevados da PAD (p = 0,001) do que suas contrapartes de baixo peso (69,75 ± 12,03 e 54,46 ± 11,24 mmHg, respectivamente), mas semelhantes àqueles com IMC normal. Não foram encontradas diferenças nos valores de PAD em indivíduos normais, indivíduos com sobrepeso e com baixo peso entre os grupos de estatura normal. Foi encontrado um aumento na PAS (p = 0,01) entre os indivíduos com baixa estatura leve quando comparados os indivíduos com sobrepreso com suas contrapartes de baixo peso e IMC normal (114,70 ± 15,46, 97,38 ± 10,87 e 104,72 ± 12,24 mmHg, respectivamente). Embora não tenham sido observadas diferenças nas médias de PAS entre os grupos de baixa estatura leve e estatura normal, foi encontrado um intercepto significativo (p = 0,01), revelando maior PAS entre os indivíduos com baixa estatura leve. Houve correlação entre PAS e gordura abdominal (r = 0,42, ρ = 0,02) no grupo com baixa estatura leve. CONCLUSÃO: Indivíduos de baixa estatura leve com sobrepeso apresentaram maior PAS do que os de estatura normal e sobrepeso. Esses achados confirmam que a baixa estatura leve aumenta o risco futuro de hipertensão e essas alterações são evidentes em indivíduos jovens.

Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

Healthy maternal bonding as a resilience factor for depressive disorder

INTRODUCTION: Depressive disorders (DDs) are very prevalent disorders particularly in women, a high-risk gender group. Determining the risk and protective factors associated with the development of DDs is fundamental to planning preventive and therapeutic strategies. In this study, we evaluated the correlations between healthy maternal attachment and the development of DDs in adulthood. METHODS: We evaluated 52 women at 6 months to 1 year after premature childbirth at Maternidade Vila Nova Cachoeirinha. They were evaluated using the following instruments: Brazilian Criteria of Economic Classification,Parental Bonding Inventory (PBI),Center for Epidemiologic Studies Depression Scale (CES-D), and Edinburgh Postnatal Depression Scale (EPDS). Cut-off scores on the CES-D and EPDS were used to classifythe subjects as currently having a DD or having probable postpartum disorder (PPD) after childbirth. Multiple logistic regression was used to evaluate the risk factors associated with DDs. RESULTS: We found that 49.1% of the sample had a current depressive episode, and 73.6% had probable PPD. Based on logistic regression, current depression (odds ratio = 1.092 [confidence interval: 1.005; 1.186]), and a PPD (odds ratio = 1.108 [confidence interval: 1.011; 1.21]) were negatively correlated with affective maternal relationships. CONCLUSIONS: Women who reported healthy attachment with their mothers did not develop DDs when faced with stressful situations such as premature childbirth.

PReS-FINAL-2170: Work disability in adult patients with juvenile idiopathic arthritis (JIA)

Introduction Approximately 20% JIA patients enters adulthood with clinically active disease and disabled, therefore work condition may be affected. Objectives To assess the prevalence of work disability among adult patients with JIA regularly attending a tertiary heumatology center and to determine possible associated risk factors. Methods This was a cross-sectional study that enrolled 43 JIA patients according to 2004 revised ILAR criteria. A questionnaire was developed in order to evaluate working status and labor activity: occupation, current/previous work, employment status and withdrawal rate were actively searched. Demographic data, JIA characteristics, clinical activity (DAS28>2.6), therapeutic intervention, comorbidities, physical activity, sedentarism (WHO definitions), functional class (1991 ACR criteria), HAQ and SF-36 were recorded. The prevalence of work disability was calculated using 95% confidence interval, and compared to all parameters; qualitative variables were analyzed using tests of association (chi-square test) and quantitative variables by Mann-Whitney or student test. Results Patients' mean age was 29+7.4 yrs (range 19-41) with mean JIA duration = 17.2+12.3 yrs (range 3-33); 63% were males and 37% females. JIA subtypes were 64% polyarticular, 11% oligoarticular, 9% systemic, 9% ERA, 2% extended oligoarticular, 2% psoriatic arthritis; 7% had uveitis. Serum RF was positive in 21% and ANA in 21%. The majority (72%, n = 31) of JIA patients were employed, whereas 28% (n = 12) were currently not working. In the latter group, 83% (10/12) were retired due to JIA related disability. Further analysis comparing those currently working vs. Those not working revealed similar age (25,3 yrs vs.29,5 yrs, p = 0,09). Although not significantly, most patients currently working had Poly onset JIA (22 vs. 6 p = 0,37), higher frequencies of good education level >12 yrs of school (31 vs.9, p = 0,38), functional class I (p = 0,96), practiced regular physical activity (9 vs. 0, p = 0,89), were singles (26 vs. 8, p = 0,15). Both groups had comparable HAQ and DAS 28 scores (0,62 vs. 0.59, p = 0,47 and 2,51 vs.2,07, p = 0,64) and similar arthroplasty rate (8 vs. 4, p = 0,427). Frequencies of hypertension (3 vs.1, p = 0,999), dyslipidemia (1 vs. 1, p = 0,125), diabetes (1 vs. 0 p = 0,999), depression (1 vs. 0, p = 0,999) and smokers (3 vs. 1, p = 0,99) were alike in both groups. Remarkably, employed patients had higher SF 36 mental health component (84.0 vs. 70.42, P = 0.01). Conclusion High prevalence of almost 1/3 work disability and of retirement due to disease related incapacity remain major problems for adult JIA individuals. We also identified worse mental health in employed patients indicating that further research is needed, in addition to intense affirmative disability actions in order to remove possible disabling barriers and to adapt restrictive environments for these patients. Moreover, enhanced strategies and policy for inclusion of JIA patients in the job market is urged.