Effect of Bauhinia forficata aqueous extract on the maternal-fetal outcome and oxidative stress biomarkers of streptozotocin-induced diabetic rats

Ethnopharmacological relevance: Bauhinia forficata Link, commonly known as paw-of-cow, is widely used in Brazilian folk medicine for the treatment of diabetes.Aim of this study: To evaluate the effect of Bauhinia forficata treatment on maternal-fetal outcome and antioxidant systems of streptozotocin-induced diabetic rats.Materials and methods: Virgin female Wistar rats were injected with 40 mg/kg streptozotocin before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats at increasing doses: 500 mg/kg from 0 to 4th day of pregnancy, 600 mg/kg from 5th to 14th day and 1000 mg/kg from 15th to 20th day. At day 21 of pregnancy the rats were anaesthetized with ether and a maternal blood sample was collected for the determination superoxide dismutase (SOD) and reduced glutathione (GSH). The gravid uterus was weighed with its contents and fetuses were analyzed.Results and conclusion: The data showed that the diabetic dams presented an increased glycemic level, resorption, placental weight, placental index, and fetal anomalies, and reduced GSH and SOD determinations, live fetuses, maternal weight gain, gravid uterine weight, and fetal weight. It was also verified that Bauhinia forficata treatment had no hypoglycemic effect, did not improve maternal outcomes in diabetic rats, but it contributed to maintain GSH concentration similarly to non-diabetic groups, suggesting relation with the decreased incidence of visceral anomalies. (C) 2007 Elsevier B.V. All rights reserved.

Maternal-Fetal Outcome, Lipid Profile and Oxidative Stress of Diabetic Rats Neonatally Exposed to Streptozotocin

Background: There is no evidence about the integrated issue on glycemia, lipid profile, oxidative stress, and anomaly frequency of pregnant diabetic rats neonatally exposed to streptozotocin.Objective: Evaluating the impact of hyperglycemia in diabetic rats neonatally exposed to streptozotocin on maternal reproductive and fetal outcomes and the relationship with lipid profile and maternal oxidative stress.Material and Methods: Ten 90-day-old female Wistar rats were mated to obtain offspring. Some of these newborns received streptozotocin (70 mg/kg, i.p. - n5-STZ group) and the remainder given only citrate buffer (control group) on their day 5 of life. At adult life, these rats (n =13 animals/group) were mated and, at day 21 of pregnancy, they were killed to obtain a maternal blood samples for biochemical determinations. The gravid uterus was weighed with its contents and fetuses were analyzed.Results: At day 0 of pregnancy, glycemic means of n5-STZ rats were significantly greater compared to those of control rats, but presented fetuses classified as small for pregnancy age. The n5-STZ rats showed increased total cholesterol, triglycerides, MDA concentrations, lower SOD activity and increased frequency fetal visceral anomalies as compared to the control group.Conclusion: This study showed that the experimental model used led to mild hyperglycemia during pregnancy, although it did not lead to increased macrosomic fetus rates. The hyperglycemic maternal environment caused metabolic alterations, including increased triglyceride and total cholesterol concentrations, and elevated oxidative stress, contributing to increase fetal visceral anomalies.

Effect of Morus nigra aqueous extract treatment on the maternal-fetal outcome, oxidative stress status and lipid profile of streptozotocin-induced diabetic rats

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

Prediction of postnatal outcome in fetuses with pulmonary hypoplasia by fetal-MRI: Comparison between lung volumetry and pulmonary signal intensity values

Purpose: Pulmonary hypoplasia is a determinant parameter for extra-uterine life. In the last years, MRI appears as a complement to US in order to evaluate the degree of pulmonary hypoplasia in foetuses with congenital anomalies, by using different methods - fetal lung volumetry (FLV), lung-to-liver signal intensity ratio (LLSIR)-. But until now, information about the correlation between the MRI prediction and the real postnatal outcome is limited. Methods and materials: We retrospectively reviewed the fetal MRI performed at our Institution in the last 8 years and selected the cases with suspicion of fetal pulmonary hypoplasia (n = 30). The pulmonary volumetry data of these foetuses were collected and the lung-to-liver signal intensity ratio (LLSIR) measures performed. These data were compared with those obtained from a control group of 25 foetuses considered as normal at MRI. The data of the study group were also correlated with the autopsy records or the post-natal clinical information of the patients. Results: As expected, the control group showed higher FLV and LLSIR values than the problem group at all gestational ages. Higher values of FLV and LLSIR were associated with a better post-natal outcome. Sensitivity, specificity, positive and negative predictive values and accuracy for the relative LLSIR and the relative FLV showed no significant differences. Conclusion: Our data show that not only the FLV but also the relative LLSIR inform about the degree of fetal lung development. This information may help to predict the fetal outcome and to evaluate the need for neonatal intensive care.

Obstetric Outcome in Pregnant Women on Long-term Dialysis: A Case Series

Background: Although still uncommon, pregnancy frequency in women on maintenance hemodialysis therapy has increased in the past 20 years. Most published reports suggest that intensified hemodialysis regimens result in better pregnancy outcomes. The small number of patients investigated in all reported series is the main limitation of the available studies. Study Design: Retrospective case series. Setting & Participants: Data for all pregnancies that occurred in 1988-2008 in women undergoing maintenance hemodialysis (52 pregnancies) at the Sao Paulo University Medical School (Sao Paulo, Brazil). Outcomes & Measurements: We analyzed maternal and fetal outcomes of 52 pregnancies, as well as their relationship with various clinical, laboratory, and hemodialysis parameters, such as pre-eclampsia, pregnancy before or after dialysis therapy, hemodialysis dose, polyhydramnios, anemia, and predialysis serum urea level. In addition, logistic regression models for a composite adverse fetal outcome (perinatal death or extremely premature delivery) and linear regression models for birth weight were built. Results: 87% overall rate of successful delivery, with a mean gestational age of 32.7 +/- 3.1 weeks. Pre-eclampsia was associated with a poor prognosis compared with pregnancies without pre-eclampsia: a successful delivery rate of 60% versus 92.9% (P = 0.02), extremely premature delivery rate of 77.8% versus 3.3% (P = 0.001), lower gestational age (P = 0.001), and birth weight (P = 0.001). Patients with an adverse composite fetal outcome had a higher frequency of pre-eclampsia (P = 0.001), lower frequency of polyhydramnios (P = 0.03), lower third-trimester hematocrit (P = 0.03), and higher predialysis serum urea level (P = 0.03). The same results were seen for birth weight. Limitations: Retrospective data analysis. The absence of creatinine clearance measurements did not allow evaluation of the impact of residual renal function on fetal outcome. Conclusions: Outcomes of pregnancy in women undergoing hemodialysis often are good. Preeclampsia, third-trimester hematocrit, polyhydramnios, and predialysis serum urea level are important variables associated with fetal outcome and birth weight. Am J Kidney Dis 56:77-85. (C) 2010 by the National Kidney Foundation, Inc.Inc

Assessment of fetal risk associated with exposure to cancer chemotherapy during pregnancy: a multicenter study

The objective of the present study was to evaluate and quantify fetal risks involved in the administration of cancer chemotherapy during gestation, as well as to assess the long-term effects on the exposed children. In this retrospective, cohort study, we reviewed the records of women aged 15 to 45 years with a diagnosis of malignancy or benign tumors with malignant behavior at three reference services in the State of Rio Grande do Sul, Brazil, from 1990 to 1997. All patients with a diagnosis of pregnancy at any time during the course of the disease were selected, regardless of whether or not they received specific medication. Fetal outcomes of 14 pregnancies with chemotherapy exposure were compared to that of 15 control pregnancies in which these drugs were not used. Long-term follow-up of the exposed children was carried out. Fisher's exact test was used to compare the groups. Continuous variables were compared by the Wilcoxon-Mann-Whitney test. We found an increased rate of prematurity (6/8 vs 2/10; RR: 3.75; CI: 1.02-13.8; P = 0.03) in the exposed group. There was a trend to an increased fetal death rate (4/12 vs 0/10; P = 0.07) in the group exposed to chemotherapy. No malformations were detected in any child, which can be related to our small sample size as well as to the fact that most exposures occurred after the first trimester of pregnancy. Other larger, controlled studies are needed to establish the actual risk related to cancer chemotherapy during pregnancy.

Biomarkers, medical treatment and fetal intrapartum surveillance in intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterized by maternal pruritus and elevated liver enzymes. It usually begins in the third trimester of pregnancy and resolves spontaneously after delivery. ICP is considered benign for the pregnant woman, but it is associated with an increased risk for unexplained term stillbirth and preterm delivery. There are no specific laboratory markers to diagnose ICP. The diagnosis is currently based on the presence of maternal pruritus and elevated values of alanine aminotransaminases (ALT) and serum bile acids (BA). Recently, ursodeoxycholic acid (UDCA) has been used for treatment. Mechanisms leading to intrauterine fetal death (IUFD) may be multifactorial and are unknown at present. For this thesis, 415 pregnant women with ICP were studied. The aim was to evaluate the value of the liver enzyme glutathione S-transferase alpha (GSTA) as a specific marker of ICP and to assess the effect of maternal UDCA therapy on maternal laboratory values and fetal outcome. The specific markers predisposing the fetus to heart arrhythmia were studied by comparing waveform analysis of fetal electrocardiograms (FECG) during labor in pregnancies complicated by ICP with controls. The levels of maternal GSTA were high and the values correlated with the value of ALT in patients with ICP. UDCA therapy reduced the values of the liver enzymes and alleviated maternal pruritus, but it did not influence maternal hormonal values. Although the newborns experienced an uneventful perinatal outcome, severe ICP was still associated with preterm birth and admission to the neonatal intensive care unit (NICU). There were no significant differences in intrapartum FECG findings between fetuses born to ICP women and controls.

The impact of statin use on fetal development:a meta-analysis

INTRODUCTION: Statin use inadvertently during pregnancy and proposed use of statins for the treatment of preeclampsia, led us to question the evidence behind their current contraindicated status. Several studies have evaluated the relationship between statin use in pregnancy with fetal outcome but their results have not been quantitatively assessed by meta-analysis. Our objective was to undertake a systematic review of all published clinical evidence to assess the effects of statin use in pregnancy on subsequent fetal wellbeing. METHODS: A comprehensive search strategy was performed of all electronic databases and the Merck reporting database for studies published from 1966 to 2014. Two reviewers independently screened citations and undertook study quality assessment and data extraction. We obtained summary estimates of adverse fetal events that were classified as potentially fatal, clinically significant morbidity or minor adverse event. We identified 602 titles and reviewed 30 articles for inclusion and exclusion criteria. Meta-analysis was performed on seven studies (3 cohort, 3 case-series and 1 case-control). RESULTS: Of the 922 cases of statin exposure in pregnancy, 27 exposures were associated with lethal or clinically significant fetal morbidity and 10 with minor adverse events. Statin exposure was limited to the first trimester in all but two cases. The pooled rate of lethal or clinically significant fetal abnormalities in pregnant women exposed to statins was 0.01 (95% CI 0.00-0.04), less than the European rate of 0.026 (95% CI 2.54- 2.57)EUROCAT. The rate of fetal abnormality for simvastatin was 0.03 (95% CI 0.00-0.08), atorvostatin 0.11 (95% CI 0.00-0.52), pravastatin 0.01 (95% CI 0.00-0.2) and lovastatin use 0.04 (95% CI 0.00-0.28). Systems based anomalies were also calculated, congenital heart disease was 0.8 (95% CI 0.02-0.12) compared with the background rate of 0.79 (95% CI 0.78- 0.80). CONCLUSIONS: The published data suggests that statins may not be teratogenic when given inadvertently during pregnancy and prospective studies such as The StAmP Trial may provide more data

Natural course of subsequent pregnancy after peripartum cardiomyopathy

OBJECTIVE: To assess the effect of subsequent pregnancy after peripartum cardiomyopathy (PPCM) on maternal and fetal outcome. METHODS: Prospective study of 34 patients with the diagnosis of PPCM (mean age= 26years). At the time of first diagnosis 5 were in NYHA functional class (FC) II for heart failure, one in FC III and 28 in FC IV. After clinical treatment, patients were advised to avoid new pregnancies and a follow-up was obtained. RESULTS: There were 12 (35.3%) subsequent pregnancies in patients (pt) aged 19 to 44 years (mean 32), divided into two groups: GI: 6 pts who had normalized their heart size and GII: 6 pts with persistent cardiomegaly. GI had initially mild clinical manifestations ( 3 were in FC II, 1 in FC II and 2 in FC IV) and complete recovery of cardiac function (FC I). A new pregnancy was well-tolerated in 5 (83.3%); 1 pt presented with preeclampsia, and progressed to FC II. Presently, 5 pt are in FC I and 1 in FC II. GII pts had more severe heart failure at the onset of PPCM (1 pt in FC II and 5 in FC IV); during follow-up, 4 pt were in FC I and 2 in FC II. A new pregnancy was well tolerated in all of them, but the eldest, who had had 2 pregnancies and had a progressive worsening of clinical status, dying 8 years after the last pregnancy and 13 years after the diagnosis of PPCM. The remaining 5 pt are still alive, 3 in FC I and 2 in FC II, with worsening of FC in 1. Subsequent pregnancies occurred 3-7 years after clinical treatment of PPCM and no fetal distress was observed. CONCLUSION: Subsequent pregnancies are well-tolerated after PPCM, but not devoid of risk. No fetal distress was observed. A minimum interval of 3 years after the recovery of function seems to be safe for subsequent pregnancies.

Risk Prediction of Cardiovascular Complications in Pregnant Women With Heart Disease

Abstract Background: Heart disease in pregnancy is the leading cause of non- obstetric maternal death. Few Brazilian studies have assessed the impact of heart disease during pregnancy. Objective: To determine the risk factors associated with cardiovascular and neonatal complications. Methods: We evaluated 132 pregnant women with heart disease at a High-Risk Pregnancy outpatient clinic, from January 2005 to July 2010. Variables that could influence the maternal-fetal outcome were selected: age, parity, smoking, etiology and severity of the disease, previous cardiac complications, cyanosis, New York Heart Association (NYHA) functional class > II, left ventricular dysfunction/obstruction, arrhythmia, drug treatment change, time of prenatal care beginning and number of prenatal visits. The maternal-fetal risk index, Cardiac Disease in Pregnancy (CARPREG), was retrospectively calculated at the beginning of prenatal care, and patients were stratified in its three risk categories. Results: Rheumatic heart disease was the most prevalent (62.12%). The most frequent complications were heart failure (11.36%) and arrhythmias (6.82%). Factors associated with cardiovascular complications on multivariate analysis were: drug treatment change (p = 0.009), previous cardiac complications (p = 0.013) and NYHA class III on the first prenatal visit (p = 0.041). The cardiovascular complication rates were 15.22% in CARPREG 0, 16.42% in CARPREG 1, and 42.11% in CARPREG > 1, differing from those estimated by the original index: 5%, 27% and 75%, respectively. This sample had 26.36% of prematurity. Conclusion: The cardiovascular complication risk factors in this population were drug treatment change, previous cardiac complications and NYHA class III at the beginning of prenatal care. The CARPREG index used in this sample composed mainly of patients with rheumatic heart disease overestimated the number of events in pregnant women classified as CARPREG 1 and > 1, and underestimated it in low-risk patients (CARPREG 0).

Role of Membrane Transporters, P-Glycoprotein and Mrp1, in The Placental Transfer of Drugs With Special Reference to Saquinavir and Quetiapine

Drug transporting membrane proteins are expressed in various human tissues and blood-tissue barriers, regulating the transfer of drugs, toxins and endogenous compounds into or out of the cells. Various in vitro and animal experiments suggest that P-glycoprotein (P-gp) forms a functional barrier between maternal and fetal blood circulation in the placenta thereby protecting the fetus from exposure to xenobiotics during pregnancy. The multidrug resistance-associated protein 1 (MRP1) is a relatively less studied transporter protein in the human placenta. The aim of this study series was to study the role of placental transporters, apical P-gp and basal MRP1, using saquinavir as a probe drug, and to study transfer of quetiapine and the role of P-gp in its transfer in the dually perfused human placenta/cotyledon. Furthermore, two ABCB1 (encoding P-gp) polymorphisms (c.3435C>T, p.Ile1145Ile and c.2677G>T/A, p.Ala893Ser/Thr) were studied to determine their impact on P-gp protein expression level and on the transfer of the study drugs. Also, the influence of the P-gp protein expression level on the transfer of the study drugs was addressed. Because P-gp and MRP1 are ATP-dependent drug-efflux pumps, it was studied whether exogenous ATP is needed for the function of ATP-dependent transporter in the present experimental model. The present results indicated that the addition of exogenous ATP was not necessary for transporter function in the perfused human placental cotyledon. Saquinavir and quetiapine were both found to cross the human placenta; transplacental transfer (TPTAUC %) for saquinavir was <0.5% and for quetiapine 3.7%. Pharmacologic blocking of P-gp led to disruption of the blood-placental barrier (BPB) and increased the placental transfer of P-gp substrate, saquinavir, into the fetal circulation by 6- to 8-fold. In reversed perfusions P-gp, MRP1 and possibly OATP2B1 had a negligible role in the fetal-to-maternal transfer of saquinavir. The TPTAUC % of saquinavir was about 100-fold greater from the fetal side to the maternal side compared with the maternal-to-fetal transfer. P-gp activity is not likely to modify the placental transfer of quetiapine. Higher P-gp protein expression levels were associated with the variant allele 3435T, but no correlation was found between the TPTAUC % of saquinavir and placental P-gp protein expression. The present results indicate that P-gp activity drastically affects the fetal exposure to saquinavir, and suggest that pharmacological blockade of the P-gp activity during pregnancy may pose an increased risk for adverse fetal outcome. The blockade of P-gp activity could be used in purpose to obtain higher drug concentration to the fetal side, for example, in prevention (to decrease virus transfer to fetal side) or in treating sick fetus.

Metformin in gestational diabetes mellitus

METFORMIININ KÄYTTÖ RASKAUSDIABETEKSESSA Raskausdiabeteksella tarkoitetaan sokeriaineenvaihdunnan häiriötä, joka todetaan ensimmäisen kerran raskauden aikana. Hoidolla voidaan vähentää raskausdiabetekseen liittyviä äidin ja vastasyntyneen haittoja. Lääkitystä tarvitaan, jos ruokavaliohoidolla ei saavuteta hyvää sokeritasapainoa. Perinteisesti lääkityksenä on käytetty insuliinia, mutta metformii¬nin käyttöä insuliinin vaihtoehtona on ehdotettu. Metformiini läpäisee istukan, mutta sen läpäisymekanismi ei ole selvillä. Tämän tutkimuskokonaisuuden pääasiallisin tarkoitus oli verrata metformiinin tehokkuutta ja turvallisuutta insuliiniin raskausdiabeteksen hoidossa selvittämällä lääkkeen vaiku¬tusta äitiin ja vastasyntyneeseen. Lisäksi haluttiin tutkia, mitkä tekijät ennustavat insulii¬nin tarvetta metformiinin lisänä, jotta saavutettaisiin hyvä sokeritasapaino. Metformiinin annoksen vaikutus äitiin ja vastasyntyneeseen arvioitiin mittaamalla metformiinin pitoisuus äidistä, ja sikiön puolelta napanuoran veressä. Tässä tutkimuksessa selvitettiin myös aktiivisen kuljetusproteiinin (OCT) merkitystä metformiinin kulkeutumiseen istukan läpi perfusiomalla istukkaa ex vivo . Ex vivo istukkaperfuusiotutkimuksen tulokset viittasivat siihen, että OCT-kuljetusproteiinilla ei ollut todennäköisesti merkittävää osuutta metformiinin kulkeutumisessa istukan läpi. Metformiinin pitoisuusmittaukset synnytyksen yhteydessä osoittivat metformiinin siirtyvän sikiöön istukan läpi suuressa määrin (96 %) kertymättä kuitenkaan sikiön verenkiertoon. Metformiinin pitoisuudella ei ollut vaikutusta vastasyntyneen hyvinvointiin. Maksi¬maalisella metformiinin annostuksella ja korkealla metformiinipitoisuudella todettiin olevan suotuisa vaikutus äidin painon nousuun raskauden aikana. Insuliiniin verrattuna metformiini ei lisännyt äidin, sikiön tai vastasyntyneen haittatapahtumia, eikä sillä ollut vaikutusta synnytystapaan. Sokeritasapaino insuliini- ja metformiinilääkityksen aikana oli yhtäläinen arvioitaessa sitä HbA1c- ja fruktosamiinimittauksilla, mutta 21 % metformiinin käyttäjistä tarvitsi lisäksi insuliinia hyvän sokeritasapainon saavuttamiseksi. Tutkimuksesssa todettiin, että mitä iäkkäämpi äiti oli, mitä varhaisemmassa raskauden vaiheessa sokerirasitus oli tehty ja lääkitys aloitettu, ja mitä korkeammat HbA1c ja fruktosamiinipitoisuudet olivat, sitä suuremmalla todennäköisyydellä metformiinin lisänä tarvittiin insuliinia.

Desenlaces maternos y fetales en el manejo expectante de la preeclampsia lejos del término

Introducción La preeclampsia hace parte del espectro de los trastornos hipertensivos asociados al embarazo y es causa de alta morbimortalidad materna. La edad gestacional ha sido relacionada con la presentación más severa de esta cuando ocurren lejanas al término. Hoy en día existe la posibilidad de proporcionar manejo expectante en estos casos en unidades de cuidado obstétrico especializadas, con el fin de disminuir el riesgo de morbimortalidad asociada a la prematurez extrema. Metodología Se realizó un estudio de corte transversal que incluyó pacientes con preeclampsia lejos del término entre las 24 y 34 semanas que recibieron manejo expectante entre 2009 y 2012 en la Unidad de Cuidado Intensivo Obstétrico de la Clínica Colsubsidio Orquídeas. Resultados Se incluyeron 121 pacientes con preeclampsia lejos del término, quienes recibieron manejo expectante. La edad promedio fue 29.8, el promedio de días de manejo expectante fue 4 días, con una mediana de tres días. La edad gestacional de ingreso fue 30 1/7 semanas y la edad promedio de terminación 30 5/7 semanas. El 88.4% recibieron esquema de maduración completo. El 81.6% presentaron preeclampsia severa. El desenlace materno más frecuente fue Síndrome Hellp (37%) y el desenlace fetal fue restricción de crecimiento intrauterino (29%). Discusión Se debe considerar el manejo expectante en toda paciente con preeclampsia previa a la semana 34 para manejo antenatal con corticoesteroides, el cual demostró ser un factor protector para muerte perinatal temprana. No se encontraron diferencias significativas entre la aparición de complicaciones y la cantidad de días de manejo expectante.

Efeitos silibina sobre modelo pré-eclâmpsia induzida em ratas por tratamento com Nω-Nitro-L-arginina metil ester

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)