Motivation: The prevalence of non-communicable diseases such as diabetes mellitus (DM) and cardiovascular disease (CVD) is rapidly increasing in industrialized societies. Experts believe that lifestyle, and in particular its nutritional aspects, plays a decisive role in increasing the burden of these chronic conditions. Dietary habits would, therefore, be modified to exert a positive impact on the prevention and treatment of chronic diseases of lifestyle. It is believed that the state of hyperglycaemia that is observed following food intake under certain dietary regimes contributes to the development of various metabolic conditions. This is not only true for individuals with poor glycaemic control such as some diabetics, but could also be true for healthy individuals. It would, therefore, be helpful to be able to reduce the amplitude and duration of postprandial hyperglycaemia. Selecting the correct type of carbohydrate (CHO) foods may produce less postprandial hyperglycaemia, representing a possible strategy in the prevention and treatment of chronic metabolic diseases. At the same time, a key focus of sport nutrition is the optimal amount of CHO that an athlete should consume and the optimal timing of consumption. The most important nutritional goals of the athlete are to prepare body CHO stores pre-exercise, provide energy during prolonged exercise and restore glycogen stores during the recovery period. The ultimate aim of these strategies is to maintain CHO availability to the muscle and central nervous system during prolonged moderate to high intensity exercise, since these are important factors in exercise capacity and performance. However, the type of CHO has been studied less often and with less attention to practical concerns than the amount of CHO. The glycaemic index (GI) refers to the blood glucose raising potential of CHO foods and, therefore, influences secretion of insulin. In several metabolic disorders, secretion of insulin is inadequate or impossible, leading to poor glycaemic control. It has been suggested that low GI diets could potentially contribute to a significant improvement of the conditions associated with poor glycaemic control. Insulin secretion is also important to athletes since the rate of glycogen synthesis depends on insulin due to it stimulatory effect on the activity of glycogen synthase. Objectives: Three main objectives were identified for this study. The first was to conduct a meta-analysis of the effects of the GI on markers for CHO and lipid metabolism with the emphasis on randomised controlled trials (RCT's). Secondly, a systematic review was performed to determine the strength of the body of scientific evidence from epidemiological studies combined with RCT's to encourage dieticians to incorporate the GI concept in meal planning. Finally, a systematic review of the effect of the GI in sport performance was conducted on all available literature up to date to investigate whether the application of the GI in an athlete's diet can enhance physical performance. Methodology: For the meta-analysis, the search was for randomised controlled trials with a cross-over or parallel design published in English between 1981 and 2003, investigating the effect of low GI vs high GI diets on markers of carbohydrate and lipid metabolism. The main outcomes were serum fructosamine, glycosylated haemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC) and triacylglycerols (TG). For the systematic review, epidemiological studies as well as RCT's investigating the effect of LGI vs HGI diets on markers for carbohydrate and lipid metabolism were used. For the systematic review on the effect of the GI on sport performance, RCT's with either a cross-over or parallel design that were published in English between January 1981 and September 2004 were used. All relevant manuscripts for the systematic reviews as well as meta-analysis were obtained through a literature search on relevant databases such as the Cochrane Central Register of Controlled Trials, MEDLINE (1981 to present), EMBASE, LILACS, SPORTDiscus, ScienceDirect and PubMed. This thesis is presented in the article format. Results and conclusions of the individual manuscripts: For the meta-analysis, literature searches identified 16 studies that met the strict inclusion criteria. Low GI diets significantly reduced fructosamine (p<0.05), HbA1c, (p<0.03), TC(p<0.0001) and tended to reduce LDL-c (p=0.06) compared to high GI diets. No changes were observed in HDL-c and TG concentrations. Results from this meta analysis, therefore, support the use of the GI concept in choosing CHO-containing foods to reduce TC and improve blood glucose control in diabetics. The systematic review combined the results of the preceding meta-analysis and results from epidemiological studies. Prospective epidemiological studies showed improvements in HDL-c concentrations over longer time periods with low GI diets vs. high GI diets, while the RCT's failed to show an improvement in HDL-c over the short-term. This could be attributed to the short intervention period during which the RCT's were conducted. Furthermore, epidemiological studies failed to show positive relationships between LDL-c and TC and low GI diets, while RCT's reported positive results on both these lipids with low GI diets. However, the epidemiological studies, as well as the RCT's showed positive results with low GI diets on markers of CHO metabolism. Taken together, convincing evidence from RCT's as well as epidemiological studies exists to recommend the use of low GI diets to improve markers of CHO as well as of lipid metabolism. 3 From the systematic review regarding the GI and sport performance it does not seem that low GI pre-exercise meals provide any advantages over high GI pre-exercise meals. Although low GI pre-exercise meals may better maintain CHO availability during exercise, low GI pre-exercise meals offer no added advantage over high GI meals regarding performance. Furthermore, the exaggerated metabolic responses from high GI compared to low GI CHO seems not be detrimental to exercise performance. However, athletes who experience hypoglycaemia when consuming CHO-rich feedings in the hour prior to exercise are advised to rather consume low GI pre-exercise meals. No studies have been reported on the GI during exercise. Current evidence suggests a combination of CHO with differing Gl's such as glucose (high GI), sucrose (moderate GI) and fructose (low GI) will deliver the best results in terms of exogenous CHO oxidation due to different transport mechanisms. Although no studies are conducted on the effect of the GI on short-term recovery it is speculated that high GI CHO is most effective when the recovery period is between 0-8 hours, however, evidence suggests that when the recovery period is longer (20-24 hours), the total amount of CHO is more important than the type of CHO. Conclusion: There is an important body of evidence in support of a therapeutic and preventative potential of low GI diets to improve markers for CHO and lipid metabolism. By substituting high GI CHO-rich with low GI CHO-rich foods improved overall metabolic control. In addition, these diets reduced TC, tended to improve LDL-c and might have a positive effect over the long term on HDL-c. This confirms the place for low GI diets in disease prevention and management, particularly in populations characterised by already high incidences of insulin resistance, glucose intolerance and abnormal lipid levels. For athletes it seems that low GI pre-exercise meals do not provide any advantage regarding performance over high GI pre-exercise meals. However, low GI meals can be recommended to athletes who are prone to develop hypoglycaemia after a CHO-rich meal in the hour prior to exercise. No studies have been reported on the effect of the GI during exercise. However, it has been speculated that a combination of CHO with varying Gl's deliver the best results in terms of exogenous CHO oxidation. No studies exist investigating the effect of the GI on short-term recovery, however, it is speculated that high GI CHO-rich foods are suitable when the recovery period is short (0-8 h), while the total amount rather than the type of CHO is important when the recovery period is longer (20-24 h). Therefore, the GI is a scientifically based tool to enable the selection of CHO-containing foods to improve markers for CHO and lipid metabolism as well as to help athletes to prepare optimally for competitions. Recommendations: Although a step nearer has been taken to confirm a place for the GI in human health, additional randomised, controlled, medium and long-term studies as well as more epidemiological studies are needed to investigate further the effect of low GI diets on LDL-c. HDL-c and TG. These studies are essential to investigate the effect of low GI diets on endpoints such as CVD and DM. This will also show whether low GI diets can reduce the risk of diabetic complications such as neuropathy and nephropathy. Furthermore, the public at large must be educated about the usefulness and application of the GI in meal planning. For sport nutrition, randomised controlled trials should be performed to investigate the role of the GI during exercise as well as in sports of longer duration such as cricket and tennis. More studies are needed to elucidate the short-term effect of the GI post-exercise as well as to determine the mechanism of lower glycogen storage with LGI meals post-exercise. / Thesis (Ph.D. (Dietetics))--North-West University, Potchefstroom Campus, 2005.

Background: Several previous studies have reported that dyslipidemia is associated with the risk of hypertension, but these studies are mainly conducted in European and US populations, with a very few studies in the Asian population. Moreover, the effects of atherosclerotic indices, including atherogenic coefficient (AC) and atherogenic risk of plasma (AIP), on hypertension in Asians have not been well described so far. Methods: From 2010 to 2016, altogether 211,833 Chinese adults were ultimately recruited at the health centers in 11 Chinese cities (including Shanghai, Beijing, Nanjing, Suzhou, Shenzhen, Changzhou, Chengdu, Guangzhou, Hefei, Wuhan, and Nantong). Differences in continuous variables between the two groups were analyzed by the Mann–Whitney test, while those in categorical variables were examined by the Chi-squared test. Logistic regression was applied to evaluate the association between lipid profiles and the risk of hypertension. The predictive values of AC and AIP for the incidence of hypertension were analyzed using the area under the receiver operating characteristic (ROC) curve. Meanwhile, Bayesian network (BN) models were performed to further analyze the associations between the different covariates and the incidence of hypertension. Results: A total of 117,056 participants were included in the final analysis. There were significant differences in baseline characteristics between normotension and hypertension groups (p < 0.001). In multivariate logistic regression, the risk of hypertension increased by 0.2% (1.002 [1.001–1.003]), 0.2% (1.002 [1.001–1.003]), and 0.2% (1.002 [1.001–1.003]) per 1 mg/dl increase in total cholesterol (TC), low-density lipoprotein (LDL), and non-high-density lipoprotein cholesterol (non-HDL-c), respectively. However, after adjusting for body mass index (BMI), an increase in HDL level was associated with a higher risk of hypertension (p for a trend < 0.001), and the risk of hypertension increased by 0.6% per 1 mg/dl increase in HDL-c (1.006 [1.003–1.008]). In women, AC had the highest predictive value for the incidence of hypertension with an area under the curve (AUC) of 0.667 [95% confidence interval (CI): 0.659–0.674]. BN models suggested that TC and LDL were more closely related to the incidence of hypertension. Conclusions: Overall, lipid profiles were significantly abnormal in the hypertensive population than in the normotensive population. TC and LDL were strongly associated with the incidence of hypertension. TC, LDL, and non-HDL-c levels show a positive association, HDL-c shows a negative association, while TG is not significantly associated with the risk of hypertension. After adjusting for BMI, HDL-c turns out to be positively associated with the risk of hypertension. In addition, AC has a good predictive value for the incidence of hypertension in women.

Background: Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) have been associated with higher circulating concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). ApoB is the primary apolipoprotein component of LDL-C, and acts as a ligand for LDL-C receptors in various cells throughout the body. Circulating concentrations of ApoB are considered to be a better indicator of heart disease risk than TC or LDL-C. Objectives: Explore associations of concentrations of PFOA and PFOS with serum ApoB in adults. Methods: We analyzed data from 2744, 20-80 years old participants in the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Linear regression models were used to estimate adjusted predicted means of serum ApoB (in g/L) for quartiles of PFOA and PFOS (in ng/mL) to describe patterns of associations. Results: Adjusted predicted mean concentrations of serum ApoB did not appear to vary meaningfully with increasing concentrations of PFOA (Q1 1.11, Q2 1.02, Q3 1.01, Q4 1.02) or increasing concentrations of PFOS (Q1 1.06, Q2 1.05, Q3 1.07, Q4 0.99) in study participants. Conclusions: Exposure to PFOA or PFOS does not appear to alter Apo B concentrations in adults.

Global obesity is linked to chronic diseases including hypercholesterolemia, a cardiovascular disease risk factor, thus weight reduction in obesity is a key priority for combatting obesity. The cholesterol transporters ABCG5, ABCG8 and NPC1L1 mediate cholesterol trafficking across the intestinal wall, thus are important in regulating cholesterol metabolism and circulating levels. The objective of this study was to examine if single nucleotide polymorphisms (SNP) of cholesterol transporters ABCG5, ABCG8 and NPC1L1 are associated with changes in cholesterol synthesis and absorption and lipid parameters (LP) subsequent to weight loss (WtL) in overweight individuals. Eighty-nine individuals from two WtL trials (Trial A (n = 54) and Trial B (n = 35)) completed a 20-wk WtL period. After 10% WtL, lipid parameters excluding LDL-C were improved in Trial A, while all lipid parameters were ameliorated after 12% of WtL when Trial A and B were combined. Post-WtL, cholesterol synthesis (CS) was reduced; however, cholesterol absorption was not changed in either Trial A or the combined trials. Polymorphisms in ABCG8 V632A were associated with changes in TC and TG levels after WtL in both trial A and the combined data. SNPs in ABCG5 Q604E, ABCG8 T400K, were associated with changes in CS because of WtL in Trial A; however, the association is no longer seen in combined analysis. In conclusion, cardio-protective changes in LP due to weight loss were mediated by reductions in CS. Additionally, polymorphisms in ABCG8 were associated with amelioration in LP after WtL. Thus, the benefits in CVD risk subsequent to weight loss vary across individuals due to genetic factors associated with cholesterol trafficking.

Global obesity is linked to chronic diseases including hypercholesterolemia, a cardiovascular disease risk factor, thus weight reduction in obesity is a key priority for combatting obesity. The cholesterol transporters ABCG5, ABCG8 and NPC1L1 mediate cholesterol trafficking across the intestinal wall, thus are important in regulating cholesterol metabolism and circulating levels. The objective of this study was to examine if single nucleotide polymorphisms (SNP) of cholesterol transporters ABCG5, ABCG8 and NPC1L1 are associated with changes in cholesterol synthesis and absorption and lipid parameters (LP) subsequent to weight loss (WtL) in overweight individuals. Eighty-nine individuals from two WtL trials (Trial A (n = 54) and Trial B (n = 35)) completed a 20-wk WtL period. After 10% WtL, lipid parameters excluding LDL-C were improved in Trial A, while all lipid parameters were ameliorated after 12% of WtL when Trial A and B were combined. Post-WtL, cholesterol synthesis (CS) was reduced; however, cholesterol absorption was not changed in either Trial A or the combined trials. Polymorphisms in ABCG8 V632A were associated with changes in TC and TG levels after WtL in both trial A and the combined data. SNPs in ABCG5 Q604E, ABCG8 T400K, were associated with changes in CS because of WtL in Trial A; however, the association is no longer seen in combined analysis. In conclusion, cardio-protective changes in LP due to weight loss were mediated by reductions in CS. Additionally, polymorphisms in ABCG8 were associated with amelioration in LP after WtL. Thus, the benefits in CVD risk subsequent to weight loss vary across individuals due to genetic factors associated with cholesterol trafficking.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O transtorno do estresse pós-traumático (TEPT) e alterações lipídicas são as temáticas principais dessa Dissertação. Seu objetivo principal foi investigar a associação entre o TEPT e as concentrações séricas de colesterol total (CT), lipoproteína de baixa densidade (LDL), lipoproteína de alta densidade (HDL) e triglicerídeos (TG) através de uma revisão sistemática da literatura seguida de metanálise. Adicionalmente, a relação entre essas variáveis lipídicas e os grupos de sintomas do TEPT revivescência, esquiva/entorpecimento emocional e hiperestimulação autonômica foi avaliada em um segundo estudo com dados primários. A metanálise incluiu 18 artigos, totalizando 2.110 indivíduos com TEPT e 17.550 indivíduos sem TEPT. As diferenças de médias ponderadas (DMP) mg/dL dos parâmetros lipídicos foram calculadas por modelos de efeitos aleatórios e modelos de meta-regressão foram ajustados para investigar possíveis fontes de heterogeneidade. O estudo encontrou que o TEPT foi associado a um pior perfil lipídico quando comparados a controles sem o transtorno (DMPCT= 20,57, IC 95% 12,21 28,93; DMPLDL= 12,11, IC 95% 5,89 18,32; DMPHDL= -3,73, IC 95% -5,97 -1,49; DMPTG= 35,87, IC 95% 21,12 50,61). A heterogeneidade estatística entre os resultados dos estudos foi alta para todos os parâmetros lipídicos e a variável que mais pareceu explicar essas inconsistências foi idade. O segundo artigo faz parte de um estudo maior conduzido em 2004 com 157 policiais do sexo masculino do Batalhão de Choque da Polícia Militar do Estado de Goiás (BPMCHOQUE). Somente oficiais de férias ou em dispensa inclusive dispensa médica não foram avaliados. O instrumento utilizado para o rastreio do TEPT foi a versão em português para civis da Post-Traumatic Stress Disorder Checklist (PCL-C). Trinta e nove participantes (25%) foram excluídos do estudo: dois porque falharam no preenchimento dos questionários e 37 cujas amostras de sangue não foram coletadas por vários motivos. Neste trabalho, encontrou-se uma forte correlação positiva entre as concentrações séricas de CT e LDL com o grupo de sintomas de hiperestimulação autonômica, somente no grupo TEPT: &#961;= 0,89 (p<0,01) e &#961; =0,92 (p<0,01), respectivamente. Em suma, espera-se que os resultados dessa Dissertação possam colaborar para o estabelecimento de um melhor acompanhamento clínico de pacientes com TEPT, particularmente porque estes parecem estar sob um maior risco de doenças cardiovasculares devido a um pior perfil lipídico. / Post-traumatic stress disorder (PTSD) and lipid profile changes are the main themes of this Dissertation, whose main purpose was to investigate the association between PTSD and serum lipid concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and Triglycerides (TGs). Additionally, the relationship between these serum lipid parameters and PTSD symptom clusters - re-experiencing, avoidance and hyperarousal was assessed in a second study with primary data. The meta-analysis included 18 articles, for an overall number of 2,110 people with PTSD and 17,550 individuals without PTSD. Pooled weighted mean differences (WMD) - mg/dL - of serum lipid parameters were calculated using random effects model and meta-regression models were fitted to investigate the sources of heterogeneity. The study showed that PTSD was associated with worsened lipid profile when compared to controls without PTSD (DMPCT= 20.57, IC 95% 12.21 28.93; DMPLDL= 12.11, IC 95% 5.89 18.32; DMPHDL= -3.73, IC 95% -5.97 -1.49; DMPTG= 35.87, IC 95% 21.12 50.61). Statistical heterogeneity between the results of the studies was high for all lipid parameters and the variable that most explained these inconsistencies was age. The second article is part of a larger study conducted in 2004 with 157 active duty male police officers of an elite unit of the Police Force of the State of Goiás-Brazil (BPMCHOQUE). Only officers on vacation or on leave including those on sick leave were not assessed. The diagnostic tool applied to screen for PTSD was a Portuguese version of the PTSD Checklist Civilian Version (PCL-C). Thirty nine (25%) participants were excluded: 2 respondents who failed to fill out the questionnaires and 37 whose blood samples were not collected for various reasons. The study found a significant and strong positive correlation between TC and LDL-C with hyperarousal symptom cluster, only in the full PTSD group: &#961;= 0.89 (p<.01) and &#961;= 0.92 (p<.01), respectively. As a synthesis, the results found in this Dissertation can contribute to a better clinical follow-up of PTSD patients, especially because they appear to be at higher risk for cardiovascular diseases due to worsened serum lipid profile.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O transtorno do estresse pós-traumático (TEPT) e alterações lipídicas são as temáticas principais dessa Dissertação. Seu objetivo principal foi investigar a associação entre o TEPT e as concentrações séricas de colesterol total (CT), lipoproteína de baixa densidade (LDL), lipoproteína de alta densidade (HDL) e triglicerídeos (TG) através de uma revisão sistemática da literatura seguida de metanálise. Adicionalmente, a relação entre essas variáveis lipídicas e os grupos de sintomas do TEPT revivescência, esquiva/entorpecimento emocional e hiperestimulação autonômica foi avaliada em um segundo estudo com dados primários. A metanálise incluiu 18 artigos, totalizando 2.110 indivíduos com TEPT e 17.550 indivíduos sem TEPT. As diferenças de médias ponderadas (DMP) mg/dL dos parâmetros lipídicos foram calculadas por modelos de efeitos aleatórios e modelos de meta-regressão foram ajustados para investigar possíveis fontes de heterogeneidade. O estudo encontrou que o TEPT foi associado a um pior perfil lipídico quando comparados a controles sem o transtorno (DMPCT= 20,57, IC 95% 12,21 28,93; DMPLDL= 12,11, IC 95% 5,89 18,32; DMPHDL= -3,73, IC 95% -5,97 -1,49; DMPTG= 35,87, IC 95% 21,12 50,61). A heterogeneidade estatística entre os resultados dos estudos foi alta para todos os parâmetros lipídicos e a variável que mais pareceu explicar essas inconsistências foi idade. O segundo artigo faz parte de um estudo maior conduzido em 2004 com 157 policiais do sexo masculino do Batalhão de Choque da Polícia Militar do Estado de Goiás (BPMCHOQUE). Somente oficiais de férias ou em dispensa inclusive dispensa médica não foram avaliados. O instrumento utilizado para o rastreio do TEPT foi a versão em português para civis da Post-Traumatic Stress Disorder Checklist (PCL-C). Trinta e nove participantes (25%) foram excluídos do estudo: dois porque falharam no preenchimento dos questionários e 37 cujas amostras de sangue não foram coletadas por vários motivos. Neste trabalho, encontrou-se uma forte correlação positiva entre as concentrações séricas de CT e LDL com o grupo de sintomas de hiperestimulação autonômica, somente no grupo TEPT: &#961;= 0,89 (p<0,01) e &#961; =0,92 (p<0,01), respectivamente. Em suma, espera-se que os resultados dessa Dissertação possam colaborar para o estabelecimento de um melhor acompanhamento clínico de pacientes com TEPT, particularmente porque estes parecem estar sob um maior risco de doenças cardiovasculares devido a um pior perfil lipídico. / Post-traumatic stress disorder (PTSD) and lipid profile changes are the main themes of this Dissertation, whose main purpose was to investigate the association between PTSD and serum lipid concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and Triglycerides (TGs). Additionally, the relationship between these serum lipid parameters and PTSD symptom clusters - re-experiencing, avoidance and hyperarousal was assessed in a second study with primary data. The meta-analysis included 18 articles, for an overall number of 2,110 people with PTSD and 17,550 individuals without PTSD. Pooled weighted mean differences (WMD) - mg/dL - of serum lipid parameters were calculated using random effects model and meta-regression models were fitted to investigate the sources of heterogeneity. The study showed that PTSD was associated with worsened lipid profile when compared to controls without PTSD (DMPCT= 20.57, IC 95% 12.21 28.93; DMPLDL= 12.11, IC 95% 5.89 18.32; DMPHDL= -3.73, IC 95% -5.97 -1.49; DMPTG= 35.87, IC 95% 21.12 50.61). Statistical heterogeneity between the results of the studies was high for all lipid parameters and the variable that most explained these inconsistencies was age. The second article is part of a larger study conducted in 2004 with 157 active duty male police officers of an elite unit of the Police Force of the State of Goiás-Brazil (BPMCHOQUE). Only officers on vacation or on leave including those on sick leave were not assessed. The diagnostic tool applied to screen for PTSD was a Portuguese version of the PTSD Checklist Civilian Version (PCL-C). Thirty nine (25%) participants were excluded: 2 respondents who failed to fill out the questionnaires and 37 whose blood samples were not collected for various reasons. The study found a significant and strong positive correlation between TC and LDL-C with hyperarousal symptom cluster, only in the full PTSD group: &#961;= 0.89 (p<.01) and &#961;= 0.92 (p<.01), respectively. As a synthesis, the results found in this Dissertation can contribute to a better clinical follow-up of PTSD patients, especially because they appear to be at higher risk for cardiovascular diseases due to worsened serum lipid profile.

Universidade Federal do Cearà / O presente trabalho relata o estudo quÃmico dos constituintes volÃteis das folhas e frutos de Myrcia sp., coletados no municÃpio de Amontada-CE em marÃo de 2005 e a obtenÃÃo de fraÃÃes e substÃncias provenientes do decocto das folhas frescas e do extrato etanÃlico das folhas secas de Cissus verticillata, bem como o estudo concomitante do seu potencial farmacolÃgico como hipoglicemiante atravÃs de testes realizados com a fraÃÃo solÃvel em metanol, fraÃÃo rica em tiramina e com a tiramina, obtidos de C. verticillata. Os Ãleos essenciais de Myrcea sp. foram analisados por cromatografia gÃs-lÃquido acoplada à espectrometria de massa (CGL/EM) e, quantitativamente, atravÃs do uso de CGL acoplada a detector do tipo FID. A anÃlise do Ãleo essencial das folhas de Myrcia sp. (GAOFOLHAS), permitiu a identificaÃÃo de treze componentes: d-elemeno, b-elemeno, trans-cariofileno, a-humuleno, b-chamigreno, germacreno D, b-selineno, a-guaieno, a-selineno, a-Z-bisaboleno, d-cadineno, epi-a-murolol e a-cadinol. O Ãleo essencial dos frutos de Myrcia sp. (GAOFRUTOS) permitiu a identificaÃÃo de onze componentes: d-elemeno, b-elemeno, trans-cariofileno, a-guaieno, a-humuleno, germacreno D, b-selineno, a-selineno, germacreno A, d-cadineno e germacreno B. O estudo fitoquÃmico do decocto de C. verticillata resultou na fraÃÃo rica em tiramina (CVFDSM-F19-24) que apÃs fracionamento cromatogrÃfico permitiu o isolamento da substÃncia tiramina, inÃdita no gÃnero Cissus. Os testes realizados com esta fraÃÃo e com a tiramina, em ratos com diabetes aloxan-induzida, mostraram reduÃÃo na glicemia, colesterol total, triglicÃrides e nÃveis de VLDL e aumento nos nÃveis de HDL. O fracionamento cromatogrÃfico da fraÃÃo hexÃnica, proveniente do extrato etanÃlico das folhas secas de C. verticillata, permitiu o isolamento dos esterÃides, b-sitosterol e b-sitosterol-glicosilado. A caracterizaÃÃo estrutural das substÃncias isoladas de C. verticillata foi realizada atravÃs do uso de tÃcnicas espectroscÃpicas, tais como, infravermelho e RMN de 1H e 13C, incluindo tÃcnicas uni e bidimensionais (HMBC e HMQC), bem como a comparaÃÃo com dados descritos na literatura. / The present work reports on the volatile constituents from leaves and fruits of Myrcia sp. collected in Amontada County-Cearà State, in march/2006. It also reports on the phytochemical analysis of the decoction solution from fresh leaves, and the ethanol extract of dried leaves of Cissus verticillata in a concomitant study of its pharmacological potential as hipoglycemiant. GLC/MS and GLC/FID analysis of the essential oil from leaves (GAOFOLHAS) allowed the identification of 13 components: d-elemene, b-elemene, trans-caryophyllene, a-humulene, b-chamigrene, germacrene D, b-selinene, a-guaiene, a-selinene, a-Z-bisabolene, d-cadinene, epi-a-murolol and a-cadinol, while the essential oil from fruits (GAOFRUTOS) allowed the identification of 11 components: d-elemene, b-elemene, trans-cariophylene, a-guaiene, a-humulene, germacrene D, b-selinene, a-selinene, germacrene A, d-cadinene and germacrene B. The silica-gel chromatography analysis of the decoction solution of fresh leaves of C. verticillata allowed the separation of a fraction rich in tyramine, and from it, pure tyramine. Pharmacological tests on rats with aloxan-induced glycemia with both the tyramine rich fraction and pure tyramine allowed reduction on the glycemia levels, as well as for total cholesterol, triglycerids and VLDL, but HDL increasing. Silica-gel chromatography analyses of the ethanol extract from dried leaves of C. verticillata allowed the isolation of b-sitosterol and its glucoside derivative. Structure determination of all substances of C. verticillata was accomplished by means of spectroscopic techniques such as IR, 1H and 13C NMR, including uni and bi-dimensional pulse sequences (HMBC and HMQC) ad comparison with data from the literature.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.