R. Mandraffino

Università degli Studi di Messina, Messina, Sicily, Italy

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Publications (7)34.45 Total impact

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    ABSTRACT: Background Circulating progenitor cells (CPCs), including CD34+ cells and endothelial progenitor cells (EPCs), play a role in delaying atherosclerosis and cardiovascular disease. Toll-like receptor 3 (TLR3), a member of the pathogen recognition receptors that mediates immune response and activates inflammatory genes, is involved in the development of atherosclerosis. TLR3 has been recently detected in EPCs and its “in vitro” activation appears to induce cytokine expression and apoptosis. We measured the expression of TLR3 and Interleukine1β- mRNA in CPCs isolated from patients with rheumatoid arthritis. Objectives The aim was to evaluate whether systemic inflammation is associated with CPC number and CPC expression of TLR3 and IL-1β. Methods CD34+ cells were isolated from peripheral blood from 21 patients with rheumatoid arthritis (RA patients) and from 21 matched controls. TLR3 and IL-1β -RNA expression were measured in enriched sample of CD34+ cells. Plasma C-reactive protein (CRP) and fibrinogen levels were also measured. Results With respect to controls, CD34+ cell number was lower in RA patients. CRP and fibrinogen levels were higher in RA patients than in controls. TLR3-mRNA anf IL-1βexpression were significantly higher in RA patients with respect to controls. CRP and fibrinogen levels were associated with IL-1β e TLR3 expression; moreover, the increased expression of TLR3 and IL-1β were associated with lowering CPC number. Conclusions RA is associated to an increased expression of TLR3 and of IL-1β in CPCs, which appear to affect the decrease of CPC number. It is likely that this novel association may at least in part contribute to explain the increase of cardiovascular morbidity and mortality in patients suffering from RA. Further studies could clarify whether the modulation of TLR3 expression in CPCs may modify the CV risk in patients affected by RA. References Herbrig K et al. Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells. Ann Rheum Dis 2006;65(2):157-63. Yang M et al. The functional expression of TLR3 in EPCs impairs cell proliferation by induction of cell apoptosis and cell cycle progress inhibition. Int Immunopharmacol 2011, 11(12):2118-2124. Raicevic G et al. Inflammation modifies the pattern and the function of Toll-like receptors expressed by human mesenchymal stromal cells. Hum Immunol 2010, 71(3):235-244. Ito C et al. Cilostazol enhances IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle via PKA-dependent pathway. Cell Signal 2002, 14(7):625-632. Zimmer S et al. Activation of endothelial toll-like receptor 3 impairs endothelial function. Circ Res 2011, 108(11):1358-1366. Disclosure of Interest None Declared
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Vitamin D deficiency was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical setting and its serum levels are commonly reduced in Rheumathoid Arthritis. (RA). Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA an impairment of the number and the activity of circulating progenitor cells, including CD34+ cells and endothelial progenitor cells, appears to be involved in development of endothelial damage and cardiovascular diseases. Objectives This study investigates the association between vitamin D deficiency and circulating progenitor cell number (CPCs). Methods Circulating progenitor cells number and vitamin D levels were measured in 30 patients affected by RA and in 30 controls matched for age and gender. C-reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR), carotid intima-media thickness (cIMT), augmentation index (AIx), pulse wave velocity (PWV) were also evaluated. We investigated the relationships among vitamin D and cell number, inflammatory markers, and vascular parameters. Results In RA patients the levels of vitamin D were reduced with respect to controls (21.5±6.9 vs 37.6±13.2 ng/ml, p <0.001); CPCs number (1.80±0.59 vs 2.32± 0.34 cells/µL, p <0.001) was also significantly reduced. PWV and AIx were higher in RA, while cIMT was not different between RA patients and controls. Vitamin D correlate inversely with CPCs number and PWV (rs -0.49 p < 0.005 and rs -0.56, p< 0.001 respectively). In RA we identify no association between vitamin D and cIMT, CRP, ESR, fibrinogen. CPCs number correlates with CRP (rs -0.50, p<0.005) and ESR (rs= -0.57, p<0.001). Conclusions Our findings suggest that Vitamin D deficiency is a common finding in RA and is associated with reduced CPCs counts. Future studies are needed to determine whether vitamin D supplementation could improve CPCs levels and arterial stiffness indices in patients affected by rheumathoid arthritis. References Semba RD et al. Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr. 2010 Feb;64(2):203-9. Cutolo M at al. Vitamin D in rheumatoid arthritis. Autoimmun Rev. 2007 Nov;7(1):59-64. Haque UJ et al. Association of vitamin D with cardiometabolic risk factors in rheumatoid arthritis. ArthritisCare Res (Hoboken). 2012 Oct;64(10):1497-504. Herbrig K et al. Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells. Ann Rheum Dis 2006;65(2):157-63. Reynolds JA et al. 25-Hydroxyvitamin D deficiency is associated with increased aortic stiffness in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2012 Mar;51(3):544-51. Disclosure of Interest None Declared
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Objectives: To evaluate the association between inflammation, oxidative stress, and circulating progenitor cell (CPC) number and redox equilibrium, vascular lesions and accelerated atherosclerosis in rheumatoid arthritis (RA). Method: Circulating CD34+ cells were isolated from 33 RA patients and 33 controls. Reactive oxygen species (ROS) levels and mRNA expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase type 1 (GPx-1) antioxidant enzymes, and the gp91phox-containing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase NOX2 were measured in CD34+ cells. C-reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR), carotid intima-media thickness (cIMT), and arterial stiffness (AS) were also evaluated. We investigated the relationships between inflammatory markers, vascular parameters, cell number, and antioxidant enzymes. Results: CD34+ cell number was lower in RA patients than in controls. In CD34+ cells from RA patients, ROS levels, MnSOD mRNA, and NOX2 mRNA were higher, while mRNA expression of GPx-1 and CAT was significantly lower. The AS, pulse wave velocity (PWV), and augmentation index (AIx) were higher, as was cIMT. CD34+ cell number was inversely correlated with CRP, ROS, PWV, and AIx, and with the CAT/MnSOD and GPx-1/MnSOD ratios. CRP was correlated with MnSOD mRNA, PWV, and AIx but not with CAT and GPx-1 mRNA. Conclusions: Our data show a link between inflammation, oxidative stress, and the impairment of the antioxidant system of CPCs and their number, and with arterial stiffness in RA subjects. This could suggest a perspective on the accelerated development of vascular damage and atherosclerosis in RA.
    Full-text · Article · Dec 2013 · Scandinavian journal of rheumatology
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    ABSTRACT: We describe a case of mycetoma caused by Actinomadura pelletieri with simultaneous involvement of the spine, abdominal wall and retroperitoneal space in a man who had suffered from 'Madura foot' 10 years earlier. The characteristics of this case were analysed and contextualized among those of other cases of mycetoma caused by other micro-organisms found through a review of the international literature. The rarity of the disease in industrialized countries and its possible atypical presentations may hinder a prompt diagnosis. Culture techniques that allow detection of slow-growing fungi and actinomycetes should be routinely used when dealing with tissue samples from patients from tropical and subtropical regions with chronic granulomatous infections.
    Full-text · Article · Apr 2011 · Journal of Medical Microbiology
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    ABSTRACT: Cigarette smoking is involved in vascular inflammation and impairment of circulating progenitor cells (CPCs), including endothelial progenitor cells (EPCs). The study aim was to evaluate the redox balance of these cells in relation to smoking exposure. Circulating cells from 36 healthy smokers and 26 controls were isolated and identified by flow cytometry. ROS generation, mRNA and protein cell expression, and enzymatic activity of MnSOD, catalase, and GPx-1 were evaluated. Smokers showed higher levels of CRP and fibrinogen and lower levels of HDL-C. ROS and MnSOD were higher (p<0.001), while catalase and GPx-1 were lower (p<0.001) as was EPC number (p<0.001) in smokers. CPC and EPC correlated with HDL-C, CRP, ROS and enzyme expression and activity. Our data suggest that smoking exposure involves antioxidant enzymes in CPCs and EPCs and that the inflammatory response in smokers plays an important role in impairing cells and their antioxidant functions.
    Full-text · Article · Sep 2010 · Clinical biochemistry

  • No preview · Article · Nov 2009 · Nutrition Metabolism and Cardiovascular Diseases

  • No preview · Article · Nov 2008 · Nutrition Metabolism and Cardiovascular Diseases