Chiara Bellia

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.

Hyperhomocysteinemia and Cardiovascular Risk: Effect of Vitamin Supplementation in Risk Reduction

Homocysteine is a sulfur-containing aminoacid produced during metabolism of methionine. Since 1969 the relationship between altered homocysteine metabolism and both coronary and peripheral atherotrombosis has been known; in recent years experimental evidences have shown that elevated plasma levels of homocysteine are associated with an increased risk of atherosclerosis and cardiovascular ischemic events. Several mechanisms by which elevated homocysteine impairs vascular function have been proposed, including impairment of endothelial function, production of Reactive Oxygen Species (ROS) and consequent oxidation of low-density lipids. Folic acid and B vitamins, required for remethylation of homocysteine to methionine, are the most important dietary determinants of homocysteinemia and daily supplementation typically lowers plasma homocysteine levels. Recently, large-scale intervention trials have been conducted to determine whether lowering homocysteine concentrations through B vitamins supplementation can decrease cardiovascular risk in healthy subjects or improve survival in patients with coronary heart disease. Some of these trials found no significant beneficial effects of combined treatment with folate and vitamin B(12), with or without vitamin B(6), in spite of adequate homocysteine lowering. In conclusion, it is still unclear whether decreasing plasma levels of homocysteine through diet or drugs may be paralleled by a reduction in cardiovascular risk.

Adiponectin, resistin and IL-6 plasma levels in subjects with diabetic foot and possible correlations with clinical variables and cardiovascular co-morbidity

IntroductionIt is very suggestive that diabetic foot is characterized by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. On this basis the aim of our study was to evaluate plasma levels of adiponectin, resistin and IL-6 in subjects with diabetic foot in comparison with subjects without foot complications.Materials and methodsWe recruited 34 subjects with type 2 diabetes mellitus and foot ulceration hospitalized for every condition related to diabetic disease, but not for new vascular events (group A). As controls we recruited 37 patients with type 2 diabetes mellitus without foot ulceration (group B) hospitalized for every condition related to diabetic disease, but not for new vascular events. Adiponectin, Resistin and IL-6 serum levels were evaluated.ResultsSubjects of group A showed lower median plasma levels of adiponectin [7.7450 (4.47-12.17) μg/ml vs 8.480 (5.15-12.87) μg/ml], higher median plasma levels of IL-6 [3.21 (1.23-5.34) pg/ml vs 2.73 (1.24-3.97 pg/ml)] and of resistin [3.860 (2.96-6.29 ng/ml) vs 3.690 (2.,37-6.5 ng/ml)].ConclusionOur study demonstrated that diabetic subjects with diabetic foot showed in comparison with diabetics without diabetic foot higher IL-6 and resistin plasma levels, lower adiponectin plasma levels.

Extensive Molecular Analysis of Patients Bearing CFTR-Related Disorders

Cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RDs) may present with pancreatic sufficiency, normal sweat test results, and better outcome. The detection rate of mutations is lower in CFTR-RD than in classic CF: mutations may be located in genes encoding proteins that interact with CFTR or support channel activity. We tested the whole CFTR coding regions in 99 CFTR-RD patients, looking for gene mutations in solute carrier (SLC) 26A and in epithelial Na channel (ENaC) in 33 patients who had unidentified mutations. CFTR analysis revealed 28 mutations, some of which are rare. Of these mutations, RT-PCR demonstrated that the novel 1525-1delG impairs exon 10 splicing; by using minigene analysis, we excluded the splicing effect of three other novel intronic variants. Analysis of SLC26A genes revealed several variants, some of which are novel, that did not affect mRNA expression. Other mutations occurred in the ENaC genes encoding the ENaC subunits, but their frequency did not significantly differ between patients and controls. Our data, although obtained on a preliminary cohort of CFTR-RD patients, exclude a role of mutations in SLC26A and in SCNN genes in the pathogenesis of such disease; we confirm that CFTR analysis has a relevant role in CFTR-RD patients; and it appears mandatory to use CFTR scanning techniques and approaches to reveal the effect of novel mutations.

Therapeutical approach to plasma homocysteine and cardiovascular risk reduction.

Homocysteine is a sulfur-containing aminoacid produced during metabolism of methionine. Since 1969 the relationship between altered homocysteine metabolism and both coronary and peripheral atherotrombosis is known; in recent years experimental evidences have shown that elevated plasma levels of homocysteine are associated with an increased risk of atherosclerosis and cardiovascular ischemic events. Several mechanisms by which elevated homocysteine impairs vascular function have been proposed, including impairment of endothelial function, production of reactive oxygen species (ROS) and consequent oxidation of low-density lipids. Endothelial function is altered in subjects with hyperhomocysteinemia, and endothelial dysfunction is correlated with plasma levels of homocysteine. Folic acid and B vitamins, required for remethylation of homocysteine to methionine, are the most important dietary determinants of homocysteine and daily supplementation typically lowers plasma homocysteine levels; it is still unclear whether the decreased plasma levels of homocysteine through diet or drugs may be paralleled by a reduction in cardiovascular risk.

Prothrombotic gene variants as risk factors of acute myocardial infarction in young women

BackgroundAcute myocardial infarction (AMI) in young women represent an extreme phenotype associated with a higher mortality compared with similarly aged men. Prothrombotic gene variants could play a role as risk factors for AMI at young age.MethodsWe studied Factor V Leiden, FII G20210A, MTHFR C677T and beta-fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females) and in 698 AMI (245 females) patients. The data were compared to those obtained in 909 unrelated subjects (458 females) from the general population of the same geographical area (southern Italy).ResultsIn young AMI females, the allelic frequency of either FV Leiden and of FII G20210A was significantly higher versus the general population (O.R.: 3.67 for FV Leiden and O.R.: 3.84 for FII G20210A; p<0.001). Among AMI patients we showed only in males that the allelic frequency of the MTHFR C677T variant was significantly higher as compared to the general population. Such difference was due to a significantly higher frequency in AMI males of the MTHFR C677T variant homozygous genotype (O.R. 3.05).Discussion and conclusionOur data confirm that young AMI in females is a peculiar phenotype with specific risk factors as the increased plasma procoagulant activity of FV and FII. On the contrary, the homozygous state for the 677T MTHFR variant may cause increased levels of homocysteine and/or an altered folate status and thus an increased risk for AMI, particularly in males. The knowledge of such risk factors (that may be easily identified by molecular analysis) may help to improve prevention strategies for acute coronary diseases in specific risk-group subjects.

Changes in serum fetuin-A and inflammatory markers levels in end-stage renal disease (ESRD): effect of a single session haemodialysis.

Abstract Background: The aim of the present study was to evaluate the effect of a single haemodialysis (HD) session on serum fetuin-A levels, considered a negative acute phase response marker; moreover, we evaluated the behaviour of fibrinogen and high sensitivity C-reactive protein (hsCRP) as acute phase response and chronic/subclinical inflammation markers, respectively, after a single HD session. Methods: Serum fetuin-A, albumin, hsCRP and fibrinogen were measured in 72 patients before and after a single HD session. Results: After a single HD session, we observed a significant increase in fibrinogen levels, while fetuin-A levels decreased (p<0.05). Also, hsCRP levels were significantly increased. Conclusions: The significant decrease of fetuin-A levels after a single HD session is consistent with the hypothesis of HD-induced inflammation; activated acute phase response and fetuin-A deficiency might account for increased cardiovascular risk and accelerated atherogenesis in dialysis patients. Clin Chem Lab Med 2008;46:212–4.

Activity of mannose-binding lectin in centenarians

We analyzed MBL2 gene variants in two cohorts of centenarians, octo‐nonagenarians and nonagenarians, and in the general population, one from Sardinia Island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. We also assessed in vitro the effect of mannose‐binding lectin (MBL) on various human cells at different stage of senescence. The frequency of high and null activity haplotypes was significantly lower, and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general population from the same geographic area. Furthermore, serum MBL concentration (also after normalization to serum albumin) was significantly lower in centenarians and in octo‐ and nonagenarians as compared to the general population, suggesting that intermediate MBL haplotype/activity may be protective. We also demonstrated that in vitro MBL protein bound to senescent IMR90 fibroblasts thereby causing cell lysis, but not to other types of cycle‐arrested cells not in senescence. This implicates a novel role of MBL in the clearance of senescent cells.

Utility of serum procalcitonin and C-reactive protein in severity assessment of community-acquired pneumonia in children

OBJECTIVES Although the importance of serum Procalcitonin (PCT) levels at diagnosis is well established in adult Community-Acquired Pneumonia (CAP), its use remains controversial in pediatric CAP. The aim of our study is to investigate the role of PCT and C-Reactive Protein (CRP) in the assessment of pediatric CAP severity defined by the extent of consolidation on chest X-rays and the presence of pleural effusion. In this particular setting, no clinical severity score is available at present and chest X-ray, although important for diagnosis confirmation, is not recommended as routine test. DESIGN AND METHODS The study involved 119 children admitted to the Department of Pediatric Infectious Disease for radiographically documented CAP aged 1 year to 14 years, without chronic diseases. Baseline PCT, CRP and routine laboratory tests were performed on admission. RESULTS The median PCT (μg/L) and CRP (mg/L) were 0.11 (0.05–0.58) and 21.3 (4.2–48.1), respectively. PCT showed a good correlation with CRP, neutrophils and WBC (r = 0.538, P < 0.001; r = 0.377, P < 0.001; r = 0.285, P0.002, respectively). CRP, but not PCT, was associated with lobar consolidation (P = 0.007) and pleural effusion (P = 0.002). Logistic regression analysis revealed that only CRP was a predictor of lobar consolidation (OR: 1.078; 95% CI: 1.017–1.143; P = 0.011) and pleural effusion (OR: 1.076; 95% CI: 1.005–1.153; P = 0.036). CONCLUSION Our findings revealed that PCT is correlated to the main inflammatory markers in children with CAP. CRP, unlike PCT, is able to predict the extent of chest X-ray infiltration and ultimately the severity of the disease confirming its usefulness in the management of pneumonia

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)-1β, 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-1β, 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-1β, 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.