M.Sc. (Chemistry) / The objective of the project was the synthesis of thiosemicarbazone-triazole hybrid compounds and evaluation of their biological activities against malaria and obesity. In achieving our objective, compound 63 was synthesized from the reaction of benzaldehyde 62 with propargyl bromide. Click chemistry reaction of compound 63 with benzyl azide provided triazole 68. Schiff’s base condensation of triazole 68 with methyl hydrazine carbodithioate 67 furnished compound 69 which then underwent nucleophilic substitution reaction and afforded thiosemicarbazone-triazole hybrids 61a-j. The structures of the compounds were characterized using NMR spectroscopy and elemental analysis. Hybrids 61a-h were then investigated for their biological activities against malaria and obesity. The antimalarial activities of the hybrids against the 3D7 strain of the malaria parasite plasmodium falciparum showed that only hybrid 61f exhibited less than 50% parasite viability (46% compared to 37% of chloroquine). The dose response of the hybrids was not carried out due to their poor activities. Hybrids 70a-h that incorporated electron donating group in their aromatic linker were synthesized similarly as hybrids 61a-h were synthesized. Their antimalarial activities showed that all except 70c and 70g exhibited less than 50% parasite viability. The test results indicated that the addition of methoxy group to the hybrids 61b, 61e and 61f decreased their percentage parasite viability which were exhibited by their corresponding hybrids 70b, 70e and 70f, respectively. Hybrid 70f was found to be marginally active with a dose response of 7.09 μM. The anti-obesity and anti-diabetic effects of hybrids 61a-h were investigated against the mitochondrial genes (Acc-1, Cpt-1 and Pgc-1) and glucose transport genes (Glut-4, Mef2a and Nrf-1), respectively. The test results against the mitochondrial genes showed that hybrids 61e and 61h consistently exhibited on the 3 genes which indicated that the presence of a non-polar short branched chain of the amine moiety might be important in the up-regulation of oxidative (Cpt-1 and Pgc-1) and down regulation of lipid accumulation (Acc-1) genes. The test results on the glucose transport genes showed that 61e followed by 61f consistently exhibited on the 3 genes which indicated that the presence of a non-polar short branched chain of the amine moiety might be important in the up-regulation of Glut-4, Mef2a and Nrf-1.Hybrids 70a-h were also tested against obesity and type 2 diabetes mellitus. Their investigation on the mitochondrial genes showed that the addition of methoxy group to the hybrids 61a-h that have a non-polar long branched chain of the amine moiety could be a reason for the expression and suppression of Cpt-1, Pgc-1 and Acc-1, respectively. The test results of hybrids 70a-h on glucose transport genes showed that the addition of methoxy group to the hybrids 61a-h that have a non-polar short (straight and branched) alkyl chain of the amine moiety might be a reason for the up-regulation of Glut-4, Mef2a and Nrf-1. Carbohydrate incorporated thiosemicarbazone-triazole hybrid compound 75 was successfully synthesized. However, the synthesis of more libraries of compound 75 and investigation of their biological activities against malaria and obesity were not carried out due to time constraints.

No description available.

Background The telemedicine application has great potential to address the prevalence of overweight and obesity, a severe the public healthcare burden in the 21st century. However, no exiting systematic review has been investigated the effectiveness of telemedicine application of weight reduction. The absence of quantitative evaluations and relatively rigorous qualitative assessments explains the carry-out of the present systematic review with a meta-analysis. Objectives The objectives are to determine the aggregated effect of thetelemedicine application to the management of overweight and obesity, in particular to investigate the effect of thetelemedicine application on reducing body weight, and to evaluate major contributable factors to commit a successful telemedicine intervention in body weight lowering. Methods This meta-analysis is guided by the PRISMA statement, with the automatic and manual searching by input keywords in the main databases. Only RCTs with absolute reduction of body weight as outcome measure, comparing the effect of the telemedicine application interventions with other stated interventions in reducing human body weightare potentially to be included. The selected RCTs are subject to the Jaded scale and the CONSORT for quality assessment. The studies identification and the data extraction were performed by two independent reviewers separately.The heterogeneity across the selected RCTs was assessed by Cochran Q test and I-square statistic. The meta-analysis was conducted with random-effect models and sensitivity analyses were performed by eliminating studies with extreme outcome values. Publication bias was examined through visual inspection of funnel plots and statistical assessments of the Begg‟s rank correlation test and the fail-safe N. Results 723 studies were identified from the preliminary database searches, 32 full-text articles were retrieved to review, after which, 12 RCTs were subject to the quality assessment process. Only 10 RCTs of high quality were selected into the meta-analysis. The generalizability of the meta-analysis is great since the patients subgroups were broadly from different geographical and cultural settings with the age ranging from 18 to 70, and no comorbidity conditions were excluded. The single element, the telemedicine application intervention, contributed to a significant extra 4.17 kg absolute reduction of human body weight in the average time period of 42 weeks. The outcome of the sensitivity analysis excluding the studies with extreme outcome measures was also consistent with the finding, which means the telemedicine application intervention contributed to a significant extra 2.58 kg absolute reduction of human body weight in the average time period of 46.5 weeks. Conclusions The telemedicine application is an effective public health intervention with broad generalizability for weight reduction in the future. Further studies to assess the effect of the telemedicine intervention among the populations of the developing countries, especially the large Chinese population, and to evaluate the confounding effect of the Hawthorne effect are critically important to support the international guideline on the promotion of the telemedicine intervention. / published_or_final_version / Public Health / Master / Master of Public Health

The purpose of this study was to assess the efficacy of two different modes of exercise in an overweight and obese population over a 12-week period. Subjects: Forty-four overweight or obese individuals were recruited from a weight loss organisation. Participants were randomised into one of two groups which were matched according to age, gender and body mass index (BMI). The interventions consisted of either intermittent interval exercise (INT group), or intermittent steady-state exercise (SS group). Participants in both groups were on an identical strict caloric diet during the intervention period. Methods: Baseline and post-intervention testing consisted of the assessment of aerobic fitness, blood lipid profile, resting metabolism, body composition, vascular function, quality of life and activity levels. The exercise regime for the INT group consisted of a 1:2 min ratio of moderate intensity (70 75% V&O2peak) to low intensity exercise (40 45% V&O2peak), while the SS group exercised continuously between 50 55% V&O2peak. Total work per session was the same per group. Exercise consisted of walking/jogging twice daily for 15 mins five days per week. Eighteen participants dropped out of the study leaving 12 in the INT group and 14 in the SS group. Results: Peak oxygen uptake and exercise time to exhaustion increased significantly over time in the interventions (P < 0.001). Significant positive changes occurred in several blood tests, including liver function, insulin like growth factor (IGF- 1) and lipid levels (cholesterol, triglyceride, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) and coronary risk ratio, all P < 0.05 over time). Additionally, uric acid and VLDL levels significantly decreased over time in the SS and INT groups, respectively (P < 0.05), whereas IGF-1 levels significantly increased in the SS group over time (P < 0.05). Body composition measures, including BMI, body mass, fat mass, percent of body fat, gynoid obesity and hip circumference, as well as waist circumference decreased significantly over time (P < 0.05). Several components of the SF-36 quality of life questionnaire (physical function, role physical, bodily pain, general health, vitality, social function and mental health) improved significantly over time (P < 0.05), while mental health also significantly improved over time in the SS group (P < 0.01). Finally, anxiety and depression levels were significantly reduced over time (P < 0.05). However, none of these changes over time significantly differed between the two groups. Conclusion: Both exercise interventions resulted in significant improvement over time in numerous health and fitness variables in an overweight and obese population. No significant differences were found, in the interaction term during a 2-way ANOVA, between the two groups at post-intervention. A longer intervention period, or changes to interval duration and intensities may result in more significant differences between the two training methods.

Orientador: Lúcia Regina Ribeiro / Coorientador: Mário Sérgio Mantovani / Banca: Maria Inês de Moura Campos Pardini / Banca: Raquel Alves dos Santos / Resumo: Em diversas partes do mundo, a prevalência da obesidade tem aumentado rapidamente. A Organização Mundial da Saúde estima que, em 2015, haverá 700 milhões de pessoas obesas (índice de massa corporal ≥30kg/m2) em todo o mundo. No Brasil, aproximadamente, 50% da população acima dos 20 anos apresentam sobrepeso (índice de massa corporal ≥25kg/m2) e 16% já demonstram quadro de obesidade. A obesidade é um dos fatores desencadeadores de diversas doenças crônicas, assim, é importante identificar características que predispõem indivíduos à obesidade, ou condições negativas que ocorrem durante o desenvolvimento da obesidade, as quais alteram o metabolismo e o estado de saúde de maneira negativa. O objetivo do presente estudo foi avaliar diferenças na expressão de genes-alvo do PPARα em células mononucleares periféricas do sangue (PBMCs) e na concentração plasmática de ácidos graxos livres no sangue, entre indivíduos obesos e não-obesos, após 24 horas de jejum. Este estudo foi o primeiro realizado na população brasileira. Em ambos os grupos (obeso e não-obeso), a concentração plasmática de ácidos graxos livres (AGL) elevou-se de forma significante após as 24horas de jejum, em especial, no grupo não-obeso, onde a média da concentração elevou-se 3 vezes se comparada com a média da concentração no tempo 0h. A média da concentração plasmática basal (0h) de AGL revelou-se 2 vezes maior no grupo obeso quando comparada com a média do grupo não-obeso. No entanto essa diferença não foi observada após as 24h de jejum. Os genes estudados participam diretamente na β-oxidação mitocondrial hepática e musculoesquelética e são ativados por PPARα. Após o jejum, todos os genes estudados evidenciaram um incremento na expressão (fold change) quando comparados com o... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The prevalence of obesity has increased rapidly in many parts of the world. The World Health Organization estimates that in 2015, there should be 700 million obese people (body mass index ≥ 30kg / m²) around the world. In Brazil, approximately 50% of the population aged 20 years and older are overweight (body mass index ≥ 25kg / m²) and 16% already meet the criterion for obesity. Obesity is considered a trigger factor for several chronic diseases, so it is important to identify traits that predispose individuals to obesity or negative conditions that occur during the development of obesity, affecting metabolism and health negatively. The aim of this study was to evaluate differences in the expression of PPAR-alpha target genes in peripheral blood mononuclear cells (PBMCs) and in plasma free fatty acid concentration in the blood of obese and non-obese subjects, after 24 hours of fasting. This was the first study conducted in the Brazilian population. In both groups (obese and non-obese), plasma free fatty acid (FFA) concentration increased significantly after 24 hours of fasting, especially in the non-obese group, in which the mean concentration rose 3 times compared with the mean concentration at time 0h. The baseline (0h) mean of plasma FFA concentration was 2 times higher in the obese group compared with the mean from the non-obese group. This difference, however, was not observed after 24h of fasting. The studied genes participate directly in hepatic and musculoskeletal mitochondrial beta-oxidation and are activated by PPAR-alpha. After fasting, all the studied genes had an increase in fold change compared with time 0h, in both groups. By identifying the preferential beta-oxidation during fasting, the CPT1A gene presented an increase in fold change compared with the CPT1B gene, indicating thus that beta-oxidation... (Complete abstract click electronic access below) / Mestre

University of Macau / Institute of Chinese Medical Sciences

The global number of obese people has reached pandemic proportions. High caloric diets and reduced physical exercise are to blame for this growing epidemic. Obesity has a very complex association with several other metabolic disorders, such as insulin resistance (IR), diabetes mellitus type 2 (DMT2) and cardiovascular disease. This puts a huge burden on health care systems world wide and claims many lives. Sutherlandia frutescens is a traditionally used herb, which is known to have anti-diabetic properties. However, the direct mode of action of S. frutescens still remains to be elucidated. The aim of this study was to investigate the developmental stages of high fat diet (HFD)-induced IR, to illuminate the pathogenesis of IR with a focal point on modifications in the lipid metabolism. Furthermore, the effects of S. frutescens as a treatment or prevention drug for IR and associated metabolic changes were examined. Two sets of experiments were conducted on male Wistar rats. In the first experiment rats, one week post weaning received a low fat diet (LFD), high fat diet (HFD) or HFD supplemented with S. frutescens (50mg/kg BW/d). Rats were sacrificed at week 0, 1, 2, 4, 8 and 12 in the feeding regime. In a second experiment rats were fed with a LFD or a HFD for 12 weeks and treated thereafter with S. frutescens (50mg/kg BW/d), metformin (13mg/kg BW/d) or water (control) for 28 days. Rats in the second experiment were sacrificed at week 12 to confirm IR while concurrently run rats were sacrificed after 28 days of treatment. For all the experiments rats were anaesthetized, blood was removed and rats were dissected. Plasma samples were analyzed for insulin, glucose, blood lipid parameters and cytokines. Liver, muscle and adipose tissue were analyzed for glucose uptake, total lipid content, lipid profile and fatty acid profile. It was shown that the intake of HFD caused IR and hyperinsulinaemia. The developmental stages in experiment one confirmed that an increase in plasma free fatty acids preceeded the onset of IR. Plasma and tissue lipid parameters (free fatty acid-, triglyceride- and cholesterol concentrations) showed pathological modifications in the HFD group. An ectopic accumulation of fat was observed in muscle and liver, as well as a change in membrane fatty acid profile. The results for circulating cytokines were somewhat inconclusive. Rats supplemented with S. frutescens did not develop HFD-induced IR (study one) or IR was reversed (study two). S. frutescens treatment also resulted in positive changes in plasma and tissue lipid parameters. In summary, an animal model for HFD-induced IR was established and the detrimental effect of elevated plasma FFA on glucose and lipid metabolism was observed. A novel discovery suggests that the anti-diabetic mode of action of S. frutescens is through modulation of lipid metabolism. It was also established that S. frutescens has the potential to prevent IR in vivo.

This study compared the results of two methods of behavioral treatment in combination with a very-low-calorie-diet in the treatment of obesity. Subjects were 28 male and 106 female patients admitted to the medically supervised fasting program at Risk Factor Clinic in Portland, Oregon. Subjects were matched by gender, percent over ideal body weight, and age. Subject group I received a smorgasbord of behavioral techniques from various group leaders in a 60-minute weekly session. Presentation was didactic and theoretical and subjects were accountable to themselves for utilization of the techniques. Subject group II participated in 90-minute weekly sessions with a primary leader facilitating a problem solving and educational session in which patients were continually encouraged to participate. Subjects set goals and made weekly commitments to facilitate skill acquisition and behavior change. The leader collected data from patients each week on program compliance and physical activity.

While limited health literacy has been associated with poorer health decisions and poorer health outcomes, there remains a gap in the literature related to the influence of health literacy on weight and weight-related behaviors. The primary aim of this study is to examine the influence of child and parent health literacy status on childs body mass index (BMI) and health behaviors, within an adapted evidence-based family-based childhood obesity intervention, iChoose, implemented in the medically underserved Dan River Region (DRR). Previously developed measures were used to assess health literacy and health behaviors. iChoose consisted of 101-parent-child dyads. Using the New Vital Sign (NVS), 46% of children and 13% of parents had low to limited health literacy levels at baseline. Younger children and parents who were African American, had no high school diploma, and earned <$25,000/year were significantly more likely to have low health literacy when compared to their counterparts. Health literacy levels for these individuals ranged between 0 to 3, which is considered low to limited health literacy. Health literacy levels were further examined between health outcomes. However, BMI, fruit and vegetable intake, sugar-sweetened beverages (SSB), minutes of moderate to vigorous physical activity, and screen time did not differ by health literacy levels at baseline. Among children, improvements in the NVS was significantly correlated with decreases in SSB consumption (r = -.275, p < .05), but with no other outcomes. There were no significant correlations among changes in parent NVS score and changes in child health behaviors. Results from this study fill a gap in understanding the associations in health literacy and weight and weight-related behavioral outcomes in children. It also provides insights into the opportunities and challenges in measuring health literacy among children. Future research is needed to explore further health literacy measurement issues among children and the influence of both child and parent health literacy in family-based childhood obesity treatment efforts. Additional efforts are also needed to assist community and health care providers in finding more effective strategies to guide children with low health literacy to better health outcomes. / Master of Science

Orientador: Antonio Carlos Cicogna / Banca: Camila Renata Corrêa Camacho / Banca: Alessandra Medeiros / Resumo: As modificações da função cardíaca decorrentes da obesidade podem estar associadas a diversos fatores, como o sistema β-adrenérgico, que executa importante papel na regulação do desempenho do coração e encontra-se hiperativo na presença de excesso de tecido adiposo corporal. Considerando a carência de informações a respeito da via β-adrenérgica cardíaca nessa patologia e a frequente associação entre ácidos graxos saturados e complicações cardiovasculares, a proposta desse estudo foi investigar se a obesidade acarreta alteração no comportamento dos componentes do sistema β-adrenérgico miocárdico de ratos obesos por dieta hiperlipídica saturada. Ratos Wistar foram distribuídos em dois grupos: controle (C; n=18; dieta normolipídica saturada) e obeso (Ob; n=19; dieta hiperlipídica saturada) por 30 semanas. A obesidade foi determinada pelo índice de adiposidade e foram avaliadas as comorbidades. O perfil morfológico cardíaco foi estimado por análise macroscópica post mortem. As expressões proteicas de receptores β1 e β2, adenilato ciclase (AC), proteína Gαs e proteína quinase A (PKA) foram realizadas pelo método de Western Blotting, e os níveis de adenosina monosfato cíclico (AMPc) e atividade da PKA, pela técnica de ELISA. Os ratos obesos apresentaram aumento no índice de adiposidade (p<0,001) e várias comorbidades como, hipertensão arterial sistêmica (p=0,009), intolerância à glicose (p<0,001), resistência insulínica (p=0,02) e dislipidemia, caracterizada pela hipertrigliceridemia (p=0,001) e hipercolesterolemia (Colesterol total, p=0,037; LDL, p=0,033). Não foi encontrada remodelação cardíaca no estudo macroscópico (p>0,05). A expressão proteica da AC miocárdica foi significativamente elevada no grupo Ob em relação ao C (p=0,025); adicionalmente, não houve alteração nos demais componentes avaliados (p>0,05). Em conclusão, a obesidade por dieta hiperlipídica saturada... / Abstract: The changes in cardiac function resulting from obesity may be associated with several factors such as the β-adrenergic system, which performs an important role in regulating heart performance and is hyperactive in the presence of excess body fat. Considering the lack of information on cardiac β-adrenergic pathway in this disease and the frequent association between saturated fatty acids and cardiovascular complications, the purpose of this study was to investigate wheter the obesity leads to change in behavior of the components of myocardial β-adrenergic system in obese rats by saturated high-fat diet. Male Wistar rats were divided into two groups: control (C, n=18; saturated normolipidic diet) and obese (Ob; n=19; saturated high-fat diet) for 30 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Cardiac morphological profile was estimated by post-death macroscopic analysis. The protein expressions of β1 and β2 receptors, adenylate cyclase (AC), Gαs protein e protein kinase A (PKA) were performed by the method of Western Blotting, and cyclic adenosine monosfato (cAMP) levels and activity of PKA, by ELISA. Obese rats showed increased adiposity index (p<0.001) and several comorbidities such as hypertension (p=0.009), glucose intolerance (p<0.001), insulin resistance (p=0.02) and dyslipidemia, characterized by hypertriglyceridemia (p=0.001) and hypercholesterolemia (total cholesterol, p=0.037; LDL, p=0.033). There was no cardiac remodeling in the macroscopic study (p>0.05). Protein expression of myocardial AC was significantly elevated in the Ob group compared to C (p=0.025); additionally, there was no change in the other components evaluated. In conclusion, obesity by saturated high-fat diet resulted in increased protein levels of AC in myocardial β-adrenergic system, without affecting the other componentes / Mestre