Made available in DSpace on 2014-06-11T19:35:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-09-01Bitstream added on 2014-06-13T20:46:39Z : No. of bitstreams: 1 braganeto_ar_dr_botfm.pdf: 558985 bytes, checksum: 2d6e135d455babda4cdff06b19ed7964 (MD5) / Financiadora de Estudos e Projetos (FINEP) / Avaliar a influência do índice apoptótico e da imuno-expressão da survivina em tecido molar no prognóstico e tratamento de pacientes com mola hidatiforme completa (MHC). Estudo observacional, retrospectivo, incluindo 78 pacientes com MHC diagnosticadas, tratadas e acompanhadas no Centro de Doenças Trofoblásticas de Botucatu/SP, Brasil, entre 1995 e 2006. Baseado nas curvas de regressão da gonadotrofina coriônica, as pacientes foram divididas em dois grupos: remissão espontânea (MHC-RE - 59 pacientes) e evolução para NTG pós-molar (MHC-NTG - 19 pacientes). Avaliação imunohistoquímica do trofoblasto viloso foi realizada pela técnica da avidina-biotina-peroxidase, usando dois marcadores: anticorpo policlonal anti-caspase-3 (diluição 1:200; Cell Signaling Technology; TX, USA) e anticorpo monoclonal anti-survivina (clone 5E8; diluição 1:100; Neomarkers, TX, USA). O índice apoptótico foi expresso em porcentual (número de células caspase-3 positivas / número de células contadas x 100). A imuno-expressão da survivina foi determinada por um método semi-quantitativo. Foi significativo o efeito do índice apoptótico sobre a evolução de pacientes com MHC, de tal modo que, o aumento de 1 unidade no índice apoptótico reduziu, em média, 61% a chance de desenvolvimento de NTG pósmolar (OR = 0,61, 95% IC: 0,45-0,84). Nenhuma influência significativa da imunoexpressão da survivina foi observada no desenvolvimento de NTG pós-molar (p > 0,01; teste exato de Fisher). Não foi possível estabelecer correlações entre efeito do índice apoptótico e da imuno-expressão da survivina e variáveis do tratamento. Nesse estudo, o índice apoptótico foi bom preditor do desenvolvimento de NTG depois de MHC, com potencial para ser usado como biomarcador prognóstico dessa doença. Ao contrário, a imuno-expressão... / To assess the influence of the apoptotic index and survivin expression of molar tissue on the prognosis and treatment of patients with complete hydatidiform mole (CHM). This retrospective observational study included 78 patients with CHM, who were diagnosed, treated and followed up in the Center of Trophoblastic Diseases, Botucatu/SP, Brazil, between 1995 and 2006. Based on chorionic gonadotrophin regression curves, patients were divided into two groups: spontaneous remission (CHM-RE - 59 patients) and post-molar GTN (CHM-NTG - 19 patients). Immunohistochemical analysis of the villous trophoblast was perfomed by avidin-biotin-peroxidase, using anti-caspase-3 polyclonal antibodies (1:200; Cell Signaling Technology; TX, USA) and anti-survivin monoclonal antibodies (clone 5E8; 1:100; Neomarkers, TX, USA). The apoptotic index was expressed in percent (number of caspase-3-positive cells / number of cells counted x 100). Survivin immuno-expression was determined by a semiquantitative method. The influence of the apoptotic index on the prognosis of patients with CHM was significant. A 1-unit increase in the apoptotic index represented an average 61% reduction in the chance of developing post-molar GTN (OR = 0.61, 95% CI: 0.45-0.84). No significant influence of survivin immuno-expression was observed on the development of post-molar GTN (p > 0.01; Fisher’s exact test). No correlations of treatment variables with apoptotic index or survivin immunoexpression were found. In this study, the apoptotic index was a good predictor of GTN development after CHM and may be a useful prognostic biomarker of this disease. On the other hand, survivin immuno-expression in the villous trophoblast had no influence on the development of post-molar GTN.

No description available.

Preterm labour is one of the leading causes of perinatal mortality and morbidity. Most premature babies die before the age of five, and if they survive they face a high risk of disabilities and impairments. SP-A and SP-D are pattern recognition, innate immune molecules that are responsible for the maintenance of pulmonary immunity and surfactant homeostasis. They have been localised in the human reproductive tract and implicated in pregnancy and the initiation of labour. We hypothesised that SP-A and SP-D could play an active role in the activation of the myometrium and the timing of parturition. In this study we investigated the effects of the recombinant forms of SP-A and SP-D (rhSP-A and rhSP-D) on contractile events in the myometrium. We validated the expression of surfactant proteins A and D in the in vitro model of myometrium cell line, ULTR, using qPCR, immunofluorescence and ImageStream technology. We demonstrate that rhSP-A and rhSP-D treatments led to an increase in cell motility and had an effect on the contractile response of ULTR cells when grown on collagen matrices showing reduced surface area. We studied this effect further by measuring the expression of contraction-associated protein genes. rhSP-A and rhSP-D led to an increase in the expression of oxytocin receptor and connexin 43. We reported that both rhSP-A and rhSP-D induce the secretion of pro-inflammatory cytokines, such as IL-6 and IL-8. We also propose a new model for functional progesterone withdrawal showing a cross-talk between progesterone (including non-genomic effects) and SP-A. Emerging evidence has linked shredding of the uterine wall with ovarian cancer cases, suggestive of an interaction between myometrium and ovaries. We investigated the effects of rhSP-D in ovarian cancer in vitro using SKOV3 cells as a model. Conditioned media from ULTRs treated with rhSP-D resulted in growth arrest of SKOV3. We also demonstrated that rhSP-D led to a decrease in cell motility and cell proliferation in these cells. This was followed by an inhibition of the mTOR pathway activity. We expanded on our observations by measuring expression of SP-A and SP-D in human myometrial samples as well as the expression of SP-D in human ovaries. Collectively, this study presents novel interactions of SP-A and SP-D at both myometrial and ovarian level, rendering them key molecules for conditions such as preterm labour as well as implicating them as therapeutic targets for ovarian cancer.

During normal pregnancy, the fetus is not rejected by the maternal immune system despite bearing paternal MHC antigen. It has been proposed that this is due to the local production of immunoregulatory factors by the maternal decidua. This study was designed to investigate immunosuppressive factors derived from early human decidua. In the first part of the study, assays were standardised in order to monitor the immunoregulatory activity of factors derived from human decidua. These included mitogen induced lymphocyte proliferation, mixed lymphocyte culture, and the proliferation of human monocytic and T lymphoid cell lines. Using these assays, two fractions from the FPLC separation of the 10-100 KDa crude decidual supernatant with immunosuppressive activity have been identified and partially characterised. One contained molecules of 183 KDa under non-reducing SDS-PAGE analysis, and 70 and 29 KDa under reducing conditions (large molecular weight fraction; LMWF). Another had molecules of 7-14 KDa under non-reducing conditions (small molecular weight fraction; SMWF). Both of them inhibited mitogen-induced lymphoproliferation and the mixed lymphocyte reaction. In addition they inhibited the growth of a monocytic cell line (Mono Mac 6), but not that of a T lymphoblastic cell line (Jurkat E6.1). The suppression of cellular growth by the LMWF, but not the SMWF, was due to the arrest of the cells in the G0/G1 phase of the cell cycle. Neither fraction affected the expression of MHC class II on Mono Mac 6 cells. The decidua-derived suppressive factors showed some similarity to human transforming growth factor type beta (hTGFbeta), but their activity could not be eliminated by neutralising antibodies to hTGFbeta1 and (32. In contrast to the decidua factors, hTGFbeta1 was able to significantly suppress the expression of MHC class II molecules. In addition, acidification of LMWF decreased their suppressive activity, whereas others have shown that similar treatment of TGFbeta isolated from decidua enhanced its activity. Although some similarity to human decidua-associated protein hDP200 could be demonstrated with LMWF, lgG-like molecules could not be demonstrated in the latter. A low molecular weight protein with immunosuppressive activity-PP14- has been demonstrated in human decidua. Despite similarity, the SMWF clearly showed a distinct M.w distribution pattern to PP14 when analysed by Western blot. This suggests that SMWF was not PP14. In the final part of the study, the supernatants of decidual mononuclear cell cultures (non-fractionated or fractionated) were used to investigate the cells which may produce the factors. The preliminary results suggest that non-leukocytic decidua cells are unlikely to be responsible for the activity. Either T lymphocytes or NK cells are the more likely source, as the suppressive activity was largely increased in populations enriched for these cells, and concanavalin A enhanced their suppressive activity. However, the precise cellular source of these factors needs to be elucidated further.

Research has demonstrated that prenatal exposure to antiepileptic drugs is associated with an increased risk of physical malformations. The potential risk such exposure conveys to the developing brain and therefore the later cognitive functioning of the child is now the focus of both national and international research. This thesis investigated the relationship between prenatal exposure to antiepileptic drugs and child cognitive functioning. This investigation was undertaken in three phases: a systematic review of the published literature; an original research piece investigating prenatal exposure to sodium valproate and levetiracetam and finally a critical review of the research undertaken as part of this thesis and in the wider published literature. The systematic review identified 30 studies which had investigated the cognitive abilities of children with a history of prenatal exposure to antiepileptic drugs. Methodological quality of the studies was considered against the criteria of the Newcastle Ottawa Scale. Differential findings were noted across the antiepileptic drug types, with the largest number of studies documenting increased risks associated with prenatal exposure to sodium valproate. A lack of high quality research across all antiepileptic drugs, and in particular the more recently licensed antiepileptic drugs is highlighted. In the research paper presented here children aged between five and nine years of age exposed to either levetiracetam (n=37), sodium valproate (n=40) or who were born to women with epilepsy but did not require medication (n=43) were recruited from throughout the UK. Demographic and health information was collected from prospective records and supplemented with maternal interview. Formal standardised neuropsychological assessments were undertaken to inform on the child's current level of intellectual, memory, language, attentional and executive functioning. Following adjustment for variables likely to influence child cognitive ability, prenatal exposure to sodium valproate was found to be associated with poorer intellectual and language functioning in a dose dependent manner. When stratified by dose, 57.9% of children exposed to doses of sodium valproate above 800mg daily scored below the average range for their global intellectual ability. Prenatal exposure to levetiracetam was not found to be associated with poorer cognitive functioning. The critical review highlighted a number of methodological strengths of this research, despite time and resource implications. However, consideration should be given to the retrospective nature of this cohort and the potential for recruitment bias. This thesis concludes that women who require continuation of their treatment during pregnancy to control their seizures should be counselled regarding the risks and the benefits of their treatment to allow them to make informed decisions.

Regulatory T cells (Tregs) are CD 4+ T lymphocytes with regulatory and reparative properties. Tregs are functionally and differentially controlled by Foxp3 transcription factor, and they are considered a key factor inducing feto-maternal tolerance. Disruption of this unique type of time-limited immune tolerance leads to pregnancy complications including miscarriages, intrauterine growth retardation of the fetus, and premature delivery. Tregs' production and functional properties are influenced by the cytokine environment, especially by TGF-β1, IL-2, and retinoic acid. These pleiotropic factors are involved in the differentiation of tolerogenic populations of decidual cells. In the present work, a detailed immunophenotyping of Tregs was performed, and a determination of serum concentrations of TGF-β1 during physiological pregnancy was realized. The examined subpopulations of Tregs have shown different signs or markers of their functional and maturity properties. In some subpopulations, apparent changes in Treg counts were observed during pregnancy. Moreover, typical development was observed for TGF-β1 serum levels. The main goal of the current work was an examination of differences in Treg subpopulation counts in women with premature deliveries compared to females with full term births....

Introduction: In 2012, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention expanded their recommendation for the Tdap vaccination to include the antepartum period. Regardless of immunization history, the recommendation states that medical practitioners should administer the Tdap vaccination to every pregnant woman in each occurring pregnancy (Munoz, et al., 2014; Shakib, et al., 2013; Goldfarb, Little, Brown, Riley, 2014). Methods: To describe treatment practices and uptake of Tdap vaccine, a cross-sectional descriptive survey design was utilized. The purpose of survey is to gather information regarding prevalence, distribution, and interrelations of variables within a population (Polit & Beck). In this study, the survey questionnaire was conducted in an online format. Results: Of the six HBM questions included in the study, except for question four, the results of the chi-squared analysis suggest that any single measured dimension of the HBM cannot predict a health behavior, in this case receipt of the Tdap vaccination. The population is split regarding infants' perceived susceptibility to pertussis infection. Strong agreement to the benefit of vaccination was revealed. Question six regarded available information, although the majority were satisfied a significant percentage indicated a desire for more information. Discussion: This Doctorate of Nursing Practice project developed a survey based on the Health Belief Model with the intention of assessing perceived susceptibility, perceived severity, perceived benefits and perceived barriers to the health care preventative action of receiving the Tdap vaccination in the third trimester of pregnancy. Through in-depth literature review, consideration of the updated ACIP guidelines, and support of a developed theoretical framework, an eight-question survey was developed. The data examined in this project may serve to illustrate limitations in provider care that can be immediately improved upon, such as information sharing. The primary limitation of the study is in the sample size of 44 eligible survey responses and the uniform demographics of the population. Despite these limitations, the survey design may be extended to other populations of interest, with greater demographic variation for further study.

This thesis explores fifteen women’s accounts of pregnancy over the course of gestation. It highlights the fluidity and dynamism of these women’s experiences, placing these in the context of the breadth of medical interventions they engaged with. Much existing literature concerning pregnancy focuses on specific instances of contact with medical professionals or technological interventions. This study explores the mundane and routine elements of the everyday practice of pregnancy, including during the first trimester. This is a period rarely addressed in academic literature. The thesis draws on data from in-depth interviews with women in Scotland, experiencing a continuing pregnancy for the first time. These were conducted at three points over the course of gestation. Interviews aimed to explore women’s interactions with medical interventions, their conceptualisations of the foetus, and changing experiences of embodiment. Analysis took place in several stages, incorporating three ‘readings’ of interviews and the development of a case study for each participant. This was inspired by the voice centred relational method of analysis. Themes were then identified and developed within, and between, individual women’s accounts. Participants’ narratives, particularly in early pregnancy, resonated with Rothman’s (1988) concept of the ‘tentative pregnancy’, originally developed to describe pregnancy in the wake of amniocentesis. Tentativeness emerged as a key theme characterising women’s experiences. Tentativeness was especially evident during the first trimester, largely due to women’s understanding that the risk of miscarriage was at its highest during this period. Women described managing their emotions at this time, in order to balance excitement about their wanted pregnancy with the possibility that it may end in a pregnancy loss. One aspect of this emotion work, explored in this thesis, was the effort made by women to keep their pregnancy a secret from wider family and friends for the first twelve weeks of gestation. Medical intervention and its associated technologies played a key role in both constructing pregnancy as tentative, but paradoxically, also provided a means to resolve this through reassurance. Women engaged with these interventions flexibly. In contrast to much existing literature, this thesis highlights that while contact with prenatal technologies cemented the reality of the pregnancy for some, they also had the power to add to the ambiguity of participants’ status as a ‘pregnant woman’. In later pregnancy, women’s shifting embodied experiences contributed to a reduction in tentativeness. The ability to feel definite foetal movements, coupled with medical and popular discourses of foetal viability, allowed women to feel less anxious about the safety of the pregnancy and the foetus. As a result, women reported changed interactions with health professionals and advice during the final trimester of pregnancy. This thesis, engaging with literature from sociology, science and technology studies (STS) and anthropology, makes theoretical contributions in three areas. First, its consideration of gestation over time nuances discussions of pregnancy in terms of risk. Second, this research further contributes to literature regarding pregnant embodiment, and conceptualisations of the foetus. Third, the thesis demonstrates that relationships between forms of knowledge mobilised by participants during pregnancy were complex, shifting over the course of gestation, and reflective of women’s experiences of pregnancy as tentative.

Magister Artium - MA / Globally, teenage pregnancy remains a disturbing phenomenon which impacts on the lives of teenagers, their families and society as a whole. Numerous attempts at addressing the problem have seen a decline in fertility rates but agreement still exists that the incidence of young girls bearing children is unacceptably high. Studies conducted over the years have emphasised both the causes and consequences of teenage births. Many studies too have explored the benefits of preventative strategies. Yet, despite all this, teenage pregnancy remains a cause for concern with many teenage girls remaining sexually active after a first pregnancy, and exposing themselves to subsequent pregnancies and births. This study was focused on teenage girls who had experienced unintended repeat pregnancies. Through the research a deeper understanding of the meanings that female teenagers ascribe to repeat pregnancies, were sought. A sample group of teenage mothers were allowed to take a step back from their experience of the repeat pregnancy; to think deeply about the experience, and to reflect on what they had learnt and how it has impacted on their current lives. The researcher employed a qualitative approach with a descriptive, explorative design in order to obtain a rich description of the experiences of teenage mothers who have been through a repeat pregnancy. The goal of the study was to explore and describe the reflections of these teenage mothers who had experienced unintended, repeat pregnancies. Data was obtained through semi-structured individual interviews where an interview guide was used. The data was analysed according to the steps outlined by Creswell (2009). Findings were noted and recommendations made. These recommendations are designed for role-players involved with teenagers and youth in general. Emphasis was placed on recommendations to professionals, like educators, healthcare workers and social workers who are at the coalface of dealing with teenagers who engage in sexual activity. Finally, recommendations for further research were made.

Masters of Art / Globally, teenage pregnancy remains a disturbing phenomenon which impacts on the lives of teenagers, their families and society as a whole. Numerous attempts at addressing the problem have seen a decline in fertility rates but agreement still exists that the incidence of young girls bearing children is unacceptably high. Studies conducted over the years have emphasised both the causes and consequences of teenage births. Many studies too have explored the benefits of preventative strategies. Yet, despite all this, teenage pregnancy remains a cause for concern with many teenage girls remaining sexually active after a first pregnancy, and exposing themselves to subsequent pregnancies and births. This study was focused on teenage girls who had experienced unintended repeat pregnancies. Through the research a deeper understanding of the meanings that female teenagers ascribe to repeat pregnancies, were sought. A sample group of teenage mothers were allowed to take a step back from their experience of the repeat pregnancy; to think deeply about the experience, and to reflect on what they had learnt and how it has impacted on their current lives. The researcher employed a qualitative approach with a descriptive, explorative design in order to obtain a rich description of the experiences of teenage mothers who have been through a repeat pregnancy. The goal of the study was to explore and describe the reflections of these teenage mothers who had experienced unintended, repeat pregnancies. Data was obtained through semi-structured individual interviews where an interview guide was used. The data was analysed according to the steps outlined by Creswell (2009). Findings were noted and recommendations made. These recommendations are designed for role-players involved with teenagers and youth in general. Emphasis was placed on recommendations to professionals, like educators, healthcare workers and social workers who are at the coalface of dealing with teenagers who engage in sexual activity. Finally, recommendations for further research were made.