VDBP, CYP27B1, and 25-Hydroxyvitamin D Gene Polymorphism Analyses in a Group of Sicilian Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a chronic demyelinating disease of central nervous system regarded as one of the most common causes of neurological disability in young adults. The exact etiology of MS is not yet known, although epidemiological data indicate that both genetic susceptibility and environmental exposure are involved. A poor vitamin D status has been proposed as the most attractive environmental factor. Several evidence have highlighted the importance of mutations in vitamin D-regulating genes for vitamin D status. The purpose of our study was to assess the genetic variants of VDBP and CYP27B1 in MS patients and in a control group. A total of 192 subjects, including 100 MS patients and 92 healthy controls, were genotyped by polymerase chain reaction followed by restriction fragment length polymorphism analyses. Serum 25-hydroxyvitamin D levels were measured in MS patients and controls by high-performance liquid chromatography. We did not observe any statically significant difference in the distribution of genotypic VDBP variants between the study groups. 25(OH)D plasma levels were significantly higher in the control group versus MS patients; MS patients who carried Gc2 showed lower 25(OH)D plasma levels and those who carried Gc1f showed higher levels. We observed only wild-type allele for CYP27B1 mutations analyzed both in MS patients and in the control group. In conclusion, our findings do not support a role of an independent effect of the investigated vitamin D-related gene variants, VDBP and CYP27B1, in the risk of MS.

Cardiovascular adaptation to mudpack therapy in hypertensive subjects treated with different antihypertensive drugs.

OBJECTIVE: In selected hypertensive subjects, cardiovascular adaptation to warm environments may be inadequate or even harmful: heating associated to mudpack therapy may cause unexpected hypotension. How different antihypertensive drugs may affect the cardiovascular response to mudpack therapy is poorly studied. AIMS: To evaluate the effects of ß-blockers and angiotensin II receptor antagonists/ACE inhibitors on the acute cardiovascular adaptation to mudpack treatment in SPA in elderly hypertensive patients. PATIENTS AND METHODS: Thirty-one elderly subjects were divided in normotensive subjects (N; n=10) and hypertensive patients treated with ACE-inhibitors/Angiotensin II receptor antagonists (HTA; n=12) or with selective ß1-blockers (HTB; n=9). Systolic (SBP) and diastolic (DBP) blood pressure were continuously recorded (10 min) in supine position, immediately before and during mudpack treatment (40°C). Heart rate (HR), stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were assessed. RESULTS: During mudpack treatment SBP did not significantly change in both HTA and N groups (132±11 and 112±13 mmHg, respectively), but significantly decreased in HTB (111±18 mmHg, p < 0.01 vs baseline) patients. HR increased in all groups (HTA: 72±10 bpm; HTB: 65±6 bpm; N: 70±10 bpm; p < 0.01 vs baseline). A significant reduction (p < 0.01 vs baseline) in SV and CO occurred in HTB, but not in HTA and N groups. TPR significantly increased in HTB (1335±464 dyn.s.cm-5, p < 0.01 vs baseline) but not in HTA and N subjects (1389±385 dyn.s.cm-5 and 1245±323 dyn.s.cm-5, respectively). CONCLUSIONS: Mud treatment did not cause relevant haemodynamic changes in normotensive and HTA-treated hypertensive subjects. Conversely, ß-blocking treatment apparently limited the cardiovascular adaptation to thermic stress, through a possible reduction in myocardial contractility, thereby, causing a significant decrease, although not dangerous, in systolic blood pressure.

Anthropometric characteristics of top-class Kenyan marathon runners.

AIM: This study aims to: 1) describe the current anthropometric profiles of Kenyan marathon runners and 2) establish a set of reference values useful for future investigations on athlete selection, talent identification, and training programme development. METHODS: The participants were 14 male top-class Kenyan marathon runners (mean [s] age 27.71 [3.75] yrs, height 171.21 [6.12] cm, body mass 57.71 [4.02] kg, marathon personal best 02h 07min 16s (01min 55s); training volume: 180-220 km·wk-1; high:low intensity training ratio: 1:2). The anthropometric profiles included the measurement of skinfolds, and segment lengths, breadths, and girths. To estimate body density (BD) multiple regression equations were calculated using the sum of 7-skinfolds method and then converted to percentage of body fat (%BF). The somatotype, somatotype dispersion mean (SDM), somatotype attitudinal mean (SAM), and height to weight ratio (HWR) as well as the skinfolds extremity to trunk ratio (E:T) were also calculated. RESULTS: The mean (s) of BD, %BF, SDM, SAM, HWR and E:T were 1.13 (0.02), 8.87 (0.07) %, 4.58 (3.62), 0.51 (0.09), 44.32 (1.06), and 0.36 (0.11), respectively. The mean (s) endomorphy, mesomorphy, and ectomorphy were 1.53 (0.32), 1.61 (1.81), and 3.86 (0.78), respectively. CONCLUSION: Top-class Kenyan marathon runners seem to have ectomorphy as dominant, with endomorphy and mesomorphy more than one-half unit lower. Despite population comparisons would be required to identify any connection between specific anthropometric dimensions, these reference data should be useful to practitioners and researchers, providing useful information for talent identification and development and for the assessment of training progression in marathon.

Polymorphisms of alpha-actinin-3 and ciliary neurotrophic factor in national-level Italian athletes.

AIM: The R577X polymorphism of the alpha-actinin-3 (ACTN3) gene and the IVS1-6G>A polymorphism of the ciliary neurotrophic factor (CNTF) gene have been associated with a favourable muscle phenotype (more muscle fibres with high glycolytic activity), reduced predisposition for congenital dystrophy and resistance to sarcopenia in old age. The aim of this study was to look for evidence of selective pressure towards genotypes favourable for strong muscle activity in a sample of national-level Italian athletes. METHODS: We analysed two stop codon polymorphisms in the DNA of 50 Italian athletes, specialised in power or endurance sports, and compared their genotypic distribution with those of a population of 50 controls. In a representative sub-group of athletes (N.=42) we then compared the genetic data with anaerobic threshold, assessed by an incremental exercise test up to exhaustion. RESULTS: The athlete group showed an allelic distribution of ACTN3 (R/R:64%, R/X:16%, X/X:20%) and CNTF (G/G:72%, G/A:26%, A/A:2%), significantly imbalanced towards alleles R/R and G/G, respectively, compared to controls (ACTN3=R/R:40% R/X:22% X/X:38% and CNTF=G/G:52%, G/A:24%, A/A:24%) (p=0.0024 and p=0.0001, respectively). Only the ACTN3 577X/X polymorphism showed a significant association with the anaerobic threshold of athletes (F-ratio= 4.037; p=0.025). Factorial ANOVA demonstrated a non significant interaction between favourable allelic patterns of ACTN3 and CNTF genes on aerobic performance in the athlete group. CONCLUSION: The relationship found between favourable muscle phenotype and this genetic profile may have interesting implications in sport performance and training, athlete selection and different clinical activities, such as physical rehabilitation and modifying phenotypes associated with neuromuscular diseases.

Cardiovascular responses during an indoor race walking competition.

AIM: This study aims to examine the cardiovascular responses during an indoor race walking competition over the distance of 3-km for female and 5-km for male athletes. METHODS: During the Italian indoor RW Championship heart rate was monitored on eleven well trained race walkers (five men and six women) and then refereed as percentages of individuals' theoretical maximum heart rate (206-0.7·age). To provide a measure of relative intensity, five HR zones were assessed. Alterations in % HRmax both for the five and three 1000-m split distances were determined. RESULTS: During the 5-km race the athletes spent 79.7% (15 min 45 s) at HR5 (i.e., 90-100% of HRmax). Specifically, % HRmax increased by 10% in the last compared to the first 1000-m sector (P=0.006, effect size = 2.47±0.83, very large), with the first 1000-m sector lower than the subsequent ones (P=0.01, effect size=2.17 to 2.47, very large). While, for the 3-km the athletes spent 86.9% (11 min 35 s) at HR5 (i.e., 90-100% of HRmax) with no differences observed in the % HRmax between the three 1000-m sectors (P>0.01). CONCLUSION: The dissemination of performance and physical attributes identified within the present study reveal that the exercise intensity of indoor race walking competitions has a high-intensity profile and will assist coaches and athletes in formulating appropriate training, competition and recovery.

Plasma levels of dioxins, furans, non-ortho-PCBs, and TEQs in the Seveso population 17 years after the accident.

BACKGROUND: The Seveso accident (Italy) in 1976 caused the contamination of a large population by 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3, 7,8-TCDD). The contaminated territory was divided into three zones: A (very high contamination), B (high contamination), and R (low contamination). We report here the plasma concentrations of seven polychlorinated dibenzo-para-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), four non-ortho-polychlorinated biphenyls PCBs (nPCBs), and Toxic Equivalencies (TEQs) in a sample of residents in the most polluted zones A and B and in a reference non-contaminated zone. METHODS: From December 1992 to March 1994, 62 individuals were randomly selected from the population living in zone A (No. =7) and B (No. =55). A sample of 59 subjects living in a surrounding non-contaminated area (non-ABR), frequency-matched by gender, age, and smoking history, was used as reference. All subjects were administered a questionnaire surveying demographic, lifestyle, medical history, and accident-related factors. We assayed plasma PCDD, PCDF, and nPCB concentrations by high-resolution gas chromatography/high resolution mass spectrometric (HRGC/HRMS) analysis, with results reported as pg/g of lipid, or parts per trillion (ppt). We calculated TEQs using the WHO 2005 Toxic Equivalency Factors (TEFs). RESULTS: We found elevated median levels of 2,3, 7,8-TCDD in plasma samples of subjects living in zone A (73.3 ppt) and zone B (12.4 ppt), compared with residents in the reference zone (5.5 ppt). In analyses adjusted for gender, age, smoking, and body mass index (BMI), none of the other congeners showed levels higher than reference in the contaminated zones. Compared with men, women showed higher levels (113%) of 2,3, 7,8-TCDD and a slight elevation (17%) of TEQ for the other congeners. Age was strongly positively associated with most congener levels; TEQs for PCDDs, PCDFs, and nPCBs showed respectively 12%, 24%, and 41% increases for every 10 years of age. Current smokers had lower (from -37% to -67%) TEQ levels than subjects who had never smoked. BMI was negatively associated with levels of a few congeners, but with no impact on TEQ values. CONCLUSIONS: The Seveso accident caused a severe exposure of the population to 2,3,7,8-TCDD only. None of the other congeners analyzed showed variation across zones. Age showed a strong positive association with TEQs for all classes of compounds (PCDDs, PCDFs, and nPCBs).

How physical exercise changes rat myotendinous junctions: an ultrastructural study.

Myotendinous junctions can be easily injured by overloading or trauma, and exercise training may be a way of increasing their resistance to mechanical stress. To this end, we examined herein the morphological changes induced by moderate exercise training in the myotendinous junctions of extensor digitorum longus and gastrocnemius muscles in rats. Twelve Sprague-Dawley rats were used in this investigation. Six of them were trained to run on a treadmill for 1 h/day, 3 days/week over 10 weeks in order for them to achieve a running rate of 25 m/min at the end of the training period. Six age-matched sedentary rats were used as controls. The rats were sacrificed 24 h after the final training session, and the extensor digitorum longum (EDL) and the gastrocnemium were excised; the myotendinous junctions (MTJ) were then prepared and observed with electron microscopy. Digitation branching was evaluated by counting the bifurcations in the MTJ protrusions. Our observations indicate that exercise does indeed induce changes in MTJ morphology. In both muscles the number of bifurcated interdigitations increased significantly, as well as, in gastrocnemius, the branching of the finger-like processes. It was demonstrated that the MTJ is able to adapt to an increase in tensile force by enlarging the muscle-tendon contact area and, consequently, mechanical resistance.

Global DNA methylation and low-level exposure to benzene.

INTRODUCTION: Global genomic hypomethylation is a common event in cancer tissues that is frequently observed in hematopoietic malignancies, including leukemia. Benzene, an established leukemogen at high doses, has been suggested to induce hypomethylation based on investigations of DNA methylation in LINE-1 and Alu repetitive elements. Whether global genomic DNA methylation content is reduced in response to benzene exposure is still undetermined. METHODS: We measured global DNA methylation in 78 gasoline station attendants and 58 controls in peripheral blood cells using high-resolution gas chromatography-mass spectrometry. PCR-Pyrosequencing measures of DNA methylation at Alu and LINE-1 repetitive elements, representing a large proportion of methylation in non-coding regions, were also available. Exposure markers included personal airborne benzene, and urinary benzene, t,t-muconic acid (t,t-MA) and S-phelylmercapturic acid. RESULTS: Mean global DNA methylation was 5.474 (+/- 0.083) %5mC in controls and 5.409 (+/- 0.142) %5mC in exposed participants (p = 0.01). All methylation markers were negatively correlated with airborne benzene. Alu and LINE-1 methylation, but not global DNA methylation, were negatively associated with t,t-MA; no association with the other urinary biomarkers was found. Multiple linear regression analysis adjusted for gender and age confirmed the results of correlation analysis and showed a 1.6% decrease in global DNA methylation associated with being gasoline station attendants. Alu and LINE-1 methylation levels were not associated with global DNA methylation. CONCLUSION: Our results show that benzene exposure is associated with alterations in both global DNA and repetitive element methylation. Global and repetitive element methylation levels are not correlated in blood DNA, likely representing independent responses to benzene exposure.

Heart adaptations to long-term aerobic training in paraplegic subjects: an echocardiographic study.

STUDY DESIGN: Case-control. OBJECTIVES: To execute an echocardiographic comparison between trained and untrained spinal cord injury (SCI) subjects, and to evaluate whether long-term heart adjustments to endurance training are comparable to those observed in able-bodied (ABL) subjects. SETTING: Italy. METHODS: We enrolled: (1) 17 male SCI patients (lesion level T1-L3, 34±8 years, body mass index (BMI) 23.0±2.8 kg m(-2)), 10 of whom were aerobically trained for >5 years (SCI(T)); (2) 18 age-, sex- and BMI-matched ABL subjects (35±6 years, BMI 23.6±2.8 kg m(-2)), 10 of whom were aerobically trained for >5 years (ABL(T)). Training frequency and volume were recorded by a dedicated questionnaire. All subjects underwent a trans-thoracic echocardiography; SCI subjects also performed an exhaustive incremental exercise test. Comparisons were made between ABL and SCI groups, between trained and untrained subjects within each group (analysis of variance). RESULTS: Effects of SCI-Compared with ABL subjects, SCI patients showed lower end-diastolic volume (76±21 vs. 113±23 ml, P<0.05) and ejection fraction (61±7% vs. 65±5%, P<0.05). Effects of training-Compared with untrained status, the intra-ventricular septum thickness (SCI, +18%; ABL, +4%), the posterior wall thickness (SCI, +17%; ABL, +2%) and the total normalized heart mass (SCI, +48%; ABL, +5%) were higher in both SCI(T) and in ABL(T). VO2peak was higher in the SCI(T) subgroup compared with the SCI(U) group. CONCLUSIONS: Heart seems to positively adapt to long-term endurance training in SCI patients. Regular exercise may therefore increase heart size, septum and posterior wall thickness, which likely contributes to improved VO2peak. These morphological and functional changes may reduce cardiovascular risk in SCI individuals.

Spinal curvature: comparison of frontal measurements with the Spinal Mouse and radiographic assessment.

AIM: The Spinal Mouse is an external non-invasive device which measures the spinal shape and mobility of the spine in several planes. The aim of the present study was to evaluate the reliability and the validity of the Spinal Mouse to assess frontal standing measurements of the spine in a sample of young healthy volunteers. METHODS: Twenty-six young volunteers of both sex took part in the study. Angle data of vertebral inclination of each subject in frontal view were measured by Spinal Mouse and standard radiography for vertebral segments from T1-T2 down to L5-S1. RESULTS: Repetition of the measurements by Spinal Mouse performed by two examiners in different days resulted in no significant difference for the parameter examined, as well as measurements performed by the two examiners in the same day (P<0.05). The ICC values showed no correlation between the two devices in the following pairs of vertebrae: T2-T3, T4-T5, T5-T6, T7-T8, T8-T9, T9-T10, T11-T12, T12-L1, L1-L2, L3-L4, L4-L5. CONCLUSION: The Spinal Mouse results, concerning the standing frontal curvature of the spine, even if reliable, were poor when compared with the standard radiography.