Orientador: José Roberto Bosqueiro / Resumo: O termo Diabetes mellitus (DM) descreve uma desordem metabólica, caracterizada por hiperglicemia crônica, resultante da falta de produção de insulina e/ou de resistência à ação do mesmo. Atualmente, muitos medicamentos são utilizados para tratar diabetes, incluindo insulina exógena e drogas alopáticas como biguanidas, sulfonilureias e inibidores de alfa-glicosidases. Entretanto, possuem muitos efeitos adversos que diminuem a qualidade de vida do paciente e a resposta por uso prolongado. Somado ao fato de que a incidência do DM vem se elevando de modo alarmante, os estudos com plantas que possuam efeitos antidiabéticos vêm despertando o interesse por parte dos pesquisadores. Estudos anteriores do nosso grupo de pesquisa sobre o efeito hipoglicemiante do extrato de folhas de Bauhinia holophylla nos permitiu identificar e isolar a molécula responsável pelo efeito hipoglicemiante. Tal molécula é denominada litospermosídeo, um cianoglicosídeo não- cianogênico. Assim, o presente estudo teve como objetivo realizar a caracterização geral do efeito do litospermosídeo no quadro diabético de camundongos diabéticos induzidos por estreptozotocina e tratados por 14 dias nas doses 1, 5, 10 e 20mg/Kg, na busca de uma alternativa para o tratamento do diabetes. Foram utilizados camundongos machos Swiss, que foram separados em 1 grupo normoglicêmico e 5 grupos diabéticos. A glicemia de jejum mensurada nos dias 7 e 14, e a ingestão hídrica e alimentar e o peso corpóreo foram medidos diariamente.... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The term Diabetes mellitus (DM) describes a metabolic disorder characterized by chronic hyperglycemia resulting from lack of insulin production and/or resistance to insulin action. Many medications are currently being used to treat diabetes, including exogenous insulin and allopathic drugs such as biguanides, sulfonylureas, and alpha-glycosidase inhibitors. However, they have many adverse effects that decrease the quality of life of the patient and the response for prolonged use. In addition to the fact that the incidence of DM is rising alarmingly, studies with plants that have anti-diabetic effects have aroused the interest of the researchers. Previous studies by our research group on the hypoglycemic effect of Bauhinia holophylla leaf extract have allowed us to identify and isolate the molecule responsible for the hypoglycemic effect. Such a molecule is called lithospermoside, a noncyanogenic cyanoglicoside. The aimed of this study was to characterize the lithospermoside effect in the diabetic group of diabetic mice induced by streptozotocin and treated for 14 days at doses 1, 5, 10 and 20mg / kg, in the search for an alternative treatment of diabetes. Male Swiss mice were used, which were separated into 1 normoglycemic group and 5 diabetic groups. Fasting glycemia measured on days 7 and 14, and water and food intake and body weight were measured daily. On the 14th day, insulin sensitivity and glucose tolerance were analyzed. After 14 days, the animals were euthanized and ... (Complete abstract click electronic access below) / Mestre

Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Type 2 diabetes mellitus (T2DM) is often characterized with hyperglycemia, delayed gastric emptying time and a blunted response of gut hormones during feeding that may modulate hunger and satiety. We hypothesized that poor diabetes control is associated with greater hunger suppression, satiation and satiety than good control. We studied 9 T2DM men, after an overnight fast and in response to a 689 kcal mixed meal, twice with or without oral antihyperglycemic agents in a crossover design. Untreated, subjects had higher fasting and postprandial glucose, showed prolonged gastric emptying time and higher thermic effect of food; all factors associated with hunger suppression. Treated, glycemia decreased by 24% and postprandially GLP-1 and PYY3-36 , peptides associated with hunger suppression, were higher than without medication. Thus, no differences were observed in satiation scores between studies. However food intake from a buffet offered 5 hours post meal, an index of satiety, related to hunger scores only in the study with medication.

To examine the effects of Momordica charantia (MC) and cinnamon on glucose uptake and adiponectin secretion (AS) fat cells, 3T3-L1 adipocytes were treated with a water extract of cinnamon (CE) and three concentrations of MC water and ethanol extracts. The treatment combination of 0.2 mg/ml MC water extract and 0.5 nM insulin was associated with an increased glucose uptake into the cells (61%) and increased AS from the cells (75%). Without insulin, 0.2 mg/ml of CE increased glucose uptake (100%) and completely inhibited AS from the cells. Sub-optimal concentrations of insulin did not further enhance the CE activity and, in combination with 50 nM insulin, a dose-dependent decrease in glucose uptake was observed. The present results indicate that preferentially water-soluble component(s) in MC enhance the glucose uptake action of sub-optimal concentrations of insulin in 3T3-L1 adipocytes. This effect is accompanied by and may be a result of increased AS. CE increases glucose uptake in these adipocytes but inhibits AS.

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

Diabetes has been labelled as one of the largest crises in the twenty-first century. Saudi Arabia is one of the top 10 countries for prevalence of diabetes and one in five people has the condition. Medication adherence assessment is vital to help clinicians reach therapy outcomes and identify gaps in patient management. The aim of this PhD was to explore oral hypoglycaemic medication (OHM) adherence in patients with Type 2 diabetes patients in Saudi Arabia and to identify factors associated with OHM adherence. The aim was addressed by: 1) Conducting a systematic review to identify which tools could be used to measure adherence to OHM as well as to quantify adherence levels across different countries; 2) Undertaking a cross-sectional study to quantify the prevalence of adherence to OHM in a group of patients in Saudi Arabia using a validated measure of adherence. An interview study on a subset of these patients then explored in detail Type 2 diabetic patients' beliefs and attitudes towards their OHM regimen, including factors which helped or hindered their medication taking behaviour. The systematic review included 37 studies. It showed that the level of OHM adherence varied widely across all measures: 36% to 95% when dispensing records were used, 37% to 98% with self-report, and 17% to 97% with pill counts. The term 'adherence' was most commonly used. There was no identified studies assessing OHM adherence in Saudi Arabia. The cross-sectional study showed that the level of OHM adherence was 40%, Lower adherence was associated with patients of younger age (OR, 1.084; 95% CI, 1.056-1.112), individual taking a higher number of non-OHM (OR, 0.848; 95% CI, 0.728-0.986) and having a higher HbA1c level (OR, 0.808; 95% CI, 0.691-0.943). The interview study identified several factors affecting OHM adherence using a validated theoretical framework. Facilitators of OHM adherence were OHM scheduling, knowledge about OHM, knowledge on other relevant behaviours such as diet and physical activity, knowing how to take OHM appropriately and how to manage hypoglycaemia. In addition, OHM adherence was facilitated by beliefs of preventing diabetic complications, avoiding insulin injections, achieving an improved quality of life, accepting diabetes, being optimistic about the future, and having high self-confidence. Conversely, barriers to OHM adherence were forgetfulness, cognitive overload, lack of knowledge of sexual health implications of OHM, and knowledge of OHM side effects or drug-drug interactions. Furthermore, side effects of OHM such as weight gain or hypoglycaemia, knowing how to measure blood sugar, feeling no symptoms, and having many medications to take were additional barriers to OHM adherence. The MASA study also showed that there are several social- and physical-related factors affecting OHM adherence such as the patient-physician relationship and perceived family support. The work in this PhD suggests that targeting suboptimal OHM adherence behaviour needs to be done in a comprehensive manner. The key benefit is to provide future researchers with a comprehensive range of factors that can be targeted when defining targets for an intervention(s). Further systematic intervention development and testing is required to choose and prioritise the most promising interventions to improve OHM adherence.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-03-02T16:09:36Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO PARA DEPÓSITO_AMANDA DAMASCENO LEÃO.pdf: 4254308 bytes, checksum: 37ca5d3f981b6ef7d24669240e08a3cc (MD5) / Made available in DSpace on 2017-03-02T16:09:36Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO PARA DEPÓSITO_AMANDA DAMASCENO LEÃO.pdf: 4254308 bytes, checksum: 37ca5d3f981b6ef7d24669240e08a3cc (MD5) Previous issue date: 2016-03-03 / CNPq / Hidróxidos duplos lamelares são materiais inorgânicos, estruturados bidimensionalmente, dotados de carga elétrica e com capacidade de interagir e carrear moléculas orgânicas. Proporcionam aumento de solubilidade, estabilidade e alteração na liberação da molécula intercalada ou adsorvida. A presente dissertação objetivou o aumento da taxa de dissolução aquosa do hipoglicemiante glibenclamida utilizada no tratamento do diabetes mellitus tipo II, para tanto realizou-se a adsorção do fármaco em HDLs do tipo Mg2Al(OH)8(Cl).nH2O e Zn2Al(OH)8(Cl).nH2O. Os sistemas foram obtidos através de síntese por co-precipitação e caracterizados pelas técnicas: análise elementar; difratometria de raios X; espectroscopia na região do infravermelho (FTIR), microscopia eletrônica de varredura (MEV) e calorimetria exploratória diferencial (TGA-DSC) acoplada à espectrometria de massa (MS). O percentual de glibenclamida nos sistemas segundo a análise elementar foi de 25,23% para Mg2Al(OH)8(Cl).nH2O e de 26,85% para Zn2Al(OH)8(Cl).nH2O, observou-se retardamento de 130°C na decomposição do fármaco em Zn2Al(OH)8(Cl).nH2O e alteração na estrutura cristalina em ambos os sistemas. Para a avaliação das alterações do perfil de dissolução, os sistemas foram submetidos ao teste de dissolução usando meio ácido com pH 1,2 e meio básico com pH 7,3, no qual, foi observado o aumento de 500% na taxa de dissolução da glibenclamida no HDL Mg2Al(OH)8(Cl).nH2O e de 300% na taxa de dissolução de Zn2Al(OH)8(Cl).nH2O em meio básico. Assim, pode-se concluir que os novos sistemas obtidos apresentaram aumento significativo da taxa de dissolução da glibenclamida podendo portanto, ser considerados como promissores para aplicações tecnológicas futuras. / HDLs are inorganic materials, two-dimensionally structured, equipped with electric charge and the ability to interact and caries organic molecules. Provide increased solubility, stability and change in the release of the intercalated or adsorbed molecule. This work aimed to increase the aqueous solubility of hypoglycemic glibenclamide, used in the treatment of diabetes mellitus type II, for both held the adsorption of the drug in the HDLs type Mg2Al(OH)8(Cl).nH2O and Zn2Al(OH)8(Cl).nH2O. The systems were obtained through synthesis by co-precipitation and characterized by the techniques: elemental analysis; X-ray diffraction; scanning electron microscopy (SEM); in the infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC-TGA) coupled with mass spectrometry (MS). The loading of the glibenclamide in the systems according to the elemental analysis was 25.23% for Mg2Al(OH)8(Cl).nH2O and 26.85% for Zn2Al(OH)8Cl.nH2O, the retardation was observed 130° C the decomposition of the drug in Zn2Al(OH)8(Cl).nH2O and also to change the crystalline structure of both systems. For the evaluation of the change of the dissolution profile systems were subjected to the dissolution test using pH 1.2 with acidic and basic medium at pH 7.3, which showed an increase of 100% in the solubility of glibenclamide in LDH Mg2Al (OH)8(Cl).nH2O and 60% Zn2Al (OH)8(Cl).nH2O. Thus, one may conclude that the obtained new systems have provided substantial increase of the solubility of glibenclamide and can therefore be considered promising for future technological applications.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Os efeitos antiinflamatÃrio, hipoglicemiante e hipolipemiante da lovastatina foram avaliados sobre os modelos da peritonite e edema de pata induzidos por carragenina 1% e modelo de diabetes mellitus induzida por aloxano. A lovastatina reduziu o edema de pata, expresso em mL, induzido por carragenina 1% com as doses de 2, 5 e 10 mg/kg na 2 h (1,33  0,12; 1,03  0,19; 1,19  0,21; respectivamente), na 3 h (2,30  0,17; 1,76  0,23; 1,93  0,21) e 4 h (2,44  0,12; 1,85  0,21; 2,06  0,35) em comparaÃÃo ao grupo controle (1,83  0,21; 2,86  0,24 e 3,26  0,13). A indometacina (20 mg/kg), utilizada como droga de referÃncia, tambÃm reduziu o edema nas horas citadas (0,96  0,09; 1,28  0,23 e 1,36  0,17). A lovastatina reduziu a migraÃÃo de neutrÃfilos induzida pela carragenina nas doses de 2 mg/kg (16,0  2,1 x 103/mm3), 5 mg/kg (16,1  2,0 x 103/mm3) e 10 mg/kg (15,5  2,3 x 103/mm3) em comparaÃÃo ao grupo controle (58,7  10,5 x 103/mm3). A dexametasona (1mg/kg) utilizada como padrÃo apresentou resultado semelhante (14,3  3,5 x 103/mm3). Para avaliaÃÃo dos efeitos hipoglicemiante e hipolipemiante induziu-se o distÃrbio metabÃlico atravÃs da injeÃÃo de aloxano (40 mg/kg. i.v.) e utilizou-se diferentes esquemas de tratamento com lovastatina. Sobre o tratamento curativo a lovastatina reduziu a hiperglicemia causada pelo aloxano no quinto dia de tratamento com as doses de 2 mg/kg (reduÃÃo de 41,7%), 5 mg/ kg (43,3%), 10 mg/kg (45,3%) e 20 mg/kg (42,2%). O controle manteve a hiperglicemia (334,1  27,7; 335,5  24,1). Efeitos semelhantes foram encontrados sobre os nÃveis de triglicerÃdeos: 2 mg/kg (reduÃÃo de 70%), 5 mg/kg (55,4%) e 10 mg/kg (47,6%) e 20 mg/kg (31%); sobre os nÃveis de colesterol: 2 mg/kg (reduÃÃo de 33,6%), 5 mg/kg (36,7%), 10 mg/kg (35%) e 20 mg/kg (39,8%); Sobre a AST: 2 mg/kg (reduÃÃo de 36%), 5 mg/kg (45%), 10 mg/kg (43%) e 20 mg/kg (37,8%). Sobre a ALT somente a dose de 20 mg/kg mostrou reduÃÃo (38,9%). Foi realizado um tratamento preventivo onde ratos foram previamente tratados por 5 dias com lovastatina 2mg/kg e em seguida induziu-se o diabetes. A lovastatina preveniu o aparecimento da hiperglicemia (170,7  28,2 mg/dL) em comparaÃÃo ao controle (312,4  22,0). O mesmo ocorreu em relaÃÃo aos triglicerÃdeos (252,8  46,7 e 461,3  34,7; LOV e veÃculo, respectivamente) e colesterol (112,4  9,7 e 191,6  18,9), contudo nÃo houve diferenÃa entre os grupos em relaÃÃo à AST (34,4  1,3 e 35,7  2,1 UI/L) e ALT (44,2  1,1 e 43,9  1,2 UI/L). TambÃm foi realizado um tratamento sub-crÃnico por 23 dias com lovastatina apÃs a induÃÃo do diabetes. Os parÃmetros foram analisados no dia 0, dia 5 e dia 23. Sobre a glicemia as doses de 2 mg/kg (309,2  30,5; 172,0  38,0 e 176,7  33,1) e 5 mg/kg (346,3  21,5; 226,7  25,8 e 125,8  20,4) mostraram reduÃÃo em comparaÃÃo ao controle (373,0  47,5; 347,5  26,2 e 338,6  25,3). O mesmo ocorreu com os triglicerÃdeos: 2 mg/kg (373,1  97,6; 67,0  48,4 e 179,8  40,3), 5 mg/kg (606,9  102,0; 195,2  30,5 e 56,1  10,0) e controle (573,0  27,2; 485,7  54,2 e 459,7  33,7); colesterol: 2 mg/kg (108,0  8,4; 74,0  5,8 e 73,4  5,1), 5 mg/kg (117,5  7,2; 75,9  4,9 e 74,3  6,4) e controle (130,0  6,3; 121,8  4,9 e 116,4  7,8). O tratamento mostrou efeito somente sobre a AST: 2 mg/kg (30,4  2,3; 38,4  3,4 e 29,4  1,1), 5 mg/kg (38,7  7,7; 46,7  3,5 e 32,5  5,5) e controle (41,8  1,8; 40,9  6,3 e 69,6  2,4). A associaÃÃo da lovastatina (2 mg/kg) com glibenclamida (5 mg/kg) nÃo potencializou o efeito de ambas as drogas sozinhas na reduÃÃo da glicemia no quinto dia de tratamento: LOV 2 (reduÃÃo de 64,5%), GLIB 5 (78%) e LOV + GLIB (77,6%). Resultado semelhante foi obtido na associaÃÃo com metformina (50 mg/kg): LOV 2 (reduÃÃo de 64,5%), METF 50 (72%) e LOV + METF (75%). Os resultados encontrados demonstram que a aÃÃo antiinflamatÃria da lovastatina à um importante efeito paralelo, principalmente na prevenÃÃo e tratamento dos distÃrbios inflamatÃrios vasculares associados com aterosclerose e diabetes. AlÃm disso, o efeito hipoglicemiante mostrado pela droga parece ser independente dos seus efeitos hipolipemiantes, demonstrando uma possÃvel aÃÃo auxiliar no tratamento de indivÃduos diabÃticos. / The anti-inflammatory, hypoglicemic and hypolipidemic effects of lovastatin were evaluated on animal models of carrageenan-induced peritonitis and paw edema and alloxan induced diabetes. Lovastatin reduced the paw edema, mL, induced by carrageenan at the doses of 2, 5 and 10 mg/kg during the period of measures: 2nd h (1,33  0,12; 1,03  0,19; 1,19  0,21; respectively), 3rd h (2,30  0,17; 1,76  0,23; 1,93  0,21) and 4th h (2,44  0,12; 1,85  0,21; 2,06  0,35) when compared to control group (1,83  0,21; 2,86  0,24 e 3,26  0,13). Indometacin used as reference drug also reduced the edema (0,96  0,09; 1,28  0,23 e 1,36  0,17). Lovastatin reduced carrageenan-induced neutrophil migration at the doses of 2 mg/kg (16,0  2,1 x 103/mm3), 5 mg/kg (16,1  2,0 x 103/mm3) e 10 mg/kg (15,5  2,3 x 103/mm3) when compared to control group (58,7  10,5 x 103/mm3). Dexametasone used as reference drug showed similar results (14,3  3,5 x 103/mm3). To evaluate the hypoglycemic and hypolipidemic effects a metabolic disorder was induced by injection of alloxan (40 mg/kg, i.v.) and different treatments schedules with lovastatin were used. On curative treatment, lovastatin reduced the alloxan induced-hyperglycemia, mg/dL on the fifth day of treatment at the doses of 2 mg/kg (reduction de 41,7%), 5 mg/ kg (43,3%), 10 mg/kg (45,3%) and 20 mg/kg (42,2%). Control group keep the level of hyperglycemia (334,1  27,7; 335,5  24,1). Similar results were found above triglycerides levels : 2 mg/kg (reduction of 70%), 5 mg/kg (55,4%), 10 mg/kg (47,6%) and 20 mg/kg (31%); Over cholesterol levels: 2 mg/kg (reduction of 33,6%), 5 mg/kg (36,7%), 10 mg/kg (35%) and 20 mg/kg (39,8%); Over AST levels: 2 mg/kg (reduction of 36%), 5 mg/kg (45%), 10 mg/kg (43%) and 20 mg/kg (37,8%). Over ALT levels only the dose of 20 mg/kg showed reduction (38,9%). A five-day preventive treatment with lovastatin (2 mg/kg) was carried out before the diabetes induction. Lovastatin prevent the hyperglycemia (170,7  28,2 mg/dL) when compared to control (312,4  22,0). The same happened to triglycerides 252,8  46,7 e 461,3  34,7, LOV e control, respectively) and cholesterol (112,4  9,7 e 191,6  18,9), however no difference between the groups were found when analyzing AST (34,4  1,3 e 35,7  2,1 UI/L) and ALT (44,2  1,1 e 43,9  1,2 UI/L). Also a subchronic treatment with lovastatin was undertaken. The parameters were evaluated at the day 0, day 5 and day 23. On glycemia lovastatin at the doses of 2 mg/kg (309,2  30,5; 172,0  38,0 e 176,7  33,1) and 5 mg/kg (346,3  21,5; 226,7  25,8 e 125,8  20,4) showed reduction when compared to control group (373,0  47,5; 347,5  26,2 e 338,6  25,3). The same occured with triglycerides: 2 mg/kg (373,1  97,6; 67,0  48,4 e 179,8  40,3), 5 mg/kg (606,9  102,0; 195,2  30,5 e 56,1  10,0) and control (573,0  27,2; 485,7  54,2 e 459,7  33,7); Cholesterol: 2 mg/kg (108,0  8,4; 74,0  5,8 e 73,4  5,1), 5 mg/kg (117,5  7,2; 75,9  4,9 e 74,3  6,4) and control (130,0  6,3; 121,8  4,9 e 116,4  7,8). The treatment showed effect only over AST levels: 2 mg/kg (30,4  2,3; 38,4  3,4 e 29,4  1,1), 5 mg/kg (38,7  7,7; 46,7  3,5 e 32,5  5,5) and control (41,8  1,8; 40,9  6,3 e 69,6  2,4). The association of lovastatin (2 mg/kg) and glybenclamide (5 mg/kg) did not enhance the effects of both drugs alone on glucose levels at the day 5 of treatment: LOV 2 (reduction of 64,5%), GLIB 5 (78%) e LOV + GLIB (77,6%). A similar effect was found when lovastatin was associated to metformin (50 mg/kg): LOV 2 (reduction of 64,5%), METF 50 (72%) e LOV + METF (75%). The results found show that the anti-inflammatory effect of lovastatin is an important parallel action, especially to prevent and treat vascular inflammatory disorders associated to atherosclerosis and diabetes. Besides that, the hypoglycemic effect of the drug seems to be independent of its hypolipidemic actions, suggesting an auxiliary action to treat diabetic patients.

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