Biofilme subgengival, conteúdo vaginal, âmnio e parênquima placentários foram obtidos de 93 puérperas. Os periodontopatógenos (BPPG) P.g., A.a, F.n e T.f foram identificadas por PCR, corioamnionite e vilosite por histopatologia e analisados estatisticamente. Roturas de membranas (22,2%), cesáreas (65,6%), pretermo (36,6%), baixo peso (34,4%), morte perinatal (5,4%), CAM (34,4%) e vilosite (5,5%) foram observados. Periodontite agressiva (62,4%) e cáries (83,9%). Periodontite ou BPPG em qualquer sitio não se associou com maior freqüência ou com maior risco de corioamnionite ou de desfecho reprodutivo ruim. No biofilme observou-se Aa em 2 (2,1%), Fn em 16 (17,20%), Pg em 30 (32,30%) e Tf em 29 (31.2%); na vagina, Aa em 3 (3,2%), Fn em 2 (2,1%), Pg em 16 (17,2%) e Tf em 3 (3,2%); no âmnio, Fn em 4 (4,2%) e Pg em 9 (9,7%); na placenta, Fn em 1 (1,07%), Pg em 4 (4,3%) e Tf em 1 (1,1%). P.g e F.n foram observados simultaneamente: 6/30 casos de Pg na boca estavam na vagina, 3 no âmnio e 1 na placenta; dos 16 Fn na boca, 1 foi encontrado na placenta. Esta taxa de disseminação sugere que as BPPG na vagina, âmnio ou placenta não se originaram na boca das puérperas. / Subgingival biofilm and buccal samples, vaginal contents, amnion and placental parenchyma were obtained from 93 pregnant. The periodontopathogens (PPG) Pg, Aa, Fn, and Tf were identified by PCR, the diagnosis of chorioamnionitis (CAM) and villitis by histopathology methods and its relationships with adverse perinatal outcome (APO) statically analyzed. Rupture of membranes (22.2%), cesarean (65.6%), preterm (36.6%), low fetal weight (34.4%), perinatal death (5.4%), CAM (34.4%), and villitis (5.5%) were observed. Aggressive periodontitis (62,4%), and 83.9% had caries. Periodontitis or PPG (Aa, Fn, Pg, and Tf) in any site not associated with greater frequency or at greater risk of CAM or APO. In the subgingival biofilm Aa was observed in 2 (2.1%), Fn in 16 (17.20%), Pg in 30 (32.30%) and Tf in 29 (31.2%); in the vagina, 3 in Aa (3.2%), Fn 2 (2.1), Pg 16 (17.2%) and Tf 3 (3.2%); amnion, Fn in 4 (4.2%) and Pg 9 (9.7%); in the placenta, Fn 1 (1.07%), Pg 4 (4.3%) and Tf 1 (1.1%). Only Fn and Pg were observed simultaneously: 30 mothers with Pg in the mouth, 6 were detected in the vagina, 3 in amnion and 1 in the placenta; Fn 16 with the mouth, 1 was found in the placenta. This low rate of spread suggests that most of periodontopathogens present in vagina, amnion or placenta did not belong to the pregnant mouth.

Orientadora: Claudia Regina Bonini-Domingos / Banca: Ana Cristina Silva Pinto / Banca: Maria Stella Figueiredo / Banca: Flávia Cristina Rodrigues Lisoni / Banca: Marília de Freitas Calmon / Resumo: Níveis elevados de Hb F na vida adulta podem apresentar efeitos benéficos para indivíduos com anemia falciforme e talassemia beta. Dentre os elementos genéticos que atuam na regulação da expressão da Hb F são conhecidos os fatores de transcrição e os microRNAs. Os objetivos do trabalho foram rastrear, por footprinting filogenético, fatores de transcrição que apresentam sítios de ligação nas regiões não-codificantes dos genes da γ-globina, e microRNAs candidatos à regulação desses genes, além de avaliar a expressão desses microRNAs selecionados in silico em diferentes grupos de indivíduos com perfis distintos de expressão de Hb F. As análises in silico para o rastreamento dos fatores de transcrição foram realizadas comparando as sequências dos genes HBG1 e HBG2 de espécies de primatas do Velho e do Novo Mundo com as sequências da espécie Homo sapiens. O rastreamento in silico dos microRNAs preditos à regulação dos genes da γ-globina foi realizado a partir da utilização de bancos de dados públicos de microRNA. Para as análises de expressão dos microRNAs selecionados foram analisadas 38 amostras de sangue periférico, divididas em cinco grupos de estudo: grupo controle, anemia falciforme em uso ou não de hidroxiureia (HU), e talassemia beta na presença e ausência do alelo β0. Todas as amostras foram submetidas aos testes clássicos de diagnóstico de hemoglobinopatias, quantificação das frações de globinas por cromatografia e análise molecular para a genotipagem dos indivíduos com anemia falciforme (PCR-RFLP) e talassemia beta (PCR-AE e sequenciamento genômico), além da caracterização dos haplótipos βS e β-Tal (PCR-RFLP). Os reticulócitos foram isolados a partir do sangue total e submetidos à extração de microRNA. As análises de expressão dos microRNAs foram realizadas por PCR em tempo real (RT-PCR e q-PCR). As análises in silico apontaram... / Abstract: High levels of Hb F in adulthood may have beneficial effects for sickle cell anemia and beta-thalassemia. Some of the genetic elements that act in the regulation of Hb F expression are transcription factors and microRNAs. The aim of this study was to use phylogenetic footprinting to screen transcription factors that have binding sites in the γ-globin genes' noncoding regions, and miRNAs candidates to modulating Hb F levels, also evaluating the expression of microRNAs selected from in silico analyses in different groups with distinct profiles of Hb F expression. In silico analysis to screening of transcription factors were performed using bioinformatics tool VISTA, comparing the sequences of HBG1 and HBG2 genes in species of the Old and New World primates with the Homo sapiens sequences. The screening of predicted microRNAs to regulation of γ-globin genes was performed using public databases of microRNA. For the expression analyses of the selected microRNAs, we analized thirty-eight peripheral blood samples, divided into five groups: control group, sickle cell anemia using or not hydroxyurea (HU), and beta-thalassemia with and without allele β0. All samples were tested to hemoglobinopathies by classical diagnostic tests, quantification of globin fractions by chromatography and molecular analyses for genotyping of sickle cell anemia (PCR-RFLP) and beta-thalassemia (PCR-AE and genomic sequencing), and the characterization of haplotypes βS and β-Tal (PCR-RFLP). The reticulocytes were isolated from whole blood and submitted to microRNAs extraction. The analyses of the microRNAs expression were performed by real-time PCR (RT-PCR and qPCR). In silico analyses showed 13 transcription factors conserved between the analyzed species, which have binding sites in non-coding regions of both γ-globin genes, involved in regulating of the Hb F expression: BP1, CDC5, c-MYB, COUPTFII, CP2, GATA-1, GATA-2, NF-E2... / Doutor

Maternal alcohol consumption during pregnancy is a public health concern due to the possible lifelong physical and cognitive effects in offspring. Prevention of alcohol-exposed pregnancies (AEP) should begin preconceptionally, either by preventing unintended pregnancies or by discouraging alcohol consumption in women who are at-risk for pregnancy. The purpose of this dissertation is to utilize the Theory of Planned Behavior's construct of perceived behavioral control (PBC)--including perceived power and control beliefs--to guide the measurement and understanding of two behaviors related to AEP among non-pregnant women: birth control use and binge drinking. For the first specific aim--to estimate the prevalence of alcohol-exposed pregnancies--a secondary data analysis was conducted using surveillance data from North Dakota and South Dakota women who have had a child with FAS. The FAS prevalence estimates (per 1,000 live births) in both states (ND=0.8/1,000; SD=0.9/1,000) were found to be higher than that calculated from national averages (0.7/1,000) using a comparable surveillance methodology. The goal of Specific Aim 2 was to determine risk for AEP among a random group of women, while Specific Aim 3 determined the control beliefs and perceived power to using birth control and decreasing binge drinking levels, and Specific Aim 4 focused on relating PBC of these two behaviors to behavioral intentions. Data for aims 2-4 were derived from a mailed, cross-sectional survey of 190 non-pregnant women randomly chosen from an electronic health records system in the upper Midwest. Of the 190 women included in the analyses, eight (6.6%) were binge drinking while being at-risk for pregnancy (i.e., being sexually active but not always using an effective form of birth control) (Specific Aim 2). This is lower than national estimates. For Specific Aim 3, there were high direct PBC scores for both birth control and binge drinking, and there was a positive correlation between birth control direct and indirect scores (although a negative correlation between binge drinking direct and indirect scores). Finally, Specific Aim 4 uncovered high intentions to both use birth control and to not binge drink. Also, the direct birth control PBC measure was significantly associated with birth control intention when controlling for other variables, although neither PBC nor intention appeared to be associated with actual birth control behavior. For binge drinking, the intention score and the direct measure of PBC were significantly associated with one another; as well, the direct measure of PBC and intention were both significantly associated with actual binge drinking behavior. Therefore, the relationship between PBC and intention was validated for both behaviors, and the association between PBC, intention, and actual behavior was indicated for binge drinking. Overall, the study both supported and disagreed with previous research, indicating that additional research with this theory and topic matter is necessary.

Abstract available in the Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy.

The Breech Baby Study is a mixed methods study which combines qualitative and quantitative inquiry. This study explores psycho-social-cultural risk factors for breech presentation from an evolutionary perspective. The quantitative component of the study uses Florida birth certificate and Medicaid data sets from 1992-2003 to evaluate the influence of ethnicity and socio-economic status on breech presentation. Ethnicity and socio-economic status account for less than two percent of the variance of risk factors for breech presentation. The qualitative study includes 114 mothers of breech and cephalic presentation babies who completed the State Trait Personality Inventory and a socio-demographic survey. Of these, 52 mothers of cephalic presentation babies and 23 mothers of breech presentation also participated in an in-depth interview about formative life experiences and peri-conception through delivery. The primary data analysis found mothers of breech presentation babies exhibit psycho-social-cultural characteristics unlike those found in mothers of cephalic presentation babies. These characteristics include being idealistic, analytical, polished, overextended, and fearful. Mothers of cephalic presentation babies were better equipped to adapt to unexpected situations and to be pragmatic in the face of unresolvable circumstances. Mothers of breech presentation babies were further separated into two categories. One category is achievement focused woman while the other is non-present focused woman. While both sets of breech presentation mothers were idealistic, the achievement focused mothers were more likely to be analytical, polished, and overextended. In contrast, the non-present focused mothers had a history of abuse and were more likely to have an unresolved pregnancy outcome or to be fearful. Breech presentation is interpreted by attachment theory, evolutionary ecological reproductive theory, and developmental plasticity theory as a fetal strategy to adapt to the intra-uterine relationship environment and an attempt to predict the extra-uterine relationship environment.

Fetal programming is a relatively new and quickly growing field of research in the livestock industry. The concept of fetal programming is simply defined as the effects a change in maternal nutritional intake has on offspring, whether it be a genetic or physical change. The intention of this study was to specifically look at the effects of nutrient restriction of cows during the second trimester of gestation on the growth and performance of the resulting calves. In this study, thirty-two cows of predominantly angus influence from the Utah state university herd were chosen, naturally bred to a pure bred angus sire, and then allocated into two treatments: maintenance and restricted. These groups were treated uniformly for first and third trimesters of gestation, while in the second trimester, they were managed in a way that the maintenance group maintained a greater level of body condition and weight compared with the restricted group. Calf growth and performance was measured and compared for effects of fetal programming. Previous studies in beef found positive effects on carcass characteristics. However, little work has been done to ensure that fetal programming is not detrimental to calves early in life. Though this study did find that nutrient restriction resulted in more excitable cattle, no negative effects caused by programming were found in growth and performance of the offspring.

A more conservative supreme court will likely have the chance to overrule Roe v. Wade. Many states have passed heartbeat laws that will probably be taken all the way to the supreme court, these cases will ask the supreme court to affirm fetal personhood, giving fetuses a constitutionally recognized right to due process and making abortion illegal. In this thesis, I will defend an expansion of protections for pregnant peoples through a socialized right to abortion.

Fetal alcohol spectrum disorders (FASD) are caused by alcohol exposure during pregnancy and is the leading cause of mental retardation. Alcohol exposure during development results in the loss of neurons in the developing brain. The underlying molecular mechanisms are unclear and there currently is no cure for FASD. Ethanol-induced neuronal death is accompanied by neuroinflammation. Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. Using a third trimester equivalent mouse model of ethanol exposure, we found that treatment of Bindarit (MCP-1 synthesis inhibitor) and RS504393 (CCR2 antagonist) significantly reduced ethanol-induced microglia activation/neuroinflammation, and neuroapoptosis in the developing brain. Moreover, ethanol plus MCP-1 caused more neuronal death in a neuron/microglia co-culture system than neuronal culture alone, and Bindarit and RS504393 attenuated ethanol-induced neuronal death in the co-culture system. Ethanol activated TLR4 and GSK3β, two key mediators of microglial activation in the brain and cultured microglial cells (SIM-A9). Blocking MCP-1/CCR2 signaling attenuated ethanol-induced activation of TLR4 and GSK3β. Further, we determined whether knocking out of MCP-1/CCR2 ameliorates neonatal alcohol exposure-induced long-lasting behavioral deficits in adolescent and adult mice. C57BL/6 and MCP-1-/-/CCR2-/- mice were exposed to alcohol (5 g/kg) by subcutaneously injection on PD4. A series of behavioral tests including Open Field (PD 35-36 and PD 70-71), Rotor-Rod (PD 38 and PD 73), Balance Beam (PD 40 and PD75) and Morris Water Maze (PD 42 and PD77) were performed in the adolescence and adulthood. We found that MCP-1-/-/CCR2-/- mice were resistant to neonatal alcohol exposure-induced deficits in motor function in the Rotor-Rod and Balance Beam tests; MCP-1 and CCR2 deficiency also protected mice against neonatal ethanol exposure induced long lasting deficits in learning and memory in the Morris Water Maze testing. Collectively, these results suggest that MCP-1/CCR2 signaling plays an important role in ethanol-induced microglial activation/neuroinflammation and neurodegeneration in the developing brain and also plays an important role in developmental alcohol exposure induced long-lasting behavioral deficits in adolescence and adulthood.

Fetal growth restriction (FGR) is a common and potentially life-threatening complication that affects 5-10% of human pregnancies. Maternal genetic predisposition and fetal male sex are known risk factors, but the underlying mechanisms are unknown. To study a known maternal genetic risk factor and the impact of fetal sex, we employed a published transgenic (TG) mouse model, which was designed to mimic a common human angiotensinogen (AGT) promoter variant associated with a 20% increase in circulating AGT levels. We hypothesized that TG dams would deliver growth restricted pups and that the underlying mechanism would be related to differences in maternal uterine pregnancy-induced vascular remodeling, abnormal blood flow to the placenta, and placental damage. In addition, since growth restricted human males are at an increased risk of developing adult onset hypertension, which has been associated with reduced nephron development, we tested for developmental programming in our mouse model and the impact of fetal sex. Our results show that TG dams have reduced uterine and placental angiogenesis when their pups were males, but relatively normal angiogenesis in the female siblings compared with wild-type controls. The uterine placental bed in TG dams had abnormal pro-angiogenic/anti-angiogenic expression ratios that were related to differences in uterine natural killer cell activation and fetal sex. The abnormal phenotype could be rescued by delivering vascular endothelial growth factor (VEGF) to uterine endothelial cells. Male progeny from TG dams had abnormal kidney epigenetic changes, fewer nephrons as adults, and they developed stress-induced hypertension. We conclude that the combination of maternal genetic risk and fetal male sex affect uteroplacental angiogenesis leading to FGR and the programming of stress-induced hypertension.

Orientador: Doris Hissako Sumida / Banca: Carlos Antonio de Miranda Bomfim / Banca: Rossana Abud Cabrera Rosa / Resumo: A programação fetal sugere que estímulos adversos quando aplicados durante o início do desenvolvimento fetal podem alterar o metabolismo da prole, aumentando o risco de doenças na sua vida adulta. Estudos demonstraram que a doença periodontal materna em ratas promove resistência insulínica (RI) em sua prole adulta. Entretanto, estudos que investigaram os efeitos da lesão periapical (LP) materna sobre a saúde da prole são escassos. A LP é uma inflamação no ápice da raiz dental ocasionada geralmente a partir de infecção por bactérias advindas do sistema de canal radicular. Esta patologia está associada com o aumento de fator de necrose tumoral-alfa (TNF-α) que pode estimular quinase do inibidor kappa B (IKK) e c-Jun amino-terminal quinase (JNK), as quais promovem a fosforilação do substrato do receptor de insulina 1 (IRS-1) em resíduos de serina, resultando na atenuação do sinal insulínico (SI), contribuindo com a RI. Nesse contexto, tornou-se fundamental investigar se a LP materna também promove RI em sua prole adulta. Em vista disso, os objetivos deste estudo foram avaliar os efeitos da LP materna em ratas sobre as concentrações plasmáticas de glicose, insulina e TNF-α, sensibilidade à insulina e as vias insulínica e inflamatória no músculo gastrocnêmio (MG) e tecido adiposo branco periepididimal (TABp) de sua prole adulta. Para tanto, as 15 ratas Wistar (2 meses de idade) foram distribuídas em 3 grupos: 1) ratas controle; 2) ratas com uma LP induzida em primeiro molar superi... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Fetal programming suggests that adverse stimuli applied during early fetal development can alter metabolism of the offspring, increasing the risk of disease in adulthood. Studies have shown that maternal periodontal disease in rats promotes insulin resistance (IR) in their adult offspring. However, there is a scarcity of research that investigated the relationship between maternal periapical lesion (PL) and health of offspring. PL is inflammatory process around the apex of a tooth root, caused by bacterial infection of the pulp and root canal system. This pathology is associated with increased tumor necrosis factor-alpha (TNF-α) which may stimulate inhibitor of kappa B kinase (IKK) and c-Jun amino-terminal kinase (JNK), which promote phosphorylation of substrate insulin receptor 1 (IRS-1) on serine residues, resulting in insulin signal (IS) attenuation, contributing to IR. In this context, it has become essential to investigate whether maternal PL also promotes IR in their offspring. This study aimed to investigate the effects of maternal PL in rats on plasma concentrations of glucose, insulin and TNF-α, insulin sensivity and the insulin and inflammatory signaling pathways in gastrocnemius muscle (GM) and periepididimal white adipose tissue (pWAT) of their adult offspring. Fifteen female Wistar rats (2 months old) were distributed in 3 groups: 1) control rats; 2) rats with 1 PL, which was induced in the right maxillary first molar; 3) rats with 4 PL, which were induced in the... (Complete abstract click electronic access below) / Mestre