This thesis presents quantitative tools for the metabolomic analysis of amniotic fluid (AF) using vibrational spectroscopy. A total of 300 AF samples were collected for this retrospective cohort study and both Raman and near infrared (NIR) spectra were measured. Spectral data was compressed using a Haar wavelet transform and stage-wise multilinear regression (MLR). Calibration models were calculated for glucose, lactate and uric acid concentrations in AF. Birth weight, gestational diabetes mellitus (GDM) and gestational age were classified with the resulting compressed Raman and NIR spectra, using a genetic algorithm (GA) and a cross-validation approach. Results show that both Raman and NIR spectra of AF were not able to estimate the concentrations of glucose, lactate or uric acid with high precision. However, metabolomic analysis of AF Raman and NIR spectra was capable of estimating the development of GDM, abnormal birth weights as well as gestational ages with sensitivities >75% and specificities >77%. In addition, Raman and NIR metabolomic profiles showed a statistical difference in patients delivering preterm. Of the two spectroscopic analyses studied, NIR spectroscopy of AF has the potential to become a robust and non-invasive diagnostic tool for maternal and fetal health.

Orientador: Iracema de Mattos Paranhos Calderon / Coorientador: Silvana Andréa Molina Lima / Banca: Maria Yolanda Makuch / Banca: Maria de Lourdes S. M.Ferreira / Resumo: Avaliar a qualidade de vida (QV) de gestantes portadoras de Diabetes Mellitus (DM) prévio, DM gestacional (DMG) e de Hiperglicemia Gestacional Leve (HGL). Trata-se de estudo longitudinal e prospectivo. A amostra foi constituída por 105 gestantes, sendo 66 Hiperglicêmicas (HG) e 39 Normoglicêmicas (NG). Como instrumento de avaliação foi utilizado o questionário já validado WHOQOL-BREF / AVALIAÇÃO DA QUALIDADE DE VIDA, sendo aplicado às gestantes em dois momentos: momento 1 (M1)- primeira consulta de pré-natal ou no diagnóstico da doença e momento 2 (M2) -corresponde à internação para o parto. A maioria das gestantes considerou a QV como boa no início da gestação. No final da gestação, nenhuma gestante considerou que sua QV fosse boa. A maioria das gestantes estava satisfeita com as condições de saúde. Entretanto, as gestantes NG estavam mais satisfeitas que as do grupo HG. Em relação aos domínios, no início da gestação, o grupo HG apresentou escores menores no domínio físico em relação ao grupo NG. No final da gestação, os escores dos domínios físico, psicológico e meio ambiente foram significativamente menores nas gestantes com diabete ou hiperglicemia. O estudo evidenciou que gestantes portadoras de diabete ou hiperglicemia tiveram prejuízo de aspectos determinantes da QV / Abstract: To evaluate life quality (LQ) in pregnant women with previous Diabetes Mellitus (DM) gestational DM (DMG) and Mild Gestational Hyperglycemia (MGH). It is a prospective and longitudinal study. The sample comprised 105 pregnant women, 66 Hyperglycemic (HG) and 39 Normoglicemic (NG). A validated WHOQOL-BREF / LIFE QUALITY EVALUATION questionnaire applied to pregnant women into two moments: moment 1 (M1)- first prenatal appointment or during disease diagnostic and moment 2 (M2) - corresponds to admission to delivery. Most pregnant women considered LF as good at the beginning of the gestational period. At the end of gestation none of the pregnant women considered her LQ as good. Most pregnant women were satisfied with life conditions. Therefore NG pregnant women were more satisfied than the ones in HG group. Related to areas, at the beginning of the gestational period HG group showed lower scores in physical area related to NG group. At the end of the gestational period scores of physical, psychological and environment were significant lower in diabetic pregnant women with diabetes or hyperglycemia. The study demonstrated that pregnant women with diabetes or hyperglycemia were impaired in determinant aspects of LQ / Mestre

Orientador: Steve Sol Witkin / Coorientador: Débora Cristina Damasceno / Coorientador: Iara Moreno Linhares / Banca: Marilza Vieira Cunha Rudge / Banca: Gustavo Tadeu Volpato / Resumo: Não disponível / Abstract: Embryo implantation and formation of a functional placenta are essential steps for the establishment of pregnancy, survival and development of the embryo and the fetus in the intrauterine environment. Among the various factors involved in embryo-fetal development, heat shock proteins (hsp) play a central role. These proteins function as molecular chaperones and have a highly conserved amino acid sequence, being essential for survival of all organisms from bacteria to plants and mammals. The hsp are essential for cellular survival, thus it is understandable that hsp have gained considerable interest in almost every medical field including reproduction, immunology and infectious diseases. Recent studies have reported the involvement of hsp in various stages of embryonic and fetal development, from formation of the male and female gametes until parturition. Further studies are needed to elucidate the mechanisms by which hsp influence reproductive processes. The purpose of this review is to present and discuss the involvement of hsp on embryonic and fetal development / Mestre

Orientador: Marilza Vieira Cunha Rudge / Coorientador: Angélica Mércia Pascon Barbosa / Banca: Rodrigo Castro / Banca: Cláudia Rainho / Resumo: Não disponível / Abstract: Not available / Mestre

Orientador: Marilza Vieira Cunha Rudge / Coorientador: Angélica Mércia Pascon Barbosa / Coorientador: Débora Cristina Damasceno / Banca: Maeli Dal Pai / Banca: José Tadeu Nunes Tamanini / Resumo: Não disponível / Abstract: Not available / Mestre

Orientador: Marilza Vieira Cunha Rudge / Coorientador: Steven Sol Witkin / Banca: Debora Cristina Damasceno / Banca: Carlos Antonio Negrato / Resumo: O diabete gestacional (DMG) e a hiperglicemia gestacional leve têm consequências importantes para a mãe e o recém-nascido. Gestantes portadoras de hiperglicemia gestacional leve (HGL) não atingem os critérios diagnósticos para DMG, porém, os recém-nascidos apresentam macrossomia mediada pela glicemia, mesma mortalidade perinatal e resultados perinatais adversos semelhantes ao das DMG. Estudos relatam que as atividades das proteínas de choque térmico (Heat Shock Proteins- hsp) são relevantes para relacionar com as doenças maternas. A família das hsp consiste de diversas proteínas, altamente conservadas durante a evolução. O objetivo do presente estudo foi estudar os níveis de hsp 60, hsp70 e seus respectivos anticorpos no soro materno entre 24-28 semanas e 34-38 semanas de gestação e 6 semanas pós parto em 208 mulheres normoglicêmicas (ND), 121 mulheres com hiperglicemia gestacional leve, 55 mulheres com diabete gestacional e 178 mulheres com overt diabetes. Níveis de hsp60, hsp70, anti-HSP60 e anti-HSP70 foram quantificados através da técnica de ELISA. hsp60 e hsp70 estão diminuídos nos três grupos hiperglicêmicos em cada momento estudado quando comparados com as concentrações do grupo controle. No grupo ND, mas não nos grupos hiperglicêmicos, níveis de hsp60 aumentaram, e níveis de hsp70 diminuíram. Níveis de anti-HSP60 foram similares entre os grupos enquanto níveis de anti-HSP70 foram menores nos três grupos hiperglicêmicos em comparação ao grupo ND durante a gestação, mas não no pós parto. Como conclusão, concentrações circulantes de hsp60 e hsp70 estão diminuídas em mulheres hiperglicêmicas durante a gestação, independente do grau de hiperglicemia, quando comparado com mulheres normoglicêmicas. Outros estudos serão necessários para entender os mecanismos responsáveis por estas alterações nos níveis de hsp60 e hsp70 na hiperglicemia e as consequências na gestação / Abstract: Objective The aim of the present study was to compare serum levels of heat shock proteins (hsp) 60, hsp70 and their respective antibodies in maternal serum. Research design and methods In maternal serum at 24-28 and 34-38 weeks gestation and at 6 weeks postpartum from 208 normoglycemic (ND) women and 121 women with mild gestational hyperglycemia (MGH), 55 with gestational diabetes (GDM) and 178 with overt diabetes. hsp60, hsp70, anti-HSP60 and anti-HSP70 levels were quantitated by enzyme-linked immunosorbent assay (ELISA). Results Hsp60 and hsp70 levels were decreased in all three hyperglycemic groups at each time period compared to concentrations in the ND controls. In the ND group, but not in the hyperglycemic mothers, hsp60 levels increased, and hsp70 levels decreased with each successive sample. Anti-HSP60 levels were similar between groups while anti-HSP70 levels were lower in the three hyperglycemic groups than in the ND controls during pregnancy, but not postpartum. Conclusions Circulating hsp60 and hsp70 concentrations are decreased in hyperglycemic women during pregnancy, regardless of the degree of hyperglycemia, compared to ND women. Further studies are warranted to explore the mechanism(s) responsible for these alterations in hsp60 and hsp70 levels in hyperglycemia and consequences for pregnancy outcome / Mestre

Made available in DSpace on 2015-10-06T13:02:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-27. Added 1 bitstream(s) on 2015-10-06T13:19:22Z : No. of bitstreams: 1 000847213.pdf: 755377 bytes, checksum: f0567c34b115ec1d572fb955ce24c7da (MD5) / O objetivo deste estudo foi avaliar a qualidade de vida em gestantes diabéticas, em uso de insulina, que realizaram o acompanhamento pré-natal hospitalar ou ambulatorial no serviço especializado de diabete e gravidez. Trata-se de um estudo coorte única concorrente, desenvolvido no Centro de Investigação do Diabete Perinatal do Hospital das Clínicas da Faculdade de Medicina de Botucatu. A coleta de dados foi realizada no período de janeiro de 2011 a março de 2013, mediante aplicação de um questionário de avaliação de qualidade de vida a todas gestantes portadoras de diabete melito prévio à gestação (Tipo 1e 2) ou diabete melito gestacional, em uso de insulina, que foram submetidas a acompanhamento ambulatorial ou hospitalar. De acordo com World Health Organization Quality Of Life, adaptado para o português-WHOQOL-BREF, a maioria das gestantes dos grupos ambulatorial e hospitalar considerou a qualidade de vida como boa no início da gestação (Momento 1) e no final da gestação (Momento 2), sendo ainda maior a avaliação de qualidade de vida no grupo hospitalar. Em relação à condição de saúde, a maioria das gestantes do grupo ambulatorial estava satisfeita no início da gestação (Momento 1) e no final da gestação (Momento 2). Já no grupo hospitalar, apenas 36,3% (momento 1) e 33,3% (momento 2) estavam satisfeitas. Considerando os locais de atendimento, a evolução dos escores dos domínios (físico, psicológico, social e meio ambiente), nos momentos 1 e 2, não apresentaram diferenças significativas entre si. Pode-se concluir que, neste estudo, aplicação do WHOQOL-BREF, ao longo da gestação, evidenciou que as gestantes diabéticas apresentaram boa qualidade de vida, independente do tipo de acompanhamento / The arm of this study is asssessing quality of life in diabetic pregnant women taking insulin, which conducted the hospital prenatal care or outpatient service specializing in diabetes and pregnancy. It is a single cohort competitor followed by 09 months, developed the Specialized Service of Diabetes and Pregnancy, Faculty of Medicine of Botucatu. The data collection was conducted from January 2011 to March 2013 through a questionnaire for assessing quality of life to all pregnant women with diabetes prior to pregnancy (Type 1, 2) or DMG, taking insulin, which underwent ambulatory or hospital monitoring. According World Health Organization Quality of Life in brazilian version- WHOQOL - BREF, most of the pregnant patient and hospital groups considered the quality of life as good in early pregnancy (Time 1) and at the end of pregnancy (Time 2), and further assessment of quality of life in the hospital group. Regarding health status, most mothers in the outpatient group was met at the beginning of pregnancy (Time 1) and at the end of pregnancy (Time 2). In the hospital group, only 36.3% (First moment) and 33.3% (Second moment) were satisfied. Considering the local service, the evolution of the domain scores (physical, psychological, social and environmental), at times 1 and 2, no significant differences between them. Can conclude that in this study, applying the WHOQOL-BREF, throughout gestation, showed that diabetic patients had a good quality of life independent of the type of monitoring

Made available in DSpace on 2015-12-10T14:22:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-27. Added 1 bitstream(s) on 2015-12-10T14:28:25Z : No. of bitstreams: 1 000848960_20171206.pdf: 336411 bytes, checksum: 4b13dac70d2e6e73d387371f9671281f (MD5) Bitstreams deleted on 2017-12-08T12:00:20Z: 000848960_20171206.pdf,. Added 1 bitstream(s) on 2017-12-08T12:01:09Z : No. of bitstreams: 1 000848960.pdf: 2171545 bytes, checksum: 13c2ff245dc616fb0c0c0561d9291935 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / FAPESP: 2012/25053-5

Made available in DSpace on 2015-12-10T14:23:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-26. Added 1 bitstream(s) on 2015-12-10T14:29:42Z : No. of bitstreams: 1 000848431.pdf: 1712821 bytes, checksum: 88153c25e0bdb23f2fdd66f4f09a158e (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / FAPESP: 2012/25207-4

Made available in DSpace on 2014-06-11T19:35:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-11-22Bitstream added on 2014-06-13T20:26:35Z : No. of bitstreams: 1 morceli_g_dr_botfm.pdf: 2926108 bytes, checksum: 69461ed77dc58094a09147606e52bd3f (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Not available