Orientador: Jose Antonio Rocha Gontijo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T13:32:34Z (GMT). No. of bitstreams: 1 Custodio_AugustoHenrique_M.pdf: 4527903 bytes, checksum: 4f67c2ab2501e1bba65a4d2cf2320dfe (MD5) Previous issue date: 2014 / Resumo: A programação fetal é um processo fisiológico que assegura, durante o desenvolvimento intrauterino, a adaptação para o mundo exterior. Ou seja, o organismo é "moldável" por estímulos durante sua formação e dependendo do insulto experimentado, existe a possibilidade de mudanças estruturais e funcionais que podem predispor o indivíduo a doenças na vida adulta. O modelo de restrição proteica, assim como outros modelos, leva a um "stress" gestacional e, segundo a hipótese de Barker, programa a prole ao desenvolvimento de doenças na vida adulta, dentre elas a hipertensão arterial. Os rins são órgãos fundamentais na manutenção do equilíbrio hemodinâmico. Mudanças morfológicas e neuroendócrinas nos rins levam a alterações hidroeletrolíticas frequentemente associadas à patogênese da hipertensão arterial. A gênese desta doença ainda não está bem descrita, por envolver alterações multifatoriais, dentre elas, modificações da atividade neural tanto central quanto periférica, que podem ser um indicativo da elevação pressórica em nosso modelo. A atividade simpática renal é um importante modulador da excreção dos eletrólitos e, quando alterada, promove maior ou menor retenção de sais, principalmente o sódio, podendo contribuir para a elevação da volemia e consequentemente da hipertensão arterial. Diversos neuropeptídeos estão envolvidos na atividade simpática renal e os níveis destes são um importante marcador na gênese da hipertensão. Dentre esses peptídeos estão a Substância P (SP), seu receptor NK1R e o Peptídeo Relacionado ao Gene da Calcitonina (CGRP). Nossos resultados mostraram redução na imunorreatividade de SP, CGRP e aumento do receptor 1 para neurocinina nos gânglios da raiz dorsal da prole de ratas submetidas à restrição proteica gestacional. Identificamos também a elevação dos níveis de CGRP na parede pélvica renal. Assim, acreditamos que haja alterações na neuromodulação da atividade aferente renal, o que pode ser um fator contribuinte para a manutenção do estado hipertensivo neste modelo experimental / Abstract: A fetal programming is a physiologic process that ensures an adaptation for external world during the intra uterine development. In this period, the organism is "moldable" by stimulus that happens during its formation, which ensures adequate phenotypes formation for different environments. Kidneys are the most important organs when it has to do with maintaining the organism hemodynamic balance and also morphological and neuroendocrine alterations, which leads to fluid and eletrolytes changes, frequently associated to arterial hypertension pathogenesis. The genesis of this disease is not well described yet. It involves multifactorial changes like the neural activity in both central as peripheral, which, in our model, may be an indicative of increased pressure. The renal sympathetic activity is an important excretion modulator of electrolytes and when amended, promotes greater or lesser retention of salts, mainly sodium, contributing to the increase in blood volume and consequently hypertension. Several neuropeptides are involved in renal sympathetic activity, and these levels are an important marker in the genesis of hypertension. Among these peptides we find substance P (SP) and its receptor NK1R, and Related Peptide Calcitonin Gene (CGRP). Our research showed reduced immunoreactivity of SP, CGRP and increased neurokinin 1 receptor in dorsal root ganglia among the offspring of rats subjected to gestational protein restriction. According to this result, we believe that there are changes in afferent renal activity neuromodulation which may be a contributing factor for maintenance of hypertension in this experimental model / Mestrado / Medicina Experimental / Mestre em Ciências

The major physiological function of the carotid body is to respond to a low partial pressure of oxygen in the systemic arterial blood. The structure and functions of the adult carotid body have been extensively investigated over the past fifteen years. However, the carotid body in children has been relatively neglected with only a handful of studies being performed. To date, no study has been undertaken to investigate the effects of intrauterine hypoxia on the carotid body of foetuses. Clinically, intrauterine growth retardation has been ascribed, amongst other causes, to placental insufficiency that results in chronic hypoxia in the fetus. Intrauterine growth retardation can be divided into two types: - Type I (symmetrical) and type II (asymmetrical). In Type II intrauterine growth retardation, growth retardation does not become clinically evident until the third trimester. There is relative brain sparing with a greater deprivation in the size of abdominal organs, such as the liver and the kidneys. Previous studies have shown that there is no correlation between volume of the carotid body and hypoxia in children. However, Heath et al. made the observation that there are three variants of chief cells (progenitor, light and dark) within the carotid body and that an increase in the relative percentage of the dark subtype is an indicator of hypoxia. Using this observation, the present study set out to test two hypotheses: Firstly, whether the carotid body is functional in utero; and secondly whether there are any objective morphological changes in the carotid bodies of fetuses that have been subjected to intrauterine growth retardation. The carotid bodies from 72 fetuses with a gestational age between thirty and forty weeks were removed from the archived autopsy material, and differential cell counts were performed of the various cells present within the carotid bodies, using haematoxylin and eosin stained sections of the carotid bodies. The cases were assigned to three groups: - I) cases that had clinical and pathological evidence of intrauterine growth retardation, 2) negative controls and 3) positive controls. The three main groups were categorised as follows: -: (1) Intrauterine growth retardation (all cases with a weight for gestational age that is below the tenth centile and a brain to liver ratio of greater than four.) (2) Negative controls (all cases in whom there is a normal weight for age, a brain to liver ratio of less than three and no histological evidence of an episode of significant hypoxia before death). (3) Positive controls (all cases in whom there was clinically significant hypoxia present before death). The groups comprised of: 20 hypoxic positive controls, 15 negative controls, and 16 test cases which had suffered from intrauterine growth retardation. The remaining 21 cases were 7 dysmorphic infants, 3 congenital infection cases (congenital syphilis) and 11 cases that fitted the negative control criteria but had suffered significant hypoxia, thus excluding them from that category. The results showed that no significant difference was present in the percentage of sustentacular cells between any of the three groups. The results of the percentage of dark chief cells were as follows: l) mean percentage of dark chief cells in the intrauterine growth retardation group was 21.1 ±10.9%. 2) mean percentage of dark chief cells in the negative controls was 12.3 ±7.3%. 3) mean percentage of dark chief cells in the positive controls was 21.2 ±9.8%. A significant difference was present between the intrauterine growth retardation cases and the negative controls p=0.013, and between the positive and negative controls p=0.006. The dark chief cell count in the intrauterine growth retardation group showed no significant difference from the positive controls. No age-related difference appeared to be present in any of the groups. The conclusions reached are: a) Clinical hypoxia correlates with morphological changes in the carotid body, manifesting as an increase in the percentage of dark chief cells. b) intrauterine growth retardation cases show similar morphological changes in the carotid body to cases that have suffered from clinical hypoxia. c) therefore, by deduction intrauterine growth retardation fetuses have probably also been exposed to significant hypoxia while in utero. d) the fact that morphological changes in response to hypoxia are occurring in the carotid bodies of fetuses is an indication that the carotid body may be functional in utero. The results of the study indicate that a dark chief cell percentage of greater than 20% indicates that the fetus has been subjected to significant hypoxia, while a percentage of less than 10% indicates that it has not. A percentage of between 10 and 20% is unhelpful in determining whether hypoxia has taken place. The results of this study indicate that histological examination of the carotid bodies in neonates suspected of intrauterine growth retardation could be a useful additional means of assessment.

No description available.

O Ferro (Fe) atua em vários processos metabólicos, principalmente do neurodesenvolvimento, cujo conteúdo corporal é ainda de difícil determinação, podendo sofrer influência de fatores como a prematuridade e o Crescimento Intrauterino Restrito (CIUR). Este estudo objetivou descrever a evolução hematológica e do conteúdo de Fe em Recém-Nascidos (RN) de Termo (T) e Pré-Termo Tardios (PT T), com e sem CIUR, em aleitamento materno exclusivo, durante os primeiros dois meses de vida, analisando a influência da prematuridade, presença de CIUR e evolução nutricional. Incluiu-se 95 RN: Grupo 1A, 25 RN PT T sem CIUR; Grupo 1B, 24 RN PT T com CIUR; Grupo 2A, 21 RN T sem CIUR e Grupo 2B, 25 RN T com CIUR. A presença de CIUR foi determinada pelo peso nascimento <P5 para a curva de Alexander. Determinou-se ao nascimento, com um e dois meses de idade: medidas antropométricas (peso, comprimento e perímetro cefálico) e Índice de Massa Corporal (IMC), Hemoglobina (Hb), Hematócrito (Ht), Reticulócitos (Ret), Volume Corpuscular Médio (VCM), Hemoglobina Corpuscular Média (HCM), Variação da Distribuição das Células Vermelhas (RDW), Capacidade de Ligação do Fe (CLFe), Saturação de Transferrina (SatTf), Fe sérico e Ferritina. As análises estatísticas basearam-se: Teste não paramétrico de Kolmogorov-Smirnov para testar normalidade. ANOVA One-Way ou Kruskall-Wallis para a análise das variáveis contínuas; Teste Exato de Fischer ou Qui-quadrado para comparação de proporções; Coeficiente de Pearson para análise de correlações. Odds Ratio e respectivos 95% Intervalos de Confiança para avaliação do risco de anemia. Significância de 5%. As medidas antropométricas e IMC evoluíram com aumento ao longo do tempo (p<0,001). Os valores hematológicos reduziramse ao longo do tempo (p<0,001). A Hb foi maior nos grupos com CIUR ao nascimento e no T sem CIUR com dois meses (p<0,001). A variação relativa da Hb entre dois meses e nascimento foi maior no PT T com CIUR e menor no T sem CIUR (p<0,001). As reservas de Fe modificaram-se em todos os grupos. A CLFe foi maior no T sem CIUR ao nascimento (p<0,001) e com um mês vida (p=0,008). O Fe foi maior no T sem CIUR ao nascimento (p<0,001) e menor no PT T com CIUR que os grupos RN T com um mês de vida (p=0,007). A ferritina não apresentou diferenças entre os grupos. A Resumo _____________________________________________________________________________________________ xxxii SatTf foi maior no T sem CIUR ao nascimento (p<0,001) e a variação relativa da SatTf superior no PT T com CIUR (p=0,001). A Hb correlacionouse com o peso em todos os grupos (p<0,001) e a Ferritina nos PT T sem CIUR (r=-0,3250; p=0,0068) e com CIUR (r=-0,3280; p=0,0063). A anemia foi mais frequente nos grupos com CIUR (90,5% PT T com CIUR e 90% T com CIUR), sendo maior entre os RN de T com CIUR em relação aos sem CIUR (OR=16,500; p=0,0013) e nos PT T com CIUR em relação aos T sem CIUR (OR=17,417; p=0,0005). Provavelmente, as diferentes evoluções das reservas de Fe e a maior redução da hemoglobina no PT T com CIUR deveram-se à influência da prematuridade e do CIUR sobre seu crescimento. O CIUR parece ser o fator mais importante no desenvolvimento de anemia em RN em aleitamento materno exclusivo, pois somente os grupos com CIUR apresentaram risco de anemia aos dois meses de idade / Iron (Fe) acts in several metabolic processes, especially neurodevelopmental ones, which body content is still the difficult access and could be influenced by factors, such as, prematurity and Intrauterine Growth Restriction (IUGR). This study aimed at describing the hematological evolution and iron body content in Term (T) and Late Pre-Term (LPT) Newborns (NB), with and without IUGR, exclusive breastfeeding, during the first two months of life, and analyzing the prematurity influence, UGR presence and nutritional evolution. 95 NB were included: Group 1A, 25 LPTNB without IUGR, Group 1B, 24 LPTNB with IUGR, Group 2A, 21 TNB without IUGR and Group 2B, 25 TNB with IUGR. The presence of IUGR was determined by birth weight <P5 of Alexander Curve. At birth, one and two months of age were determined: anthropometric measures (weight, length, cephalic circumference) and Body Mass Index (BMI), Hemoglobin (Hb), Hematocrit (Ht), Reticulocytes, mean corpuscular volume, mean corpuscular hemoglobin, red blood cells distribution width, serum Fe, ferritin, Iron Binding Capacity (IBC) and Transferrin Saturation (TfSat). Statistical analysis was based on: Kolmogorov-Smirnov Test was used to verify normality. ANOVA One-Way or Kruskal-Wallis Test for continuous variables analysis, Fisher\'s Exact Test or Chi-Square Test for Comparison of proportions, Pearson Coefficient for correlations analysis, Odds Ratio and 95% Confidence Intervals for evaluation of anemia risk, Multiple Regression Stepwise Backward and Binary Logistic Regression for risk factors of Hb and anemia analysis at two months. Significance was set at 5%. The anthropometric measures and BMI increased along the time (p<0.001) and the hematological values decreased (p<0.001). The Hb was higher in groups with IUGR at birth and in T without IUGR at 2 months (p<0.001). The relative variation between 2 months and birth was higher in LPT with IUGR and lower in T without IUGR (p<0.001). The iron stores were modified in all the groups along the time. The IBC was higher in T without IUGR at birth (p<0,001) and 1 month of life (p=0.008). The serum iron was higher in T without IUGR at birth (p<0.001) and lower in LPT with IUGR than in the T NB groups at 1 month at life (p=0.007). Ferritin levels did not differ among the groups. The TfSat levels were higher in T without IUGR at birth (p<0.001) and the relative variation of TfSat was higher in LPT with IUGR (p=0.001). The Hb correlated with weight in all the groups (p<0.001) and the Ferritin in LPT without IUGR (r=-0.3250; p=0.0068) and with IUGR (r=-0.3280; p=0.0063). The anemia was more frequent in IUGR groups (90.5% in LPT with IUGR and 90% in T with IUGR). The anemia risk was hugher in T with IUGR than in without IUGR (OR=12.37, p=0.0022) and in LPT with IUGR in relation to T without IUGR (OR=13.06, p=0.0019). The different evolutions of the iron stores and the higher reduction of Hb in LPT with IUGR could be an effect of prematurity and IUGR influence on their growth. The IUGR must be the most important anemia development factor in exclusive breastfeeding NB, because only groups with IUGR showed risk for anemia at two months of age

Orientadores: Ricardo Barini, Lourenço Sbragia Neto / Tese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas / Made available in DSpace on 2018-11-27T12:29:22Z (GMT). No. of bitstreams: 1 Bueno_MarciaPereira_D.pdf: 2898828 bytes, checksum: 2c6dcaa4a20ec185bea4b47114c30a0e (MD5) Previous issue date: 2010 / Resumo: A restrição do crescimento intrauterino (RCIU) limita o desenvolvimento fetal adequado aumentando a morbidade e mortalidades perinatais. Os mecanismos fetais adaptativos na RCIU podem desencadear alterações endócrinas e metabólicas que explicariam a ocorrência de doenças na idade adulta. O objetivo do estudo foi avaliar na RCIU experimental pela ligadura da artéria uterina se existem alterações na morfometria e histologia do fígado, intesti no e rins e se existem diferenças na expressão dos receptores de insulina, IR-(3, IRS-1, IRS-2, IGF-IR(3 no grupo de fetos submetidos à RCIU. O presente experimento foi submetido ao Comitê de Ética e Experimentação Animal da Universidade Estadual de Campinas (CEEA-UNICAMP) e aprovado como projeto de pesquisa N° 1644-1. Para realização do estudo utilizamos fetos de ratas Sprague Dawley divididos em 3 grupos. Grupo I (RCIU) - 40 fetos submetidos à ligadura da artéria uterina unilateral com 18,5 dias de gestação, Grupo II (Controle-RCIU) - 40 fetos do corno oposto ao da ligadura da artéria uterina e Grupo III (Controle Externo) - 40 fetos sem procedimento cirúrgico ou alimentar. Os resultados mostraram no modelo experimental de RCIU uma diminuição do peso corporal (PC), hepático (PH) e intestinal (PI) (p<0,01) no grupo RCIU, as relações entre PH/PC, PI/PC, PR/PC foram mantidas, fetos RC IU tem diminuição das camadas submucosas e mucosas intestinais (p<0,05); diminuição da camada cortical renal e do número de glomérulos, com aumento do volume glomerular (p<0,05). Na RCIU encontramos menor expressão hepática do IR-(3, IRS-1 e IRS-2, menor expressão do IRS-2 no intestino e rins e maior expressão do IGF-IR(3 em todos os tecidos. O modelo experimental estudado causou uma RCIU simétrica com alterações morfométricas e do metabolismo da glicose que poderiam justificar no futuro um maior risco de doenças metabólicas / Abstract: Intrauterine growth restriction (IUGR) limits appropriate fetal development increasing morbidity and perinatal mortality. Adaptive mechanisms in fetal IUGR may leave to endocrine and metabolic alterations that could explain the occurrence of diseases in adulthood. The aim of this study was to evaluate whether experimental IUGR by uterine artery ligation causes changes in morphology and histology of the liver, intestines and kidneys. We also evaluated if there were differences in the expression of insulin receptors, IR-(3, IRS-1, IRS-2, IGF-IR(3 of fetuses subjected to IUGR. This experiment was submitted to the Ethics and Animal Experimentation of the Campinas State University (UNICAMP CEEA) and was approved as a research project No. 1644-1. The study used fetuses Sprague-Dawley rats divided into 3 groups. Group I (IUGR) - 40 fetuses who underwent uterine artery ligation sided with 18.5 days of pregnancy Group II (Control-IUGR) - 40 fetuses of the horn opposite to the uterine artery ligation, and Group III (External Control) - 40 fetuses without surgery or food The results showed the experimental model of IUGR, a reduction in body weight (BW), liver (PH) and intestine (PI) (p <0.01) in IUGR, the relationship between PH/PC, PI/PC, PR/PC have been retai ned, IUGR fetuses have reduced layers of the intestinal mucosa and submucosa (p<0,05), decreased renal cortical layer and the glomerular number and increased volume rate (p<0,05). In IUGR found lower hepatic expression of IR-(3, IRS-1 and IRS-2, reduced expression of IRS-2 in the intestine and kidney and increased expression of IGF-IR(3 in all tissues. The experimental model studied caused a symmetrical IUGR with histological changes and glucose metabolism that could justify a greater risk of metabolic diseasesin the future / Doutorado / Ciencias Biomedicas / Doutor em Tocoginecologia

O Ferro (Fe) atua em vários processos metabólicos, principalmente do neurodesenvolvimento, cujo conteúdo corporal é ainda de difícil determinação, podendo sofrer influência de fatores como a prematuridade e o Crescimento Intrauterino Restrito (CIUR). Este estudo objetivou descrever a evolução hematológica e do conteúdo de Fe em Recém-Nascidos (RN) de Termo (T) e Pré-Termo Tardios (PT T), com e sem CIUR, em aleitamento materno exclusivo, durante os primeiros dois meses de vida, analisando a influência da prematuridade, presença de CIUR e evolução nutricional. Incluiu-se 95 RN: Grupo 1A, 25 RN PT T sem CIUR; Grupo 1B, 24 RN PT T com CIUR; Grupo 2A, 21 RN T sem CIUR e Grupo 2B, 25 RN T com CIUR. A presença de CIUR foi determinada pelo peso nascimento <P5 para a curva de Alexander. Determinou-se ao nascimento, com um e dois meses de idade: medidas antropométricas (peso, comprimento e perímetro cefálico) e Índice de Massa Corporal (IMC), Hemoglobina (Hb), Hematócrito (Ht), Reticulócitos (Ret), Volume Corpuscular Médio (VCM), Hemoglobina Corpuscular Média (HCM), Variação da Distribuição das Células Vermelhas (RDW), Capacidade de Ligação do Fe (CLFe), Saturação de Transferrina (SatTf), Fe sérico e Ferritina. As análises estatísticas basearam-se: Teste não paramétrico de Kolmogorov-Smirnov para testar normalidade. ANOVA One-Way ou Kruskall-Wallis para a análise das variáveis contínuas; Teste Exato de Fischer ou Qui-quadrado para comparação de proporções; Coeficiente de Pearson para análise de correlações. Odds Ratio e respectivos 95% Intervalos de Confiança para avaliação do risco de anemia. Significância de 5%. As medidas antropométricas e IMC evoluíram com aumento ao longo do tempo (p<0,001). Os valores hematológicos reduziramse ao longo do tempo (p<0,001). A Hb foi maior nos grupos com CIUR ao nascimento e no T sem CIUR com dois meses (p<0,001). A variação relativa da Hb entre dois meses e nascimento foi maior no PT T com CIUR e menor no T sem CIUR (p<0,001). As reservas de Fe modificaram-se em todos os grupos. A CLFe foi maior no T sem CIUR ao nascimento (p<0,001) e com um mês vida (p=0,008). O Fe foi maior no T sem CIUR ao nascimento (p<0,001) e menor no PT T com CIUR que os grupos RN T com um mês de vida (p=0,007). A ferritina não apresentou diferenças entre os grupos. A Resumo _____________________________________________________________________________________________ xxxii SatTf foi maior no T sem CIUR ao nascimento (p<0,001) e a variação relativa da SatTf superior no PT T com CIUR (p=0,001). A Hb correlacionouse com o peso em todos os grupos (p<0,001) e a Ferritina nos PT T sem CIUR (r=-0,3250; p=0,0068) e com CIUR (r=-0,3280; p=0,0063). A anemia foi mais frequente nos grupos com CIUR (90,5% PT T com CIUR e 90% T com CIUR), sendo maior entre os RN de T com CIUR em relação aos sem CIUR (OR=16,500; p=0,0013) e nos PT T com CIUR em relação aos T sem CIUR (OR=17,417; p=0,0005). Provavelmente, as diferentes evoluções das reservas de Fe e a maior redução da hemoglobina no PT T com CIUR deveram-se à influência da prematuridade e do CIUR sobre seu crescimento. O CIUR parece ser o fator mais importante no desenvolvimento de anemia em RN em aleitamento materno exclusivo, pois somente os grupos com CIUR apresentaram risco de anemia aos dois meses de idade / Iron (Fe) acts in several metabolic processes, especially neurodevelopmental ones, which body content is still the difficult access and could be influenced by factors, such as, prematurity and Intrauterine Growth Restriction (IUGR). This study aimed at describing the hematological evolution and iron body content in Term (T) and Late Pre-Term (LPT) Newborns (NB), with and without IUGR, exclusive breastfeeding, during the first two months of life, and analyzing the prematurity influence, UGR presence and nutritional evolution. 95 NB were included: Group 1A, 25 LPTNB without IUGR, Group 1B, 24 LPTNB with IUGR, Group 2A, 21 TNB without IUGR and Group 2B, 25 TNB with IUGR. The presence of IUGR was determined by birth weight <P5 of Alexander Curve. At birth, one and two months of age were determined: anthropometric measures (weight, length, cephalic circumference) and Body Mass Index (BMI), Hemoglobin (Hb), Hematocrit (Ht), Reticulocytes, mean corpuscular volume, mean corpuscular hemoglobin, red blood cells distribution width, serum Fe, ferritin, Iron Binding Capacity (IBC) and Transferrin Saturation (TfSat). Statistical analysis was based on: Kolmogorov-Smirnov Test was used to verify normality. ANOVA One-Way or Kruskal-Wallis Test for continuous variables analysis, Fisher\'s Exact Test or Chi-Square Test for Comparison of proportions, Pearson Coefficient for correlations analysis, Odds Ratio and 95% Confidence Intervals for evaluation of anemia risk, Multiple Regression Stepwise Backward and Binary Logistic Regression for risk factors of Hb and anemia analysis at two months. Significance was set at 5%. The anthropometric measures and BMI increased along the time (p<0.001) and the hematological values decreased (p<0.001). The Hb was higher in groups with IUGR at birth and in T without IUGR at 2 months (p<0.001). The relative variation between 2 months and birth was higher in LPT with IUGR and lower in T without IUGR (p<0.001). The iron stores were modified in all the groups along the time. The IBC was higher in T without IUGR at birth (p<0,001) and 1 month of life (p=0.008). The serum iron was higher in T without IUGR at birth (p<0.001) and lower in LPT with IUGR than in the T NB groups at 1 month at life (p=0.007). Ferritin levels did not differ among the groups. The TfSat levels were higher in T without IUGR at birth (p<0.001) and the relative variation of TfSat was higher in LPT with IUGR (p=0.001). The Hb correlated with weight in all the groups (p<0.001) and the Ferritin in LPT without IUGR (r=-0.3250; p=0.0068) and with IUGR (r=-0.3280; p=0.0063). The anemia was more frequent in IUGR groups (90.5% in LPT with IUGR and 90% in T with IUGR). The anemia risk was hugher in T with IUGR than in without IUGR (OR=12.37, p=0.0022) and in LPT with IUGR in relation to T without IUGR (OR=13.06, p=0.0019). The different evolutions of the iron stores and the higher reduction of Hb in LPT with IUGR could be an effect of prematurity and IUGR influence on their growth. The IUGR must be the most important anemia development factor in exclusive breastfeeding NB, because only groups with IUGR showed risk for anemia at two months of age

Abstract not available

Objective. Most biomarker studies of maternal smoking have been based on a single blood or urinary cotinine value, which is inadequate in capturing maternal tobacco exposure over the entire pregnancy. This thesis used maternal hair biomarkers to investigate the association between maternal active and passive smoking, and birthweight for gestational age (BW for GA). / Methods. Subjects were 444 term controls drawn from 5,337 participants of a multi-centre nested case-control study of preterm birth in Montreal. Maternal hair, collected after delivery, was measured for average nicotine and cotinine concentration across the pregnancy, assuming hair growth of 1 cm/month. The BW for GA z-score used Canadian population-based standards. Multiple linear regression was used to assess effects on the z-score, after controlling for potential confounders. / Results. In regression models for maternal active smoking analysis, the addition of hair nicotine to models containing either self-report or hair cotinine or both self-report and cotinine explained significantly more variance in the BW for GA z-score (p=0.009, p=0.017, and p=0.033, respectively). In maternal passive smoking analysis, no significant effect of ETS on BW for GA was found using hair biomarkers. / Conclusion. These results indicate that hair biomarkers are sensitive tools capable of predicting reductions in birthweight for maternal active smoking. The stronger results obtained for nicotine are reflective of the fact that hair nicotine is a better measure of maternal smoking, but it could also suggest that nicotine plays an aetiologic role in affecting foetal growth.

A world-wide series of epidemiological studies has demonstrated that there is an association between being born small and the risk of visceral obesity, a more central deposition of subcutaneous fat and insulin resistance in adult life. In the lamb, intrauterine growth restriction (IUGR) results in a low birth weight and an increased visceral fat mass by 45d of postnatal life. In this thesis I have investigated the effect of IUGR on adipose tissue development and function during fetal and early postnatal life in the sheep. IUGR was induced by removal of the majority of endometrial caruncles in non pregnant ewes prior to mating which resulted in the subsequent placental restriction of fetal growth (PR). Fetal blood samples were collected from 116d gestation and visceral perirenal adipose tissue (PAT) collected from PR and control fetuses at 145d. In lambs IUGR was defined as a birth weight less than 2 standard deviations below the mean of a cohort of singleton Merino lambs. Blood samples were collected throughout the first 3 weeks of life and PAT and subcutaneous adipose tissue (SAT) was collected at 21 d. It was determined whether IUGR alters the expression of genes which regulate adipogenesis (IGF1, IGFR1, IGF2, IGFR2, PPARy, and RXRα), adipocyte metabolism (LPL, G3PDH, GAPDH) and adipokine signalling (leptin, adiponectin) in adipose tissue depots before and after birth using qRT-PCR. PR fetuses were hypoglycaemic, hypoinsulinaemic, hypoxic, and had a lower body weight than Control fetuses. The expression of both IGF1 and leptin mRNA in PAT, the major fetal adipose depot, was lower in the PR fetuses, although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus restriction of placental and hence fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue which may alter the functional development of the perirenal fat depot and contribute to altered leptin signalling in the growth restricted newborn and the subsequent emergence of an increased visceral adiposity. At 21d of postnatal life there was no increase in the relative mass of perirenal or subcutaneous fat in IUGR lambs compared with controls. Thus, this study has investigated the effect of IUGR on the development of adipose tissue prior to the development of an obese phenotype. At 21d of life there was a sex specific effect of IUGR on the expression of PPARy and leptin mRNA in perirenal visceral fat such that PPARy and leptin mRNA expression was decreased in male IUGR lambs, but not females. Interestingly PAT mass was greater in females than males, independent of birth weight. Plasma insulin concentrations during the first 24h after birth predicted the size of the adipocytes and expression of adiponectin in visceral adipose tissue in both males and females at 21d. Thus, the nutritional environment before, and immediately after birth, may program adipocyte growth and gene expression in visceral adipose tissue. The differential effect of sex and birth weight on PPARy and leptin expression in visceral fat may be important in the subsequent development of visceral obesity and the insulin resistant phenotype in later life. At 21d of life there was no difference between Control and IUGR lambs in the relative mass of subcutaneous fat, or the expression of PPARy, RXRα, leptin, adiponectin, LPL, G3PDH, and GAPDH in subcutaneous fat at 21d of life. We have shown that the growth of the subcutaneous fat depot is related to plasma glucose, insulin and leptin concentrations, and to the development of perirenal fat. Thus, in contrast to perirenal adipose tissue, the postnatal, but not the fetal nutritional environment, programs subcutaneous adipocyte growth and gene expression. This thesis speculates that there may be a factor secreted from visceral fat that influences the development of the subcutaneous fat depot. At 21d of life there was also an effect of sex, but not IUGR, on the expression of IGF mRNA in adipose tissue. Male lambs had a higher expression of IGF1 mRNA in both PAT and SAT, and a higher expression of IGF1R and IGF2R in SAT compared with female lambs. It is likely that these differences in IGF mRNA levels reflect sexual dimorphism of the GH-IGF axis. When male and female lambs were combined there was a higher expression of IGF1 mRNA in SAT compared with PAT, and a higher expression of IGF2, IGF1R and IGF2R mRNA in PAT compared with SAT. These differences in IGF mRNA expression provide a potential mechanism to explain the sex and depot specific variations in mitogenic potency of IGF1 and proliferative capacities of preadipocytes, the regional variation in adipocyte metabolism, and the difference in incidence of visceral obesity between men and women in adult life. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1347421 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

A world-wide series of epidemiological studies has demonstrated that there is an association between being born small and the risk of visceral obesity, a more central deposition of subcutaneous fat and insulin resistance in adult life. In the lamb, intrauterine growth restriction (IUGR) results in a low birth weight and an increased visceral fat mass by 45d of postnatal life. In this thesis I have investigated the effect of IUGR on adipose tissue development and function during fetal and early postnatal life in the sheep. IUGR was induced by removal of the majority of endometrial caruncles in non pregnant ewes prior to mating which resulted in the subsequent placental restriction of fetal growth (PR). Fetal blood samples were collected from 116d gestation and visceral perirenal adipose tissue (PAT) collected from PR and control fetuses at 145d. In lambs IUGR was defined as a birth weight less than 2 standard deviations below the mean of a cohort of singleton Merino lambs. Blood samples were collected throughout the first 3 weeks of life and PAT and subcutaneous adipose tissue (SAT) was collected at 21 d. It was determined whether IUGR alters the expression of genes which regulate adipogenesis (IGF1, IGFR1, IGF2, IGFR2, PPARy, and RXRα), adipocyte metabolism (LPL, G3PDH, GAPDH) and adipokine signalling (leptin, adiponectin) in adipose tissue depots before and after birth using qRT-PCR. PR fetuses were hypoglycaemic, hypoinsulinaemic, hypoxic, and had a lower body weight than Control fetuses. The expression of both IGF1 and leptin mRNA in PAT, the major fetal adipose depot, was lower in the PR fetuses, although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus restriction of placental and hence fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue which may alter the functional development of the perirenal fat depot and contribute to altered leptin signalling in the growth restricted newborn and the subsequent emergence of an increased visceral adiposity. At 21d of postnatal life there was no increase in the relative mass of perirenal or subcutaneous fat in IUGR lambs compared with controls. Thus, this study has investigated the effect of IUGR on the development of adipose tissue prior to the development of an obese phenotype. At 21d of life there was a sex specific effect of IUGR on the expression of PPARy and leptin mRNA in perirenal visceral fat such that PPARy and leptin mRNA expression was decreased in male IUGR lambs, but not females. Interestingly PAT mass was greater in females than males, independent of birth weight. Plasma insulin concentrations during the first 24h after birth predicted the size of the adipocytes and expression of adiponectin in visceral adipose tissue in both males and females at 21d. Thus, the nutritional environment before, and immediately after birth, may program adipocyte growth and gene expression in visceral adipose tissue. The differential effect of sex and birth weight on PPARy and leptin expression in visceral fat may be important in the subsequent development of visceral obesity and the insulin resistant phenotype in later life. At 21d of life there was no difference between Control and IUGR lambs in the relative mass of subcutaneous fat, or the expression of PPARy, RXRα, leptin, adiponectin, LPL, G3PDH, and GAPDH in subcutaneous fat at 21d of life. We have shown that the growth of the subcutaneous fat depot is related to plasma glucose, insulin and leptin concentrations, and to the development of perirenal fat. Thus, in contrast to perirenal adipose tissue, the postnatal, but not the fetal nutritional environment, programs subcutaneous adipocyte growth and gene expression. This thesis speculates that there may be a factor secreted from visceral fat that influences the development of the subcutaneous fat depot. At 21d of life there was also an effect of sex, but not IUGR, on the expression of IGF mRNA in adipose tissue. Male lambs had a higher expression of IGF1 mRNA in both PAT and SAT, and a higher expression of IGF1R and IGF2R in SAT compared with female lambs. It is likely that these differences in IGF mRNA levels reflect sexual dimorphism of the GH-IGF axis. When male and female lambs were combined there was a higher expression of IGF1 mRNA in SAT compared with PAT, and a higher expression of IGF2, IGF1R and IGF2R mRNA in PAT compared with SAT. These differences in IGF mRNA expression provide a potential mechanism to explain the sex and depot specific variations in mitogenic potency of IGF1 and proliferative capacities of preadipocytes, the regional variation in adipocyte metabolism, and the difference in incidence of visceral obesity between men and women in adult life. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1347421 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008