Characterization of fetal antigen 1/delta-like 1 homologue expressing cells in the rat nigrostriatal system: effects of a unilateral 6-hydroxydopamine lesion.

Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been suggested as a potential supplementary marker of dopaminergic neurons. The present study aimed at investigating the distribution of FA1/dlk1-immunoreactive (-ir) cells in the early postnatal and adult midbrain as well as in the nigrostriatal system of 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc dopaminergic neurons and/or due to the stab wound. Our findings hint to a significant role of FA1/dlk1 in the SNc during early postnatal development. The differential expression of FA1/dlk1 in the SNc and the striatum of dopamine-depleted rats could indicate a potential involvement of FA1/dlk1 in the cellular response to the degenerative processes.

Maternal factors, fetal parameters and the risk of shoulder dystocia

Introduction. Shoulder dystocia is a serious complication of vaginal birth, with an incidence ranging from 0.15% to 2.1% of all births. There are approximately 4 million births per year in the United States and shoulder dystocia will be experienced by approximately 20,000 women each year. Although studies have been reported on shoulder dystocia, few studies have addressed both maternal and fetal risk factors. The purpose of this study was to identify maternal and fetal risk factors for shoulder dystocia while proposing factors that could be used to predict impending shoulder dystocia. ^ Material and methods. Articles were reviewed from Medline Pubmed using the search phrase "Risk factors of shoulder dystocia" and Medline Ovid using the search words "Dystocia", "Shoulder" and "Risk factors". Rigorous selection criteria were used to identify articles to be included in the study. Data collected from identified articles were transferred to STATA 10 software for trend analysis of the incidence of shoulder dystocia and the year of publication and a pair wise correlation was also determined between these two variables. ^ Results. Among a total of 343 studies identified, only 20 met our inclusion criteria and were retained for this review. The incidence of shoulder dystocia ranged from 0.07% to 2% and there was no particular trend or correlation between the incidence of shoulder dystocia and year of publication between 1985 and 2007. Pre-gestational and gestational diabetes, postdatism, obesity, birth weight > 4000g and fundal height at last visit > 40cm were identified as major risk factors in our series of studies. ^ Conclusion. Future strategies to predict shoulder dystocia should focus on pre-gestational and gestational diabetes mellitus, postdatism, obesity, birth weight > 4000g and fundal height at last visit > 40cm. ^

Obesity during pregnancy on vagal tone, hemoglobin A1c, oxygenation, and perinatal outcomes

Purpose: To examine the effect of obesity and gestational weight gain on heart rate variability (HRV), oxygenation (HbO 2 and SpO2), hemoglobin A1c (HbA1c) and the frequency of pregnancy complications in obese (O) and non-obese (NO) women.^ Design: The study was an observational comparison study with a repeated measures design. ^ Setting: The setting was a low risk prenatal, university clinic located in a large southeastern metropolitan city. ^ Sample: The sample consisted of a volunteer group of 41 pregnant women who were observed at the three time points of 20, 28, and 36 weeks gestation. ^ Analysis: Analysis included general linear modeling with repeated measures to test for group differences with changes over time on vagal response, HbA1c, and oxygenation. Odds ratios were computed to compare the frequency of birth outcomes. ^ Findings: The interaction effect of time between O and NO women on HbO2 was significant. The mean HP, RSA, and HbO2 changed significantly over time within the NO women. The mean HbA 1c increased significantly over time within the O women. Women with excess gestational weight gain had significantly lower heart period than women with weight gain within the IOM recommendations. Obese women were more likely to have Group B streptococcal infections, gestational hypertension, give birth by cesarean or instrument assistance, and have at least one postnatal event. ^ Conclusions: Monitoring HRV, oxygenation, and HbA1c using minimally invasive measures may permit early identification of alterations in autonomic response. Implementation of interventions to promote vagal tone may help to reduce risks for adverse perinatal outcomes related to obesity. Future studies should examine the effect of obesity on the vagal response and perinatal outcomes. ^

A GENETIC MARKER STUDY OF NON - INSULIN DEPENDENT DIABETICS IN THE MEXICAN-AMERICAN COMMUNITY FROM STARR COUNTY, TEXAS (PLASMA GLUCOSE, HEMOGLOBIN ANALYSIS)

Diabetes mellitus occurs in two forms, insulin-dependent (IDDM, formerly called juvenile type) and non-insulin dependent (NIDDM, formerly called adult type). Prevalence figures from around the world for NIDDM, show that all societies and all races are affected; although uncommon in some populations (.4%), it is common (10%) or very common (40%) in others (Tables 1 and 2).^ In Mexican-Americans in particular, the prevalence rates (7-10%) are intermediate to those in Caucasians (1-2%) and Amerindians (35%). Information about the distribution of the disease and identification of high risk groups for developing glucose intolerance or its vascular manifestations by the study of genetic markers will help to clarify and solve some of the problems from the public health and the genetic point of view.^ This research was designed to examine two general areas in relation to NIDDM. The first aims to determine the prevalence of polymorphic genetic markers in two groups distinguished by the presence or absence of diabetes and to observe if there are any genetic marker-disease association (univariate analysis using two by two tables and logistic regression to study the individual and joint effects of the different variables). The second deals with the effect of genetic differences on the variation in fasting plasma glucose and percent glycosylated hemoglobin (HbAl) (analysis of Covariance for each marker, using age and sex as covariates).^ The results from the first analysis were not statistically significant at the corrected p value of 0.003 given the number of tests that were performed. From the analysis of covariance of all the markers studied, only Duffy and Phosphoglucomutase were statistically significant but poor predictors, given that the amount they explain in terms of variation in glycosylated hemoglobin is very small.^ Trying to determine the polygenic component of chronic disease is not an easy task. This study confirms the fact that a larger and random or representative sample is needed to be able to detect differences in the prevalence of a marker for association studies and in the genetic contribution to the variation in glucose and glycosylated hemoglobin. The importance that ethnic homogeneity in the groups studied and standardization in the methodology will have on the results has been stressed. ^

HEMATOCRIT AND HEMOGLOBIN, ATP AND DPG CONCENTRATIONS IN ANDEAN MAN: VARIABILITY BY SEX, AGE, VILLAGE, ALTITUDE, WEIGHT, SMOKING HABITS AND GENETIC CONSTITUTION

The Departmento de Arica in northern Chile was chosen as the investigation site for a study of the role of certain hematologic and glycolytic variables in the physiological and genetic adaptation to hypoxia.^ The population studied comprised 876 individuals, residents of seven villages at three altitudes: coast (0-500m), sierra (2,500-3,500m) and altiplano (> 4,000m). There was an equal number of males and females ranging in ages from six to 90 years. Although predominantly Aymara, those of mixed or Spanish origin were also examined. The specimens were collected in heparinized vacutainers precipitated with cold trichloroacetic acid (TCA) and immediately frozen to -196(DEGREES)C. Six variables were measured. Three were hematologic: hemoglobin, hematocrit and mean cell hemoglobin concentration. The three others were glycolytic: erythrocyte 2,3-diphosphoglycerate (DPG), adenosine triphosphate (ATP) and the percentage of phosphates (DPG + ATP) in the form of DPG.^ Hemoglobin and hematocrit were measured on site. The DPG and ATP content was assayed in specimens which had been frozen at -196(DEGREES)C and transported to Houston. Structured interviews on site provided information as to lifestyle and family pedigrees.^ The following results were obtained: (1) The actual village, rather than the altitude, of examination accounted for the greatest proportion of the variance in all variables. In the coast, a large difference in levels of ionic lithium in the drinking water exists. The chemical environment of food and drink is postulated to account, in part, for the importance of geographic location in explaining the observed variance. (2) Measurements of individuals from the two extreme altitudes, coast and altiplano, did not exhibit the same relationship with age and body mass. The hematologic variables were significantly related to both age and body build in the coast. The glycolytic variables were significantly related to age and body mass in the altiplano. (3) The environment modified male values more than female values in all variables. The two sexes responded quite differently to age and changes in body mass as well. The question of differing adaptability of the two sexes is discussed. (4) Environmental factors explained a significantly higher proportion of total variability in the altiplano than in the coast for hemoglobin, hematocrit and DPG. Most of the ATP variability at both altitudes is explained by genetic factors. ^

Malaria infection and fetal growth during the war : evidence from Liberia

This study investigates whether the Liberian civil war increased infant mortality by exposing pregnant women to a high risk of malaria infection, thus retarding fetal development. I find that the war-induced, one-percent increase in maternal infection risk resulted in a 0.44 percent increase in one-year mortality. This mortality effect gradually increased following childbirth as maternal passive immunity waned. The consequences were pronounced for infants conceived in rainy seasons by young mothers residing in rural, battle-intensive areas, with no gender difference detected. I also provide evidence suggesting the wartime culling of the weakest infants associated with maternal malaria infection.

El ejercicio físico durante el embarazo, su influencia en la salud materna y fetal

El ejercicio físico durante el embarazo, su influencia en la salud materna y fetal

Influencia del ejercicio físico desarrollado durante el embarazo en la respuesta cardiaca fetal = Influence of a physical activity program performed during pregnancy on fetal heart response

INTRODUCCIÓN: El riesgo de padecer enfermedades cardiovasculares y los índices de obesidad infantil han ido en aumento durante los últimos años empobreciendo la salud de la población. La Teoría de Barker relaciona el estado de salud de la madre con el desarrollo fetal, asociando a un deficiente estado físico y hábitos de vida negativos de la mujer embarazada con el aumento del riesgo de padecer cardiopatías en la infancia y adolescencia, así como predisponer al recién nacido a padecer sobrepeso y/u obesidad en su vida posterior. Por otro lado los estudios efectuados sobre ejercicio físico durante el embarazo reportan beneficios para salud materna y fetal. Uno de los parámetros más utilizados para comprobar la salud fetal es su frecuencia cardiaca, mediante la que se comprueba el buen desarrollo del sistema nervioso autónomo. Si se observa este parámetro en presencia de ejercicio materno podría encontrarse una respuesta crónica del corazón fetal al ejercicio materno como consecuencia de una adaptación y mejora en el funcionamiento del sistema nervioso autónomo del feto. De esta forma podría mejorar su salud cardiovascular intrauterina, lo que podría mantenerse en su vida posterior descendiendo el riesgo de padecer enfermedades cardiovasculares en la edad adulta. OBJETIVOS: Conocer la influencia de un programa de ejercicio físico supervisado en la frecuencia cardiaca fetal (FCF) en reposo y después del ejercicio materno en relación con gestantes sedentarias mediante la realización de un protocolo específico. Conocer la influencia de un programa de ejercicio físico en el desarrollo del sistema nervioso autónomo fetal, relacionado con el tiempo de recuperación de la FCF. MATERIAL Y MÉTODO: Se diseñó un ensayo clínico aleatorizado multicéntrico en el que participaron 81 gestantes (GC=38, GE=43). El estudio fue aprobado por el comité ético de los hospitales que participaron en el estudio. Todas las gestantes fueron informadas y firmaron un consentimiento para su participación en el estudio. Las participantes del GE recibieron una intervención basada en un programa de ejercicio físico desarrollado durante la gestación (12-36 semanas de gestación) con una frecuencia de tres veces por semana. Todas las gestantes realizaron un protocolo de medida de la FCF entre las semanas 34-36 de gestación. Dicho protocolo consistía en dos test llevados a cabo caminando a diferentes intensidades (40% y 60% de la frecuencia cardiaca de reserva). De este protocolo se obtuvieron las principales variables de estudio: FCF en reposo, FCF posejercicio al 40 y al 60% de intensidad, tiempo de recuperación de la frecuencia cardiaca fetal en ambos esfuerzos. El material utilizado para la realización del protocolo fue un monitor de frecuencia cardiaca para controlar la frecuencia cardiaca de la gestante y un monitor fetal inalámbrico (telemetría fetal) para registrar el latido fetal durante todo el protocolo. RESULTADOS: No se encontraron diferencias estadísticamente significativas en la FCF en reposo entre grupos (GE=140,88 lat/min vs GC= 141,95 lat/min; p>,05). Se encontraron diferencias estadísticamente significativas en el tiempo de recuperación de la FCF entre los fetos de ambos grupos (GE=135,65 s vs GC=426,11 s esfuerzo al 40%; p<,001); (GE=180,26 s vs GC=565,61 s esfuerzo al 60%; p<,001). Se encontraron diferencias estadísticamente significativas en la FCF posejercicio al 40% (GE=139,93 lat/min vs GC=147,87 lat/min; p<,01). No se encontraron diferencias estadísticamente significativas en la FCF posejercicio al 60% (GE=143,74 lat/min vs GC=148,08 lat/min; p>,05). CONLUSIÓN: El programa de ejercicio físico desarrollado durante la gestación influyó sobre el corazón fetal de los fetos de las gestantes del GE en relación con el tiempo de recuperación de la FCF. Los resultados muestran un posible mejor funcionamiento del sistema nervioso autónomo en fetos de gestantes activas durante el embarazo. ABSTRACT INTRODUCTION: The risk to suffer cardiovascular diseases and childhood obesity index has grown in the last years worsening the health around the population. Barker´s Theory related maternal health with fetal development establishing an association between a poorly physical state and an unhealthy lifestyle in the pregnant woman with the risk to suffer heart disease during childhood and adolescence, childhood overweight and/or obese is related to maternal lifestyle. By the other way researches carried out about physical exercise and pregnancy show benefits in maternal and fetal health. One of the most studied parameters to check fetal health is its heart rate, correct fetal autonomic nervous system development and work is also corroborated by fetal heart rate. Looking at this parameter during maternal exercise a chronic response of fetal heart could be found due to an adaptation and improvement in the working of the autonomic nervous system. Therefore its cardiovascular health could be enhanced during its intrauterine life and maybe it could be maintained in its posterior life descending the risk to suffer cardiovascular diseases in adult life. OBJECTIVES: To know the influence of a supervised physical activity program in the fetal heart rate (FHR) at rest, FHR after maternal exercise related to sedentary pregnant women by a FHR assessment protocol. To know the influence of a physical activity program in the development of the autonomic nervous system related to FHR recovery time. MATERIAL AND METHOD: A multicentric randomized clinical trial was design in which 81 pregnant women participated (CG=38, EG=43). The study was approved by the ethics committee of all of the hospitals participating in the study. All of the participants signed an informed consent for their participation in the study. EG participants received an intervention based on a physical activity program carried out during gestation (12-36 gestation weeks) with a three days a week frequency. All of the participants were tested between 34-36 weeks of gestation by a specific FHR assessment protocol. The mentioned protocol consisted in two test performed walking and at a two different intensities (40% and 60% of the reserve heart rate). From this protocol we obtained the main research variables: FHR at rest, FHR post-exercise at 40% and 60% intensity, and FHR recovery time at both walking test. The material used to perform the protocol were a FH monitor to check maternal HR and a wireless fetal monitor (Telemetry) to register fetal beats during the whole protocol. RESULTS: There were no statistical differences in FHR at rest between groups (EG=140,88 beats/min vs CG= 141,95 beats/min; p>,05). There were statistical differences in FHR recovery time in both walking tests between groups (EG=135,65 s vs CG=426,11 s test at 40% intensity; p<,001); (EG=180,26 s vs CG=565,61 s test at 60% intensity; p<,001). Statistical differences were found in FHR post-exercise at 40% intensity between groups (EG=139,93 beats/min vs CG=147,87 beats/min; p<,01). No statistical differences were found in FHR at rest post-exercise at 60% intensity between groups (EG=143,74 beats/min vs CG=148,08 beats/min; p>,05). CONCLUSIONS: The physical activity program performed during gestation had an influence in fetal heart of the fetus from mother in the EG related to FHR recovery time. These results show a possible enhancement on autonomic nervous system working in fetus from active mothers during gestation.

La posición fetal intrauterina afecta al desarrollo de las estructuras feto-placentarias de la coneja

Un total de 129 fetos de conejas multíparas fueron estudiados según su posición intrauterina. Los más próximos al ovario presentaron mejores valores morfométricos que los más alejados a esta posición, asociándose asimismo un mayor peso placentario a un mayor peso fetal. Estas diferencias fueron mantenidas en la valoración de órganos fetales, como el cerebro, hígado y aparato digestivo, mostrándose un mayor desarrollo en los fetos adyacentes al ovario. A su vez se observó una correlación positiva entre el peso placentario y el peso de estos órganos. Las diferencias de peso dentro de la misma camada podrían estar asociadas a un mayor desarrollo placentario y por consiguiente mayor disponibilidad de nutrientes.

Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein

CREB, the cAMP response element binding protein, is a key transcriptional regulator of a large number of genes containing a CRE consensus sequence in their upstream regulatory regions. Mice with a hypomorphic allele of CREB that leads to a loss of the CREBα and Δ isoforms and to an overexpression of the CREBβ isoform are viable. Herein we report the generation of CREB null mice, which have all functional isoforms (CREBα, β, and Δ) inactivated. In contrast to the CREBαΔ mice, CREB null mice are smaller than their littermates and die immediately after birth from respiratory distress. In brain, a strong reduction in the corpus callosum and the anterior commissures is observed. Furthermore, CREB null mice have an impaired fetal T cell development of the αβ lineage, which is not affected in CREBαΔ mice on embryonic day 18.5. Overall thymic cellularity in CREB null mice is severely reduced affecting all developmental stages of the αβ T cell lineage. In contrast γδ T cell differentiation is normal in CREB mutant mice.

Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia

The TEL (ETV6)−AML1 (CBFA2) gene fusion is the most common reciprocal chromosomal rearrangement in childhood cancer occurring in ≈25% of the most predominant subtype of leukemia— common acute lymphoblastic leukemia. The TEL-AML1 genomic sequence has been characterized in a pair of monozygotic twins diagnosed at ages 3 years, 6 months and 4 years, 10 months with common acute lymphoblastic leukemia. The twin leukemic DNA shared the same unique (or clonotypic) but nonconstitutive TEL-AML1 fusion sequence. The most plausible explanation for this finding is a single cell origin of the TEL-AML fusion in one fetus in utero, probably as a leukemia-initiating mutation, followed by intraplacental metastasis of clonal progeny to the other twin. Clonal identity is further supported by the finding that the leukemic cells in the two twins shared an identical rearranged IGH allele. These data have implications for the etiology and natural history of childhood leukemia.