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.

Vitamin D receptor polymorphisms and 25-hydroxyvitamin D in a group of Sicilian multiple sclerosis patients.

Multiple sclerosis (MS) is an auto-immune disease whose etiology remains controversial. Both genetic and environmental factors are thought to be involved in the risk of developing the disease. The purpose of our study was to assess the association of Vitamin D receptor (VDR) polymorphisms with MS and to investigate the interaction of these polymorphisms with vitamin D levels. A total of 179 Sicilian subjects, including 104 MS patients and 75 healthy controls, were studied. The most common VDR polymorphisms (Fok-I, Bsm-I, Taq-I and Apa-I) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analyses in both groups and serum 25-hydroxyvitamin D [25(OH)D] levels were determined in MS patients by high-performance liquid chromatography (HPLC). The distribution of genotype and allele frequencies of the four VDR polymorphisms did not differ significantly between MS patients and healthy controls, and were unrelated to the forms and the course of MS. Low serum levels of 25(OH)D were observed in MS patients but no association was observed between VDR and 25(OH)D levels except for Fok-I. Moreover, MS patients with FF and Ff genotype had a significantly lower serum levels of 25(OH)D compared with ff carriers (P < 0.05 FF vs Ff and Ff vs ff). Our findings showed no association between VDR polymorphisms and risk of MS. Interestingly, F allele could confer a genetic predisposition to lower 25(OH)D levels.

Arterial stiffness indexes and serum cytokine levels in seronegative spondyloarthritis: relationships between stiffness markers and metabolic and immunoinflammatory variables.

OBJECTIVE: The aim of this study was to investigate the relationship between immunoinflammatory markers and indexes of arterial stiffness in patients with seronegative spondyloarthritis (SpA). METHOD: We enrolled consecutive patients with inflammatory seronegative SpA referred to a rheumatology outpatient clinic. Control subjects were patients admitted in the same period for any cause other than chronic inflammatory disease or acute cardiovascular and cerebrovascular events. Carotid-femoral pulse wave velocity (PWV) was measured and the aortic pressure waveform was used to calculate the augmentation index (Aix). We also evaluated plasma levels of C-reactive protein (CRP), interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, and interleukin (IL)-6 as markers of immunoinflammatory activation. RESULTS: This study enrolled 53 patients with SpA and 55 control subjects. After adjustment for blood glucose, cholesterol, and triglyceride levels, and systolic (SBP) and diastolic blood pressure (DBP), patients with seronegative SpA showed higher mean PWV and Aix compared to controls. Moreover, in patients with seronegative SpA, we observed higher mean plasma levels of IL-6, IL-1ß, and TNF-α in subjects with mean PWV > 8 m/s in comparison with those with PWV < 8 m/s. Multivariate analysis revealed a significant association between PWV > 8 m/s and male gender, age, diabetes, hypertension, low density lipoprotein cholesterol (LDL-C) > 120 mg/dL, total cholesterol (TC) > 200 mg/dL, coronary artery disease (CAD), microalbuminuria, carotid plaque, and plasma levels of IL-6, IL-1ß, and TNF-α. CONCLUSIONS: These findings emphasize the role of inflammatory variables and metabolic factors in indexes of high arterial stiffness. Thus, an inflammatory-metabolic background may influence the pathogenesis of increased arterial stiffness in seronegative inflammatory arthritis.

Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C.

Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients underwent antiviral therapy with PEG-IFN alfa-2a plus ribavirin. HCV-RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up. Mean serum values of homocysteine were higher in patients than in controls (15.8 ± 5.8 µg/L vs 12.5 ± 5.8 µg/L; P < 0.001), with a similar CC, CT and TT MTHFR distribution (23.6%, 48.7% and 27.7% in G1-CHC vs 34%, 48.5% and 17.5% in controls; P = 0.14). In genotype 1, HCV MTHFR TT homozygosis was independently linked to higher LDL (OR 1.016; CI 1.002-1.031; P = 0.03), but not to homocysteine. No association were found between homocysteine, MTHFR and histological features or both rapid virological response (RVR) and SVR. Low cholesterol (OR 0.988, 95%CI 0.975-0.999, P = 0.04) was independently linked to severe fibrosis, and high LDL was the only independent positive predictors of both RVR and SVR (OR 1.036; 95%CI 1.017-1.055; P < 0.001; and OR 1.016; 95%CI 1.001-1.031; P = 0.04 respectively). In patients with genotype 1 hepatitis C, showing higher homocysteine serum levels than controls, MTHFR C677T homozygosis, via modulating cholesterol levels, could interfere with liver fibrosis and response to antiviral therapy.

Fetuin-A and CD40 L plasma levels in acute ischemic stroke: differences in relation to TOAST subtype and correlation with clinical and laboratory variables.

INTRODUCTION: Accumulating evidence suggests that inflammation plays an important role in the acute phase of ischemic stroke. CD40 L is a well recognized atherosclerotic inflammatory marker, whereas recent evidence suggests a pro-inflammatory role of Fetuin-A. To analyze the role of an inflammatory marker such as CD40 L and of a candidate pro-inflammatory marker such as Fetuin-A in acute stroke we evaluated their serum levels in subjects with acute ischemic stroke and their possible association with other laboratory and clinical variables. MATERIALS AND METHODS: We enrolled 107 consecutive patients with a diagnosis of acute ischemic stroke admitted to the Internal Medicine Department at the University of Palermo between November 2006 and January 2008, and 102 hospitalized control patients without a diagnosis of acute ischemic stroke. RESULTS: Patients with acute ischemic stroke in comparison to control subjects without acute ischemic stroke had significantly higher CD40 L levels and Fetuin-A serum levels. No significant differences in plasma CD40 L or Fetuin-A levels among different TOAST groups were detected. At intragroup (intra-TOAST-subtype) correlation analysis, among subjects classified as lacunar, CD40 L plasma levels were positively correlated with LDL-cholesterol and with diabetes, whereas Fetuin-A was significantly (positively) correlated with hypertension and white blood cell count. Among subjects with LAAS subtype, CD40 L levels were positively correlated with triglyceride plasma levels and Fetuin-A, whereas Fetuin-A levels were positively correlated with LDL-cholesterol. DISCUSSION: Our findings suggest a pro-inflammatory role of Fetuin-A and CD40 L in acute stroke setting. Whether this role should be construed as direct or as a simple expression of a general inflammatory activation will be up to future studies to clarify.

Direction and reliability of head tilt in humans.

It has been proposed that asymmetry in the inner ear underlies various manifestations of brain-behaviour asymmetry in the human. Specifically, Previc (1991) argued that an otolith imbalance manifests itself in an asymmetrical head posture, and later (1994) suggested that head tilt may be consonant with other measures of human laterality. The present study tested the reliability of head tilt across days and assessed its relationship with handedness, footedness, and eyedness. As in Previc's earlier studies, a majority of our subjects tilted rightward. Head tilt proved to be highly stable across days but was not correlated with the other laterality measures. These findings suggest that head tilt may reflect an underlying asymmetric substrate that appears not to be directly related to other measures of cerebral hemispheric dominance.

Exercise-induced asthma (EIA): its prevention with the combined use of ipratropium bromide and fenoterol.

Until now very few studies have been performed on the prevention of exercise-induced asthma (EIA) in children with ipratropium bromide + fenoterol. This is why we decided to study 30 children aged between 6 and 15 years, whose EIA was confirmed by a test including a 6-min free race on day 1 of the study. The criterion was a decrease of more than 20% of the basal values of forced expiratory volume in 1 s (FEV1) or FMF. Children whose FEV1 or FMF baseline values were under 60% of those expected according to Polgard tables were excluded. Three tests were performed, the first to determine EIA, the second was performed 72 h later after inhalation of placebo. 72 h after day 2 the patients returned in order to repeat the test, but this time, aerosol therapy with the combination ipratropium + fenoterol was applied prior to the race. The dosage of the combination was 1 puff of aerosol per 10 kg body weight, up to a maximum of 4 puffs. Each puff of the combination contains 0.02 mg of ipratropium bromide and 0.05 mg fenoterol. Functional assessment of children was carried out by means of forced spirometry. There were no significant differences between the placebo group and the group which received no medication, but there was a significant difference between the treated group and the other two, not only in the FEV1 and FMF values but also in forced vital capacity TEST.(ABSTRACT TRUNCATED AT 250 WORDS)