Pharmacogenetic influence of eNOS gene variant on endothelial and glucose metabolism responses to L-arginine supplementation: Post hoc analysis of the L-arginine trial.

OBJECTIVE: To evaluate whether variants of the eNOS gene are associated with endothelial and metabolic responses to L-arginine (L-arg) supplementation. MATERIAL AND METHODS: We examined a single nucleotide polymorphism of the eNOS gene (rs753482-A>C) to investigate the effects of this variant on endothelial function (EF), colony-forming unit-endothelial cell (CFU-EC) number, asymmetric-dimethylarginine (ADMA) level, insulin sensitivity index (ISI), and insulin secretion (IS) in a post hoc analysis of the L-arg trial. The L-arg trial (6.4 g/day for 18 months) was a single-center, randomized, double-blind, parallel-group, placebo-controlled, phase III trial in individuals with impaired glucose tolerance and metabolic syndrome. followed by a 12-month extended follow-up period after termination of the study drug (NCT 00917449). RESULTS: At baseline, EF, CFU-EC numbers, ADMA levels, and ISI were impaired in subjects carrying minor allele C (both heterozygotes, AC and homozygotes, CC) as compared to subjects carrying major allele A (homozygotes, AA) (p<0.01). Compared to placebo, L-arg increased EF, CFU-EC numbers, and ISI, and improved ADMA levels and IS (p<0.01). The greatest improvements were found in AA subjects treated with L-arg, while the worst results were found in AC+CC subjects treated with placebo. In the placebo-treated subjects, EF, CFU-EC, ISI, and IS were significantly lower and ADMA was significantly higher in AC+CC subjects than in AA subjects. CONCLUSIONS: Treatment with L-arg induced similar improvements in EF, CFU-EC numbers, ADMA levels, ISI, and IS in both AA subjects and AC+CC subjects. The presence of minor allele resulted in the worst prognosis in terms of EF, CFU-EC numbers, ADMA levels, ISI, and IS during the 30-month observation period.

Improving hand functional use in subjects with multiple sclerosis using a musical keyboard: a randomized controlled trial.

BACKGROUND AND PURPOSE: Playing an instrument implies neuroplasticity in different cerebral regions. This phenomenon has been described in subjects with stroke, suggesting that it could play a role in hand rehabilitation. The aim of this study is to analyse the effectiveness of playing a musical keyboard in improving hand function in subjects with multiple sclerosis. METHODS: Nineteen hospitalized subjects were randomized in two groups: nine played a turned-on musical keyboard by sequences of fingers movements (audio feedback present) and 10 performed the same exercises on a turned-off musical keyboard (audio feedback absent). Training duration was half an hour per day for 15 days. Primary outcome was the perceived hand functional use measured by ABILHAND Questionnaire. Secondary outcomes were hand dexterity, measured by Nine-Hole Peg Test, and hand strength, measured by Jamar and Pinch dynamometers. Two-way analysis of variance was used for data analysis. RESULTS: The interaction time × group was significant (p = 0.003) for ABILHAND Questionnaire in favour of experimental group (mean between-group difference 0.99 logit [IC95%: 0.44; 1.54]). The two groups showed a significant time effect for all outcomes except for Jamar measure. DISCUSSION: Playing a musical keyboard seems a valid method to train the functional use of hands in subjects with multiple sclerosis.

Axonal injury and overall tissue loss are not related in primary progressive multiple sclerosis.

BACKGROUND: There is an increasing body of evidence that magnetic resonance imaging-occult tissue damage is an important component of primary progressive multiple sclerosis (PPMS) pathology. Proton magnetic resonance spectroscopy (1H-MRS) can be used to measure in vivo whole-brain N-acetylaspartate (WBNAA) concentrations, the decrease of whose levels is considered a marker of neuronal-axonal injury. OBJECTIVES: To study WBNAA 1H-MRS as a tool to provide information about irreversible brain damage in PPMS and to investigate the relationship between WBNAA and other magnetic resonance imaging measures of MS disease burden, including brain atrophy. METHODS: The following magnetic resonance pulse sequences of the brain were obtained from 32 patients with PPMS and 16 age-matched healthy subjects: (1) dual-echo turbo spin-echo; (2) T1-weighted spin-echo; and (3) 1H-MRS to measure WBNAA concentration. Brain total lesion volumes were measured. Normalized brain volumes were calculated using a fully automated technique. Absolute WBNAA amounts were calculated using a phantom replacement method and were then corrected for individual subjects' brain size. RESULTS: Levels of WBNAA concentrations and normalized brain volumes were significantly lower in patients with PPMS (mean values, 10.2 mm and 1500.0 mL, respectively) than in healthy controls (mean values, 12.9 mm and 1585.2 mL). Both WBNAA concentrations and normalized brain volumes were included as independent factors in the final model of a multivariable analysis predicting the subjects' condition. No significant correlations were found between WBNAA values and normalized brain volumes, WBNAA and T2-weighted or T1-weighted lesion volumes. CONCLUSIONS: Axonal-neuronal damage in the brain of patients with PPMS seems to occur, at least partially, independently of the burden of magnetic resonance imaging-visible lesions. Whole-brain N-acetylaspartate values and normalized brain volumes were unrelated in this cohort, thereby suggesting that 1H-MRS and atrophy assessment may provide in vivo complementary information about the actual extent of brain damage in PPMS.