none

Thesis (Ph. D.)--North Carolina State University. / Includes vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 109-126).

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Diss. (sammanfattning) Umeå : Umeå universitet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2005. / Härtill 4 uppsatser.

Made available in DSpace on 2014-06-11T19:23:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2002Bitstream added on 2014-06-13T19:30:04Z : No. of bitstreams: 1 venancio_ls_me_botfm.pdf: 1914070 bytes, checksum: 72ddcf8e9e33b9d3805a5466d9239406 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Estudos recentes indicam que um nível plasmático elevado de homocisteína é um fator de risco importante e prevalente para doença vascular aterosclerótica coronariana, cerebral e periférica, e para as doenças tromboembólicas. A homocisteína é um aminoácido sulfurado sintetizado em condições fisiológicas a partir da metionina alimentar, sendo utilizado em diversas vias metabólicas. A hiperhomocisteinemia, definida como nível plasmático acima de 15 μmol/L, pode ser atribuída a ocorrência de defeitos genéticos de algumas enzimas do metabolismo da homocisteína, ou à deficiências nutricionais das vitaminas B6, B12 e folato, ou ainda, estar relacionada à outros fatores de risco para aterosclerose, como a obesidade, a dislipidemia, a hipertensão arterial e o hábito tabágico. Foram sugeridos alguns mecanismos biologicamente plausíveis de dano vascular causado pelo aumento da homocisteína no plasma, incluindo agressão direta ao endotélio, indução do estresse oxidativo na parede vascular, alteração na produção de óxido nítrico, alterações das propriedades antitrombóticas e oxidação de lipoproteínas. Com o objetivo de avaliar a freqüência de hiperhomocisteinemia e a sua relação com indicadores relacionados ao estado nutricional (antropométrico, dietético e laboratorial), foi realizado um estudo transversal (cross-sectional ) com 40 pacientes (mediana 61 anos) portadores de doença arterial periférica atendidos no Hospital das Clínicas da Faculdade de Medicina de Botucatu (UNESP). Detectou-se freqüência elevada de pacientes portadores de isquemia crônica de membros (75%), com diagnóstico de sobrepeso (32,5%) ou obesidade (20%), com aumento da adiposidade corporal (100%) e redução da massa muscular (62,5 a 71%), com ingestão insuficiente das vitaminas B6 (85%), B12 (60%) e folato (72,5%)... / Recent studies denotes a high plasmatic level of homocysteine is a important factor of risk and prevalent to cardiovascular, cerebral and peripheral atherosclerotic diseases, and to thromboembolic diseases. Homocysteine is a synthesized sulfur amino acid in physiologic conditions derived to alimentary methionine, it has been used in various metabolism ways. Hyperhomocysteinemia, defined as a plasmatic level above 15μ mol/ L, can be attributed to the occurrence of genetics defect of some enzymes from the metabolism of homocysteine, or of the nutritional deficiency of vitamins B6, B12 and folate, or further, be related to the others factors of risk to atherosclerosis such as obesity, dyslipidemia, hypertension and smoking. It was suggested that some plausible biological mechanisms of vascular damage caused by the increase of homocysteine in the plasma, including oxidative stress in the vascular wall, modification in the production of nitric oxide, modification of the antithrombotics proprieties and oxidation of lipoproteins. The main goal to evaluate the frequency of hyperhomocysteinemia and its relation to the indicators related to the nutritional condition (anthropometric, dietetics and laboratorial), it was accomplished a cross-sectional study among 40 patients (median 61 years) with peripheral arterial disease attended at the Hospital of Medicine School in Botucatu (UNESP). It was detected a high frequency of patients with chronic limb ischemia (75%), overweight diagnosis (32,5%) or obesity (20%), increase of corporal adiposity (100%) and reduce of muscular mass (62,5% to 71%), insufficient intake of vitamins B6 (85%), B12 (60%) and folate (72,5%) and exceeding of protein (80%) and methionine (85%), increased serum level of triglyceride (52,5%), total cholesterol (60%), LDL- c (95%) and reduce of HDL-c (60%). Hyperhomocysteinemia was found in 60% of the patients... (Complete abstract, click electronic access below)

The terminal reaction in the formation of methionine from serine or formaldehyde has been studied in a cell-free system derived from bovine brain. The enzyme responsible for this reaction, N^5-methyltetra-hydrofolate:homocysteine transmethylase, catalyzes the conversion of homocysteine to methionine by the transfer of the N^5-methyl group of N^5-methyltetrahydrofolate to homocysteine. The conversion requires a reducing system such as a reduced flavin, and cofactors adenosine triphosphate and Mg^++, or S-adenosylmethionine. The enzyme is one of two in the mammalian system known for its dependence on vitamin B_12. A 374-fold purification of the transmethylase has been achieved by protamine sulfate and ammonium sulfate fractionations followed by various column chromatography procedures. The partially purified transmethylase exhibits absorption maxima at 343, 405, and 472 mu with a broad band extending from 508 to 566 mu. These peaks are due to a form of vitamin B_12 bound to the transmethylase. The enzyme exhibits a pH optimum at 6.8 and a temperature optimum at 45°.

Elevated levels in blood serum (≥10μmol/L) of the amino acid homocysteine is strongly correlated with the incidence of heart failure (HF). We present evidence that the cyclic thioester, homocysteine thiolactone (HTL), a metabolic product of homocysteine, irreversibly modifies proteins that regulate the contractile process in cardiac muscle. Two proteins found in the sarcoplasmic reticulum (SR), the Ca2+ pump (SERCA2), and the ryanodine receptor (RyR2), are responsible for controlling the cytosolic Ca2+ concentration and hence the contractile state of the heart. While both improper Ca2+ handling and elevated homocysteine levels have been considered bio-markers in HF, a direct connection between the two has not previously been made. We show that HTL reacts with lysine residues on RyR2, generating a Nε-homocysteine-protein, which results in carbonyl formation and a change in the Ca2+ sensitivity of RyR2. This is a new molecular mechanism linking elevated levels of Homocysteine, improper Ca2+ handling and heart failure. This work was supported by NIH 1 R41 HL105063-01 to J. Abramson and R. Strongin.

No description available.