Mise en évidence de dysfonctions liées au développement de l'endométriose péritonérale Contributions angio-inflammatoires des cytokines et prostaglandines

L’endométriose est une maladie gynécologique, touchant les femmes en âge de procréer. Cette pathologie est caractérisée par la présence de tissu endométrial ectopique, c’est-à-dire en dehors de la cavité utérine. Des dysfonctions du système immunitaire sont de plus en plus souvent suspectées comme étant un des éléments responsables de la pathogenèse de cette maladie. L’objectif général de ce projet a donc été d’étudier les mécanismes cellulaires de molécules pro-inflammatoires aux propriétés variées et à l’expression anormalement élevée dans cette pathologie, que sont MIF et les prostaglandines PGE2 et PGF2α, dans les anomalies inflammatoires et invasives en cause dans cette pathologie. La première partie de nos travaux a porté sur l’étude d’un modèle murin de l’endométriose déficient du gène MIF. Le nombre et le volume des lésions collectées à partir des souris déficientes pour le gène MIF sont significativement inférieurs à ceux mesurés dans des souris sauvages utilisées comme contrôle. L’analyse par PCR des cellules isolées des lésions de souris déficientes du gène MIF a révélé une expression réprimée des protéines d’adhésion, d’inflammation et d’angiogenèse. Ces données démontrent pour la première fois que le MIF agit directement sur la croissance et la progression de lésions d’endométriose in vivo. Une partie de nos travaux a porté sur les molécules nécessaires au métabolisme de PGE2 et PGF2α dans l’endomètre eutopique des femmes normales et l’endomètre eutopique et ectopique des femmes atteintes d’endométriose. Selon nos données, l’expression de certains de ces facteurs est perturbée durant cette maladie, ce qui peut avoir des effets délétères sur la physiologie de la procréation. La stimulation des cellules ectopiques par PGF2α entraîne une libération accrue de VEGF et CXCL-8, ceci via l’induction de COX-2 et des deux variants d’épissage du récepteur FP. De plus, la PKC joue un rôle dans ce phénomène, dépendamment et indépendamment de la PLC. Par son effet inducteur sur la libération de VEGF et CXCL-8, PGF2α pourrait favoriser l’aspect inflammatoire et le développement ectopique des lésions d’endométriose, notamment par des phénomènes d’angiogenèse et de prolifération cellulaire accrus. L’effet de PGF2α sur la libération de VEGF et CXCL-8 par les cellules endométriales ectopiques pourrait également expliquer les quantités élevées de ces cytokines dans le liquide péritonéal des femmes atteintes d’endométriose, un phénomène suspecté dans l’infertilité et les douleurs associées à cette maladie. Nos derniers résultats obtenus à partir du liquide péritonéal montrent un profil cytokinique en faveur de l’angiogenèse et la prolifération des lésions d’endométriose, avec une forte augmentation des facteurs suivants : EGF, FGF-2, IL-1α, MIP-1β, TGFα, PDGF-AA, PDGF-BB, MCP-3, sCD40L, Gro Pan, IL-17α, MDC et Rantes, confortant nos observations préalables redéfinissant la maladie comme étant d’origine angio-inflammatoire. L’endométriose et ses symptômes sont des phénomènes complexes ayant probablement plus qu’une seule origine. Parmi les nombreux facteurs à l’expression altérée dans l’endométriose, notre étude montre que MIF, PGE2 et PGF2α, ainsi qu’une pléthore de facteurs pro-angiogéniques pourraient être de ceux jouant un rôle dans l’infertilité et les douleurs reliées à cette maladie.

Diet and Probiotics during Pregnancy - Endorsing developmental Programming

Maternal obesity has been shown to increase the risk for adverse reproductive health outcomes such as gestational diabetes, hypertension, and preeclampsia. Moreover, several studies have indicated that overnutrition and maternal obesity adversely program the development of offspring by predisposing them to obesity and other chronic diseases later in life. The exact molecular mechanisms leading to developmental programming are not known, but it has recently been suggested that obesity-related low-grade inflammation, gut microbiota and epigenetic gene regulation (in particularly DNA methylation) participate in the developmental programming phenomenon. The aim of this thesis was to evaluate the effect of diet, dietary counseling and probiotic intervention during pregnancy in endorsing favorable developmental programming. The study population consisted of 256 mother-child pairs participating in a prospective, double-blinded dietary counselling and probiotic intervention (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12) NAMI (Nutrition, Allergy, Mucosal immunology and Intestinal microbiota) study. Further overweight women were recruited from maternal welfare clinics in the area of Southwest Finland and from the prenatal outpatient clinic at Turku University Hospital. Dietary counseling was aimed to modify women’s dietary intake to comply with the recommended intake for pregnant women. Specifically, counseling aimed to affect the type of fat consumed and to increase the amount of fiber in the women’s diets. Leptin concentration was used as a marker for obesity-related low-grade inflammation, antioxidant vitamin status as an efficiency marker for dietary counselling and epigenetic DNA methylation of obesity related genes as a marker for probiotics influence. Results revealed that dietary intake may modify obesity-associated low-grade inflammation as measured by serum leptin concentration. Specifically, dietary fiber intake may lower leptin concentration in women, whereas the intakes of saturated fatty acids and sucrose have an opposite effect. Neither dietary counselling nor probiotic intervention modified leptin concentration in women, but probiotics tended to increase children’s leptin concentration. Dietary counseling was an efficient tool for improving antioxidant vitamin intake in women, which was reflected in the breast milk vitamin concentration. Probiotic intervention affected DNA methylation of dozens of obesity and weight gain related genes both in women and their children. Altogether these results indicate that dietary components, dietary counseling and probiotic supplementation during pregnancy may modify the intrauterine environment towards favorable developmental programming.

Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development.

In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders.

Handgrip dynamometry and patient-generated subjective global in patients with non-resectable lung cancer

Rationale: Undernutrition is frequently associated with advanced lung cancer. Accurate nutritional assessment tools are important to provide the proper nutritional therapy. Hand grip strength (HGS) has already been used in these patients and the findings suggest it is a good indicator of nutritional status. The aim of this study was to evaluate the association between nutritional status and hand grip strength in patients with nonresectable lung cancer.

A decrease in dkk1, a Wnt inhibitor, contributes to placental and fetal lipid accumulation in an obesity-prone rat model

Placenta, as the sole transport mechanism between mother and fetus, links the maternal physical state and the immediate and life-long outcomes of the offspring. The present study examined the mechanisms behind the effect of maternal obesity on placental lipid accumulation and metabolism. Pregnant Obese Prone (OP) and Obese Resistant (OR) rat strains were fed a control diet throughout gestation. Placentas were collected on gestational d21 for analysis and frozen placental sections were analyzed for fat accumulation as well as β-Catenin and Dkk1 localization. Additionally, DKK1 was overexpressed in JEG3 trophoblast cells, followed by treatment with NEFA and Oil Red O stain quantification and mRNA analysis to determine the relationship between placental DKK1 and lipid accumulation. Maternal plasma and placental NEFA and TG were elevated in OP dams, and offspring of OP dams were smaller than OR. Placental Dkk1 mRNA content was 4-fold lower in OP placentas, and there was a significant increase in β-Catenin accumulation as well as mRNA content of fat transport and TG synthesis enzymes, including Ppar-delta, Fatp1, Fat/Cd36, Lipin1, and Lipin3. There was significant lipid accumulation within the decidual zones in OP but not OR placentas, and the thickness of the decidual and junctional zones was significantly smaller in OP than OR placentas. Overexpression of DKK1 in JEG3 cells decreased lipid accumulation and the mRNA content of PPAR-Delta, FATP1, FAT/CD36, LIPIN1, and LIPIN3. Our results indicate that Dkk1 may be regulating placental lipid metabolism through Wnt-mediated mechanisms. Additionally, recent studies have suggested that maternal obesity may also program early development of non-alcoholic fatty liver disease (NAFLD), rates of which have correlated with the increase in the obesity epidemic. In the current study, livers of OP offspring had significantly increased TG content (P<0.05) and lipid accumulation when compared to offspring of OR dams. Additionally, hepatic Dkk1 mRNA content was significantly decreased in OP livers when compared to OR (P<0.05), and treating H4IIECR rat hepatocyte cells with NEFA showed that Dkk1 mRNA was also decreased in NEFA-treated cells (P<0.05) that also had lipid accumulation. Chromatin Immunoprecipitation (ChIP) analysis of the Dkk1 promoter in fetal livers showed a pattern of histone modifications associated with decreased gene transcription in OP offspring, which agrees with our gene expression data. These results demonstrate that the hepatic Dkk1 gene is epigenetically regulated via histone modification in neonatal offspring in the current model of gestational obesity, and future studies will be needed to determine whether these changes contribute to excessive hepatic lipid accumulation in offspring of obese dams.

Musicoembriologia – qual o impacto no neurodesenvolvimento infantil

Introdução: A musicoembriologia engloba a audição de música durante a gravidez, com o objetivo de melhorar a relação materno-fetal e o neurodesenvolvimento infantil. Contudo, a relação entre estes ainda não está bem estabelecida, pelo que permanece um tema controverso. Objetivo: Rever a evidência disponível sobre o impacto da audição de música durante a gravidez no neurodesenvolvimento infantil. Material e Métodos: Pesquisa de meta-análises (MA), revisões sistemáticas (RS), ensaios clínicos aleatorizados e contro- lados (ECAC), e normas de orientação clinica (NOC), em inglês e português, publicados entre 01/2004 e 04/2014, nas bases de dados Pubmed/Medline, sítios de medicina baseada na evidência e Índex de Revistas Médicas Portuguesas, utilizando os termos MeSH: music; pregnancy; child; neurodevelopment. Para a avaliação dos níveis de evidência (NE) e atribuição de forças de recomendação (FR) foi utilizada a escala SORT (Strength of Recommendation Taxonomy) da American Family Phisician. Resultados: Foram encontrados onze artigos, dos quais quatro foram selecionados: três ECAC e uma RS. Um ECAC (NE 1) mostrou melhoria significativa do comportamento neonatal nas crianças cujas mães ouviram música durante a gravidez. Outro ECAC (NE 2) demonstrou uma melhoria da relação ma- terno-fetal com a musicoembriologia. Outro ECAC (NE3) e a RS (FR B) demonstraram que o ambiente intrauterino é importante no neurodesenvolvimento neonatal, sobretudo no desenvolvi- mento do córtex cerebral motor e neurosensorial. Conclusões: A evidência disponível demonstrou que a au- dição de música durante o período embrionário apresenta benefício no neurodesenvolvimento infantil. (FR B) No entanto os estudos obtidos são em número reduzido e apresentam grande heterogeneidade em termos metodológicos. São necessários mais estudos, com populações controladas e metodologia semelhantes, para a recomendação global desta medida.

Dor abdominal em adolescente

Doente do sexo feminino de 16 anos de idade, recorreu ao serviço de urgência por dor abdominal com duas semanas de evolução localizada à fossa ilíaca esquerda (FIE) associada a obstipação. Negava atividade sexual, referindo último cataménio três semanas antes. Apresentava palpação abdominal dolo- rosa na FIE, sem defesa ou sinais de irritação peritoneal. Estudo analítico inicial e exame sumário de urina normais. Ecografia abdomino-pélvica revelou quisto complexo na região anexial esquerda e ascite de médio volume. Foi doseada a hormona gonadotrofina coriónica sérica que foi positiva (2608 mUI/mL). A ecografia transvaginal revelou quisto simples com área adjacente de aspeto reticular, não evidenciando qualquer imagem de saco gestacional intrauterino. Foi submetida a laparotomia exploradora, constatando-se hemoperitoneu e gravidez ectópica tubar esquerda e efetuada salpingectomia esquerda. Os autores pretendem alertar para uma causa rara de dor abdominal na adolescência, que deverá ser considerada de for- ma a evitar um desfecho potencialmente fatal.

Anthropometric characteristics and the burden of altered nutritional status among neuropsychiatric patients at Zomba Mental Hospital in Zomba, Malawi

Objective To determine the prevalence of overnutrition and undernutrition among neuropsychiatric inpatients and outpatients at Zomba Mental Hospital in Zomba, Malawi. Methods In this analytical cross-sectional study (n = 239), data were collected from psychiatric patients who were either inpatients (n = 181) or outpatients (n = 58) at Zomba Mental Hospital, which is the largest mental health facility in Malawi. Information was collected about patient demographics, anthropometric data, dietary information, and tobacco and alcohol use, among other variables. Data were entered and analysed in SPSS 16.0 (SPSS Inc., Chicago, IL, USA). Means were generated and compared between male and female patients, and between inpatients and outpatients. Results The study recruited 158 male and 81 female patients, with mean ages of 31.24 ± 11.85 years and 33.08 ± 15.18 years (p = 0.328), respectively. Male patients were significantly taller (165.27 ± 7.25 cm) than female patients (155.30 ± 6.56 cm) (p < 0.001); were significantly heavier than females (60.02 ± 10.56 kg versus 55.64 ± 10.53 kg); and had a significantly lower mean body mass index (BMI) than females (21.87 ± 3.21 vs. 23.01 ± 3.78) (p = 0.016). Overweight and obese patients comprised 17.6% of the participants, and 8.8% were underweight. There were no significant differences in the prevalence of overweight, obesity, and underweight between male and female participants, or between inpatients and outpatients. Conclusion Our study—the first one of its kind in Malawi—characterised the anthropometry of neuropsychiatric patients at a major metal health facility in Malawi, and has shown a high proportion of overweight patients and a notable presence of underweight patients among them. Being overweight or obese is a risk factor for metabolic disorders. Being underweight may aggravate mental illness or disturb the effect of medication. There is need, therefore, to include nutrition screening and therapeutic or supplementary feeding as part of a comprehensive care and treatment plan for neuropsychiatric patients.

National survey of the portuguese elderly nutritional status : study protocol

© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Should I choose an IUD?

This brochure discusses the IUD. It covers such topics as: What is an IUD? ; How do hormonal IUDs work? ; Why should I choose an IUD? ; How do non-hormonal IUDs work? ; How is the IUD put in? ; How will the IUD affect my period? ; What other birth control methods can I choose from?

¿Debería escoger un dispositivo intrauterino (DIU)?

This brochure printed in Spanish discusses the IUD. It covers such topics as: What is an IUD? ; How do hormonal IUDs work? ; Why should I choose an IUD? ; How do non-hormonal IUDs work? ; How is the IUD put in? ; How will the IUD affect my period? ; What other birth control methods can I choose from?

Validación de curvas antropométricas de crecimiento intrauterino: Hospital Vicente Corral, Cuenca, Ecuador, 2013

Se realizó un estudio transversal en el Hospital Vicente Corral de Cuenca (Ecuador) en febrero-agosto de 2013, para la valoración de las curvas intrauterino del Centro Latinoamericano de Atención Perinatal (CLAP), Olsen, Alarcón-Pittaluga, Lubchenco-Bataglia y Babson-Benda con el objetivo de identificar el patrón antropométrico de crecimiento fetal más adecuado para la clasificación de los recién nacidos hasta que el Ecuador cuente con patrones propios. La muestra se conformó con neonatos, cuyas madres eran menores de 21 años. Se incluyó a niños nacidos vivos, con edad gestacional entre 22 y 42 semanas cumplidas y que contaron con todas las medidas antropométricas. Se excluyó a niños con malformaciones congénitas mayores. Se valoraron la sensibilidad, especificidad e índice kappa de Cohen de las curvas antropométricas estudiadas según las variables peso, talla, perímetro cefálico y sexo del recién nacido. Las curvas del CLAP (36.6-43.5%) y de Olsen (37.0-40.9%) identificaron porcentajes similares de PEG15. Las curvas de Babson-Benda detectaron muy pocos PEG (1.3-2.8%). Para la variable peso: las curvas de Olsen presentaron alta sensibilidad (81.8-97.6%), muy altas especificidad (91.8-97.5%) e índice kappa (0.807-0.873). Las curvas de Alarcón-Pittaluga tuvieron muy buena sensibilidad (98.2-99.5%); buena especificidad (74.9-77.9%) e índice kappa (0.707-0.717). Las curvas de Lubchenco-Bataglia presentaron baja sensibilidad (40.0-42.8%), muy buena especificidad (99.3-100.0%) y moderado índice kappa (0.449-458). Las curvas de Babson-Benda presentaron muy baja sensibilidad (3.5-6.4%), muy buena especificidad (100.0%) y pobre índice kappa (0.044-0.072). Se concluye que se deben utilizar las curvas antropométricas de Olsen hasta que el Ecuador cuente con curvas propias. No se recomienda utilizar las curvas de Babson-Benda ni de Lubchenco-Bataglia.

Factors Associated With Changes in Magnesium Levels in Asymptomatic Neonates: A Longitudinal Analysis

Background: Neonates and infants with hypomagnesemia present with seizures and psychomotor delay. Objectives: The present study evaluated the changes in magnesium (Mg) levels and factors associated with these in the first three days of life. Materials and Methods: We monitored 50 clinically asymptomatic neonates; they were not given any magnesium supplements even if they had hypomagnesemia at baseline. The variables analysed were: serum Mg; gestational age; birth weight; length; and the ponderal index. We used random effects (RE) models for longitudinal analysis of these data. Results: The mean standard deviation (SD) gestational age was 36.3 (3.6) weeks and the mean (SD) weight was 2604.2 (754.4) grams. About 31% of the neonates had hypomagnesemia (< 1.6 mg/dL) on day one; however, all had normal magnesium levels by day three of life (P < 0.001). At birth, after adjusting for intrauterine growth retardation status (IUGR), serum Mg levels were lower by 0.0097 mg/dL (95% CI: -0.019 to -0.0003) per 100 grams increase in weight of the neonate. After adjusting for IUGR status, the mean increase in the serum Mg levels was 0.14 mg/dL (95% confidence intervals [CI]: 0.10 to 0.18) per day. The per-day increase in magnesium levels was significantly higher in low birth weight babies (0.10, 95% CI: 0.01 to 0.18) compared with normal birth weight babies. Conclusions: Asymptomatic neonates may have a high prevalence of hypomagnesemia; however, the levels become normal without any magnesium supplementation. Even though regular monitoring of magnesium levels is useful, no supplements are required - particularly in clinically asymptomatic neonates.

Estudo sobre a migração transuterina e a razão sexual de conceptos em bovinos da raça Nelore (Bos taurus indicus)

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Agronomia e Medicina Veterinária, 2016.

Avaliação nutricional dos idosos institucionalizados no concelho de Viseu

O envelhecimento da população, bem como a alteração da dinâmica da família, têm contribuído diretamente para o aumento do número de idosos institucionalizados. A incidência da desnutrição alcança níveis elevados nestes idosos, sendo essencial o seu diagnóstico precoce para a melhoria da sua qualidade de vida. Constitui objetivo primordial do estudo a avaliação do estado nutricional de idosos institucionalizados no concelho de Viseu, Portugal. A amostra (n=120) é constituída por idosos de ambos os sexos, institucionalizados, com idade igual ou superior a 65 anos, com capacidade para se colocar de pé, sem demência e que não sejam portadores de patologia passível de afetar a digestão, absorção ou utilização dos nutrientes. A avaliação do estado nutricional é determinada tendo em conta parâmetros antropométricos, a aplicação do e Mini Nutricional Assessment (MNA) e dietéticos, através da avaliação da ingestão alimentar (registo de 3 dias). Os questionários aplicados estão validados para a população portuguesa idosa e foram aplicados após consentimento informado. Foram realizadas estatísticas descritivas e inferenciais às diferentes variáveis, de acordo com o género e estratos etários. Considerou-se um nível de confiança de 95%. Dos 120 indivíduos estudados 30% eram do sexo masculino e 70% eram do sexo feminino. As médias das idades eram de 82,36 ± 6,34 anos. A determinação do IMC mostrou que 12,5% dos idosos avaliados exibem baixo peso (IMC 19,6±2,1); 46,7% são eutróficos (IMC 25,7±1,3); 11,7% apresentam excesso de peso (IMC 29,0±0,6), sendo 29,2% classificados como obesos (IMC 33,8±2,9).A avaliação da população pelo MNA evidenciou uma percentagem de desnutrição de 1,7% com uma prevalência de risco de desnutrição (33,3%) mas identifica 65% da amostra como bem nutrida. Os 2 instrumentos utilizados para avaliação do estado nutricional, antropometria (IMC) e MNA mostraram uma correlação estatística entre si positiva. Independentemente do género e do grupo etário verificou-se que o Valor Calórico Total (VCT) ingerido diariamente apresentava valores abaixo do recomendado. Já a ingestão diária de hidratos de carbono e de proteínas apresentou valores médios superiores às recomendações nutricionais enquanto os teores de lípidos ingeridos se situava dentro dos limites recomendados estando porém os valores da ingesta média de fibra total (18g/dia) abaixo dos indicados para a população idosa (25g/dia). Quanto aos micronutrientes encontraram-se deficits de ingestão média diária de minerais e oligoelementos como o cálcio, ferro, magnésio selénio, zinco e iodo e também de algumas vitaminas (D, E, ácido fólico). Conclui-se então que no geral a população estudada apresenta um estado de nutrição normal avaliado através de IMC e do MNA dois instrumentos que estão correlacionados entre si e se complementam. Que a ingestão alimentar apresentada pelos idosos desta amostra é apenas ligeiramente inferior ao recomendado, não colocando em risco o aparecimento de desnutrição. Porém é importante a intervenção dietética no sentido de corrigir determinadas carências (vitaminas, minerais) e prevenir o risco de desnutrição detetado assim como a obesidade.