No description available.

Thesis (Ph.D.)--University of Wollongong, 2004. / Includes appendices. Typescript. Includes bibliographical references: leaf 154-184.

Diss. (sammanfattning) Göteborg : Univ., 2010.

Thesis (Ph.D)--Industrial and Systems Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Vidakovic, Branislav; Committee Member: Edwards, Paula; Committee Member: Griffin, Paul; Committee Member: Grinter, Rebecca; Committee Member: Mullis, Rebecca. Part of the SMARTech Electronic Thesis and Dissertation Collection.

No description available.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph.D.)--Michigan State University. Neuroscience, 2008. / Title from PDF t.p. (viewed on Mar. 27, 2009) Includes bibliographical references (p.178-194). Also issued in print.

Submitted in fulfillment of the requirement for the degree of Doctor of Philosophy in the Faculty of Health Sciences at the University of the Witwatersrand, Johannesburg / Renewed interest in cannabinoid compounds arose since the discovery of the endocannabinoid system in the early 1990’s and its role in mediating the body’s energy balance. The aim of this study was to investigate the effect of an organic Cannabis sativa (hereafter referred to as C. sativa) extract on β-cell secretory function using an in vivo diet-induced obese rat model and an in vitro isolated rat pancreatic islet model and to determine the associated molecular changes within the pancreatic tissue. Materials and methods: Diet-induced obese Wistar rats and rats fed on standard pellets were subcutaneously injected, over a 28 day period, with an organic C. sativa extract or the vehicle (1% Tween 80® in saline). The effect of diet and treatment was evaluated using the intraperitoneal glucose tolerance tests (IPGTTs) and quantitative polymerase chain reaction (qPCR) analysis on rat pancreata. In vitro studies were conducted using isolated rat islets exposed to 11.1 (representative of normoglycemic conditions) and 33.3 mM glucose levels (representative of hyperglycemic conditions) over a 24-(D1; acute) and 96-hour (D4; chronic) period, and treated with C. sativa extract containing an equivalent of 2.5 (T1) and 5 ng/mL (T2) tetrahydrocannabinol (THC). Glucose-stimulated insulin secretion (GSIS), immunohistocytochemistry for apoptosis and proliferation detection and western blotting for detection of cannabinoid receptor type 1 (CB1), CB2 receptors and specific transduction factors were undertaken. Antagonist studies were conducted using AM251 (A1) and AM630 (A2) to block CB1 and CB2, respectively, to determine the role of cannabinoid receptors in insulin secretion. Results: The overall increase in body weight in the experimental groups occurred at a significantly slower rate than the control groups (P < 0.01), irrespective of diet. In the lean group, the area under the curve for glucose (AUCg) was significantly higher compared to the diet-induced obese group (P < 0.001), while C. sativa treatment significantly improved the AUCg in the lean rats (P < 0.05). The cafeteria diet did not induce hyperglycemia and insulin resistance in the obese rats and C. sativa treatment maintained a plasma glycemic profile similar to the obese control rats. The lower AUCg values in the obese group may, in part, be due to the inclusion of milk products (shown to be beneficial in reducing diabetes) in the cafeteria diet. qPCR analysis showed that the cafeteria diet induced down-regulation of the following genes in the obese control group, relative to lean controls: UCP2 (P < 0.01), c-MYC (P < 0.05) and FLIP (P < 0.05), and upregulation of CB1 (P < 0.01), GLUT2 (P < 0.001), UCP2 (P < 0.001) and PKB (P < 0.05), relative to the obese control group, while c-MYC levels were down-regulated (P < 0.05), relative to the lean control group. In the in vitro study, results showed C. sativa treatment decreased chronic insulin secretion in islets cultured under normoglycemic condition for D1 (P < 0.05), but not for D4. In islets cultured under hyperglycemic conditions, C. sativa treatment for the D4 period showed a significant increase in their chronic insulin secretion (HD4T1, P = 0.07; HD4T2, P < 0.001), increase in basal insulin secretion (HD4T1, P < 0.001; HD4T2, P < 0.001), increase in GSIS (HD4T1, P < 0.05; HD4T2, P < 0.001), reduction in glucose-stimulated:basal insulin production (HD4T1, P < 0.05; HD4T2, P < 0.05), reduction in insulin content (HD4T1, P < 0.001), increase in the percentage basal : content ratio (HD4T1, P < 0.001; HD4T2, P < 0.01) and increase in the percentage GSIS : content ratio (HD4T1, P < 0.001; HD4T2, P < 0.05), relative to ND4C islets. In antagonist studies, A2 preconditioning did not affect suppress the stimulatory effect of C. sativa treatment on chronic insulin secretion under normo- and hyperglycemic conditions, relative to the NC and HC islets, respectively. qPCR studies showed that C. sativa exposure induced a 2.2-fold increase in CB1 gene expression, relative to normoglycemic control islets (P < 0.05), while c-MYC and FLIP expression was significantly reduced by 12% (ND4T1, P < 0.05) and 37% (HD4T1, P < 0.05), respectively. C. sativa treatment also induced increased secretion of anti-inflammatory cytokines/chemokines under hyperglycemic conditions. Conclusion: These results suggest that C. sativa protects pancreatic islets against the negative effects of obesity (in vivo studies) and hyperglycemia (in vitro studies). In light of these findings, further investigation into the potential of C. sativa as a complementary therapeutic agent in the treatment of the deleterious effects of hyperglycemia in diabetic patients is warranted. In addition, the significant effect of C. sativa treatment on adipose tissue in experimental rats needs further investigation to determine how the cannabinoids affect the mechanisms of adipogenesis and lipolysis in diet-induced obesity. Keywords: Diet-Induced Obesity, Cannabinoids, C. sativa, THC, β-cell, AM251, AM630.

Current treatments for obesity have been unsuccessful. It is essential that a patient-centred approach for obesity management is developed and for this to be successful other diet and lifestyle approaches need to be considered. A systematic review comparing low carbohydrate vs. low fat diets for the treatment of obesity was carried out. It found that low carbohydrate/high protein diets are as effective as, if not better, for treating obesity and cardiovascular disease risk factors. A randomised controlled trial investigating dietary approaches for the treatment of obesity and its co morbidities was carried out. Variables including weight and body composition, cardiovascular risk factors, adipokines, liver and kidney function, and health and lifestyle factors were measured. Those with metabolic syndrome were also examined. It was hypothesised that there are alternative ways of treating obese subjects depending on their phenotype. Those with a higher BMI tend to have a higher carbohydrate intake rather that a higher fat intake so may be better suited to a low carbohydrate/high protein diet rather than the conventional low fat/energy reduced diet. Subjects were initially treated with the standard dietary approach for obesity (health eating, HE) and if not successful after 3 months were randomised to either a very low calorie diet (Lighterlife, LL) or a protein sparing modified fast (PSMF). All three groups showed a significant weight loss and reduced risk for CVD at 12 months. Significant improvements were seen for plasminogen-activated receptor-1, adiponectin, leptin and IL-6 on HE and LL, but only adiponectin significantly improved on the PSMF. Neither diet showed any detrimental effects for those with a healthy liver and kidney function. Quality of life and levels of depression improved at 12 months. Of the 54 subjects with metabolic syndrome at baseline, 12 remained on HE and 32 were randomised to LL and PSMF. This indicates that most subjects did not suit a low fat dietary approach. They were successful at losing weight on LL and PSMF and showed improvement in MS risk factors, and adipokine levels at 12 months. In conclusion, the study demonstrates that a low fat diet may not necessarily be the first line of approach to treat obese subjects with a BMI over 35 kg/m2, including those with MS. A very low calorie diet such as LL or a PSMF may be better suited to the subject.

INTRODUÇÃO: A obesidade é uma doença crônica e de etiologia multifatorial, relacionada a fatores genéticos, ambientais e comportamentais. Apresenta associação com diversas alterações metabólicas já na infância, levando ao aumento do risco de doenças cardiovasculares na vida adulta. O tratamento envolve mudança de estilo de vida, com orientação de dieta balanceada e estímulo à atividade física. O tratamento nesta faixa etária tem apresentado dados limitados, além de altas taxas de abandono. Um tipo original de orientação alimentar é através da contagem de equivalentes calóricos, onde as calorias são convertidas em pontos. O objetivo deste estudo foi avaliar a variação do escore Z do índice de massa corpórea (ZIMC) de adolescentes obesos submetidos à orientação de dois grupos de dieta hipocalórica: tradicional e baseada no sistema de pontos, assim como avaliar variáveis antropométricas, composição corporal, alterações metabólicas, ingestão alimentar e o automonitoramento. MÉTODOS: Estudo clínico randomizado com duração de 24 semanas, com 66 adolescentes com idade média de 13,7 ± 0,7 anos de ambos os gêneros, com escore do IMC >= 2 a <= 4 da curva ajustada para gênero e idade da Organização Mundial da Saúde. Foram verificados peso, estatura, pressão arterial e circunferência abdominal, intensidade de atividade física e automonitoramento, assim como efetuada a orientação nutricional a cada visita. Parâmetros laboratoriais, aplicação da escala de compulsão alimentar periódica, composição corporal e estadiamento puberal, foram avaliados no início e final do seguimento. Os pacientes foram divididos em dois grupos: um que recebeu orientação de dieta hipocalórica tradicional e preenchia o registro de consumo alimentar (RCA) de três dias (Grupo A) e outro que recebeu orientação de dieta hipocalórica baseada no sistema dos pontos e preenchia o RCA diário (Grupo B). RESULTADOS: Quarenta e quatro pacientes concluíram o tratamento. Houve redução do ZIMC nos dois grupos (p < 0,0001), porém a redução observada no Grupo A não foi diferente da observada no Grupo B (p=0,87). Ocorreu aumento da massa livre de gordura (%), redução da circunferência abdominal, pressão arterial sistólica e diastólica, além da massa gorda (%). Houve diferença no escore de compulsão alimentar entre as visitas 1 e 8, o qual se manteve durante o estudo. Verificamos melhora de todos os parâmetros laboratoriais, com diminuição significativa de insulina, HOMA-IR, gama-GT e ALT, não havendo diferença entre os dois grupos. Houve redução do valor energético total nos dois grupos, acompanhada do aumento percentual de proteínas, redução de carboidratos e manutenção dos lipídios. O automonitoramento médio não foi relacionado à variação do ZIMC. CONCLUSÃO: Dieta hipocalórica com orientação tradicional ou baseada no sistema de pontos levou a redução do ZIMC, de marcadores metabólicos e do valor energético total em adolescentes obesos de forma semelhante nesta coorte de pacientes / INTRODUCTION: Obesity is a chronic illness and multifactorial etiology, related to genetic factors, environmental and behavioral. Features association with several metabolic abnormalities in childhood, leading to increased risk of cardiovascular disease in adult life. The treatment involves lifestyle change, with balanced diet guidance and encouraging physical activity. The treatment in this age group have brought limited data, in addition to high drop-out rates. A unique type of food guidance is the equivalent calorie count, where calories are converted into points. The objective of this study was to evaluate the variance of Z score of body mass index (ZIMC) of obese adolescents undergoing orientation of two groups of low-calorie diet: traditional and based on the points system, as well as evaluate anthropometric variables, body composition, food intake, metabolic changes and self-monitoring. METHODS: randomized clinical study with duration of 24 weeks, with 66 adolescents with an average age of 13.7 ± 0.7 years of both genders, with scores of BMI >= 2 to <= 4 curve adjusted for gender and age of the World Health Organization. Were verified weight, height, blood pressure and waist circumference, intensity of physical activity and self- monitoring, as well as performed the nutritional guidance to each visit. Laboratory parameters, applying the scale of binge eating, pubertal, stage and body composition were evaluated at the beginning and end of the action. The patients were divided into two groups: one that received guidance of traditional low-calorie diet and meet the food consumption record (RCA), three days (Group A) and another that received low-calorie diet guidance based on the system of points and meet the daily RCA (Group B). RESULTS: forty-four patients have completed treatment. There was a reduction of Z BMI in both groups (p 0.0001 < ), however the reduction observed in the Group was not different from that observed in Group B (p = 0.87). There was increased fat free mass (%), abdominal circumference, systolic and diastolic blood pressure and body fat (%). There was difference in binge eating score between 1 and 8 visits, which remained during the study. We improved all laboratory parameters, with significant decrease of insulin and HOMA-IR, gamma GT and ALT, and there is no difference between the two groups. There was a reduction of the total energy in both groups, accompanied by the increasing percentage of protein, carbohydrate and maintenance reduction of lipids. The average self-monitoring was not related to the variation of Z BMI. CONCLUSION: low-calorie diet with traditional or orientation based on points system led to reduction of metabolic markers, Z BMI and total energy value in obese adolescents similarly in this cohort of patients