During RT, nutritional interventions positively influenced outcomes, and counseling was of similar/higher benefit; in the medium term, only counseling exerted a significant impact on patient outcomes.
During radiotherapy, both interventions positively influenced outcomes; dietary counseling was of similar or higher benefit, whereas even 3 months after RT, it was the only method to sustain a significant impact on patient outcomes.
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 [ 3 H]dCTP incorporation/g 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
Liver injury in NASH and ASH is associated with increased hepatocyte apoptosis mediated by death receptors. Further, apoptosis correlates with active NF-kappaB expression, and disease severity. This potential mechanistic link might provide multiple interesting targets for therapeutic intervention.
Background: In our published randomized trial in colorectal cancer, group 1 (n = 37) received individualized nutritional counseling and education about regular foods, group 2 (n = 37) received dietary supplements and consumed their usual diet of regular foods, and group 3 (n = 37) consumed their usual diet of regular foods. Neither group 2 nor group 3 received individualized counseling. Early nutritional counseling during radiotherapy was highly effective at reducing acute radiotherapy toxicity and improving nutritional intake/status and quality of life (QoL). Efficacy persisted for 3 mo after the intervention. Objective: The objective was to perform long-term follow-up in survivors of that clinical trial to specifically evaluate survival, late toxicity, QoL, and nutritional variables. Design: Medical data were collected from patients' records, and prescheduled interviews were conducted by dietitians for individualized evaluations. Analyses and comparisons between groups (adjusted for stage) were performed after a median follow-up of 6.5 (range: 4.9-8.1) y.
A growing body of evidence has highlighted the role of abnormal DNA methylation patterns on inappropriate gene expression and promotion of disease. [1][2][3] DNA methylation patterns are maintained by DNA methyltransferases, 4-7 using S-adenosylmethionine (AdoMet) as the methyl group donor; AdoMet is then converted to S-adenosylhomocysteine (AdoHcy). Intracellular homocysteine (Hcy) is derived from AdoHcy hydrolysis through the action of AdoHcy hydrolase, a reversible reaction with a dynamic equilibrium that strongly favours AdoHcy synthesis rather than hydrolysis.8 Thus, an efficient metabolic removal of Hcy is required to prevent AdoHcy accumulation. The toxicity of intracellular AdoHcy accumulation lies in its high affinity binding to the catalytic region of most AdoMet dependent methyltransferases (including DNA methyltransferases), acting as its inhibitor.9 Thereby, any disturbance in Hcy metabolism is likely to disturb cellular methylation processes, including DNA methylation patterns.5,10-methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of Hcy metabolism that catalyses the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor for the remethylation of Hcy to methionine. A common 677CRT transition in the MTHFR gene is a well established genetic determinant of hyperhomocysteinaemia, and results in a thermolabile protein, with a decreased enzymatic activity. The molecular basis of this thermolability is a missense mutation in the exon 4 of the MTHFR gene, a cytosine to thymine substitution at nucleotide 677, which converts an alanine to a valine codon in the N-terminal catalytic domain of the protein. The association between this MTHFR genotype and the total Hcy (tHcy) circulating levels is well known to be contingent on folate status.
11Recently, a second polymorphism associated with decreased enzymatic activity but not with thermolability was discovered in the MTHFR gene.12 This genetic variant corresponds to an adenosine to cytosine transversion at nucleotide 1298, in exon 7, leading to a glutamate to alanine substitution within the C-terminal regulatory domain of the MTHFR protein. Subjects harbouring the 1298CC genotype have reduced enzyme activity but to a lesser extent than those bearing the 677TT genotype, probably because of the distinct locations of the two polymorphisms; the 677CRT and 1298ARC mutations are found in regions encoding the N-terminal catalytic and the C-terminal regulatory domains of the protein, respectively. 13 The effects of the 1298ARC mutation on plasma concentrations of tHcy remain controversial; we have recently reported that this MTHFR mutation displayed a significant effect on plasma tHcy levels, 14 but others have either not found any effect 12 15 or have found an association with even lower levels of plasma tHcy in homozygous individuals. 16 Although it was recently reported that the 677CRT transition in the MTHFR gene affects genomic DNA methylation, 3 17 the effect of the 1298ARC transversion has not bee...
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