SFlt-1/PlGF ratio as a prognostic marker of adverse outcomes in women with early-onset preeclampsia

Soluble fms-like tyrosine kinase 1 (sFlt-1) is an anti-angiogenic factor released in higher amounts by preeclamptic placentas and it has been implicated in the endothelial dysfunction observed in the disease. In this study we evaluated if circulating sFlt-1/PlGF ratio is useful to predict adverse outcomes in women with early-onset preeclampsia. This is a cohort study of 88 preeclamptic women with singleton pregnancies at ≤35 weeks of gestation. According to definitions used, adverse outcomes occurred in 46.5% (N = 43) of the patients. The median sFlt1/PlGF ratio (25th-75th centile) for all patients evaluated was of 42.26 (13.1-226.1). The median sFlt-1/PlGF ratio among women who had any adverse outcome (N = 43) versus no adverse outcomes (N = 45) was of 227.6 (80.3-346.1) versus 14.4 (3.35-30.0), (P < 0.0001). According to our analyses a sFlt-1/PlGF ratio cut-point of ≥85 gave a sensitivity of 74.0% and specificity of 97.0%. The positive predictive value and the negative predictive value were 96.0% and 80.0%, respectively. The median sFlt-1/PlGF ratio (25th-75th centile) for patients who delivered within <7 days was 260.0 (127.7-404.7) as compared to 14.4 (3.35-34.97) for those patients who delivered within two weeks or more (P < 0.0001). Our results suggest that sFlt-1/PlGF ratio is a promising marker for adverse outcomes in women with early-onset preeclampsia. © 2013 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Desenvolvimento do omaso de bovinos da raça Nelore (Bos taurus indicus) durante o período pré-natal

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Excess androgen during perinatal life alters steroid receptor expression, apoptosis, and cell proliferation in the uteri of the offspring

Exposure to environmental chemicals may contribute to reproductive disorders, especially when it occurs in critical periods of development. The female reproductive system can be a target for androgens derived from environmental contaminants or pathological conditions. The purpose of this study was to assess the long-term effects of androgens on uterine tissue after maternal exposure limited to the time of gestation and lactation. Pregnant Wistar rats were treated with testosterone propionate (TP) at 0.05. mg/kg, 0.1. mg/kg, 0.2. mg/kg or corn oil (vehicle), s.c., from gestational day 12 until the end of lactation. The results show changes in the pattern of expression of receptors for estrogen, progesterone, and androgen at all doses tested, and decreases in both apoptosis and cell proliferation indices at 0.1 and 0.2. mg/kg. We conclude that early TP exposure, under these experimental conditions, causes changes in cellular and molecular parameters that are essential for normal uterine function in the adult. © 2013 Elsevier Inc.

Maternal protein restriction during pregnancy affects gene expression and immunolocalization of intestinal nutrient transporters in rats

Intrauterine dietary restriction may cause changes in the functioning of offspring organs and systems later in life, an effect known as fetal programming. The present study evaluated mRNA abundance and immunolocalization of nutrient transporters as well as enterocytes proliferation in the proximal, median and distal segments of small intestine of rats born to protein-restricted dams. Pregnant rats were fed hypoproteic (6% protein) or control (17% protein) diets, and offspring rats were evaluated at 3 and 16 weeks of age. The presence of SGLT1 (sodium-glucose co-transporter 1), GLUT2 (glucose transporter 2), PEPT1 (peptide transporter 1) and the intestinal proliferation were evaluated by immunohistochemical techniques and the abundance of specific mRNA for SGLT1, GLUT2 and PEPT1 was assessed by the real-time PCR technique. Rats born to protein-restricted dams showed higher cell proliferation in all intestinal segments and higher gene expression of SGLT1 and PEPT1 in the duodenum. Moreover, in adult animals born to protein-restricted dams the immunoreactivity of SGLT1, GLUT2 and PEPT1in the duodenum was more intense than in control rats. Taken together, the results indicate that changes in the small intestine observed in adulthood can be programmed during the gestation. In addition, they show that this response is caused by both up-regulation in transporter gene expression, a specific adaptation mechanism, and intestinal proliferation, an unspecific adaptation mechanism.

Decreasing pH of mammary gland secretions is associated with parturition and is correlated with electrolyte concentrations in prefoaling mares

The objectives of this study were to determine pH of the mammary gland secretions and the corresponding electrolyte concentrations in prefoaling mares. Pregnant mares (seven primiparous and seven multiparous) were monitored daily from 310.320 days of gestation until parturition. Prefoaling mammary gland secretions were collected, and pH was immediately determined with a pH meter and pH strip test. An aliquot of prefoaling mammary secretions was frozen and stored until further analyses. After parturition, samples from day .4 to 0 (day of foaling) were thawed and electrolyte concentrations (ie, Ca2+, Mg2+, Na+, K+ and Cl-) were determined with an automated analyser. Data were analysed via a mixed model with the mare as a random effect. Correlations were determined between pH and electrolyte concentrations by the Pearson product-moment for each pair. There was significant reduction in pH of mammary secretions on the day of foaling (P<0.0001), and most mares (11/14) with a pH .7 foaled within 24 hours. There was high correlation between the two pH methods (r=0.93). Additionally, there were significant (P<0.05) increases in Ca2+ and K+ concentrations, and significant decreases in Na+ and Cl- concentrations from one day before to the day of foaling. The pH of mammary secretions was highly and significantly (P<0.001) correlated with Na + (r=0.87), Cl- (r=0.85), Ca2+ (r=-0.88); and K+(r=.0.80) concentrations, and moderately correlated with Mg 2+ (r=-0.58). Daily evening pH measure of the mammary gland secretions can predict foaling in most mares.

Elevated hyaluronan and extracellular matrix metalloproteinase inducer levels in women with preeclampsia

Purpose: Preeclampsia (PE) is a specific syndrome of pregnancy clinically identified by hypertension and proteinuria from the 20th week of gestation associated with a systemic inflammatory response and oxidative stress. While pro-inflammatory cytokines have been extensively studied in PE, other factors in the circulation that also influence the magnitude of inflammation have received much less attention. The present study compared serum concentrations of five immune-regulatory compounds in normotensive pregnant women and in women with gestational hypertension (GH) or PE. Methods: Sixty women with PE, 53 with GH and 40 normotensive women paired by gestational age were evaluated. Sera were evaluated for concentrations of extracellular matrix metalloproteinase inducer (EMMPRIN), hyaluronan, gelsolin, visfatin and histone 2B by ELISA. Differences between groups were analyzed by nonparametric tests, with a significance level of 5 %. Results: Increased levels of EMMPRIN and hyaluronan were present in preeclamptic women as compared to the GH and normotensive groups. There was no difference between groups in gelsolin, visfatin or histone 2B. Conclusion: Increased release of EMMPRIN and hyaluronan may contribute to an elevated pro-inflammatory response and tissue damage in women with PE. © 2013 Springer-Verlag Berlin Heidelberg.

High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia

Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks' gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-10, IL-12, and soluble TNF-α-receptor I (sTNFRI) concentrations, were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-α, IL-1β, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also significantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were positive correlations between Hsp70 levels and TNF-α, TNFRI, IL-1β, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiology between early- and late-onset PE, highlighting by the difference in Hsp70 levels. © 2013 Elsevier B.V. All rights reserved.

Compartmentalization of pro-inflammatory cytokine levels in renal-transplanted pregnant women

Objective: We evaluated whether chronic exposure to immunosuppression in transplant recipients modulate the placental inflammatory cytokine levels associated to gestational tolerance mechanisms. Methods: Serum samples were collected from 12 renal transplanted pregnant under immunosuppressive regimen treatment and 10 healthy women in second/third trimester of gestation. Term placental tissues (decidua and chorionic villi) were also obtained after elective caesarean. Serum IL-1β, IL-6, IL-8, IL-12p70 and TNF-α were measured, as also in placental homogenates, by Cytometric Bead Array (CBA) combined with flow cytometry and, TGF-β and IL-18 were measured by ELISA. Results: Serum levels of IL-6 (p=0.0001) and TNF-α (0.0112) were higher in the 2nd and 3rd trimesters and in decidua the spectrum of increased pro inflammatory cytokines was wider: IL-1β (p=0.0001), IL-6 (p=0.0001), IL-8 (p=0.0001), IL-12p70 (p=0.0001), TGF-β (p=0.0089) and TNF-α (p=0.0002). TGF-β1 was particularly increased in decidual compartment (p=0.001). In the chorionic villous, pro inflammatory profile also were maintained. High IL-1β (p=0.0001), IL-6 (p=0.0001), IL-8 (p=0.0001) and TNF-α (p=0.0001) levels establish a similar pattern to that seem in decidua. Conclusion: Immunosuppressors may impair the immune response, but when associated with pregnancy the cytokine levels seems to shift a proinflammatory profile in placental compartments, which might also impact on the gestational outcomes in transplanted mothers. © 2013 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.

Biochemical Profile of Amniotic and Allantoic Fluid During Different Gestational Phases in Mares

Fetal fluids have different vital functions that sustain both pregnancy and normal parturition. The biochemical composition of amniotic fluid during gestation is not well established; thus the purpose of the present study was to determine the biochemical profile of both amniotic and allantoic fluids from mares during initial, mid, and latter third phases of pregnancy. Samples were collected after slaughter, using allantocentesis and amniocentesis. Sixty samples of fetal fluids were analyzed. Alkaline phosphatase (AP), glucose, total protein (TP), urea, creatinine, Ca, chloride (Cl), Na, and K concentrations were measured using commercially available kits. The AP concentration in amniotic fluid was higher than that in allantoic fluid during the three gestational phases (P < .05). There were no differences between glucose mean values of allantoic and those of amniotic fluids (P < .05). However, glucose values were higher in the allantoic fluid in the last trimester of pregnancy. TP was higher in the amniotic fluid than in allantoic fluid (P < .05). Urea values varied among the phases; however, there were no differences between the amniotic and allantoic fluid values (P > .05). Creatinine values were higher in allantoic fluid (P < .05). Na and Cl concentrations were higher in amniotic fluid (P < .05). However, Ca and K concentrations were higher in the allantoic fluid. © 2013 Elsevier Inc. All rights reserved.

Kinetics of epsilon antitoxin antibodies in different strategies for active immunization of lambs against enterotoxaemia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise funcional da musculatura do assoalho pélvico pós-parto em mulheres primigestas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desenvolvimento sexual da prole de ratas submetidas à restrição proteica em diferentes períodos da prenhez e lactação

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Hipomineralização molar-incisivo: prevalência, severidade e etiologia em escolares de Araraquara

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Morfologia da placenta e interação materno-fetal em jumentas (Equus asinus) da raça Pêga

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito do genótipo paterno e sistemas de pastejo no desenvolvimento fetal e nas características ao nascimento de bovinos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)