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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
91

Ätstörningens påverkan på barnet och den gravida kvinnan : en litteraturöversikt / Eating disorders impact on the child and the pregnant woman : a literature review

Tångring, Emely, Zaporozhets, Elena January 2018 (has links)
Bakgrund: Ätstörning är ett tillstånd som kännetecknas av problem med ätande, aptit och vikt. Ätstörningen kan föra med sig vissa psykiatriska tillstånd och de vanligaste är ångest, depression och personlighetsstörningar. I samband med graviditet sker förändringar som kvinnor måste anpassa sig till, bland annat viktuppgång. För kvinnor som har en pågående ätstörning eller dem med tidigare ätstörning kan anpassningsprocessen bli svårare och ätstörda beteenden från tidigare år kan komma tillbaka. Forskning visar att en del kvinnor med ätstörningar upprätthåller kompensatoriska beteenden i form av intensiv träning, restriktivt matintag, bruk av laxantia samt självframkallade kräkningar för att förhindra viktuppgång under graviditeten. Mörkertalet är stort när det gäller ätstörningar och det ses en tydlig tendens i undvikande av professionell hjälp.   Syfte: Att belysa ätstörningarnas påverkan på fostret och spädbarnet samt kvinnans fysiska och psykiska hälsa under och efter graviditet.   Metod: En litteraturöversikt där sökning av artiklar genomförts i databaserna CINAHL Complete, MEDLINE, PsycINFO och PubMed. Sjutton artiklar, publicerade 2007–2017, utgör studiens resultatdel varav fem artiklar av kvalitativ design och tolv av kvantitativ design.   Resultat: Ätstörning i samband med graviditet påverkar barnet genom ökad risk för låg födelsevikt, låg Apgar-poäng och spädbarnsdöd. En ätstörning påverkar kvinnan såväl fysiskt som psykiskt både innan och under en graviditet samt postpartum. Ätstörning har visat på fertilitetsproblem och upprepade missfall hos kvinnan. Under graviditet har kvinnor med ätstörning större risk för antepartumblödning och anemi samt komplikationer i samband med förlossning så som större behov av igångsättning och kejsarsnitt än vad kvinnor utan ätstörning har. Kvinnor med ätstörningar upplever i större omfattning känslor av självkritik och otillräcklighet som förälder då fokus ligger på den egna kroppen och inte på barnet. Ångest- och depressionssyndrom har visat sig vara vanligt förekommande under och efter graviditeten hos kvinnor med ätstörningar.   Slutsats: Denna litteraturöversikt visar att kvinnans ätstörning under en graviditet kan ha negativ påverkan på fostret och spädbarnet samt risk för ogynnsamma utfall vad gäller kvinnans fysiska och psykiska hälsa. / Background: Eating disorders are a condition characterized of problems by eating, a change in appetite and weight problems. Eating disorders can cause certain psychiatric conditions and the most common are anxiety, depression and personality disorders. During pregnancy, changes that women must adapt to includes increase in body weight. For women who have an ongoing eating disorder or those with a history of eating disorder, the adaptation process may be more difficult, and disrupting behaviours from previous years may come back. Research shows that some women with eating disorders maintain their compensatory behaviours in the form of intense training, food restriction, use of laxatives and self-induced vomiting to prevent increase of body weight during pregnancy. Estimated number of unknown cases of eating disorders are high, and there is a clear tendency to avoid seeking professional help.   Aim: The aim of this study was to highlight the effects of eating disorders on the fetus and the infant as well as the physical and mental health of women during and after pregnancy.   Methods: A literature review in which searches were conducted in the databases CINAHL Complete, MEDLINE, PsycINFO and PubMed. Seventeen scientific papers, published in 2007-2017, represent the result compilation, of which five articles have a qualitative approach and twelve have a quantitative approach.   Results: Eating disorders during pregnancy affects the child through increased risk of low birth weight, low Apgar scores and infant mortality. An eating disorder affects the woman both physically and mentally, before and during pregnancy and postpartum. Eating disorders have been shown to cause fertility problems and repeated miscarriages. During pregnancy, women with eating disorders have a greater risk of antepartum bleeding, anemia and complications such as greater need of initiation of childbirth and caesarean section than women without eating disorders. These women experience feelings of self-criticism and insufficiency as a parent since focus is on their own body and not on the child. Anxiety and depression syndromes are associated with women with eating disorders during pregnancy.   Conclusion: This literature review shows that women with eating disorders during pregnancy have a negative impact on the fetus and the infant, as well as a higher risk of unfavourable outcomes in the physical and mental health of the woman.
92

Distribution chez la souris gestante du transgène GFP introduit avec un virus adéno-associé du sérotype 9

Kelu, Ken Bisabu 23 April 2018 (has links)
La thérapie génique utilisant les vecteurs viraux est une des approches thérapeutiques possible pour le développement d’une thérapie pour les maladies génétiques mono-géniques dont l’ataxie de Friedreich (FRDA). Dans le but de vérifier l’efficacité des virus adéno-associés (AAV) à transférer la copie normale du transgène dans les tissus qu’ils infectent, nous avons insérer le gène codant pour la forme améliorée de la protéine fluorescente verte (eGFP) dans les AAV sérotype 9 (AAV9). Ces AAV recombinants (AAVr) ont été ensuite administrés aux souris femelles gestantes par voie intraveineuse et intra-péritonéale. Les résultats obtenus montrent que le transgène a été transféré à la fois dans les tissus des souris femelles ainsi que dans ceux des souriceaux. / Gene therapy using viral vectors is one of the therapeutic approaches possible for the development of genetic therapies for monogenic diseases including Friedriech's Ataxia (FRDA). In order to verify the effectiveness of adeno-associated virus (AAV) to transfer a transgene in the tissues they infect, we inserted the gene encoding the enhanced form of the green fluorescent protein (eGFP) in AAV Serotype 9 (AAV9). These recombinant AAV (rAAV) were then administered by intravenous and intraperitoneal to pregnant female mice. The results obtained show that the transgene was transferred in both in the female’ mouse tissues and in those of young mice.
93

Unique Aspects of Mammary Growth and Development in Dairy Heifers and Ewe Lambs

Boesche, Katherine E. 27 September 2011 (has links)
No description available.
94

Multiplexed Separations for New Advances in Biomarker Discovery and Tissue Metabolomic Studies

Saoi, Michelle 31 July 2019 (has links)
PhD Thesis / Metabolomics offers a systemic approach to discover clinical biomarkers for early detection of chronic diseases while also revealing underlying mechanisms relevant to human disorders of complex aetiology. Metabolomic studies in support of chronic disease prevention have focused primarily on surrogate biofluids (e.g., serum, plasma) for analysis due to their routine and less invasive sample collection in a clinical setting. However, biofluids are non-organ specific and thus are reflective of confounding biochemical processes within the body that are often difficult to interpret. As a result, it is necessary to assess metabolite changes localized within tissues since they are the direct site of pathogenic processes, in order to obtain more robust and specific biomarkers. This thesis aims to contribute to new advances in biomarker discovery and tissue metabolomic studies using multiplexed separations together with innovative data workflows based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). Chapter II introduces a high throughput yet targeted screening method for accurate quantification of serum γ‐glutamyl dipeptides from a cohort of overweight Japanese non-alcoholic steatohepatitis (NASH) patients that may allow for better risk assessment of long-term survivorship complementary to histopathology. Chapter III introduces a non-targeted metabolite profiling strategy for fasting plasma samples from prediabetic, older adults undergoing short-term step reduction (<1000 steps/day) in order to identify adaptive metabolic responses to abrupt changes in physical inactivity for early detection of sarcopenia in high-risk older persons. Chapter IV describes the first metabolomics study to characterize the human skeletal muscle metabolome from mass-restricted tissue biopsies together with matching plasma samples, which identified novel metabolic signatures associated with strenuous interval exercise, as well as treatment effects from high-dose bicarbonate pretreatment that delays the onset of muscle fatigue. Lastly, in Chapter V, metabolite coverage was expanded to include fatty acids for comprehensive characterization of murine placental tissue metabolome, which revealed sex-specific metabolic adaptations during gestation from maternal dams fed a standardized diet. In summary, this thesis contributes to new innovations in metabolomics for the discovery of novel biomarkers from blood and/or tissue specimens as required for early detection of chronic diseases relevant to population health, which were also used to validate the efficacy of therapeutic interventions based on physical activity to support healthy ageing. / Thesis / Doctor of Philosophy (PhD)
95

La vitamine B12 chez les truies nullipares en gestation : faut-il actualiser les recommandations?

Simard, Francis 17 April 2018 (has links)
La présente étude avait pour objectif d'évaluer chez des truies nullipares, pendant la gestation, l'effet de différentes concentrations alimentaires en vitamine B]2 (B12) sur le statut en B12 et le métabolisme de l'homocystéine des truies gestantes. Ainsi que l'effet de ces différentes concentrations alimentaires de B12 sur les porcelets et le lait durant la lactation, afin de déterminer une teneur optimale à utiliser. Trente-huit truies ont été assignées au hasard à l'un des 5 compléments alimentaires de B12. Les résultats suggèrent que l'apport en B12 pendant la gestation influence le transfert de cette vitamine vers le porcelet qui se fait principalement via le colostrum et le ± premier ¿ lait de la truie. En outre, l'apport en B12 requis pour maximiser le statut en B12 et minimiser la concentration d'homocystéine de la truie et de ses porcelets se situerait entre 100 et 200 ug/kg d'aliment ingéré selon le critère utilisé. Ces concentrations, largement supérieures aux recommandations actuelles du NRC, méritent d'être validées en utilisant des critères de performances de reproduction des truies et ce, sur des effectifs d'animaux beaucoup plus importants.
96

Assessment of Physiological Challenges in Overwintering Black Bears (Ursus americanus): Active Gestation, Neonatal Growth, and Skeletal Muscle Conservation

Mesa Cruz, Jose Bernardo 29 June 2018 (has links)
The American black bear (ABB) (Ursus americanus) exhibits physiological strategies highly synchronized with the environment. Such strategies enable bears to exploit food resources when available and survive the winter months by hibernating without ingesting food or water. However, there are multiple aspects of ABB hibernation physiology that remain unknown. For instance, there is conflicting evidence on the occurrence of ABB pseudopregnancy (a physiological state in which a non-pregnant bear exhibits progesterone levels similar to gravid bears in the absence of an actual pregnancy). Also, there is little known about postnatal development of cubs or the influence of maternal traits on embryonic implantation and cub growth. Finally, the role of satellite cells (SCs – stem cells able to regenerate muscle fibers) play in maintaining muscle functionality during hibernating remains understudied. Therefore, I aimed to assess these four aforementioned aspects using wild ABBs held temporarily captive at Virginia Tech's Black Bear Research Center (VT-BBRC). The major findings of this dissertation are: 1) I suggest that wild ABBs do not experience pseudopregnancy as a reproductive strategy; 2) interactions between litter size and cub age best described postnatal cub weight dynamics and organ development. Twin cubs were heavier than single and triplet cubs, yet cubs from all litter sizes reached similar weights after mothers began consuming food post hibernation. Single cubs experienced delayed timing in ear, eye, and teeth development compared to other litter sizes; 3) maternal traits such as higher body weight and higher ability to gain weight in the fall are closely associated with earlier timing of embryonic implantation than in leaner females, which gained less weight per day in the fall; and 4) SC ability to generate muscle fibers is increased during ABB hibernation. I propose that maintaining the SCs are an important potential pathway for limiting muscle atrophy during bear hibernation. Understanding pre and postnatal development of ABBs is important for exploring factors related to climate, maternal characteristics, which possibly affect birthing phenology, and fitness of bears experiencing rapid anthropogenic environmental change. Functional aspects of bear muscle conservation are interesting for potentially for elucidating avenues to improve treatments for human metabolic disorders such as muscular dystrophy, sarcopenia, and disuse atrophy. / Ph. D. / The American black bear (ABB) (Ursus americanus) exhibits physiological strategies highly synchronized with the environment. Such strategies enable bears to exploit food resources when available and survive the winter months by hibernating without ingesting food or water. However, there are multiple aspects of ABB hibernation physiology that remain unknown. For instance, there is conflicting evidence on the occurrence of false pregnancies in the ABB. Also, there is little known about postnatal development of cubs or the influence of maternal traits at the beginning of active gestation and cub growth. Finally, the role of satellite cells (SCs – stem cells able to regenerate muscle fibers) play in maintaining muscle functionality during hibernating remains understudied. Therefore, I aimed to assess these four aforementioned aspects using wild ABBs held temporarily captive at Virginia Tech’s Black Bear Research Center (VT - BBRC). The major findings of this dissertation are: 1) I suggest that wild ABBs do not experience false pregnancy as a reproductive strategy; 2) interactions between litter size and age best described postnatal cub weight dynamics and organ development. Twin cubs were heavier than single and triplet cubs, yet cubs from all litter sizes reached similar weights after mothers began consuming food post hibernation. Single cubs experienced delayed timing in ear, eye, and teeth development compared to other litter sizes; 3) maternal characteristics such as higher body weight and higher ability to gain weight in the fall are closely associated with earlier timing of embryonic implantation than in leaner females, which gained less weight per day in the fall; and 4) SC ability to generate muscle fibers is increased during ABB hibernation. I propose that maintaining the SCs are an important potential pathway for limiting muscle atrophy during bear hibernation. Understanding pre and postnatal development of ABBs is important for exploring factors related to climate, maternal characteristics, which possibly affect birthing phenology, and fitness of bears experiencing environmental change. Functional aspects of bear muscle conservation are interesting for potentially for elucidating avenues to improve treatments for human metabolic disorders such as muscular dystrophy, sarcopenia, and disuse atrophy.
97

Development of Cardiovascular Regulation in Embryos of the Domestic Fowl (Gallus Gallus), with a Partial Comparison to Embryos of the Desert Tortoise (Gopherus Agassizii)

Crossley, Dane Alan 08 1900 (has links)
In adult vertebrates, cardiovascular regulation is accomplished by numerous systems with neural, hormonal and local components responsible for the majority of regulation. These regulatory components work in concert to maintain the essential function of blood perfusion to adult tissues. Given the essential nature of this function it is therefore surprising that the development of cardiovascular regulation during gestation is poorly understood. The majority of what is known is based on a single vertebrate model, the fetal lamb. The fetal lamb has been used in multiple studies due to the clear clinical applications and has been pivotal in understanding the onset of regulation in developing vertebrates. However, study on the fetal lamb is limited to the latter 40% of gestation and has the added complication of an in-utero developmental strategy. Therefore the primary focus of this dissertation was to characterize basic cardiovascular regulation in the chicken embryo to provided the needed information for it's use an alternative to the fetal lamb. Developing chicken embryos rely on both alpha and beta adrenergic tones to maintain normal heart rate and arterial blood pressure during incubation. However, on day 21, just prior to hatch, these animals lose both tones on arterial pressure suggesting the onset of adult regulation. Cholinergic tone, however, was absent throughout chicken development indicating that it must mature during the neonatal life. Adult cardiovascular reflexes become apparent late in chicken development with a clear baroreflex specifically operating initially on day. However, an adult response to changes in ambient gas tension was absent during incubation suggesting embryos possess unique regulatory systems that are absent in adult chickens. This mechanism is comprised entirely of adrenergic systems with no cholinergic action during change in ambient gas tension. Similar developmental patterns were determined in embryos of the desert tortoise suggesting fundamental differences between in-utero and ex-utero developing vertebrates.
98

Avaliação da concentração plasmática de angiopoietina 1 e 2 na predição de pré-eclâmpsia / Pré-eclâmpsia, gestação de alto risco, angiopoietinas 1 e 2, predição

Machado, Michelle de Souza Rangel 20 August 2018 (has links)
A pré-eclâmpsia afeta 3 a 5% das gestantes em todo o mundo, contribuindo para complicações materno-fetais graves. Sendo a isquemia placentária considerada um dos fatores primordiais para o desenvolvimento da doença. Essa isquemia está associada à alterações de fatores pró e anti angiogênicos, o presente estudo avaliou os fatores pró angiogênicos angiopoetina 1 e 2 (Ang-1 e Ang-2), que atuam na formação e no crescimento de novos vasos durante a placentação. O objetivo do estudo foi avaliar as concentrações plasmática de Ang-1 e Ang-2 na predição de pré-eclâmpsia e verificar a sensibilidade e especificidade dos mesmos por meio da curva ROC. Foram avaliadas 120 gestantes com idade gestacional entre 20 e 25 semanas, que participaram do projeto Coortes BRISA, que contava com um banco de 1400 gestantes, sendo que 30 gestantes com diagnóstico de pré-eclâmpsia (PE) e que realizaram o parto no Hospital das Clínicas de Ribeirão Preto e 90 gestantes saudáveis (GS) que realizaram parto na MATER ( Maternidade do Centro de Referência da saúde da Mulher). As concentrações plasmáticas de Ang-1 e de Ang- 2 foram determinadas utilizando o método ELISA. Para a análise dos dados, foi realizado ANOVA quando comparamos os grupos quanto às variáveis quantitativas. Para as comparações dos níveis pressóricos das gestantes com pré-eclâmpsia grave x pré-eclâmpsia não grave, no momento do recrutamento e com a doença estabelecida, foi utilizado o modelo de regressão linear com efeitos mistos (efeitos aleatórios e fixos). Para as comparações dos dados foi utilizado o pós-teste por contrastes ortogonais. Na comparação das concentrações de Ang-1 entre GS e PE não houve diferença estatística entre os grupos (P= 0,185) o mesmo foi observado para Ang-2 (P= 0,583). Em relação à razão Ang-1/Ang-2, também não observamos diferença estatística (P= 0,107). A capacidade preditiva dos biomarcadores foi avaliada através da curva ROC e a área sobre a curva para Ang-1, Ang-2 e a razão Ang-1/Ang-2 foram 0,47, 0,52 e 0,57 respectivamente. Nosso estudo não encontrou diferença significativa nas concentrações de Ang-1 E Ang-2 e nem na razão entre Ang-1/Ang-2. Ao realizar a curva ROC observamos, que esses biomarcadores não são bons preditores para pré-eclâmpsia. / Preeclampsia affects 3 to 5% of pregnant women worldwide, contributing to severe maternal-fetal complications. As placental ischemia, a set of primordial factors for the development of the disease was proposed. This ischemia is associated with changes in pro and anti-angiogenic functions, the present study is angiography and angiopoietin 1 and 2 (Ang-1 and Ang-2), which act in the formation and growth of new vessels during placentation. The evaluation of the evaluation of Angio-1 and Ang-2 in the prediction of pre-eclampsia and to verify their sensitivity and specificity by means of the ROC curve. There were 20 pregnant women with gestational age between 20 and 25 weeks, who participated in the BRISA Cohorts project, which had a bank of 1400 pregnant women, 30 pregnant women diagnosed with preeclampsia (PE) and who gave birth at Hospital das Clínicas of Ribeirão Preto and 90 healthy pregnant women (GS) who performed part of MATER (Maternity of the Reference Center for Women\'s Health). Plasma Ang-1 and Ang-2 tests were already using the ELISA method. For an analysis of the data, we performed ANOVA when comparing the groups as the quantitative variables. For the comparisons of pressure levels of pregnant women with severe preeclampsia vs. non-severe preeclampsia at the moment of recruitment and with the disease installed, the linear regression model with mixed effects (random and fixed lexus) was used. For the data comparisons, the orthogonal contrasts post-test was used. When comparing the Ang-1 combinations between GS and PE, it was not possible to compare the groups (P = 0.185). The same was observed for Ang-2 (P = 0.583). In relation to the Ang-1 / Ang-2 ratio, we also did not observe the statistical difference (P = 0.107). The ability to distribute the biomarkers was evaluated through the ROC curve and the area over the curve for Ang-1, Ang-2 and the Ang-1 / Ang-2 ratio were 0.47, 0.52 and 0.57 respectively. Our needs were not as significant at Ang-1 and Ang-2 concentrations nor at the Ang-1 / Ang-2 ratio. When performing a ROC curve we observed that these biomarkers are not good predictors of preeclampsia.
99

Lipopolissacarídeo no início do período pré-natal como modelo experimental de autismo e prejuízos dopaminérgicos estriatais / Early prenatal lipopolysaccharide as a rat model of autism and striatal dopaminergic impairments

Kirsten, Thiago Berti 16 August 2012 (has links)
O transtorno do espectro autista atinge uma em cada 150 crianças. Sua etiologia ainda é desconhecida, apesar de fortes evidências de fatores genéticos e recentes achados de interferências ambientais, particularmente a ativação imune materna durante a gestação. Em nossos estudos prévios expusemos ratas Wistar no início da gestação ao lipopolissacarídeo (LPS), que mimetiza uma infecção bacteriana (100 &micro;g/kg, intraperitoneal [i.p.], no dia gestacional [GD] 9,5) e observamos prejuízos no comportamento de brincar da prole masculina. Sabendo que esse teste é classicamente usado para avaliação de modelos animais de autismo e da ligação do autismo com fatores ambientais, propusemos que nosso modelo seria um modelo animal de autismo. Para avaliar essa possibilidade, foi objetivo do presente trabalho estudar se nosso modelo de LPS pré-natal (100 &micro;g/kg, i.p., no GD 9,5) causaria os outros sintomas típicos de autistas: anormalidades na comunicação (avaliado pelo teste da vocalização ultrassônica), comportamentos repetitivos e inflexibilidade cognitiva (teste de alternação espontânea no labirinto em T), ausência de demonstração de medo em situações potencialmente perigosas (estímulo olfativo aversivo do odor de gato) e hiperatividade (atividade geral em campo aberto). Visto que alguns autistas apresentam níveis elevados de citocinas pró-inflamatórias e cortisol, bem como neuroinflamação, foram quantificados os níveis de IL-1&beta;, TNF-&alpha; e corticosterona séricos, e estudado os astrócitos e micróglia do estriado e bulbo olfatório. Outro objetivo deste trabalho foi estudar os mecanismos centrais associados ao LPS pré-natal, especialmente o sistema dopaminérgico (expressão gênica e proteica de tirosina hidroxilase e receptores dopaminérgicos D1a e D2) do estriado e bulbo olfatório, baseado nos nossos achados prévios de redução de dopamina nessas regiões cerebrais. Também foram avaliados os níveis séricos de corticosterona, o desempenho reprodutivo e o tecido placentário nas mães expostas ao LPS durante a gestação. Por fim, sabendo que o autismo é mais prevalente em homens do que em mulheres, foram avaliadas também as fêmeas expostas pré-natalmente ao LPS: comportamento de brincar, interação social adulta e níveis séricos de corticosterona. A exposição pré-natal ao LPS prejudicou a comunicação, a cognição, a demonstração de medo em situações potencialmente perigosas, além de induzir comportamentos repetitivos/restritos e elevação dos níveis de IL-1&beta; na prole masculina de ratas; as fêmeas não apresentaram os prejuízos observados nos machos. Esses achados sugerem fortemente que nosso modelo de LPS pré-natal induziu comportamentos do tipo autismo em ratos, corroborando com a hipótese dos fatores ambientais no autismo. Acrescenta de maneira inédita um modelo que mimetiza uma infecção bacteriana no início da gestação como indutor do autismo. Mais ainda, a redução da expressão proteica de tirosina hidroxilase estriatal causada pelo LPS pré-natal inclui a hipoatividade do sistema dopaminérgico estriatal como um possível aspecto para explicar o autismo. A elevação nos níveis de corticosterona, prejuízo no desempenho reprodutivo e danos no tecido placentário das ratas ajudaram no entendimento da gênese dos prejuízos na prole. O estabelecimento do modelo experimental de autismo com o LPS pré-natal significa um passo importante para o entendimento dessa desordem e pode auxiliar também na busca por eventuais tratamentos, baseados nas alterações neuroimunes encontradas. / One child in about 150 children has autism spectrum disorder. Despite strong evidence of genetic factors and recent findings of environmental interferences, particularly maternal immune activation during pregnancy, autism etiology is still unknown. In our previous study, we exposed Wistar rats in the beginning of the gestation to lipopolysaccharide (LPS, 100 &micro;g/kg, intraperitoneally [i.p.], on gestational day [GD] 9.5), which mimics a bacterial infection and observed impairments in the play behavior of male offspring. Knowing that play behavior is classically used to evaluate autism animal models and the link between autism and environmental factors, we proposed that our model would be an autism animal model. To evaluate this possibility, the aim of this study was to know whether our prenatal LPS model (100 &micro;g/kg, i.p., on GD 9.5) causes other autism typical symptoms: communication abnormalities (evaluated by the ultrasonic vocalization test), repetitive behavior and cognitive inflexibility (T-maze spontaneous alternation test), absence of fear demonstration in potentially dangerous situations (aversive exposure to cat odor test) and hyperactivity (open field general activity). Because some autistic patients presents high levels of proinflammatory cytokines and cortisol as well as neuroinflammation, we quantified IL-1&beta;, TNF-&alpha; and corticosterone serum levels, and studied astrocytes and microglia of striatum and olfactory bulb. Another objective was to study the central mechanisms associated with prenatal LPS, particularly the dopaminergic system (gene and protein expression of tyrosine hydroxylase and dopamine D1a and D2 receptors) of striatum and olfactory bulb, based on our previous findings of reduced dopamine in these brain regions. We also evaluated the corticosterone serum levels, the reproductive performance and the placental tissue of mothers exposed to LPS during pregnancy. Finally, because autism is more prevalent in men than in women, we also evaluated females prenatally exposed to LPS: play behavior, social interaction and adult corticosterone serum levels. Prenatal LPS exposure impaired communication, cognition, fear demonstration of potentially dangerous situations, induced repetitive/restricted behaviors and elevated IL-1&beta; levels of male offspring; females did not present the impairments observed in males. These findings strongly suggest that our model of prenatal LPS induced autism like behaviors in rats, corroborating the hypothesis of environmental factors in autism. It adds an unprecedented way a model that mimics a bacterial infection in early pregnancy as an inducer of autism. Moreover, the striatal tyrosine hydroxylase protein expression reduction caused by prenatal LPS includes hypoactivity of the striatal dopaminergic system as a possible aspect to explain autism. The increase in the corticosterone levels, impairment of reproductive performance and placental tissue injuries of dams helped in understanding the genesis of the offspring impairments. The importance of establishing an experimental model of autism with prenatal LPS is an extra step to better understand this disorder and may also help in the search for possible treatments, based on the observed neuroimmune changes.
100

Associação entre malária gestacional, restrição do crescimento intrauterino e baixo peso ao nascer na Amazônia extremo-ocidental brasileira. / Association between gestational malaria, intrauterine growth restriction and low birth weight in the far-western Brazilian Amazon.

Dombrowski, Jamille Gregório 01 February 2018 (has links)
A malária é uma doença parasitária grave e quando ocorre durante a gravidez é uma das principais causas de mortalidade materno-infantil, podendo apresentar como consequências anemia materna, aborto, nascimento prematuro, restrição do crescimento intrauterino e baixo peso ao nascer (BPN). A infecção por Plasmodium (P.) falciparum é reconhecida como um determinante importante de consequências sérias durante a gravidez e efeitos adversos semelhantes também foram relatados em infecções por P. vivax. A despeito de sua alta prevalência e a sua possível associação com importantes complicações durante a gravidez, os efeitos da malária para gestantes e seus conceptos ainda não estão totalmente compreendidos. Este trabalho propõe estudar as consequências da malária gestacional e sua associação com a restrição do crescimento intrauterino e baixo peso ao nascer em uma área endêmica no extremo oeste da Amazônia brasileira. Foi realizado um estudo retrospectivo e prospectivo composto por gestantes da região do Vale do Alto Juruá (Acre, Brasil), no qual foram avaliadas as consequências e a extensão do efeito da malária sobre o recém-nascido através da coleta de dados epidemiológicos e material biológico. Neste estudo, foi observado um aumento no número de partos prematuros e BPN entre os recém-nascidos das gestantes infectadas por P. vivax quando comparadas com o grupo não infectado. Em relação à infecção por P. falciparum durante a gravidez, observamos que a doença representou um fator de risco para o nascimento de neonatos com perímetro cefálico reduzido, assim como uma maior probabilidade de ocorrência de casos de microcefalia e nascimentos prematuros. Além disso, todos esses efeitos adversos estavam ligados à malária placentária, caracterizada principalmente por um aumento de agregados nucleares sinciciais e infiltrados inflamatórios, bem como um forte desequilíbrio dos fatores angiogênicos e diminuição dos níveis de leptina. Muitos estudos, realizados principalmente na África, destacam os efeitos deletérios da malária por P. falciparum no contexto materno-fetal, mas pouco se sabe sobre a malária gestacional nas áreas endêmicas da América, onde predominam as infecções por P. vivax. Nossos resultados sugerem que infecções por esta espécie estão longe de serem benignas em razão da alta incidência de lesões placentárias, baixo peso ao nascer, abortos e partos prematuro em nossa casuística. Além disso, este estudo também mostrou que a malária gestacional por P. falciparum aumentou a probabilidade de partos prematuros e a ocorrência da redução do perímetro cefálico nos recém-nascidos, o que está associado à malária placentária. Assim, o conhecimento do impacto da infecção sobre a placenta e no desenvolvimento fetal poderá trazer uma importante contribuição para o entendimento da malária gestacional, além de possibilitar o desenvolvimento de ações específicas na rotina de cuidado pré-natal. / Malaria is a severe parasitic disease that, when occurs during pregnancy, it is one of the main cause of maternal-fetal mortality leading also to maternal anemia, abortion, preterm birth, intrauterine growth restriction and low birth weight. Infections by Plasmodium (P.) falciparum are known to be detrimentally involved in poor pregnancy outcomes, effects that were also described during P. vivax infections. Despite its significant prevalence and possible association to severe complications during pregnancy, the impact of malaria in pregnant women and their children are not clearly understood. Current study aims to evaluate the consequences of malaria in pregnancy and correspondent association with intrauterine growth restriction and low birth weight in an endemic area located in the furthest west region of the Brazilian Amazon. A retrospective and prospective study was performed, accounting with pregnant women living in the region of Vale do Alto Juruá (Acre, Brazil) in which the consequences and extension of malaria effects on the newborns was evaluated through the analysis of epidemiological data and biological material. In this study, we observed an increase in the number of preterm deliveries and low birth weight among children born from pregnant women infected with P. vivax when compared to non-infected pregnant women. Regarding P. falciparum infection during pregnancy, we have noticed that this is a risk factor for newborns with reduced head circumference, also increasing the probability of occurring cases of microcephaly and preterm birth. Besides, every deleterious effect was associated with placental malaria, which is mainly characterized by an increase in the syncytial nuclear aggregates and inflammatory infiltrates, as well as by an imbalance in placental angiogenic factors and a reduction in leptin levels. Several studies mainly developed in Africa, highlight the negative effects of P. falciparum malaria in the maternal-fetal context yet, little is known about malaria in pregnancy that occurs in the endemic areas of the America where infections caused by P. vivax are predominate. Our results suggest that infections promoted by this parasite species are far from being benign as it was depicted in our cohort, which has shown high incidence of placental lesions, low birth weight, abortion and preterm delivery. Moreover, the present study has shown that malaria in pregnancy caused by P. falciparum increased the probability of preterm delivery and reduction of head circumference in newborns, which is associated to placental malaria. Therefore, knowing the impact of infection in the placenta and fetal development may bring an important contribution to the understanding of malaria in pregnancy, allowing the development of specific action that can be implemented in the routine of antenatal cares.

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