Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2009. / Full text also available online. Scroll down for electronic link.

Thesis (M. Med. Sc.)--University of Hong Kong, 2005.

Thesis (M.S.)--Wisconsin. / Includes bibliographical references (leaves 60-67).

Thesis (M.S.)--Ohio State University. / Bibliography: leaves 65-66. Available online via OhioLINK's ETD Center

Dissertação (mestrado) - Universidade Federal do Rio de Janeiro. Instituto de Nutrição / Made available in DSpace on 2012-10-16T02:23:47Z (GMT). No. of bitstreams: 0

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2008. / Submitted by Diogo Trindade Fóis (diogo_fois@hotmail.com) on 2009-09-08T15:15:51Z No. of bitstreams: 1 Dissert_Daniela Gusmao.pdf: 887823 bytes, checksum: f74813e64341ff48c2455aa5b122554b (MD5) / Approved for entry into archive by Luanna Maia(luanna@bce.unb.br) on 2009-09-09T14:30:53Z (GMT) No. of bitstreams: 1 Dissert_Daniela Gusmao.pdf: 887823 bytes, checksum: f74813e64341ff48c2455aa5b122554b (MD5) / Made available in DSpace on 2009-09-09T14:30:53Z (GMT). No. of bitstreams: 1 Dissert_Daniela Gusmao.pdf: 887823 bytes, checksum: f74813e64341ff48c2455aa5b122554b (MD5) Previous issue date: 2008 / Os Receptores Ativados por Proliferadores Peroxissomais (PPAR) são conhecidos como fatores de transcrição que regulam a expressão de genes envolvidos em importantes processos fisiológicos como o metabolismo lipídico, homeostase da glicose e atividades inflamatórias. Com isso, o desenvolvimento de ligantes que atuem de forma agonista nesses receptores aponta como um promissor alvo de estudos para o tratamento de desordens como o Diabetes mellitus, dispilidemia e arteriosclerose. Atualmente, no mercado farmacêutico, o uso das tiazolidinadionas (TZD) - ligantes sintéticos do PPARy- é bem difundido na prática clínica. Esta classe de fármacos promove sensibilidade à insulina e melhora no Diabetes mellitus tipo 2, embora apresente limitações terapêuticas e efeitos indesejáveis. Os flavonóides, mais especificamente as chalconas, também são objeto de grande interesse devido às suas diversas propriedades farmacológicas. Neste estudo, uma série de chalconas sintéticas foi testada para avaliar a possível atividade agonista para PPAR. Por meio de ensaio de transfecção transitória em cultura de células U937 e ensaios de gene-repórter, os resultados obtidos mostraram que CF1 (desidroxichalcona) e CF3 (4’- metoxichalcona) apresentaram um aumento na transcrição mediada por PPARy , além de um efeito sinérgico na presença de troglitazona - ligante sintético de PPARy da família das TZD. O mesmo ensaio foi feito com as outras isoformas do PPAR (α e δ), não sendo obtido o mesmo resultado para a atividade agonista, entretanto, apresentaram efeito sinérgico na presença do ligante sintético bezafibrato. Não houve atividade agonista das chalconas CF1 e CF3 nos receptores de estrogênio (Erα e ERβ), do hormônio tireoidiano TRβ e do ácido cis-9-retinóico (RXR), o que sugere uma atividade agonista seletiva destas chalconas em PPARy. A atividade agonista da CF1 também foi comprovada in vitro por meio de ensaio de GST pull down, em que foi observado que a CF1 proporcionou interação entre PPARy e o co-ativador SRC1, o que corrobora com os resultados de transfecção. Os resultados obtidos nesta dissertação mostram chalconas como agonistas promissores para PPAR, e contribuem para futuras pesquisas do desenvolvimento de moléculas agonistas de PPAR para o tratamento de doenças crônicas como o Diabetes melittus e a dispilidemia. __________________________________________________________________________________________ ABSTRACT / Peroxisome proliferators-activated receptors (PPAR) are genes regulators of important physiological processes, such as glucose homeostasis and inflammatory processes. Therefore, the development of ligants which behave as agonist for PPAR, have special interest in the research of the treatment of illnesses such as diabetes mellitus, dislypidemia and arteriosclerosis. Presently, the usage of troglitazone a synthetic ligant for PPAR-y from thiazolidinediones (TZD) family is well known in the pharmacological marketplace. This type of drugs causes a sensibility to insulin and the improvement in treatment of diabetes mellitus 2. Despite some therapeutic limitations and some non desirable side effects as well. The flavonoids, more specifically chalcones, are also subject of interest due to their many pharmacological proprieties. The present thesis aims at the research of some kind chalcones, from the Helianthus annuus species, so that to evaluate their performances as possible PPAR agonists. Transfection assay in U937 cell were performed using expression vectors PPARy –α and –δ and the PPARE-tk-luc repórter, it has been observed that as CF1 (Chalcone) as CF3 (4’ metoxichalcone) presented an increase in the activation of PPAR-y, besides the synergetic effect related to receptor activator by troglitazone. The same experiment was done with others subtypes PPARα and PPARδ. However, the final result was not same. Equally, there was not an increase of the transcription when other receptors such as ERα, ERβ,TRβ and gal-RXR were used, which demonstrates that CF1 and CF3 actually are selective agonists of PPAR-y. The agonist activity of CF1 has also been proven in vitro by means of GST pull down assays, where it was observed that CF1 induced coativactor SRC1 recruitment and transactivation of PPAR-y, which works accordingly with the transfection assays. The results of this study demonstrate that chalcones are agonists for PPAR-y. In short, we hope that the results of the present work shall give a contribution to further researches in the usage of agonist molecules in PPAR in the treatment of chronic diseases such as diabetes mellitus and dislypidemia.

A group of alloxanized rats fed on a high salt diet were studied histologically to determine the direct or indirect effect of diabetes mellitus on the nervous system. The most significant changes observed were in the vascular system of the brain. Lesions of the arteries were identical with those found in arteriosclerosis and massive hemorrhages accompanied by multiple diffuse diapedesis not only in the arteries but also in the veins was indicative of hypertension. It is believed the hypertensive condition was induced by a combination of the diabetes and salt feeding. Associated with the vascular dysfunction generalized cerebral changes were noted. They included neuron degeneration, exhibited by loss of Nissl granules, vacuolization of the cytoplasm and cerebral softening. Also Gitter cell invasion and proliferation occurred at the sites of vascular disturbance. It appears that the neurological involvement in diabetes is a direct result of changes in the blood system and not of the disease itself. / Science, Faculty of / Botany, Department of / Zoology, Department of / Graduate

Background and Aims: Dietary intervention is one of the key components in type 2 diabetes (T2D) management. Vegetarian diet is a promising alternative in the nutritional treatment of T2D. The aims of our study were: 1. To compare the effects of vegetarian and conventional diabetic diet with the same caloric restriction on insulin resistance, volume of visceral fat and plasma concentrations of oxidative stress markers after a 12-weeks-diet-intervention and subsequent 12-weeks of diet plus aerobic exercise training in subjects with T2D. 2. To explore the effect of 12 weeks of diet intervention and subsequent 12 weeks of diet combined with aerobic exercise training on -cell function and to evaluate the role of gastrointestinal peptides in subjects with T2D. 3. To study quality of life, Beck depression score and changes in eating behaviour in response to a vegetarian and a conventional diabetic diet. 4. To explore the role of changes in fatty acid composition of serum phospholipids in diet-induced changes in insulin sensitivity in subjects with T2D. 5. To follow-up our patients 1 year from the end of the intervention.

Thesis (M.P.H.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 31-37).

Thesis (MSc. (Clinical Epidemiology))--Universiteit van Pretoria, 2003. / Summary in English and Afrikaans.