Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-07-21T17:17:47Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE_ODAIR_ALVES_DA_SILVA.pdf: 1601962 bytes, checksum: cdb9375b159cc555ab4b9ead73e8a061 (MD5) / Made available in DSpace on 2016-07-21T17:17:47Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE_ODAIR_ALVES_DA_SILVA.pdf: 1601962 bytes, checksum: cdb9375b159cc555ab4b9ead73e8a061 (MD5) Previous issue date: 2015-02-27 / Capes / Introdução: O diabetes gestacional é um estado patológico que aumenta a incidência de complicações tanto para a mãe quanto para o feto. Dessa forma, a prole exposta a um ambiente fetal adverso pode apresentar susceptibilidade a doenças crônicas mais tarde na vida adulta, incluindo anormalidades cardiovasculares e metabólicas, as quais, aumentam o risco de morte prematura. No presente estudo, foram avaliados parâmetros metabólicos, biométricos e cardiovasculares em três idades diferentes na prole de ratas com diabetes mellitus. Métodos: O diabetes foi induzido em ratas Wistar ao dia 7 de gestação através de uma dose única de estreptozotocina (50 mg/kg) administrada por via intraperitoneal. A prole de mães controles (OC) e de mães diabéticas (OD) foi avaliada em três idades diferentes: 6, 12 ou 18 meses. A glicemia de jejum, o crescimento e a composição corporal foram avaliados. A pressão arterial basal e a função cardíaca foram avaliadas em ratos conscientes (por cateterismo arterial e ventricular). A função cardíaca também foi avaliada in vitro (através do experimento de coração isolado). A resposta barorreflexa à fenilefrina (FEN) ou nitroprussiato de sódio (NPS) foi determinada pelo método de regressão linear. A Influência simpática e parassimpática sobre o coração foi avaliada por bloqueio autonômico. O índice de hipertrofia ventricular foi determinado pelo peso seco dos ventrículos em relação ao peso do corpo. Resultados: A glicemia de jejum, a pressão arterial média e o tônus simpático estiveram elevados nos ratos OD com 12 (OD12) e com 18 meses de idade (OD18), quando comparados com os ratos OC de mesma idade. Os animais do grupo OD também mostraram deficiência no controle barorreflexo da frequência cardíaca, com menor resposta taquicárdica e inotrópica após administração de NPS. O efeito bradicárdico evocado pela FEN esteve também reduzido no grupo OD18. Durante a avaliação da função cardíaca in vivo, foi observado uma menor pressão sistólica do ventrículo esquerdo e uma menor +dP/dT nos ratos OD18, mostrando disfunção sistólica. Em todos os grupos OD foi observada alta pressão diastólica final do ventrículo esquerdo e baixo -dP/dT, mostrando uma disfunção diastólica. Todos os ratos do grupo OD também apresentaram índice elevado de hipertrofia ventricular e diminuição do peso relativo dos rins. Além disso, os ratos OD com mais de 12 meses apresentaram maior acúmulo de gordura abdominal e diminuição da sensibilidade cardíaca ao isoproterenol. Conclusões: O presente estudo demonstra que o diabetes gestacional pode induzir ao aparecimento de hiperglicemia, hipertensão e insuficiência cardíaca em idade mais avançada da prole, o que são fatores de risco importantes para a morte prematura. Portanto, é de extrema importância um controle glicêmico ideal na gravidez diabética como chave para prevenir doenças cardiovasculares na idade mais avançada da prole. / Introduction: The Gestational diabetes is a condition that increases the incidence of complications for mother and fetus. Thus, the offspring exposed to an adverse fetal environment can present susceptibility to chronic diseases later in adulthood, including cardiovascular and metabolic abnormalities, which increase the risk of premature death. In the present study, we evaluated the metabolic, biometric and cardiovascular parameters in three different ages of rats from diabetic mothers. Methods: Diabetes was induced in female Wistar rats at day 7 of gestation with a single dose of STZ (50 mg / kg). The offspring from controls mothers (OC) and diabetic mothers (OD) was evaluated at three different ages: 6, 12 or 18 months. Fasting glucose, growth and body composition were evaluated. Cardiac function was assessed in conscious rats (ventricular catheterization) and in vitro (in the isolated heart experiment). The baroreflex response to phenylephrine (PHE) or sodium nitroprusside (SNP) was determined by linear regression. Sympathetic and parasympathetic influences on the heart were evaluated by autonomic blockade. The ventricular hypertrophy index was determined by dry weight of the ventricles. Results: Fasting glucose, mean blood pressure and sympathetic tone was elevated in OD rats with 12 (OD12) and 18 months (OD18) compared with age-matched OC rats. The OD subgroups showed baroreflex impairment, with lower tachycardic and inotropic response after administration of SNP. The bradycardic evoked by PHE was also reduced in OD18 group. During the evaluation of cardiac function in vivo, was observed a lower systolic pressure and lower +dP/dt in OD18 rats, showing a systolic dysfunction. All OD groups showed high end-diastolic pressure in the left ventricle and low -dP/dT, showing a diastolic dysfunction. These rats also presented ventricular hypertrophy and lower relative kidney weight. The OD rats over 12 months showed greater accumulation of abdominal fat than controls. The isolated hearts of OD12 and OD18 showed a decreased sensitivity to isoproterenol. Conclusions: This study demonstrates that gestational diabetes may induces hyperglycemia, hypertension and heart failure in older offspring, which are important risk factors for premature death. Therefore, it is of utmost importance optimal glycemic control in diabetic pregnancy as key to preventing cardiovascular disease in older offspring.

Maternal obesity has significant consequences on the lifelong health of the developing child and rising global incidences make it one of the most common comorbidities during pregnancy. Offspring of obese mothers are at an increased risk of hospitalization for respiratory infections throughout childhood, which predispose these children to non-communicable respiratory diseases in later life. Animal models of maternal high fat diet (mHFD) feeding have observed common inflammatory outcomes with obesogenic models, but the effect on offspring varies with timing of the nutritional challenge and diet composition across studies. These studies demonstrate significant alterations to circulating and lung specific immune cells but the sequence of events that link maternal diet to these fetal outcomes are unclear, nor have they been tested in the context of a bacterial respiratory infection. Streptococcus pneumonaie is the most common causative pathogen of bacterial pneumonia and meningitis, making it of high clinical relevance. We aimed to investigate the effect of a mHFD (45% kcal from fat) during gestation and lactation, on offspring outcome and recovery from Streptococcus pneumoniae infection. Immunophenotyping, both before and after infection, revealed a hypo-inflammatory phenotype in circulating monocytes of the mHFD offspring with a decreased capacity to both initiate and terminate inflammatory responses. These offspring had significantly higher bacterial counts in lung tissues during infection and sustained cellular inflammation in survivors. In this thesis, we present foundational work on the detrimental influence of excess maternal nutrition on offspring immune function and infection outcomes, which may be involved in susceptibility to inflammatory and chronic disease in later life. A better understanding of this deep and lasting influence of the maternal environment will allow us to target preconception health as a form of harm reduction, informing stake holders and institutions to direct efforts towards DOHaD knowledge translation. / Thesis / Master of Science (MSc)

Fêmeas Wistar foram alimentadas durante o período gestacional e a primeira metade da lactação (10 primeiros dias de lactação) com dieta normoprotéica (19 g proteína / Kg dieta) (grupo NP) e dieta restrita em proteínas (5 g proteína / Kg dieta) (grupo LP). Paralelamente a este esquema de alimentação, elas também receberam, diariamente, por gavagem, o óleo de peixe (Fo, rico em ácido graxo poliinsaturado- AGPi n-3). Os filhotes foram subdivididos em 4 grandes grupos: NP, NP-Fo, LP e LP-Fo, sendo acompanhados até os 6 meses de idade, data na qual ocorreu a eutanásia. No momento do sacrifício, o coração foi removido e devidamente preparado para a análise em microscopia de luz e estereologia. A partir do terceiro mês, os animais do grupo LP (ambos os gêneros) exibiram um aumento na pressão arterial sistólica (hipertensão moderada), mantendo esse comportamento até o final do experimento (6 meses de idade). No entanto, a suplementação materna com o Fo foi capaz de minimizar os efeitos da desnutrição sobre a pressão arterial. Não houve diferença significante no índice corporal entre os grupos de mães suplementadas com o Fo. O ventrículo esquerdo do grupo LP (ambos os sexos) demonstrou maior espessura quando comparado ao grupo NP (+25% nos machos, P=0,01, +22% nas fêmeas, P=0,001); entretanto, o grupo LP-Fo manifestou menor espessura quando comparado com o grupo LP (-23% nos machos, P=0,001, -12% nas fêmeas, P=0,02). Os machos do grupo LP apresentaram significativamente menor vascularização intramiocárdica quando correlacionado ao grupo NP (-50%, P=0,01), enquanto os machos do grupo LP-Fo exibiram um incremento de 89% na microcirculação, quando comparados ao grupo LP (P=0,004). Ambos os gêneros do grupo LP manifestaram maior quantidade de fibrose intersticial quando comparados ao grupo NP. Vale ressaltar que a suplementação materna de Fo foi benéfica apenas no grupo LP. Sendo assim, nossos dados sugerem claramente que a suplementação materna com Fo, durante o período perinatal, é capaz de prevenir o remodelamento cardíaco adverso e a hipertensão provocados pela restrição protéica materna in útero e na lactação, tornando-se assim uma opção não farmacológica viável para a prevenção e/ou redução dos danos ocasionados pela programação em humanos. / Female Wistar rats fed in gestation and first 10 lactation days with normal protein diet (19 g protein/kg diet) (NP group) or low-protein diet (5g protein/kg diet) (LP group), also received daily fish oil supplement (Fo, n-3 PUFA rich) during same period. Offspring put in groups NP, NP-Fo, LP, LP-Fo, until sacrifice at 6-mo-old when hearts removed, prepared for light microscopy and stereology. There was mild hypertension in both LP genders from 3- until 6 mo-old. Blood pressure affected by undernutrition was minimized by maternal Fo supplementation. In body index between groups there was no significant difference with maternal Fo supplementation. The left ventricle was thicker in both genders of LP groups compared to counterpart NP groups (+25% in male LP group, P=0.01, +22% in female LP group, P=0.001); however, less thick in LP-Fo groups compared to LP groups (-23% in male LP-Fo group, P=0.001, - 12% in female LP-Fo group, P=0.02). Male LP group offspring had significantly smaller intramyocardial microcirculation than NP group (-50%, P=0.01), while male LP-Fo group had 89% higher microcirculation than LP group (P=0.004). Both gender LP group offspring had significantly higher interstitial fibrosis compared with NP groups. The maternal Fo supplementation has beneficial effects in LP , but not in NP offspring. In conclusion, our data clearly indicate postnatal hypertension and collateral cardiovascular adverse remodeling, programmed by low-protein diet in utero and lactation was prevented by perinatal supplementation with fish oil, n-3 PUFA rich, providing a viable non-pharmacologic option for preventing and/or reducing adverse programming outcomes in human.

Fêmeas Wistar foram alimentadas durante o período gestacional e a primeira metade da lactação (10 primeiros dias de lactação) com dieta normoprotéica (19 g proteína / Kg dieta) (grupo NP) e dieta restrita em proteínas (5 g proteína / Kg dieta) (grupo LP). Paralelamente a este esquema de alimentação, elas também receberam, diariamente, por gavagem, o óleo de peixe (Fo, rico em ácido graxo poliinsaturado- AGPi n-3). Os filhotes foram subdivididos em 4 grandes grupos: NP, NP-Fo, LP e LP-Fo, sendo acompanhados até os 6 meses de idade, data na qual ocorreu a eutanásia. No momento do sacrifício, o coração foi removido e devidamente preparado para a análise em microscopia de luz e estereologia. A partir do terceiro mês, os animais do grupo LP (ambos os gêneros) exibiram um aumento na pressão arterial sistólica (hipertensão moderada), mantendo esse comportamento até o final do experimento (6 meses de idade). No entanto, a suplementação materna com o Fo foi capaz de minimizar os efeitos da desnutrição sobre a pressão arterial. Não houve diferença significante no índice corporal entre os grupos de mães suplementadas com o Fo. O ventrículo esquerdo do grupo LP (ambos os sexos) demonstrou maior espessura quando comparado ao grupo NP (+25% nos machos, P=0,01, +22% nas fêmeas, P=0,001); entretanto, o grupo LP-Fo manifestou menor espessura quando comparado com o grupo LP (-23% nos machos, P=0,001, -12% nas fêmeas, P=0,02). Os machos do grupo LP apresentaram significativamente menor vascularização intramiocárdica quando correlacionado ao grupo NP (-50%, P=0,01), enquanto os machos do grupo LP-Fo exibiram um incremento de 89% na microcirculação, quando comparados ao grupo LP (P=0,004). Ambos os gêneros do grupo LP manifestaram maior quantidade de fibrose intersticial quando comparados ao grupo NP. Vale ressaltar que a suplementação materna de Fo foi benéfica apenas no grupo LP. Sendo assim, nossos dados sugerem claramente que a suplementação materna com Fo, durante o período perinatal, é capaz de prevenir o remodelamento cardíaco adverso e a hipertensão provocados pela restrição protéica materna in útero e na lactação, tornando-se assim uma opção não farmacológica viável para a prevenção e/ou redução dos danos ocasionados pela programação em humanos. / Female Wistar rats fed in gestation and first 10 lactation days with normal protein diet (19 g protein/kg diet) (NP group) or low-protein diet (5g protein/kg diet) (LP group), also received daily fish oil supplement (Fo, n-3 PUFA rich) during same period. Offspring put in groups NP, NP-Fo, LP, LP-Fo, until sacrifice at 6-mo-old when hearts removed, prepared for light microscopy and stereology. There was mild hypertension in both LP genders from 3- until 6 mo-old. Blood pressure affected by undernutrition was minimized by maternal Fo supplementation. In body index between groups there was no significant difference with maternal Fo supplementation. The left ventricle was thicker in both genders of LP groups compared to counterpart NP groups (+25% in male LP group, P=0.01, +22% in female LP group, P=0.001); however, less thick in LP-Fo groups compared to LP groups (-23% in male LP-Fo group, P=0.001, - 12% in female LP-Fo group, P=0.02). Male LP group offspring had significantly smaller intramyocardial microcirculation than NP group (-50%, P=0.01), while male LP-Fo group had 89% higher microcirculation than LP group (P=0.004). Both gender LP group offspring had significantly higher interstitial fibrosis compared with NP groups. The maternal Fo supplementation has beneficial effects in LP , but not in NP offspring. In conclusion, our data clearly indicate postnatal hypertension and collateral cardiovascular adverse remodeling, programmed by low-protein diet in utero and lactation was prevented by perinatal supplementation with fish oil, n-3 PUFA rich, providing a viable non-pharmacologic option for preventing and/or reducing adverse programming outcomes in human.

Parental alcoholism is a major risk factor for their children's future alcohol abuse and dependence during adulthood. Thus, the purpose of this descriptive phenomenological study was to understand African-American adult female children's perceptions of self-worth, their lived experiences, and their quality of life as it relates to parental alcoholism. The research focus and questions were addressed by applying the conceptual framework of Bowen's family systems and Covington's self-worth theories. Semi-structured interviews were used to collect data from 8 African-American adult female children of alcoholics. Subsequent data analysis and thematic coding were employed by using Colazzi's 7-step method to ensure rigor. The key findings from this study revealed that although over half of the women in this sample experienced some form of abuse and exposure to familial discord and even violence, their self-worth was strengthened by resilience and through forgiveness of their parents and siblings. This study's implications for positive social change include helping researchers and practitioners to better understand parental alcoholism and how it could shape the experiences of offspring, especially in the African-American female ethnic group. Future interventions could be shaped by these findings, and researchers may use these study results as a platform for future work in this literature domain.

The effects of perceived mental/emotional problems (psychopathology) in the family-of-origin on adult offspring marital satisfaction was tested in a model considering the mediating variables of parental marital satisfaction, mother-child relationship quality, father-child relationship quality, and resolution of issues from the family-of-origin. The nationally representative sample (n = 802) drawn from the RELATionship Evaluation (RELATE) database included mostly college educated, lower-middle-class individuals in their first marriage. This sample was used to test a structural equation model that results showed fit the data well. Results showed that historical (distal) factors (such as psychopathology in the family-of-origin) explain only a small portion of the variance in adult offspring marital satisfaction and suggest that more contemporary (proximal) factors (such as individual characteristics) have a stronger relationship to adult offspring marital satisfaction. Results showed that 56% of the variance in achieving resolution of issues from the family-of-origin was explained by the other variables in the model with the best predictor being parental marital satisfaction. Direct, indirect, and total effects of each of the independent variables were examined. Results showed no direct effect of perceived mental/emotional problems (psychopathology) in the family-of-origin on adult offspring marital satisfaction. Only the mother-child relationship quality had a direct effect on adult offspring marital satisfaction. Clinical implications for practitioners are discussed. This study helps practitioners know how to help a client find resolution to issues stemming from perceived family-of-origin mental/emotional problems. This study also shows that focusing on current interpersonal processes and skills that may be part of achieving resolution is more likely to help a couple with marital problems than focusing on negative effects from the family-of-origin. Future research should focus on exploring the applicability of this model to different variables such as gender, race, income levels, etc. Future research models should also incorporate both historical and contemporary factors to help determine the direct effects of these variables on adult offspring relationship satisfaction.