Thesis (MNutr (Interdisciplinarty Health Sciences. Human Nutrition))--University of Stellenbosch, 2005. / Objectives: To determine aspects of knowledge, attitudes and practices of Medical Practitioners on obesity and weight management in three urban centres in Kenya. Research methods and procedures: A cross sectional survey of a randomly selected sample of 485 Medical Practitioners (MPs) from three urban centres in Kenya namely Nairobi, Mombasa and Kisumu was carried out. Four hundred and thirty (89% response) questionnaires were fully completed and returned. Data was gathered on the demographics of the study population; knowledge of nutrition and obesity; awareness of obesity as a health problem assessment, management (diet, exercise and pharmacology) and practices regarding obesity as well as if and how the MPs would like their knowledge of obesity improved.

Orientador: Roberto Carlos Burini / Banca: Kátia Cristina Portero Mclellan / Banca: Fábio Lera Orsatti / Resumo: As elevadas prevalências de obesidade e sarcopenia vêm se tornando relevante nos últimos anos diante de que as condições decorrentes da co-existência destes dois quadros potencializa os danos à saúde do indivíduo. O presente estudo tem como objetivo diagnosticar, avaliar a prevalência e o comportamento das variáveis funcionais da massa muscular e metabólicas da obesidade sarcopênica em adultos. Foram avaliados 523 indivíduos, de ambos os sexos, com maior prevalência do sexo feminino (72,7%), com idade média de 54,74±10,18 anos, ingressantes em programa para Mudança do Estilo de Vida (MEV) "Mexa-se Pró Saúde". Os indivíduos foram submetidos a avaliações clínicas, da pressão arterial, aptidão cardiorrespiratória, de antropometria e composição corporal, aptidão física e análises bioquímicas, incluindo resistência insulínica (HOMA-IR), estresse oxidativo (Malondialdeido - MDA) e estresse inflamatório (Proteína C-Reativa - PCR). As análises estatísticas foram realizadas pelo software SAS 9.2, adotando p<0,05. Adotou-se como critério de obesidade a circunferência abdominal elevada. Verificou-se que a indivíduos portadores de obesidade abdominal comparados aos não portadores, apresentam maiores valores de IMC, %GC, IMM, HOMA-IR, PCR, ácido úrico, triglicerídios e glicemia e valores reduzidos de HDL-c, flexibilidade e VO2max. Quando avaliada isoladamente a obesidade abdominal, foi verificado que sua presença reduz as chances de boa aptidão aeróbia e força muscular com aumento da chance de resistência insulínica. Já a sarcopenia reduz as chances de alteração na flexibilidade, redução do HDL-c e aumenta as chances de resistência insulínica. Quando combinadas, a obesidade sarcopênica se diferencia principalmente na aptidão física, onde a aptidão cardiorrespiratória se mostrou como condicionante da discriminação de obesidade sarcopência. Assim, a discriminação da ... / Abstract: Recently, obesity and sarcopenia have been showing high prevalence among population and when this conditions are combined may increases damage to the individual's health. This study aimed to diagnose, assess prevalence, muscle mass function and metabolic variables related to sarcopenic obesity in adults. Were assessed 523 individuals, of both sexes, with higher prevalence in females (72.7%) with a mean age of 54.74 ± 10.18 years old, selected for Lifestyle Modification Program (MEV). The individuals were assessed for medical anamnese, blood pressure, cardiorespiratory fitness, body composition and anthropometry, physical fitness and biochemical analyzes, including analysis of insulin resistance (HOMA-IR), oxidative stress (malondialdehyde - MDA) and inflammatory stress (C-Reactive Protein - PCR). Statistical analyzes were performed by SAS software 9.2 (p <0.05). Obesity was defined by higher measures of waist circumference. It was verified that individuals with abdominal obesity compared to non-obese, presented higher BMI,% BF, MMI, HOMA-IR, CRP, uric acid, triglycerides and blood glucose and reduced levels of HDL-c, flexibility and VO2max. When evaluated separately was found that abdominal obesity reduces the chances of good aerobic fitness and muscle strength with increased chance of insulin resistance. On the other hand, sarcopenia reduces the chances of good flexibility, adequate levels of HDL-C and increases the chances of insulin resistance. When combined, sarcopenic obesity differs mainly in physical fitness, with cardiorespiratory fitness as determinant of sarcopenic obesity discrimination. Thus, was verified that sarcopenic obesity, in this population, are related to changes on physical fitness and the cardiorrespiratory fitness is the major component associated with this pathology / Mestre

Made available in DSpace on 2015-10-06T13:03:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-24. Added 1 bitstream(s) on 2015-10-06T13:18:07Z : No. of bitstreams: 1 000847634.pdf: 947725 bytes, checksum: e2e4dde50e6a9b319bd60a8d1ef6fc64 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / 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... / 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

Made available in DSpace on 2014-08-13T14:50:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-03-21Bitstream added on 2014-08-13T18:00:00Z : No. of bitstreams: 1 000767963_20160321.pdf: 387088 bytes, checksum: 622e7627eda50fe8d795c04d6005318d (MD5) Bitstreams deleted on 2016-03-21T12:11:30Z: 000767963_20160321.pdf,. Added 1 bitstream(s) on 2016-03-21T12:12:09Z : No. of bitstreams: 1 000767963.pdf: 2461370 bytes, checksum: 380d203c6640a22f77e0960477598587 (MD5) / A obesidade, juntamente com o sobrepeso, tem sido considerada um dos mais graves problemas de saúde pública do mundo, especialmente por serem os principais fatores de risco para inúmeras doenças crônicas, como a doença coronariana, diabetes mellitus tipo II, hipertensão e alguns tipos de tumores, as quais estão associadas a altas taxas de mortalidade. Devido à gravidade da obesidade para a população mundial, a padronização de modelos experimentais é necessária para realização de estudos em busca de novos tratamentos. O uso de compostos vegetais com apelo de promoção da saúde tem crescido como mecanismo de prevenção, controle e tratamento de doenças crônicas como a obesidade. Vários estudos etnofarmacológicos indicam espécies vegetais para o tratamento de distúrbios relacionados à obesidade com um importante atrativo de que estes compostos podem reduzir os efeitos adversos provocados pelo tratamento com anorexígenos tradicionais. Considerando a necessidade de um bom modelo experimental e que tanto a ingesta de alimentos como o tratamento por via oral com diferentes compostos pode manter as funções vitais do organismo, o objetivo deste projeto foi padronizar o modelo experimental de obesidade induzida por dieta hipercalórica em ratos e camundongos e avaliar os efeitos dos extratos padronizados de óleo de café verde (Coffea arabica L.), fitoesteróis de canola (Brassica campestres L.) e da associação dos dois extratos na obesidade induzida por dieta hipercalórica em roedores. Após indução da obesidade, os animais foram tratados por 21 dias com os extratos por via oral e sacrificados no 22º dia para avaliação dos efeitos destes produtos. Os experimentos mostraram que a indução da obesidade foi efetiva tanto em camundongos como em ratos, sendo que em camundongos foram necessárias apenas 8 semanas para se desenvolver obesidade severa. O óleo de café verde foi eficaz na redução do peso ... / Obesity along with overweight has been considered one of the most serious public health problems in the world, especially because they are the main risk factors for many chronic diseases such as coronary heart disease, type II diabetes mellitus, hypertension and some types of tumors, which are associated with high mortality rates. Due to the severity of obesity in world population, standardization of experimental models is required for studies to search new treatments. The use of plants compounds to promote health has grown as a mechanism for prevention, control and treatment of chronic diseases such as obesity. Several ethnopharmacological studies indicate plants species for the treatment of disorders associated with obesity with a major attraction of these compounds may reduce adverse effects caused by current treatment with appetite suppressants. Considering the need of a good experimental model, and both food intake and the oral treatment with different compounds can maintain vital body functions, the aim of this project was to standardize the experimental model of diet-induced obesity in rats and mice and evaluate the effects of standardized extract of green coffee oil (Coffea arabica L.) phytosterols of canola (Brassica campestris L.) and their association in diet-induced obesity in rodents. After obesity induction, the animals were treated for 21 days with the extract orally and killed on day 22 to assess the effects of these products. The experiments showed that induction of obesity was effective both in mice and rats but in mice just 8 weeks were needed to develop severity obesity. The green coffee oil extract was effective in reducing body weight, levels of insulin, C-reactive protein and leptin in obese animals. The phytosterols of canola were able to reduce the levels of C-reactive protein and cholesterol. The combination of the two products reduced cholesterol, VLDL-cholesterol and ...

Made available in DSpace on 2014-06-11T19:23:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-26Bitstream added on 2014-06-13T20:30:34Z : No. of bitstreams: 1 000749201.pdf: 1076680 bytes, checksum: f8d54de9713d73b3b269d15c659a9ffc (MD5) / As elevadas prevalências de obesidade e sarcopenia vêm se tornando relevante nos últimos anos diante de que as condições decorrentes da co-existência destes dois quadros potencializa os danos à saúde do indivíduo. O presente estudo tem como objetivo diagnosticar, avaliar a prevalência e o comportamento das variáveis funcionais da massa muscular e metabólicas da obesidade sarcopênica em adultos. Foram avaliados 523 indivíduos, de ambos os sexos, com maior prevalência do sexo feminino (72,7%), com idade média de 54,74±10,18 anos, ingressantes em programa para Mudança do Estilo de Vida (MEV) “Mexa-se Pró Saúde”. Os indivíduos foram submetidos a avaliações clínicas, da pressão arterial, aptidão cardiorrespiratória, de antropometria e composição corporal, aptidão física e análises bioquímicas, incluindo resistência insulínica (HOMA-IR), estresse oxidativo (Malondialdeido – MDA) e estresse inflamatório (Proteína C-Reativa – PCR). As análises estatísticas foram realizadas pelo software SAS 9.2, adotando p<0,05. Adotou-se como critério de obesidade a circunferência abdominal elevada. Verificou-se que a indivíduos portadores de obesidade abdominal comparados aos não portadores, apresentam maiores valores de IMC, %GC, IMM, HOMA-IR, PCR, ácido úrico, triglicerídios e glicemia e valores reduzidos de HDL-c, flexibilidade e VO2max. Quando avaliada isoladamente a obesidade abdominal, foi verificado que sua presença reduz as chances de boa aptidão aeróbia e força muscular com aumento da chance de resistência insulínica. Já a sarcopenia reduz as chances de alteração na flexibilidade, redução do HDL-c e aumenta as chances de resistência insulínica. Quando combinadas, a obesidade sarcopênica se diferencia principalmente na aptidão física, onde a aptidão cardiorrespiratória se mostrou como condicionante da discriminação de obesidade sarcopência. Assim, a discriminação da... / Recently, obesity and sarcopenia have been showing high prevalence among population and when this conditions are combined may increases damage to the individual's health. This study aimed to diagnose, assess prevalence, muscle mass function and metabolic variables related to sarcopenic obesity in adults. Were assessed 523 individuals, of both sexes, with higher prevalence in females (72.7%) with a mean age of 54.74 ± 10.18 years old, selected for Lifestyle Modification Program (MEV). The individuals were assessed for medical anamnese, blood pressure, cardiorespiratory fitness, body composition and anthropometry, physical fitness and biochemical analyzes, including analysis of insulin resistance (HOMA-IR), oxidative stress (malondialdehyde - MDA) and inflammatory stress (C-Reactive Protein - PCR). Statistical analyzes were performed by SAS software 9.2 (p <0.05). Obesity was defined by higher measures of waist circumference. It was verified that individuals with abdominal obesity compared to non-obese, presented higher BMI,% BF, MMI, HOMA-IR, CRP, uric acid, triglycerides and blood glucose and reduced levels of HDL-c, flexibility and VO2max. When evaluated separately was found that abdominal obesity reduces the chances of good aerobic fitness and muscle strength with increased chance of insulin resistance. On the other hand, sarcopenia reduces the chances of good flexibility, adequate levels of HDL-C and increases the chances of insulin resistance. When combined, sarcopenic obesity differs mainly in physical fitness, with cardiorespiratory fitness as determinant of sarcopenic obesity discrimination. Thus, was verified that sarcopenic obesity, in this population, are related to changes on physical fitness and the cardiorrespiratory fitness is the major component associated with this pathology

Orientador: Luiz Claudio Di Stasi / Banca: Ana Angélica Henrique Fernandes / Banca: Maria Del Carmen Velasquez Pereda / Resumo: A obesidade, juntamente com o sobrepeso, tem sido considerada um dos mais graves problemas de saúde pública do mundo, especialmente por serem os principais fatores de risco para inúmeras doenças crônicas, como a doença coronariana, diabetes mellitus tipo II, hipertensão e alguns tipos de tumores, as quais estão associadas a altas taxas de mortalidade. Devido à gravidade da obesidade para a população mundial, a padronização de modelos experimentais é necessária para realização de estudos em busca de novos tratamentos. O uso de compostos vegetais com apelo de promoção da saúde tem crescido como mecanismo de prevenção, controle e tratamento de doenças crônicas como a obesidade. Vários estudos etnofarmacológicos indicam espécies vegetais para o tratamento de distúrbios relacionados à obesidade com um importante atrativo de que estes compostos podem reduzir os efeitos adversos provocados pelo tratamento com anorexígenos tradicionais. Considerando a necessidade de um bom modelo experimental e que tanto a ingesta de alimentos como o tratamento por via oral com diferentes compostos pode manter as funções vitais do organismo, o objetivo deste projeto foi padronizar o modelo experimental de obesidade induzida por dieta hipercalórica em ratos e camundongos e avaliar os efeitos dos extratos padronizados de óleo de café verde (Coffea arabica L.), fitoesteróis de canola (Brassica campestres L.) e da associação dos dois extratos na obesidade induzida por dieta hipercalórica em roedores. Após indução da obesidade, os animais foram tratados por 21 dias com os extratos por via oral e sacrificados no 22º dia para avaliação dos efeitos destes produtos. Os experimentos mostraram que a indução da obesidade foi efetiva tanto em camundongos como em ratos, sendo que em camundongos foram necessárias apenas 8 semanas para se desenvolver obesidade severa. O óleo de café verde foi eficaz na redução do peso ... / Abstract: Obesity along with overweight has been considered one of the most serious public health problems in the world, especially because they are the main risk factors for many chronic diseases such as coronary heart disease, type II diabetes mellitus, hypertension and some types of tumors, which are associated with high mortality rates. Due to the severity of obesity in world population, standardization of experimental models is required for studies to search new treatments. The use of plants compounds to promote health has grown as a mechanism for prevention, control and treatment of chronic diseases such as obesity. Several ethnopharmacological studies indicate plants species for the treatment of disorders associated with obesity with a major attraction of these compounds may reduce adverse effects caused by current treatment with appetite suppressants. Considering the need of a good experimental model, and both food intake and the oral treatment with different compounds can maintain vital body functions, the aim of this project was to standardize the experimental model of diet-induced obesity in rats and mice and evaluate the effects of standardized extract of green coffee oil (Coffea arabica L.) phytosterols of canola (Brassica campestris L.) and their association in diet-induced obesity in rodents. After obesity induction, the animals were treated for 21 days with the extract orally and killed on day 22 to assess the effects of these products. The experiments showed that induction of obesity was effective both in mice and rats but in mice just 8 weeks were needed to develop severity obesity. The green coffee oil extract was effective in reducing body weight, levels of insulin, C-reactive protein and leptin in obese animals. The phytosterols of canola were able to reduce the levels of C-reactive protein and cholesterol. The combination of the two products reduced cholesterol, VLDL-cholesterol and ... / Mestre

Bakgrund Övervikt och obesitas är en global epidemi med negativa konsekvenser för folkhälsan. Behandlingen kan ske genom förändrade levnadsvanor, farmakologisk- eller kirurgisk behandling. Dock är vården ojämnt fördelad där skillnader finns i utbud och kvalitet. Vad personer anser är stödjande vid behandling av övervikt eller obesitas kan vara avgörande för behandlingsutfallet och hållbarheten över tid. Därför är det viktigt att undersöka personernas perspektiv. Syfte Syftet med studien var att beskriva personers perspektiv av stöd vid behandling av övervikt och obesitas inom vården. Metod En icke-systematisk litteraturöversikt baserat på 15 vetenskapliga originalartiklar. Artikelsökningarna är gjorda, utifrån relevanta sökord för syftet, i databaserna PubMed och CINAHL. Samtliga artiklar har kvalitetsgranskats utifrån bedömningsunderlaget av Sophiahemmets Högskola. En integrerad dataanalys utfördes för sammanställandet av resultatet. Resultat Tre huvudkategorier identifierades: Behovet av individanpassning, Vårdpersonalens betydande roll och Betydelsen av sociala interaktioner. Resultatet visade på att behovet av stöd är högst subjektivt och bör anpassas utifrån varje persons behov och resurser. Vidare ska hela personen bejakas. Vårdpersonal bör inneha kunskap, visa medkänsla, lyssna och vara icke-dömmande för att ses som stödjande. Därtill ansåg många av deltagarna att behovet av stöd kvarstår under lång tid. Slutsats För att stöd ska kunna upplevas som värdefullt av personer vilka behandlas för sin övervikt eller obesitas behöver individanpassning ske. När behandlingen utformas tillsammans med och utgår från personen kan ett holistiskt synsätt intas. Detta kan medföra att sjukdoms- och vårdlidandet blir mindre samtidigt som personers välbefinnande främjas. Därtill kan obesitasrelaterade komplikationer minska som ett resultat av god personcentrerad omvårdnad med en effektivare och stödjande behandling. / Background Overweight and obesity is a global epidemic with negative consequences for public health. Treatment offered can include lifestyle changes, pharmacological or surgical treatment. However, care services are unevenly distributed with differences in supply and quality. What people with overweight or obesity consider supportive in regard to treatment can impact on treatment outcomes and sustainability over time. Therefore, it is important to investigate the person's perspective. Aim The aim of the study was to describe the person's perspective of support in the treatment of overweight and obesity in healthcare. Method A non-systematic literature review based on 15 original scientific articles. The articles were retrieved, based on various keywords for the purpose, in the databases PubMed and CINAHL. All articles have been quality reviewed based on Sophiahemmet University assessment documents. An integrated data analysis was performed to compile the results. Results Three main categories were identified: The need for individual adaptation, The important role of healthcare staff and The importance of social interactions. The results showed that the need for support is highly subjective and should be adapted based on each person's needs and resources. Healthcare professionals should possess knowledge, show compassion, listen and be non-judgmental to be seen as supportive. The need for support is belived to remain for a long time. Conclusions In order for support to be perceived as valuable by people who are being treated for their overweight or obesity, the treatment needs to be individualized. When the treatment is designed together with and based on the person, a holistic approach can be adopted. This can lead to less suffering and at the same time promote the people's well-being. In addition, obesity-related complications can be reduced as a result of good person-centered care with more effective and supportive treatment

Only a small number of the subjects who enter treatment For obesity maintain their target weight. Explanations for this include increased food efficiency and alterations in resting metabolic rate (RMR). The RMR has been shown to be reduced after weight reduction and it is believed that a benefit of exercise training is an adaptive increase in lean body weight (LBW) with a concurrent decrease in excess body fat. Since caloric restriction is essential for weight reduction, an increase or preservation of LBW is desirable. The purpose of this study was to assess the effect of caloric restriction (DO group; n = 6) and caloric restriction plus weight training (DWT group; n = 8} on total weight (TW), percent fat (% fat), lean body weight (LBW), and RMR during an 8 week study. Both groups met 3 days/week for 30-45 min/day to perform a specific exercise or flexibility routine. The DWT group performed three sets of ten lifts on seven resistive exercises, under supervision, while the DO group performed a set routine designed to increase flexibility but result in no appreciable exercise. Subjects met weekly with a Registered Dietitian to provide information regarding nutritional and caloric content of Food, as well as behavior modification techniques. Results revealed non-Significant treatment effects between the groups on the variables RMR, % fat, and LBW. A treatment effect was observed for TW, with the DO group significantly losing more weight. Total weight and % fat significantly decreased in both groups from pre to posttest. A significant difference was noted for the DWT group from 4 weeks - 8 weeks in RMR, although there was no effect from baseline - 8 weeks. Thus, resistive exercise when added to caloric restriction, increases strength, but results in Slower weight loss when compared to diet only subjects while resulting in similar losses in % fat and total weight. / Master of Science

Thesis (MScMedSc)--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Obesity is a major risk factor for ischaemic heart disease. Obesity-induced metabolic abnormalities have been associated with increased oxidative stress which may play an important role in the increased susceptibility to myocardial dysfunction and ischaemiareperfusion (I/R) injury seen in obesity. The pineal gland hormone, melatonin, has powerful antioxidant properties. Previous studies have shown that short-term or acute melatonin administration protects the normal healthy heart of lean animals against I/R damage. However, the effects of melatonin on the heart in obesity remain unknown. Moreover, the myocardial signalling mechanisms associated with the cardioprotective effects of melatonin have not been established. Using a rat model of diet induced obesity, we set out to: 1) investigate the effects of chronic melatonin administration on the development of diet-induced systemic alterations including biometric and metabolic parameters and oxidative stress, 2) determine whether chronic melatonin treatment protects the myocardium against ischaemia-reperfusion injury, and 3) determine whether melatonin treatment confers cardioprotection by altering the reperfusion injury salvage kinase (RISK) pathway signalling and the pro-apoptotic p38 MAPK, AMPK and GLUT-4 expression. Male rats weighing 200±20g were randomly allocated to four groups: 1) C, control rats receiving a standard commercial rat chow and drinking water without melatonin; 2) CM, control rats receiving melatonin (4mg/kg/day) in drinking water; 3) D, diet-induced obesity rats, receiving a high calorie diet and drinking water without melatonin; 4) DM, diet-induced obesity rats, receiving melatonin in drinking water. After 16 weeks of treatment and feeding, rats were weighed and blood and myocardial tissue collected to document biochemical and molecular biological changes. Hearts were perfused on the isolated working rat heart perfusion apparatus for the evaluation of myocardial function and infarct size. The Reperfusion Injury Salvage Kinases (RISK) pathway (PKB/Akt (Ser-473), ERK p42/ p44) and p38 MAPK (mitogenactivated protein kinase) were investigated in pre-and post-ischaemic hearts using Western blotting techniques. Post-ischaemic activation of AMPK (5’AMP-activated protein kinase) (Thr- 172) and GLUT-4 (glucose transporter) expression were also investigated. Serum and baseline myocardial glutathione (GSH) content were measured. In addition, serum lipid peroxidation products: thiobarbituric reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxide (LOOH), were also determined. The high-calorie diet caused increases in body weight, visceral adiposity, heart weight, serum insulin, leptin, blood triglycerides, and low HDL-cholesterol levels. Blood glucose levels were similar for both diet fed rats and controls. Myocardial glutathione, serum glutathione, total cholesterol, TBARS, LOOH, CD as well as total cholesterol (TC) levels were not affected by the high calorie diet. Chronic melatonin treatment reduced body weight gain, visceral adiposity, heart weight, blood triglycerides, serum insulin, HOMA index, serum leptin (DM vs D, p<0.01), and increased blood HDL-C in diet treated rats while there was no effect on these parameters in control rats, despite the reduction in body weight, heart weight and visceral adiposity. Melatonin treatment had no effect on myocardial or serum GSH and LOOH in either control or diet animals. It however reduced TBARS and CD in the diet and control groups, respectively. At baseline, chronic melatonin treatment caused a significant increase in phospho-PKB/total PKB ratio and a concomitant reduction in phospho-p38 MAPK/total p38 MAPK ratio of control hearts while there were no such effects on diet-induced-obesity hearts. Infarct size was significantly reduced by melatonin in both diet and control groups (DM: 16.6±2.0%; D: 38.4±2.6% (p < 0.001), and CM: 12.8±1.5%; C: 30.4±1.0%, p<0.001). After coronary artery occlusion and 30 minutes of reperfusion, melatonin increased percentage recovery of aortic output (DM: 28.5±6.5%; D: 6.2±6.2%, p<0.01), cardiac output (DM: 44.4±5.2%; D: 26.6±5.1%, p < 0.01) and total work (DM: 34.5±5.6%; D: 20.4±7.9%, p<0.05) of diet-induced obesity hearts, while having no effect on control hearts. During reperfusion, hearts from melatonin treated rats had increased activation of PKB/Akt (p<0.01), ERK42/44 (p<0.05), and reduced p38 MAPK activation (p<0.05). There was no difference in post-ischaemic activation of AMPK (Thr-172) and GLUT-4 expression in either control or diet fed rats. We successfully demonstrated that chronic melatonin treatment prevented the development of diet-induced metabolic abnormalities and improved ex vivo myocardial function. Melatonin protected the heart against ischaemia-reperfusion injury that was exacerbated in obesity. This was achieved by activation of the RISK pathway. The antioxidant properties of melatonin were involved in these cardioprotective effects. / AFRIKAANSE OPSOMMING: Vetsug of obesiteit is een van die hoof risikofaktore vir iskemiese hartsiekte. Obesiteitgeinduseerde metaboliese abnormaliteite gaan met verhoogde oksidatiewe stres gepaard wat op sy beurt ‘n belangrike rol mag speel in die miokardiale wanfunksie en verhoogde vatbaarheid vir iskemie-herperfusie (I/H) beskadiging, kenmerkend van vetsug. Melatonien, die hormoon afgeskei deur die pineaalklier, is ‘n kragtige anti-oksidant. Vorige studies het getoon dat kort-termyn of akute toediening van melatonien die normale hart van gesonde diere teen I/H beskadiging deur middel van sy anti-oksidant aksies beskerm. Die effek van melatonien op die hart in obesiteit is egter nog onbekend. Hierbenewens is die miokardiale seintransduksie meganismes geassosieer met die beskermende effekte van die hormoon nog nie ontrafel nie. ‘n Model van dieet-geinduseerde obesiteit in rotte is gebruik om die volgende te bepaal: (i) die effek van kroniese melatonientoediening op die ontwikkeling van dieet-geinduseerde sistemiese veranderinge soos biometriese en metaboliese parameters en oksidatiewe stres (ii) die effek van kroniese melatonienbehandeling op die respons van die hart op I/H beskadiging en (iii) die rol van herperfusie beskadiging op die aktivering van PKB/Akt en ERK42/44 (die sg RISK seintransduksiepad), die pro-apoptotiese p38MAPK, AMPK sowel as die uitdrukking van GLUT-4. Manlike Wistar rotte (200±20g) is ewekansig in vier groepe verdeel: (i) C, kontrole rotte wat ‘n standaard rotdieet en drinkwater sonder melatonien ontvang (ii) CM, kontrole rotte wat melatonien (4mg/kg/dag) ontvang (iii) D, dieet-geϊnduseerde vet rotte wat ‘n hoë kalorie dieet en drinkwater sonder melatonien ontvang (iv) DM, dieet-geϊnduseerde vet rotte wat melatonien (4mg/kg/dag) in die drinkwater ontvang. Na 16 weke van behandeling, is die rotte geweeg, bloed en hartweefsel gekollekteer vir biochemiese en molekulêre biologie bepalings. Harte is geperfuseer volgens die werkhartmodel, blootgestel aan iskemie/herperfusie vir evaluering van funksionele herstel en infarktgrootte. Uitdrukking en aktivering van PKB/Akt (Ser-473), ERKp42/p44 en p38MAPK van pre-en postiskemiese hartweefsel is met behulp van Western blot bepaal. Postiskemiese aktivering van AMPK (5’AMP-aktiveerde proteϊen kinase) (Thr-172) en GLUT-4 (glukose transporter) is op soortgelyke wyse bepaal. Serum en basislyn hartweefsel glutatioon (GSH) inhoud asook tiobarbituursuur reaktiewe substans (TBARS), gekonjugeerde diene (CD) en lipiedhidroperoksied (LOOH) konsentrasies is bepaal. Resultate Die hoë kalorie diet het ‘n toename in liggaamsgewig, visserale vet, hartgewig, serum insulien, leptien, plasma trigliseried en lae HDL-cholesterol vlakke teweegebring. Bloed glukosevlakke was egter dieselfde in die vet en kontrole rotte. Miokardiale glutatioon, serum glutatioon, totale cholesterol, TBARS, LOOH, CD is nie deur die dieet beinvloed nie. Chroniese melatonien behandeling het die liggaamsgewig, visserale vet, hartgewig, plasma trigliseried, serum insulien en leptien, HOMA indeks verlaag (DM vs D, p<0.05) en die HDL-cholesterol verhoog in die dieetrotte, terwyl dit geen effek op hierdie parameters in kontrole rotte gehad het nie (uitgesonderd ‘n afname in liggaamsgewig, hartgewig en visserale vet). Melatonien behandeling het geen effek op hart of serum GSH en LOOH in kontrole en vet rotte gehad nie. Dit het egter die TBARS en CD in beide vet en kontrole rotte verlaag. Chroniese melatonien toediening het ‘n beduidende toename in basislyn fosfo PKB//totale PKB ratio en ‘n afname in fosfo p38MAPK/totale p38MAPK ratio teweegebring in harte van kontrole rotte, maar soortgelyke effekte is nie in die harte van die vet rotte waargeneem nie. Infarktgrootte is beduidend deur melatonienbehandeling verlaag in beide dieet en kontrole groepe (DM: 16.6± 5.2%, D: 38.4 ±2.6% (p<0.001); CM: 12.8± 1.5%; C 30.4±1.0 (p<0.001). Na koronere arterie afbinding en 30 min van herperfusie, het melatonien die persentasie herstel van aorta omset (DM: 28.5± 6.5%; D: 6.2± 6.2%, p<0.01), kardiale omset ( DM: 44.4± 5.2%D: 26.6±5.1%, p<0.01) en totale werk (DM: 34.5 5.6%; D 20.4± 7.9%, p<0.05) in die harte van dieetrotte verbeter, terwyl dit sonder effek was in kontrole harte. Tydens herperfusie het harte van melatonienbehandelde rotte verhoogde aktivering van PKB/Akt (p<0.01) en ERKp42/p44 (p<0.05) getoon, terwyl aktivering van p38MAPK verlaag is (p<0.05). Geen verskil in postiskemiese aktivering van AMPK en GLUT-4 uitdrukking is in beide kontrole en dieetrotte waargeneem nie. Ons het daarin geslaag om aan te toon dat chroniese melatonienbehandeling die ontwikkeling van dieet-geϊnduseerde metaboliese abnormaliteite beduidend kan voorkom en ex vivo miokardiale funksie verbeter. Melatonien het ook die hart teen iskemie/herperfusie beskadiging beskerm in beide kontrole en dieetrotte. Bogenoemde veranderinge het met aktivering van PKB/Akt en ERKp42/p44 gepaard gegaan. Die anti-oksidant effekte van melatonien was heelwaarskynlik hierby betrokke.

Made available in DSpace on 2014-06-11T19:30:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-19Bitstream added on 2014-06-13T20:01:09Z : No. of bitstreams: 1 000740796.pdf: 3299028 bytes, checksum: 68adc36acee433e912a20b2f1b608a02 (MD5) / A sibutramina é um inibidor seletivo da recaptação neuronal de noradrenalina e serotonina amplamente utilizada para o tratamento da obesidade. Investigações anteriores demonstraram o impacto da sibutramina nas reservas espermáticas e na contratilidade de órgãos relacionados a ejaculação. Portanto, o objetivo do presente trabalho foi avaliar os parâmetros espermáticos e a contratilidade da próstata ventral e do ducto epididimário distal isolado de ratos expostos in vivo e in vitro a sibutramina. No experimento 1, ratos machos Wistar (12-16 semanas /350-450 g) foram divididos em dois grupos: tratado oralmente com sibutramina (10 mg/kg/dia) e grupo controle, que recebeu apenas o veículo (dimetilsulfóxido e solução salina). Após 30 dias de tratamento, os animais foram pesados e eutanasiados por decapitação. Os testículos direitos, epidídimos, ductos deferentes, próstatas ventrais e glândulas seminais (sem a glândula coaguladora) foram removidos e os seus pesos foram determinados. Os testículos e epidídimos direitos foram utilizados para a determinação do número de espermatozoides e os esquerdos para análise histopatológica. Além disso, os espermatozoides da cauda do epididimo direito foram usados para inseminação artificial in utero e para análise da motilidade e morfologia espermática. Os níveis séricos de testosterona, hormônio folículo estimulante (FSH) e hormônio luteinizante (LH) também foram mensurados. No experimento 2, um outro lote de ratos, seguindo o mesmo desenho experimental, foi utilizado para a realização dos ensaios in vitro de reatividade farmacológica do ducto epididimário distal isolado. No experimento 3 ratos machos adultos foram utilizados para os ensaios in vitro de reatividade farmacológica do ducto epididimário distal isolado, com e sem a presença de sibutramina, e para ensaios in vivo da reatividade farmacológica da próstata ventral, com e... / Sibutrmine is a neuronal noradrenaline and serotonin reuptake inhibitor laegely used for the treatment of obesity. Previous investigations have shown the impact of sibutraimine on ejaculation contractility related organs and sperm reserves. Therefore, the aim of the present work was to evaluate sperm parameters and the contractility of isolated distal cauda epididymidis duct and ventral prostate of rats exposed in vivo and in vitro to sibutramine. In experiment 1, Wistar male rats (12-16 weeks/350-450 g) were divided into two groups: treated orally with sibutramine (10 mg/kg/day) and control, which received only the vehicle (dimethyl sulfoxide and saline). After 30 days of treatment the animals were weighed and euthanized by decapitation. The right testis, ....