Cortisol and 17-a-hydroxy-progesterone levels in infants with refractory hypotension born at 30 weeks of gestation or less

Refractory hypotension is frequent in very low-birth weight infants, whose hypothalamic-pituitary-adrenal axis has been suggested to be immature. The objective of the present study was to evaluate basal cortisol and 17-a-OH-progesterone in the first 36 h of life in preterm infants with and without refractory hypotension (mean arterial blood pressure below the lower limit for gestational age throughout the study despite aggressive volume expansion and use of vasopressors). Thirty-five infants with £30 weeks of gestation and a birth weight £1250 g, with no postnatal use of corticosteroid or death in the first 48 h were studied. Mean arterial pressure was measured every 4 h during the first 48 h. Cortisol and 17-a-OH-progesterone were determined at 12 and 36 h and patients were divided into refractory hypotensive (N = 15) and control (N = 20) groups. The groups were not different regarding type of delivery, use of prenatal corticosteroid, requirement of mechanical ventilation, use of vasopressor drugs, morphine, fentanyl, prophylactic indomethacin, and mean sample timing. Although refractory hypotensive newborns were more immature, were smaller, suffered more deaths after 48 h of life and had a higher SNAPPE-2 score, their cortisol and 17-a-OH-progesterone levels were not different from controls at 12 h and at 36 h. The increase of cortisol in newborns with refractory hypotension 36 h after birth was significantly higher than in controls. Despite the fact that refractory hypotensive very low-birth weight neonates were submitted to a very stressful condition, their cortisol and 17-a-OH-progesterone levels were similar to controls.

Why are the rates of cesarean section in Brazil higher in more developed cities than in less developed ones?

The objective of the present study was to investigate factors associated with cesarean sections in two cities located in different regions of Brazil and to determine factors that explain the higher cesarean section rate in the more developed city, Ribeirão Preto, compared to the less developed one, São Luís. Data from two cohort studies comprising 2846 women in Ribeirão Preto in 1994, and 2443 women in São Luís in 1997/1998 were used. Adjusted and non-adjusted risk estimates were calculated using a Poisson regression model. The cesarean section rate was 33.7% in São Luís and 50.8% in Ribeirão Preto. Adjusted analysis in a joint sequential model revealed a 51% higher risk of cesarean section in Ribeirão Preto compared to São Luís (prevalence rate ratio (PRR) = 1.51). Adjustment for category of hospital admission reduced the PRR to 1.09, i.e., this variable explained 82% of the difference in the cesarean section rate between the two cities. Adjustment for the variable "the same physician for prenatal care and delivery" reduced the PRR to 1.07, with the "physician" factor explaining 86% of the difference between rates. When simultaneously adjusted for the two variables, the PRR decreased to 1.05, with these two variables explaining 90% of the difference in the cesarean section rate between the two cities, and the difference was no longer significant. The difference in the cesarean section rate between the two Brazilian cities, one more and one less developed, was mainly explained by the physician factor and, to a lesser extent, by the category of hospital admission.

Racial inequalities and perinatal health in the southeast region of Brazil

Few studies are available about racial inequalities in perinatal health in Brazil and little is known about whether the existing inequality is due to socioeconomic factors or to racial discrimination per se. Data regarding the Ribeirão Preto birth cohort, Brazil, whose mothers were interviewed from June 1, 1978 to May 31, 1979 were used to answer these questions. The perinatal factors were obtained from the birth questionnaire and the ethnic data were obtained from 2063 participants asked about self-reported skin color at early adulthood (23-25 years of age) in 2002/2004. Mothers of mulatto and black children had higher rates of low schooling (£4 years, 27.2 and 38.0%) and lower family income (£1 minimum wage, 28.6 and 30.4%). Mothers aged less than 20 years old predominated among mulattos (17.0%) and blacks (14.0%). Higher rates of low birth weight and smoking during pregnancy were observed among mulatto individuals (9.6 and 28.8%). Preterm birth rate was higher among mulattos (9.5%) and blacks (9.7%) than whites (5.5%). White individuals had higher rates of cesarean delivery (34.9%). Skin color remained as an independent risk factor for low birth weight (P < 0.001), preterm birth (P = 0.01), small for gestational age (P = 0.01), and lack of prenatal care (P = 0.02) after adjustment for family income and maternal schooling, suggesting that the racial inequalities regarding these indicators are explained by the socioeconomic disadvantage experienced by mulattos and blacks but are also influenced by other factors, possibly by racial discrimination and/or genetics.

Do socioeconomic factors explain why maternal smoking during pregnancy is more frequent in a more developed city of Brazil?

The prevalence of smoking during pregnancy in Ribeirão Preto, a rich Brazilian city, was significantly higher (21.4%) than in São Luís (5.9%), a less developed city. To assess which variables explain the difference in prevalence of smoking during pregnancy, data from two birth cohorts were used, including 2846 puerperae from Ribeirão Preto, in 1994, and 2443 puerperae from São Luís, in 1997/98. In multivariable analysis, risk of maternal smoking during pregnancy was higher in São Luís for mothers living in a household with five or more persons (OR = 1.72, 95%CI = 1.12-2.64), aged 35 years or older (OR = 1.98, 95%CI = 0.99-3.96), who had five or more children (OR = 2.10, 95%CI = 1.16-3.81), and whose companion smoked (OR = 2.20, 95%CI = 1.52-3.18). Age of less than 20 years was a protective factor (OR = 0.55, 95%CI = 0.33-0.92). In Ribeirão Preto there was association with maternal low educational level (OR = 2.18, 95%CI = 1.30-3.65) and with a smoking companion (OR = 3.25, 95%CI = 2.52-4.18). Receiving prenatal care was a protective factor (OR = 0.24, 95%CI = 0.11-0.49). Mothers from Ribeirão Preto who worked outside the home were at a higher risk and those aged 35 years or older or who attended five or more prenatal care visits were at lower risk of smoking during pregnancy as compared to mothers from São Luís. Smoking by the companion reduced the difference between smoking rates in the two cities by 10%. The socioeconomic variables in the model did not explain the higher prevalence of smoking during pregnancy in the more developed city.

Influence of He-Ne laser therapy on the dynamics of wound healing in mice treated with anti-inflammatory drugs

We determined the effects of helium-neon (He-Ne) laser irradiation on wound healing dynamics in mice treated with steroidal and non-steroidal anti-inflammatory agents. Male albino mice, 28-32 g, were randomized into 6 groups of 6 animals each: control (C), He-Ne laser (L), dexamethasone (D), D + L, celecoxib (X), and X + L. D and X were injected im at doses of 5 and 22 mg/kg, respectively, 24 h before the experiment. A 1-cm long surgical wound was made with a scalpel on the abdomens of the mice. Animals from groups L, D + L and X + L were exposed to 4 J (cm²)-1 day-1 of He-Ne laser for 12 s and were sacrificed on days 1, 2, or 3 after the procedure, when skin samples were taken for histological examination. A significant increase of collagen synthesis was observed in group L compared with C (168 ± 20 vs 63 ± 8 mm²). The basal cellularity values on day 1 were: C = 763 ± 47, L = 1116 ± 85, D = 376 ± 24, D + L = 698 ± 31, X = 453 ± 29, X + L = 639 ± 32 U/mm². These data show that application of L increases while D and X decrease the inflammatory cellularity compared with C. They also show that L restores the diminished cellularity induced by the anti-inflammatory drugs. We suggest that He-Ne laser promotes collagen formation and restores the baseline cellularity after pharmacological inhibition, indicating new perspectives for laser therapy aiming to increase the healing process when anti-inflammatory drugs are used.

Evaluation of a 1-h 75-g oral glucose tolerance test in the diagnosis of gestational diabetes

In order to evaluate the performance of a 1-h 75-g oral glucose tolerance test (OGTT) for the diagnosis of gestational diabetes mellitus (GDM), a cohort of 4998 women, 20 years or older, without previous diabetes being treated in prenatal care clinics in Brazil answered a questionnaire and performed a 75-g OGTT including fasting, 1-h and 2-h glucose measurements between their 24th and 28th gestational weeks. Pregnancy outcomes were transcribed from medical registries. GDM was defined according to WHO criteria (fasting: ≥126 mg/dL; 2-h value: ≥140 mg/dL) and macrosomia as a birth weight equal to or higher than 4000 g. Areas under the receiver operator characteristic curve (AUC) were compared and diagnostic properties of various cut-off points were evaluated. The AUCs for the prediction of macrosomia were 0.606 (0.572-0.637) for the 1-h and 0.589 (0.557-0.622) for the 2-h plasma glucose test. Similar predictability was demonstrable regarding combined adverse outcomes: 0.582 (0.559-0.604) for the 1-h test and 0.572 (0.549-0.595) for the 2-h test. When the 1-h glucose test was evaluated against a diagnosis of GDM defined by the 2-h glucose test, the AUC was 0.903 (0.886-0.919). The cut-off point that maximized sensitivity (83%) and specificity (83%) was 141 mg/dL, identifying 21% of the women as positive. A cut-off point of 160 mg/dL, with lower sensitivity (62%), had higher specificity (94%), labeling 8.6% as positive. Detection of GDM can be done with a 1-h 75-g OGTT: the value of 160 mg/dL has the same diagnostic performance as the conventional 2-h value (140 mg/dL). The simplification of the test may improve coverage and timing of the diagnosis of GDM.

Streptozotocin-induced mechanical hypernociception is not dependent on hyperglycemia

Since streptozotocin (STZ)-induced diabetes is a widely used model of painful diabetic neuropathy, the aim of the present study was to design a rational protocol to investigate whether the development of mechanical hypernociception induced by STZ depends exclusively on hyperglycemia. Male Wistar rats (180-200 g; N = 6-7 per group) received a single intravenous injection of STZ at three different doses (10, 20, or 40 mg/kg). Only the higher dose (40 mg/kg) induced a significant increase in blood glucose levels, glucose tolerance and deficiency in weight gain. However, all STZ-treated rats (hyperglycemic or not) developed persistent (for at least 20 days) and indistinguishable bilateral mechanical hypernociception that was not prevented by daily insulin treatment (2 IU twice a day, sc). Systemic morphine (2 mg/kg) but not local (intraplantar) morphine treatment (8 µg/paw) significantly inhibited the mechanical hypernociception induced by STZ (10 or 40 mg/kg). In addition, intraplantar injection of STZ at doses that did not cause hyperglycemia (30, 100 or 300 µg/paw) induced ipsilateral mechanical hypernociception for at least 8 h that was inhibited by local and systemic morphine treatment (8 µg/paw or 2 mg/kg, respectively), but not by dexamethasone (1 mg/kg, sc). The results of this study demonstrate that systemic administration of STZ induces mechanical hypernociception that does not depend on hyperglycemia and intraplantar STZ induces mechanical sensitization of primary sensory neurons responsive to local morphine treatment.

A bovine herpesvirus 5 recombinant defective in the thymidine kinase (TK) gene and a double mutant lacking TK and the glycoprotein E gene are fully attenuated for rabbits

Bovine herpesvirus 5 (BoHV-5), the agent of herpetic meningoencephalitis in cattle, is an important pathogen of cattle in South America and several efforts have been made to produce safer and more effective vaccines. In the present study, we investigated in rabbits the virulence of three recombinant viruses constructed from a neurovirulent Brazilian BoHV-5 strain (SV507/99). The recombinants are defective in glycoprotein E (BoHV-5gEΔ), thymidine kinase (BoHV-5TKΔ) and both proteins (BoHV-5gEΔTKΔ). Rabbits inoculated with the parental virus (N = 8) developed neurological disease and died or were euthanized in extremis between days 7 and 13 post-infection (pi). Infectivity was detected in several areas of their brains. Three of 8 rabbits inoculated with the recombinant BoHV-5gEΔ developed neurological signs between days 10 and 15 pi and were also euthanized. A more restricted virus distribution was detected in the brain of these animals. Rabbits inoculated with the recombinants BoHV-5TKΔ (N = 8) or BoHV-5gEΔTKΔ (N = 8) remained healthy throughout the experiment in spite of variable levels of virus replication in the nose. Dexamethasone (Dx) administration to rabbits inoculated with the three recombinants at day 42 pi did not result in viral reactivation, as demonstrated by absence of virus shedding and/or increase in virus neutralizing titers. Nevertheless, viral DNA was detected in the trigeminal ganglia or olfactory bulbs of all animals at day 28 post-Dx, demonstrating they were latently infected. These results show that recombinants BoHV-5TKΔ and BoHV-5gEΔTKΔ are attenuated for rabbits and constitute potential vaccine candidates upon the confirmation of this phenotype in cattle.

Amniotic fluid amino acid levels in non-immune hydrops fetalis: a case-control study

In a prospective case-control study, we compared the amniotic fluid amino acid levels in non-immune hydrops fetalis (NIHF) and normal fetuses. Eighty fetuses underwent amniocentesis for different reasons at the prenatal diagnosis unit of the Department of Obstetrics and Gynecology, Faculty of Medicine, Dicle University. Forty of these fetuses were diagnosed with NIHF. The study included 40 women each in the NIHF (mean age: 27.69 ± 4.56 years) and control (27.52 ± 5.49 years) groups, who had abnormal double- or triple-screening test values with normal fetuses with gestational ages of 23.26 ± 1.98 and 23.68 ± 1.49 weeks at the time of sample collection, respectively. Amniotic fluid amino acid concentrations (intra-assay variation: 2.26-7.85%; interassay variation: 3.45-8.22%) were measured using EZ:faast kits (EZ:faast GC/FID free (physiological) amino acid kit; Phenomenex, USA) by gas chromatography. The standard for quantitation was a mixture of free amino acids from Phenomenex. The levels of 21 amino acids were measured. The mean phosphoserine and serine levels were significantly lower in the NIHF group, while the taurine, α-aminoadipic acid (aaa), glycine, cysteine, NH4, and arginine (Arg) levels were significantly higher compared to control. Significant risk variables for the NIHF group and odds coefficients were obtained using a binary logistic regression method. The respective odds ratios and 95% confidence intervals for the risk variables phosphoserine, taurine, aaa, Arg, and NH4 were 3.31 (1.84-5.97), 2.45 (1.56-3.86), 1.78 (1.18-2.68), 2.18 (1.56-3.04), and 2.41 (1.66-3.49), respectively. The significant difference between NIHF and control fetuses suggests that the amniotic fluid levels of some amino acids may be useful for the diagnosis of NIHF.

Induced maturation of hepatic progenitor cellsin vitro

Hepatic progenitor cells (HPCs) are a potential cell source for liver cell transplantation but do not function like mature liver cells. We sought an effective and reliable method to induce HPC maturation. An immortalized HP14.5 albumin promoter-driven Gaussian luciferase (ALB-GLuc) cell line was established from HPCs isolated from fetal mouse liver of post coitus day 14.5 mice to investigate the effect of induction factors on ALB promoter. HP14.5 parental cells were cultured in DMEM with different combinations of 2% horse serum (HS), 0.1 µM dexamethasone (DEX), 10 ng/mL hepatic growth factor (HGF), and/or 20 ng/mL fibroblast growth factor 4 (FGF4). Trypan blue and crystal violet staining were used to assess cell proliferation with different induction conditions. Expression of hepatic markers was measured by semi-quantitative RT-PCR, Western blot, and immunofluorescence. Glycogen storage and metabolism were detected by periodic acid-Schiff and indocyanine green (ICG) staining. GLuc activity indicated ALB expression. The combination of 2% HS+0.1 µM Dex+10 ng/mL HGF+20 ng/mL FGF4 induced the highest ALB-GLuc activity. Cell proliferation decreased in 2% HS but increased by adding FGF4. Upon induction, and consistent with hepatocyte development, DLK, AFP, and CK19 expression decreased, while ALB, CK18, and UGT1A expression increased. The maturity markers tyrosine aminotransferase and apolipoprotein B were detected at days 3 and 6 post-induction, respectively. ICG uptake and glycogen synthesis were detectable at day 6 and increased over time. Therefore, we demonstrated that HPCs were induced to differentiate into functional mature hepatocytes in vitro, suggesting that factor-treated HPCs may be further explored as a means of liver cell transplantation.

Nasal CPAP in the delivery room for newborns with extremely low birth weight in a hospital in a developing country

The objective of this study was to determine the feasibility of the use of continuous positive airway pressure installed prophylactically in the delivery room (DR-CPAP), for infants with a birth weight between 500 and 1000 g in settings with limited resources. During 23 months, infants with a birth weight between 500 and 1000 g consecutively received DR-CPAP. A total of 33 infants with low birth weight were enrolled, 16 (48.5%) were females. Only 14 (42.4%) received antenatal corticosteroids and only 2 of those 14 (14.3%) infants weighing 500-750 g were not intubated in the delivery room, and apnea was given as the reason for intubation of these patients. Of the 19 infants in the 751-1000 g weight range, 9 (47.4%) were intubated in the delivery room, 6 due to apnea and 3 due to respiratory discomfort. For DR-CPAP to be successful, it is probably necessary for preterm babies to be more prepared at birth to withstand the respiratory effort without the need for intubation. Antenatal corticosteroids and better prenatal monitoring are fundamental for success of DR-CPAP.

Application of continuous positive airway pressure in the delivery room: a multicenter randomized clinical trial

This study evaluated whether the use of continuous positive airway pressure (CPAP) in the delivery room alters the need for mechanical ventilation and surfactant during the first 5 days of life and modifies the incidence of respiratory morbidity and mortality during the hospital stay. The study was a multicenter randomized clinical trial conducted in five public university hospitals in Brazil, from June 2008 to December 2009. Participants were 197 infants with birth weight of 1000-1500 g and without major birth defects. They were treated according to the guidelines of the American Academy of Pediatrics (APP). Infants not intubated or extubated less than 15 min after birth were randomized for two treatments, routine or CPAP, and were followed until hospital discharge. The routine (n=99) and CPAP (n=98) infants studied presented no statistically significant differences regarding birth characteristics, complications during the prenatal period, the need for mechanical ventilation during the first 5 days of life (19.2 vs 23.4%, P=0.50), use of surfactant (18.2 vs 17.3% P=0.92), or respiratory morbidity and mortality until discharge. The CPAP group required a greater number of doses of surfactant (1.5 vs 1.0, P=0.02). When CPAP was applied to the routine group, it was installed within a median time of 30 min. We found that CPAP applied less than 15 min after birth was not able to reduce the need for ventilator support and was associated with a higher number of doses of surfactant when compared to CPAP applied as clinically indicated within a median time of 30 min.

Treatment with 1,25(OH)2D3induced HDAC2 expression and reduced NF-κB p65 expression in a rat model of OVA-induced asthma

Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3might be useful as a novel HDAC2 activator in the treatment of asthma.

Effects of exercise and metformin on the prevention of glucose intolerance: a comparative study

We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment.

Individual difference factors and men's attraction to female body features /

Existing research on attraction to body features has suggested that men show general preferences for women with lower waist-to-hip ratios (WHR), larger breasts, and slender body weights. The present study intended to expand on this research by investigating several individual difference factors and their potential contribution to variation in what men find attractive in female body features. Two hundred and seventy-three men were assessed for sex-role identity, 2D:4D digit ratios (a possible marker of prenatal exposure to androgens, and thus masculinization), physical attractiveness, early sexual experiences (as indices of early sexual conditioning), and early family attitudes toward body features, as well as their current preferences for WHR, breast size, weight, and height in women. For WHR, as predicted, physical attractiveness, early sexual experiences, and lower (more masculine) right-hand 2D:4D ratios significantly predicted current preferences for more feminine (lower) WHR. Early sexual experiences significantly predicted later preferences for breast size; in addition, more masculine occupational preferences and lower (more masculine) left-hand 2D:4D ratios predicted preferences for larger breasts. Participants' height, education level, Unmitigated Agency (masculinity) scores, and early sexual experiences significantly predicted current preferences for height. Finally, early sexual experiences significantly predicted current preferences for weight. The results suggest that variation in preferences for women's bodily features can be uniquely accounted for by a number of individual difference factors. Strengths and weaknesses of the study, along with implications for future research, are discussed.