Detección de drogas de abuso en meconio

El consumo de sustancias está aumentando en todos los lugares del mundo. Un grupo especialmente vulnerable, es el que sufre los efectos de la exposición prenatal a drogas de abuso. Si bien no se conocen exactamente los mismos, existe evidencia científica que demuestra que tienen mayores tasas de prematurez, retraso del crecimiento intrauterino, disminución del perímetro cefálico, malformaciones cerebrales, cardíacas, esqueléticas, gastrointestinales y genitourinarias, complicaciones obstétricas, muerte súbita, retardo psicomotor y trastornos en el desarrollo neurológico y neuroconductual. La identificación de estos pacientes brinda por una parte, la oportunidad de un seguimiento acorde, así como la detección de madres que podrían insertarse en programas de recuperación. Como dato orientador, basta con indicar que en el año 1994 se calculaba que en las zonas urbanas de EEUU entre un 10-15% de los recién nacidos habían estado expuestos a cocaína intra-útero. En Argentina el primer Estudio Nacional sobre Uso de Drogas – 1999 – realizado por la Secretaría de Programación para la prevención de la Drogadicción y la Lucha contra el Narcotráfico (SEDRONAR) arrojó, como dato principal, que tres de cada diez personas mayores de 16 años consumen sustancias ilegales en Argentina, lo que representa más de 600 mil personas en todo el país. A la misma cifra, arribó el estudio realizado por un grupo de investigadores del Programa de Epidemiología Psiquiátrica del CONICET en el año 2000. A la luz de la información presente, la dimensión del abuso hace necesario reevaluar el foco de atención sanitaria puesto casi exclusivamente en la problemática de adicción, para empezar a recabar datos respecto a la exposición prenatal a drogas. Diversas metodologías han sido utilizadas como método de pesquisa de exposición prenatal a drogas. La entrevista materna y los diferentes dosajes de drogas en sangre, orina, cabello y meconio han sido las más utilizadas y, más recientemente, el estudio en líquido amniótico y aspirado gástrico. De estos procedimientos, la detección de drogas de abuso en meconio es el método ideal para la detección perinatal de drogas por su elevada sensibilidad y la facilidad para recogerlo. Su principal limitación reside en el hecho de que sólo se detecta a partir del primer trimestre de embarazo, ya que la formación de meconio empieza en la semana doce. Por las razones previamente señaladas, es que decidimos utilizar esta metodología de pesquisa para estudiar la prevalencia de uso prenatal de drogas de abuso en la ciudad de Córdoba.

Fatores preditivos de hipertensão gestacional em adolescentes primíparas: análise do pré-natal, da MAPA e da microalbuminúria

OBJETIVO: Quantificar a prevalência de HG em adolescentes primíparas; definir fatores de preditividade para a ocorrência de HG e sua repercussão nos recém-nascidos. MÉTODOS: Foram acompanhadas 29 adolescentes primíparas durante o pré-natal até a 12ª semana de puerpério, com idade média de dezesseis anos, do ambulatório do Serviço de Adolescentes da Maternidade Escola Assis Chateaubriand (MEAC) da Universidade Federal do Ceará (Fortaleza). As gestantes foram dividas em dois grupos; ou seja, nas que permaneceram normotensas (Grupo I) e naquelas que desenvolveram hipertensão gestacional -HG - (Grupo II). As variáveis investigadas na avaliação de valor de preditividade no desenvolvimento de HG foram valores antropométricos, aspectos socioeconômicos, o hábito de fumar, a hereditariedade para HAS (pai/mãe), os exames do pré-natal solicitados na primeira consulta do pré-natal e a microalbuminúria e a monitorização ambulatorial da pressão arterial (MAPA) na 28ª semana de gestação. As gestantes foram acompanhadas no parto e no puerpério tardio (12ª semana de puerpério). Os recém-nascidos das mães do nosso estudo foram avaliados ao nascer pelos índices de APGAR e de Capurro, peso, estatura e pela presença de hipóxia perinatal. RESULTADOS: A prevalência de HG foi de 51,7% . A hereditariedade para HAS apresentou-se com o maior valor de preditividade para HG com odds ratio de 10,99. A pressão arterial diastólica maior ou igual a 70 mmHg, na idade média gestacional de 35 semanas, apresentou significância estatística como valor de preditividade para HG. Na MAPA encontramos valor de preditividade para HG: carga pressórica diastólica em vigília, carga pressórica sistólica e diastólica no sono noturno, variabilidade pressórica e pressão máxima diastólica no sono. Especificamente a pressão arterial diastólica (PAD) máxima na MAPA no período do sono noturno ³64 mmHg apresentou odds ratio de 6 para HG com sensibilidade de 80% e especificidade de 60% para o desenvolvimento de HG. CONCLUSÃO: A pesquisa de fatores de preditividade de HG em adolescentes primíparas se demonstrou de fácil aplicabilidade e útil para estratificar gestantes de alto risco no desenvolvimento de HG.

Sensibilización a Anfetamina y Cocaína: Mecanismos Neurobiológicos involucrados y factores ambientales que la modulan. Amphetamine and cocaine sensitization: neurobiological mechanisms involved and modulation by environmental factors.

La exposición a drogas de abuso, estrés o noxas perinatales puede producir una respuesta sensibilizada a las propiedades estimulantes y reforzantes de la droga. Este proceso de sensibilización, que comparte muchas de las características de otras formas de plasticidad neural, ha sido asociado con etapas tempranas de la adicción o reincidencia a la misma. El objetivo primario de este proyecto es identificar si los mecanismos neurobiológicos que median la sensibilización inducida por cocaína también ocurren en un modelo de sensibilización inducido por estrés de inmovilización y una noxa perinatal tal como la exposición a plomo, y determinar la relevancia de estas adaptaciones mediante intervenciones farmacológicas o manipulación de los productos génicos. Se estudiaran neuroadaptaciones identificadas en un modelo de sensibilización inducido por cocaína, en núcleos específicos del cerebro relevantes para el proceso de sensibilización, Núcleo Accumbens (NAc) y Corteza prefrontal (CPf). Neuropéptidos como met-encefalina y el sistema renina-angiotensina (RAS), interactúan con dopamina (DA) y glutamato (GLU) en este circuito. Considerando que la liberación de GLU, la expresión de receptores AMPA (GluR1) y los metabotrópicos mGluR2/3 como cambios en el remodelado del citoesqueleto de actina de NAc y CPf, han sido afectados por la administración repetida de cocaína en forma no contingente o por autoadministración, determinaremos los niveles o el estado de fosforilación proteínas y de GLU, en los distintos modelos de sensibilización. Además, la participación de RAS cerebral ser evaluada en el desarrollo y expresión del fenómeno de sensibilización a anfetamina y cocaína. Se utilizarán técnicas de inmunoblotting, inmunoprecipitación y de microdiálisis, y pruebas conductuales para determinar las propiedades estimulantes y reforzantes de las drogas. Encontrar un paralelo en los mecanismos neurobiológicos que median la sensibilización inducida por estrés, drogas o noxas perinatales es muy relevante para entender como redes celulares comunes pueden ejercer un rol en la adicción. La identificación de nuevas moléculas que modulen la sensibilización abre una perspectiva sumamente interesante para el estudio de futuros blancos terapéuticos a ser probados para el tratamiento de la adicción a sicoestimulantes.

Infant Mortality in Novo Hamburgo: Associated Factors and Cardiovascular Causes

Background: Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. Objective: To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. Methods: This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Results: Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%), which was significantly associated with the variables ‘age at death’, ‘gestational age’ and ‘birth weight’. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. Conclusion: It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality.

Glutathion no sangue humano normal

1.) - Woodward-Fry's and Okuda-Hess technics were employed in the determination of blood glutathione in normal healthy adults of both sexes. 2.) - It was found more accurately results with the technic of Woodward and Fry than of any others for the dosage of G. S. H. of blood. 3.) - When the process of Okuda-Hess is modified by the use of an intern indicator (starch) the readings of the end-point are much more easy and therefore the results more exacts. 4.) - The averages of the data obtained for normal blood by the technic of Woodward and Fry were for men per hundred cubic cent. 27 mgrs (G.S.H); 6.6 mgrs. (G.S.S) and 33.6 mges. (G. T) and for women: 28.4 mgrs. (G.S.H), 7.8 mgrs. (G.S.S) and 36,2 mgrs. (G.T). 5.) - Autoxidation in the blood filtrate is only apreciated after 24 hs. In the first eight hours autoxidation is never observed. 6.) - The increase of glutathione in hyperglobulia is a function of the amount of red corpuscles. In acrocyanosis arterial blood is richest in these component than venous blood and this fact is in accordance with the observation of Blanchetière, Mélon and Binet for the experimental asphyxia of dogs.

Death caused by cardioinhibitory reflex cardiac arrest--a systematic review of cases.

Forensic pathologists often refer to the cardioinhibitory reflex cardiac arrest (CiRCA) following short neck trauma as a mechanism of death. We sought via a systematic review of the literature to identify circumstances under which carotid bifurcation stimulation could lead to death. Two independent reviewers selected case studies or reports from Medline, ISI Web of Knowledge, and Embase. Circumstances and contributory factors were extracted for each case. From the available data, authors independently assessed whether CiRCA was highly probable (no alternative explanation possible), probable (alternative explanation possible), or unlikely (alternative explanation highly probable). A narrative approach was used to define circumstances in which CiRCA remained possible. From the 48 published cases evoking CiRCA as a possible cause of death between 1881 and 2009, 28 were most likely to result of other mechanism of death (i.e., cerebral hypoxia due to carotid compression, mechanical asphyxia, myocardial infarction). CiRCA remained possible for 20 cases (including five based on anecdotal evidence only) with only one case with no alternative explanation other than CiRCA. Our findings support the presumption that reflex cardiac arrhythmia due to carotid bifurcation stimulation cannot provoke death alone. Actual state of knowledge suggests CiRCA might be contributory to death in the presence of drug abuse and/or cardiac pathology, often associated with physical and/or mental excitation.

Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe.

The aim of this study is to quantify the prevalence and types of rare chromosome abnormalities (RCAs) in Europe for 2000-2006 inclusive, and to describe prenatal diagnosis rates and pregnancy outcome. Data held by the European Surveillance of Congenital Anomalies database were analysed on all the cases from 16 population-based registries in 11 European countries diagnosed prenatally or before 1 year of age, and delivered between 2000 and 2006. Cases were all unbalanced chromosome abnormalities and included live births, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. There were 10,323 cases with a chromosome abnormality, giving a total birth prevalence rate of 43.8/10,000 births. Of these, 7335 cases had trisomy 21,18 or 13, giving individual prevalence rates of 23.0, 5.9 and 2.3/10,000 births, respectively (53, 13 and 5% of all reported chromosome errors, respectively). In all, 473 cases (5%) had a sex chromosome trisomy, and 778 (8%) had 45,X, giving prevalence rates of 2.0 and 3.3/10,000 births, respectively. There were 1,737 RCA cases (17%), giving a prevalence of 7.4/10,000 births. These included triploidy, other trisomies, marker chromosomes, unbalanced translocations, deletions and duplications. There was a wide variation between the registers in both the overall prenatal diagnosis rate of RCA, an average of 65% (range 5-92%) and the prevalence of RCA (range 2.4-12.9/10,000 births). In all, 49% were liveborn. The data provide the prevalence of families currently requiring specialised genetic counselling services in the perinatal period for these conditions and, for some, long-term care.

Paper 2: EUROCAT public health indicators for congenital anomalies in Europe.

OBJECTIVE: The purpose of this article is to present the specific public health indicators recently developed by EUROCAT that aim to summarize important aspects of the public health impact of congenital anomalies in a few quantitative measures. METHODS: The six indicators are: (1) congenital anomaly perinatal mortality, (2) congenital anomaly prenatal diagnosis prevalence, (3) congenital anomaly termination of pregnancy, (4) Down syndrome livebirth prevalence, (5) congenital anomaly pediatric surgery, and (6) neural tube defects (NTD) total prevalence. Data presented for this report pertained to all cases (livebirths, fetal deaths, or stillbirths after 20 weeks of gestation and terminations of pregnancy for fetal anomaly [TOPFA]) of congenital anomaly from 27 full member registries of EUROCAT that could provide data for at least 3 years during the period 2004 to 2008. Prevalence of anomalies, prenatal diagnosis, TOPFA, pediatric surgery, and perinatal mortality were calculated per 1000 births. RESULTS: The overall perinatal mortality was approximately 1.0 per 1000 births for EUROCAT registries with almost half due to fetal and the other half due to first week deaths. There were wide variations in perinatal mortality across the registries with the highest rates observed in Dublin and Malta, registries in countries where TOPFA are illegal, and in Ukraine. The overall perinatal mortality across EUROCAT registries slightly decreased between 2004 and 2008 due to a decrease in first week deaths. The prevalence of TOPFA was fairly stable at about 4 per 1000 births. There were variations in livebirth prevalence of cases typically requiring surgery across the registries; however, for most registries this prevalence was between 3 and 5 per 1000 births. Prevalence of NTD decreased by about 10% from 1.05 in 2004 to 0.94 per 1000 in 2008. CONCLUSION: It is hoped that by publishing the data on EUROCAT indicators, the public health importance of congenital anomalies can be clearly summarized to policy makers, the need for accurate data from registries emphasized, the need for primary prevention and treatment services highlighted, and the impact of current services measured.

Synapse formation on adult-born hippocampal neurons.

It is now widely accepted that adult neurogenesis plays a fundamental role in hippocampal function. Neurons born in the adult dentate gyrus of the hippocampus undergo a series of events before they fully integrate in the network and eventually become undistinguishable from neurons born during embryogenesis. Adult hippocampal neurogenesis is strongly regulated by neuronal activity and neurotransmitters, and the synaptic integration of adult-born neurons occurs in discrete steps, some of which are very different from perinatal synaptogenesis. Here, we review the current knowledge on the development of the synaptic input and output of neurons born in the adult hippocampus, from the stem/progenitor cell to the fully mature neuron. We also provide insight on the regulation of adult neurogenesis by some neurotransmitters and discuss some specificities of the integration of new neurons in an adult environment. The understanding of the mechanisms regulating the synaptic integration of adult-born neurons is not only crucial for our understanding of brain plasticity, but also provides a framework for the manipulation and monitoring of endogenous adult neurogenesis as well as grafted cells, for potential therapeutic applications.

Efficient Subtractive Cloning of Genes Activated by Lipopolysaccharide and Interferon γ in Primary-Cultured Cortical Cells of Newborn Mice.

Innate immune responses play a central role in neuroprotection and neurotoxicity during inflammatory processes that are triggered by pathogen-associated molecular pattern-exhibiting agents such as bacterial lipopolysaccharide (LPS) and that are modulated by inflammatory cytokines such as interferon γ (IFNγ). Recent findings describing the unexpected complexity of mammalian genomes and transcriptomes have stimulated further identification of novel transcripts involved in specific physiological and pathological processes, such as the neural innate immune response that alters the expression of many genes. We developed a system for efficient subtractive cloning that employs both sense and antisense cRNA drivers, and coupled it with in-house cDNA microarray analysis. This system enabled effective direct cloning of differentially expressed transcripts, from a small amount (0.5 µg) of total RNA. We applied this system to isolation of genes activated by LPS and IFNγ in primary-cultured cortical cells that were derived from newborn mice, to investigate the mechanisms involved in neuroprotection and neurotoxicity in maternal/perinatal infections that cause various brain injuries including periventricular leukomalacia. A number of genes involved in the immune and inflammatory response were identified, showing that neonatal neuronal/glial cells are highly responsive to LPS and IFNγ. Subsequent RNA blot analysis revealed that the identified genes were activated by LPS and IFNγ in a cooperative or distinctive manner, thereby supporting the notion that these bacterial and cellular inflammatory mediators can affect the brain through direct but complicated pathways. We also identified several novel clones of apparently non-coding RNAs that potentially harbor various regulatory functions. Characterization of the presently identified genes will give insights into mechanisms and interventions not only for perinatal infection-induced brain damage, but also for many other innate immunity-related brain disorders.

Aggregate cultures of foetal rat liver cells: development and maintenance of liver gene expression.

Rotation-mediated aggregate cultures of foetal rat liver cells were prepared and grown in a chemically defined medium. Their capacity for cellular organisation and maturation was studied over a culture period of 3 wk by using both morphologic and biochemical criteria. It was found that within each aggregate, distinct liver cell types were present and attained their normal, differentiated phenotype. Parenchymal cells formed small acini with a central lumen. Within the first 2 wk in culture, albumin and ferritin mRNA levels were maintained, while the alpha-fetoprotein mRNA levels decreased, and tyrosine aminotransferase (TAT) gene expression increased. No significant response to glucocorticoids was observed in early cultures, whereas after 3 wk a marked increase in TAT mRNA levels was elicited by dexamethasone and glucagon (additive stimulatory effects). The results show that foetal rat liver cells cultured in a chemically defined medium are able to rearrange themselves into histotypic structures, and display a developmental pattern of gene expression comparable to that of perinatal rat liver in vivo. This culture system offers therefore a useful model to study the development and function of liver cells.

Respiratory symptoms in preterm infants: burden of disease in the first year of life.

OBJECTIVE: While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors. METHODS: Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. MAIN OUTCOME MEASURES: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). PATIENTS: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children's Hospital of Bern, Switzerland 1999-2006. RESULTS: Cough occurred in 80%, wheeze in 44%, re-hospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR- and CRIB-Score. CONCLUSIONS: Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.

Etiology of ethnic differences in childhood spirometry.

OBJECTIVES: Age- and height-adjusted spirometric lung function of South Asian children is lower than those of white children. It is unclear whether this is purely genetic, or partly explained by the environment. In this study, we assessed whether cultural factors, socioeconomic status, intrauterine growth, environmental exposures, or a family and personal history of wheeze contribute to explaining the ethnic differences in spirometric lung function. METHODS: We studied children aged 9 to 14 years from a population-based cohort, including 1088 white children and 275 UK-born South Asians. Log-transformed spirometric data were analyzed using multiple linear regressions, adjusting for anthropometric factors. Five different additional models adjusted for (1) cultural factors, (2) indicators of socioeconomic status, (3) perinatal data reflecting intrauterine growth, (4) environmental exposures, and (5) personal and family history of wheeze. RESULTS: Height- and gender-adjusted forced vital capacity (FVC) and forced expired volume in 1 second (FEV1) were lower in South Asian than white children (relative difference -11% and -9% respectively, P < .001), but PEF and FEF50 were similar (P ≥ .5). FEV1/FVC was higher in South Asians (1.8%, P < .001). These differences remained largely unchanged in all 5 alternative models. CONCLUSIONS: Our study confirmed important differences in lung volumes between South Asian and white children. These were not attenuated after adjustment for cultural and socioeconomic factors and intrauterine growth, neither were they explained by differences in environmental exposures nor a personal or family history of wheeze. This suggests that differences in lung function may be mainly genetic in origin. The implication is that ethnicity-specific predicted values remain important specifically for South Asian children.

Growing up with bilateral hippocampal atrophy: from childhood to teenage.

The respective roles of the medial temporal lobe (MTL) structures in memory are controversial. Some authors put forward a modular account according to which episodic memory and recollection-based processes are crucially dependent on the hippocampal formation whereas semantic acquisition and familiarity-based processes rely on the adjacent parahippocampal gyri. Others defend a unitary view. We report the case of VJ, a boy with developmental amnesia of most likely perinatal onset diagnosed at the age of 8. Magnetic resonance imaging (MRI), including quantitative volumetric measurements of the hippocampal formation and of the entorhinal, perirhinal, and temporopolar cortices, showed severe, bilateral atrophy of the hippocampal formation, fornix and mammillary bodies; by contrast, the perirhinal cortex was within normal range and the entorhinal and temporopolar cortex remained within two standard deviations (SDs) from controls' mean. We examined the development of his semantic knowledge from childhood to teenage as well as his recognition and cued recall memory abilities. On tasks tapping semantic memory, VJ increased his raw scores across years at the same rate as children from large standardisation samples, except for one task; he achieved average performance, consistent with his socio-educational background. He performed within normal range on 74% of recognition tests and achieved average to above average scores on 42% of them despite very severe impairment on 82% of episodic recall tasks. Both faces and landscapes-scenes gave rise to above average scores when tested with coloured stimuli. Cued recall, although impaired, was largely superior to free recall. This case supports a modular account of the MTL with episodic, but not semantic memory depending on the hippocampal formation. Furthermore, the overall pattern of findings is consistent with evidence from both brain-damaged and neuroimaging studies indicating that recollection requires intact hippocampal formation and familiarity relies, at least partly, on the adjacent temporal lobe cortex.