Extracellular HSP70 levels in diabetic environment in rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

IRS-1 gene polymorphism and DNA damage in pregnant women with diabetes or mild gestational hyperglycemia

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

Calcium and magnesium status is not impaired in pregnant women

Deficiencies in calcium (Ca) and magnesium (Mg) are associated with various complications during pregnancy. To test the hypothesis that the status of these minerals is inadequate in pregnancy, a cross-sectional study was conducted of the dietary intake and status of Ca and Mg in pregnant women (n = 50) attending a general public university hospital in Brazil. Dietary intake was assessed from 4-day food records; levels of plasma Mg, erythrocyte Mg, and urinary Ca and Mg excretion were determined by flame atomic absorption spectroscopy; and type I collagen C-telopeptides were evaluated by enzyme-linked immunosorbent assay. Probabilities of inadequate Ca and Mg intake were exhibited by 58 and 98% of the study population, respectively. The mean levels of urinary Ca and Mg excretion were 8.55 and 3.77 mmol/L, respectively. Plasma C-telopeptides, plasma Mg, and erythrocyte Mg were within normal levels. Multiple linear regression analysis revealed positive relationships among urinary Ca excretion, Ca intake (P = .002) and urinary Mg excretion (P < .001) and between erythrocyte Mg and Mg intake (P = .023). It is concluded that the Ca and Mg status of participants was adequate even though the intake of Ca and Mg was lower than the recommended level. (C) 2012 Elsevier Inc. All rights reserved.

Maternal Smoking Impact on the Delivery Cost: a population-based study in the Emilia-Romagna region

This doctoral thesis is devoted to the study of the causal effects of the maternal smoking on the delivery cost. The interest of economic consequences of smoking in pregnancy have been studied fairly extensively in the USA, and very little is known in European context. To identify the causal relation between different maternal smoking status and the delivery cost in the Emilia-Romagna region two distinct methods were used. The first - geometric multidimensional - is mainly based on the multivariate approach and involves computing and testing the global imbalance, classifying cases in order to generate well-matched comparison groups, and then computing treatment effects. The second - structural modelling - refers to a general methodological account of model-building and model-testing. The main idea of this approach is to decompose the global mechanism into sub-mechanisms though a recursive decomposition of a multivariate distribution.

Antiepileptic drugs and pregnancy. Population based pharmaco-epidemiological study on prescription patterns, pregnancy outcome and foetal health

Aims of the study: To assess the prevalence of Antiepileptic Drug (AED) exposure in pregnant women with or without epilepsy and the comparative risk of terminations of pregnancy (TOPs), spontaneous abortions, stillbirth, major congenital malformations (MCMs) and foetal growth retardation (FGR) following intrauterine AED exposure in the Emilia Romagna region (RER), Northern Italy (4 million inhabitants). Methods: Data were obtained from official regional registries: Certificate of Delivery Assistance, Hospital Discharge Card, reimbursed prescription databases and Registry of Congenital Malformations. We identified all the deliveries, hospitalized abortions and MCMs occurred between January 2009 and December 2011. Results: We identified 145,243 pregnancies: 111,284 deliveries (112,845 live births and 279 stillbirths), 16408 spontaneous abortions and 17551 TOPs. Six hundred and eleven pregnancies (0.42% 95% Cl: 0.39-0.46) were exposed to AEDs. Twenty-one per cent of pregnancies ended in TOP in the AED group vs 12% in the non-exposed (OR:2.24; CI 1.41-3.56). The rate of spontaneous abortions and stillbirth was comparable in the two groups. Three hundred fifty-three babies (0.31%, 95% CI: 0.28-0.35) were exposed to AEDs during the first trimester. The rate of MCMs was 2.3% in the AED group (2.2% in babies exposed to monotherapy and 3.1% in babies exposed to polytherapy) vs 2.0% in the non-exposed. The risk of FGR was 12.7 % in the exposed group compared to 10% in the non-exposed. Discussion and Conclusion: The prevalence of AED exposure in pregnancy in the RER was 0.42%. The rate of MCMs in children exposed to AEDs in utero was almost superimposable to the one of the non-exposed, however polytherapy carried a slightly increased risk . The rate of TOPs was significantly higher in the exposed women. Further studies are needed to clarify whether this high rate reflects a higher rate of MCMs detected prenatally or other more elusive reasons.

Postpartal recurrent non-ST elevation myocardial infarction in essential thrombocythaemia: case report and review of the literature

ABSTRACT: Normal pregnancy corresponds to a procoagulant state. Acute myocardial infarction during pregnancy is rare, yet considering the low non-pregnant risk score of childbearing women it is still surprisingly frequent. We report a case of postpartum recurrent non-ST elevation myocardial infarction in a 40-year-old caucasian woman with essential thrombocythaemia in the presence of a positive JAK-2 mutation and an elevated anti-cardiolipin IgM antibody titer. In the majority of cases of myocardial infarction in pregnancy or in the peripartal period, atherosclerosis, a thrombus or coronary artery dissection is observed. The combination of essential thrombocythaemia and elevated anti-cardiolipin IgM antibody titer in the presence of several cardiovascular risk factors seems to be causative in our case. In conclusion, with the continuing trend of childbearing at older ages, rare or unlikely conditions leading to severe events such as myocardial infarction must be considered in pregnant women.

Early closure of ileostomy is associated with less postoperative nausea and vomiting

Background/Aims: Temporary loop ileostomy is increasingly used in colorectal surgery but necessitates secondary closure. We evaluated postoperative complications, particularly nausea and vomiting, in patients with early, intermediate, or late elective ileostomy closure. Methods: We included all patients undergoing ileostomy closure from 2001 to 2008. Time from ileostomy construction to closure was classified as early (EC, <12 weeks), intermediate (IC, 12–18 weeks), and late (LC, >18 weeks). Using multivariable logistic regression, we compared the frequency of postoperative complications between the groups. Results: We included 134 patients (87 males; median age 71 years, range 29–91). Carcinoma of the rectum (n = 67, 50%) was the main reason for ileostomy construction. The median time to ileostomy closure was 103 days (range 8–461). Among patients with EC, IC, and LC, postoperative nausea occurred in 50.0, 73.1, and 78.6%, respectively (p = 0.006), and postoperative vomiting in 22.5, 57.7, and 59.5%, respectively (p = 0.001). Adjusting for important covariates, the odds ratio for postoperative nausea was 2.0 (95% CI 0.76–5.1) for IC and 4.1 (95% CI 1.2–14.3) for LC compared to EC (p = 0.069). For postoperative vomiting, adjusted odds ratios were 3.8 (95% CI 1.4–10.4) for IC and 4.6 (95% CI 1.4–15.5) for LC (p = 0.012). Other complications did not differ between the groups. Conclusions: These findings suggest that early ileostomy closure might reduce postoperative nausea and vomiting.

PP141. The lipid transporters ABCA1 and ABCG1 are differentially expressed in preeclamptic and IUGR placentas

INTRODUCTION The ATP-binding cassette (ABC) transporter A1 (ABCA1) and ABCG1 are highly expressed in the placenta in various compartments, including the villous syncytiotrophoblast (V-STB) and foetal endothelial cells. Among other not yet characterized functions, they play a role in the foeto-maternal transport of cholesterol and other lipophilic molecules. In humans, preliminary data suggest expressional changes of ABCA1 and ABCG1 in pathologic gestation, particularly under hypoxic conditions, but a systematic expression analysis in common human pregnancy diseases has never been performed. OBJECTIVES The aim of the present study was to characterize ABCA1 and ABCG1 expression in a large series of pathologic placentas, in particular from preeclampsia (PE) and intrauterine growth restriction (IUGR) which are associated with placental hypoxia. METHODS Placentas from 152 pathological pregnancies, including PE and/or HELLP (n=24) and IUGR (n=21), and 20 normal control placentas were assessed for their ABCA1 and ABCG1 mRNA and protein expression with quantitative RT-PCR and semi-quantitative immunohistochemical analysis, respectively. RESULTS ABCA1 protein expression in the V-STB was significantly less extensive in PE compared with normal controls (<10% of V-STB stained for ABCA1 in 58% PE placentas vs. 25% controls; p=0.035). Conversely, it was significantly more wide-spread in IUGR (>75% of V-STB stained in 57% IUGR placentas vs. 15% controls; p=0.009). Moreover, there was an insignificant trend for increased ABCA1 expression in fetal endothelial cells of stem villi in PE (p=0.0588). ABCA1 staining levels in V-STB were significantly associated with placental histopathological features related with hypoxia: they were decreased in placentas exhibiting syncytial knotting (p=0.033) and decidual vasculopathy (p=0.0437) and increased in low weight placentas (p=0.015). The significant and specific alterations in ABCA1 protein expression found at a specific cellular level were not paralleled by changes in ABCA1 mRNA abundance of total placental tissue. ABCG1 staining was universally extensive in the V-STB of normal placentas, always affecting more than 90% of V-STB surface. In comparison, ABCG1 staining of the V-STB was generally often reduced in pregnancy diseases. In particular, less than 90% of V-STB exhibited ABCG1 staining in 26% of PE placentas (p=0.022) and 35% of IUGR placentas (p=0.003). Similarly to ABCA1, ABCG1 mRNA expression in total placental tissue was not significantly different between controls and PE or IUGR. CONCLUSION ABCA1 and ABCG1 proteins are differentially expressed, with either down- or up-regulation, in the V-STB of placentas exhibiting features of chronic hypoxia, such as in PE and IUGR. This suggests that other factors in addition to hypoxia regulate the expression of placental lipid transporters. The specific changes on a cellular level were masked when only total tissue mRNA was analysed underlining the importance of cell specific expression analysis. The potential effects of decreased placental ABCA1 and ABCG1 expression on foetal nutrition and development remain to be elucidated.

Anti-oxidized low-density lipoprotein (oxLDL) antibody levels are not related to increasing circulating oxLDL concentrations during the course of pregnancy

To address the question of whether the high levels of oxidative modified low-density lipoproteins (oxLDL) in pregnancy are opposed by an appropriate humoral autoimmune response providing anti-oxLDL autoantibodies in maternal serum of healthy women throughout gestation.

The evaluation of the oxidative state of low-density lipoproteins in intrauterine growth restriction and preeclampsia

To evaluate the oxidative state of lipoproteins in pregnancies complicated by intrauterine growth restriction (IUGR) in comparison to preeclampsia (PE) and healthy pregnant control subjects (CN).

Maternal tobacco smoking and decreased leukocytes, including dendritic cells, in neonates

Maternal smoking in pregnancy is associated with respiratory diseases in the offspring, possibly due to prenatal influences on the developing immune system. We investigated whether maternal smoking in pregnancy was associated with cord blood leukocyte numbers, including precursor dendritic cells, adjusting for concomitant factors. In a prospective healthy birth cohort study, total leukocyte counts were reduced in neonates of smoking mothers [10.7 (8.4-13.0), n=14] compared with nonexposed infants [14.7 (13.7-15.7), n=74, p=0.002] [geometric mean cells x 10(3)/microL (95% confidence interval)]. All leukocyte subsets were decreased, most prominently segmented neutrophils [4.3 (2.8-5.7) versus 6.2 (5.5-6.8), p=0.021], lymphocytes [3.8 (2.9-4.8) versus 5.0 (4.5-5.6), p=0.036], and myeloid precursor dendritic cells [12.7 cells/microL (9.1-17.8) versus 18.3 (15.8-21.2), p=0.055]. These differences persisted after adjustment for possible confounders. Predictors of myeloid precursor dendritic cell numbers in multivariable models were maternal smoking (-5.1 cells/microL, p=0.042), age (-0.5 cells/microL/y, p=0.035), and, marginally, asthma (+8.1 cells/microL, p=0.075). The decrease of all leukocytes in neonates of smoking mothers could be clinically significant and suggests a decreased cell production, increased peripheral recruitment, or retention in bone marrow. Given the importance of dendritic cells in early immune responses, their decrease might reflect an impact of maternal smoking on the developing fetal immune system.

Role of aldosterone availability in preeclampsia

Preeclampsia is a hypertensive disorder unique to pregnancy and remains the leading cause of maternal and fetal morbidity and mortality. Despite active research, the etiology of this disease remains still an enigma. There is increasing evidence that a combination of several factors is responsible for the development of preeclampsia. In this review, we discuss the role of aldosterone in the regulation of body fluid in pregnancy and preeclampsia. Aldosterone is produced by the enzyme aldosterone synthase and competes with cortisol and progesterone for the mineralocorticoid receptor, thus affecting sodium reabsorption and maternal volume expansion. Aldosterone seems to play a pivotal role in controlling blood pressure during pregnancy and to contribute to the well-being of the mother-to-be. Novel findings in understanding the underlying causes of preeclampsia provide a rationale for future novel prophylactic and therapeutic interventions in the treatment of this pregnancy-associated disease.

Safety of ondansetron loading doses in children with cancer

INTRODUCTION: In highly emetogenic chemotherapy, the recommended dose of the serotonin-receptor antagonist ondansetron (5 mg/m(2) q8h) may be insufficient to prevent chemotherapy-induced nausea and vomiting. In adults, ondansetron-loading doses (OLD) of 32 mg are safe. We aimed to evaluate in children the safety of an OLD of 16 mg/m(2) (top, 24 mg) i.v., followed by two doses of 5 mg/m(2) q8h. MATERIALS AND METHODS: This retrospective single-center study included all pediatric oncology patients having received >/=1 OLD between 2002 and 2005. Adverse events (AE) definitely, probably, or possibly related to OLD were studied, excluding AE not or unlikely related to the OLD. Associations between potential predictors and at least moderate AE were analyzed by mixed logistic regression. RESULTS: Of 167 patients treated with chemotherapy, 37 (22%) received 543 OLD. The most common AE were hypotension, fatigue, injection site reaction, headache, hot flashes/flushes, and dizziness. At least mild AE were described in 139 OLD (26%), at least moderate AE in 23 (4.2%), and severe AE in 5 (0.9%; exact 95% confidence interval [CI], 0.4-2.1). Life-threatening or lethal AE were not observed (0.0%; 0.0-0.6). At least moderate AE were significantly more frequent in female patients (odds ratio [OR] 3.5; 95% CI 1.4-8.8; p = 0.010), after erroneously given second OLD (17.0; 1.9-154; p = 0.012) and higher 24 h cumulative surface corrected dose (1.26 per mg/m(2); 1.06-1.51; p = 0.009). OLD given to infants below 2 years were not associated with more frequent AE. CONCLUSIONS: Ondansetron-loading doses of 16 mg/m(2) (top, 24 mg) i.v. seem to be safe in infants, children, and adolescents.