Showing papers by "Paula Ravasco published in 2003"

Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease

Abstract: Background: The pathogenic mechanism of homocysteine’s effect on cardiovascular risk is poorly understood. Recent studies show that DNA hypomethylation induced by increases in S -adenosylhomocysteine (AdoHcy), an intermediate of Hcy metabolism and a potent inhibitor of methyltransferases, may be involved in homocysteine-related pathology. Methods: We measured fasting plasma total Hcy (tHcy), AdoHcy, and S -adenosylmethionine (AdoMet) and methylation in leukocytes in 17 patients with vascular disease and in 15 healthy, age- and sex-matched controls. Results: Patient with vascular disease had significantly higher plasma tHcy and AdoHcy concentrations and significantly lower plasma AdoMet/AdoHcy ratios and genomic DNA methylation. AdoMet concentrations were not significantly different between the two groups. More than 50% of the patients fell into the highest quartiles of plasma tHcy, AdoHcy, and [3H]dCTP incorporation/μg of DNA (meaning the lowest quartile of DNA methylation status) and into the lowest quartile of the AdoMet/AdoHcy ratios of the control group. Plasma tHcy was significantly correlated with plasma AdoHcy and AdoMet/AdoHcy ratios (n = 32; P < 0.001). DNA methylation status was significantly correlated with plasma tHcy and AdoHcy (n = 32; P < 0.01) but not with plasma AdoMet/AdoHcy ratios. Conclusion: Global DNA methylation may be altered in vascular disease, with a concomitant increase in plasma tHcy and AdoHcy.

5,10-Methylenetetrahydrofolate reductase 677C - T and 1298A - C mutations are genetic determinants of elevated homocysteine

Abstract: Methods: We studied 117 healthy volunteers (71 females, 46 males). The 677C£T and 1298A£C mutations were screened by PCR-RFLP. Levels of plasma tHcy and folate, and red blood cell folate, were determined. Results: The allele frequencies of the 677C£ Ta nd 1298A£Cmutationswere0.33and0.28,respectively. Homozygotes for the 677C£T mutation had significantly elevated plasma tHcy and RBC folate levels and significantly lowered plasma folate concentrationsthansubjectswithoutthemutation.The1298A£ C mutation showed a significant effect on plasma tHcy, but not on plasma folate or RBC folate levels. Discussion: The observed 677T allele frequency is not consistent with the idea of a north-south gradient as previously suggested. The 1298A£C mutation is common in Portugal. Both MTHFR mutations showed effects on plasma tHcy levels.

Tube feeding in mechanically ventilated critically ill patients: a prospective clinical audit.

Abstract: Background: When and whether early enteral nutrition (EN) benefits critically ill patients is debatable. This prospective clinical audit aimed to evaluate the feasibility of an early EN protocol and to identify factors that may hinder EN delivery in critically ill patients. Methods: Thirty-six medical patients with severe respiratory failure under invasive ventilation and scheduled to receive early EN, with a length of ICU stay> 72 hours, were included. As asserted by the Society of Critical Care Medicine, 8% of patients were priority 1, 72% priority 2, and 20% priority 3 for intensive therapeutic and vital support interventions. Results: Overall, because of gastrointestinal complications, only 39% of the prescribed EN was administered; only 8 (22%) patients did tolerate EN within the first 48 hours after admission and did achieve their minimum nutritional requirements. The most frequent complication (78%) was high volume of gastric residuals followed by abdominal distention (61%), both associated with hemodynamic instability (HI). Gastrointestinal dysfunction was associated with high Acute Physiologic and Chronic Health Evaluation II score (p = .01), total calorie intake (p = .02), total carbohydrate intake (p = .02), HI (p = .03), malnutrition (p = .04), volume of IV saline (p = .04), and concurrent vasoactive drug administration (p = .05). Conclusions: This audit in extremely severe intensive care patients identified several factors that impair gastrointestinal function and preclude EN at any stage, namely early EN. Nutrition management must take into account concurrent therapies, given their potential interference with nutrition and organ function.