VITAMINS

Author: OVES COSTALES DANIEL.
Year: 2004.
University: OVIEDO [www.uniovi.es].
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: In recent years there has been a tremendous growth in research on Vitamin D, as a result of the discovery that 1alfa ,25-dihidroxivitamina D3, as hormonally active, promotes cell differentiation, gene transcription, and can be applied as drug in a wide variety of diseases. In this report, structured in four chapters, was conducted by the synthesis of new biological analogs compotenciales applications of Vitamin D. The first chapter has been optimized selective synthesis of precursors ring A, by the reaction of enzymatic hydrolysis of the corresponding dicarbonatos. Hydrolysis selective one of the carbonates provides access to precursors monocarbonatados that can be used in the synthesis of new analogs of Vitamin D. The results appear in the next publication: "Regioselective enzymatic syntheses of C-3 and C-5 carbonate A-ring stereoisomeric precursors of vitamin D". D. Oves, V.Gotor-Fernández, S. Fernandez, M. Ferrero and V. Gotor, Tetrahedron: Asymmetry 2004, 15,2881-2887. The second chapter describes the synthesis of four new harbingers of a ring holding a position in the amino group C-3 and / or C-5, and have been prepared from the (S )-(+)- carvone, or the (R )-(-)- carvone. Part of the results have been published in: "Efficiente Synthesis of novel 1alfa-amino and 3beta-amino analogues of 1alfa ,25-dihydroxyvitamin D3." D. Oves, M. Ferrero, S. Fernandez and V. Gotor, J. Org. Chem. 2003,68,1154-1157. The third chapter was conducted coupling of amino derivative of ring A synthesized in Chapter 2 with the fragment rings CD-cadena side. The amino derivative of the 1alfa ,25-dihidroxivitamina D3 thus obtained were biologically evaluated in terms of its affinity to VDR, and antiproliferative ability to distinguish, and effects calcémicos. Part of the results have been published in: "Effcient Synthesis of novel 1alfa-amino and 3beta-amino analogues of 1alfa ,2-dihydroxyvitamin D3." D. Oves, M. Ferrero, S. Fernandez and V. Gotor, J. Org. Chem 2003,68,1154-1157. In the fourth chapter develops the synthesis of a new class of derivatives of Vitamin D, consisting of the union of two units of the 1alfa ,25-dihidroxivitamina D3 through a bridge nature carbamate, variable length, in the position C - 3. These ligands diméricos could join simultaneously to two domains union protéicos and induce dimerización receptor Vitamin D. The biological testing of these new derivatives are currently underway.

Author: MARTÍN GALLÁN M. PILAR.
Year: 2006.
University: BARCELONA [www.ub.es].
Place of defense: HOSPITAL VALL D'HEBRÓN.
Place of preparation: FACULTAD DE BIOLOGIA (UNIVERSITAT DE BARCELONA).

Summary: THE Diabetes mellitus type I is an autoimmune disease characterized by chronic and selective destruction of insulin-producing beta cells of the pancreas, which produces results in a pathological elevation of blood glucose levels and alterations in the metabolism of the rest of carbohydrates , lipids and proteins. The chronic hyperglycemia produces multiple biochemical consequences of which would be described oxidative damage in diabetes. The first objective of this study was to analyze the evolution of the state oxidante-antioxidante products glicoxilación (AGEs) and levels of cell adhesion molecules, in a group of children and adolescents suffering from type 1 diabetes mellitus, from the beginning and during clinical the first twenty years of disease progression. The second objective was to study the involvement of oxidative stress in the pathogenesis of microvascular complications associated with the disease and look at whether the different susceptibility to the development of complications may be related to individual differences in the antioxidant defense mechanisms. Our results indicate that the debut or clinical manifestation of diabetes, there is oxidative damage to lipids, proteins and DNA. The antioxidant enzyme activity of UC, Zn-superóxido dismutase (Cu, Zn-SOD) is high and the activity of glutathione peroxidase (GPx) decreased erythrocyte of young diabetic patients, as well as levels of antioxidants singles and erythrocyte glutathione (GSH). Once started taking insulin and in the first year and a half of development of diabetes that corresponds to the stage of clinical remission of the disease, decrease the levels of markers of oxidative damage to lipids, proteins and DNA and concentration of AGEs. The GSH concentration and the activity of GPx is normalized and increasing concentrations of antixoidantes. Over the next twenty years' development of diabetes, markers of oxidative damage to lipids, proteins, DNA and levels of AGEs increase gradually, as well as the activity of Cu, Zn-SOD, which suggests an enzyme induction in response to a overproduction of superoxide radicals. Depletion of GSH in erythrocytes of diabetic patients is directly related to the decreased activity of GPx, showing a parallel evolution during disease progression. The molecular markers of oxidative damage are higher and antioxidant capacity is lower in the group of patients with vascular complications with regard to the group of patients without complications, indicating an association between the occurrence of microangiopatías and increased oxidative stress. Levels of total lipids in the plasma are directly related to the products of oxidation of lipids and proteins and plasma concentration of AGEs. There is a parallel evolution and increasing the molecular markers of oxidative damage and total lipid concentrations in plasma as you go diabetes and is more pronounced in the group of patients with microangiopathy, indicating that hyperlipidemia diabetic increases oxidative processes and it could accelerate the development of vascular complications den diabetes. Levels of soluble cell adhesion molecules in the plasma ICAM-1 and VCAM-1 are high in the group of diabetic patients throughout the evolution dela disease and the group of patients with microangipatía is presenting the highest levels of sICAM- 1. These findings indicate that the relationship is established between hyperglycemia and tissue damage in diabetes, is determined for acute changes in cellular metabolism, oxidative changes cumulative macromolecules stable and by a decrease in plasma antioxidant capacity, a process that accelerated by hyperlipemia diabetic.