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Biomedical subjects

Marco Matucci Cerinic

Publications and source records attributed to Marco Matucci Cerinic.

12 recordsLinked to original sources
PubMed2006

Hemorheologic profile in systemic sclerosis: role of NOS3 -786T > C and 894G >T polymorphisms in modulating both the hemorheologic parameters and the susceptibility to the disease.

OBJECTIVE: Microvascular disorders are relevant in systemic sclerosis (SSc). Hyperviscosity, due to alterations of blood cells and plasma components, may play a role in the pathogenesis of microcirculatory disorders. An impaired availability of nitric oxide, related to polymorphisms in NOS3, the gene for endothelial cell nitric oxide synthase, might influence erythrocyte deformability. We undertook this study to investigate the hemorheologic profile in SSc and the role of NOS3 polymorphisms in modulating the hemorheologic status of SSc patients. METHODS: We studied 113 consecutive SSc patients (75 with limited cutaneous SSc [lcSSc] and 38 with diffuse cutaneous SSc [dcSSc]) and 113 healthy controls. The hemorheologic profile was obtained by assessing whole blood viscosity (WBV; at shear rates of 0.512 and 94.5 seconds(-1)), plasma viscosity (PLV; at a shear rate of 94.5 seconds(-1)), and erythrocyte deformability index (DI). We determined NOS3 polymorphisms by molecular analysis. RESULTS: A marked alteration of hemorheologic parameters was found both in patients with lcSSc and in those with dcSSc compared with controls (P < 0.0001). In multivariate analysis, rheologic variables were significantly associated with the disease (for WBV at a shear rate of 94.5 seconds(-1), odds ratio [OR] 5.4, 95% confidence interval [95% CI] 1.4-19.9, P = 0.01; for PLV, OR 2.8, 95% CI 1.2-6.5, P = 0.01; for DI, OR 3.9, 95% CI 1.4-10.8, P = 0.007), and NOS3 -786C and 894T alleles significantly affected the DI (for -786C allele, OR 2.3, 95% CI 1.01-5.4, P = 0.04; for 894T allele, OR 2.2, 95% CI 1.01-4.8, P = 0.04). The simultaneous presence of the -786C and 894T alleles represented a susceptibility factor for SSc (OR 2.8, 95% CI 1.4-5.7, P = 0.004). CONCLUSION: Our findings document an altered rheologic profile in SSc and demonstrate a relationship between this alteration and NOS3 polymorphisms, thus shedding light on a potential novel mechanism influencing the microcirculation in this disease.

Aged↗
PubMed2006

Angiotensin-converting enzyme in systemic sclerosis: from endothelial injury to a genetic polymorphism.

The main pathologic hallmark of systemic sclerosis (SSc) is endothelial derangement; the pathologic alterations of the vessel wall in SSc are strikingly similar to the modification detected in the atherosclerotic lesions, and it is now evident that SSc is also characterized by accelerated macrovascular disease. Peptides related to angiotensin II, the final product of the renin-angiotensin system (RAS), play a role as regulators of endothelial cell function. Angiotensin-converting enzyme (ACE), the key enzyme in the RAS, is the predominant pathway of angiotensin II formation in blood and tissues. In intron 16 of the gene encoding for ACE an insertion/deletion (I/D) polymorphism, consisting of the presence or absence of a 287-base pair Alu sequence, has been identified. This polymorphism has been related to ACE enzyme levels, and data from experimental studies reported a functional role for this polymorphism in modulating the angiotensin II levels. We previously documented a high ACE D allele frequency in SSc patients and its role in increasing the risk of SSc, thus suggesting that the I/D polymorphism might be a useful genetic marker to identify SSc patients at risk to develop a severe vascular disease, frequently leading to gangrene. Moreover, our preliminary data, besides supporting the role of ACE I/D polymorphism as a predisposing factor to SSc, demonstrated its involvement in accelerated macrovascular disease by increasing the intima media thickness. Therefore, in SSc, not only endothelial dysfunction, but also vascular damage, linked to ACE I/D polymorphism, may significantly contribute to accelerated macrovascular disease, as the ACE D allele, by regulating both the production of angiotensin II and the degradation of bradykinin, contributes to mechanisms involved in the induction and maintenance of vessel wall modification.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Systemic lupus erythematosus (SLE) in Italy: an Italian prevalence study based on a two-step strategy in an area of Florence (Scandicci-Le Signe).

BACKGROUND: The goal was to ascertain the prevalence of SLE in the population over 18 years of age in the Scandicci-Le Signe area of Florence, Italy, based on the records of general practitioners (GPs). MATERIAL/METHODS: Twenty GPs screened 32,521 patients by administering the Lupus Screening Questionnaire (LQS) and found 30 patients with suspected or definite diagnosis of SLE. To confirm the diagnoses the patients were referred to a rheumatologist who conducted routine examinations and assessed antinuclear antibodies and SLE activity (ECLAM score). RESULTS: Total population >18 years of age in the three municipalities was 71,204 persons, with 42,474 in Scandicci, 15,368 in Lastra a Signa, and 13,362 in Signa. In 23/30 patients diagnosed with SLE the diagnosis was confirmed. Eleven of the 23 SLE patients were from Scandicci and 6 each from Lastra a Signa and Signa. An overall estimated prevalence of SLE of 71/100,000 (1/1408; 95% CI=49, 92) was found in the total population of the three municipalities. Scandicci (95% CI=42, 121) had a rate of 81/100.000, while Lastra a Signa (95% CI=32, 92) and Signa (95% CI=36, 94) had estimated rates of 62/100,000 and 65/100,000, respectively. Medium ECLAM score was 4.68+/-1.81 SD. CONCLUSIONS: This is the first epidemiological study on SLE prevalence in Italy. The prevalence and point prevalence are similar to other European studies. The LQS was also confirmed as an easy and reliable tool to assess SLE diagnosis in the Italian population.

Adult↗
PubMed2004

Neprilysin levels in plasma and synovial fluid of juvenile idiopathic arthritis patients.

OBJECTIVE: Neprilysin (neutral endopeptidase, 3:4:24:11, CD10) (NEP) is a Zn metallopeptidase linked to controlling inflammation through the degradation of neuropeptides involved in neurogenic inflammation of chronic rheumatic diseases. The aim of our study was to evaluate circulating activity and cellular expression of NEP in the plasma of 58 children with juvenile idiopathic arthritis (JIA) and 52 controls. In 20 subjects requiring local steroid injection, NEP was measured in synovial fluid. METHODS: Plasma and synovial NEP were evaluated using a fluorimetric technique. Neprilysin, expressed as the antigen CD10, was determined on circulating and synovial fluid cells as mean fluorescence intensity (MFI) and as percentage of positive cells by two-color immunofluorescence. RESULTS: Circulating NEP levels were lower in JIA patients than in controls (42.0+/-16.6 vs 76.5+/-24 pmol/ml per min, P<0.001), while synovial fluid NEP values were higher than circulating levels (241.4+/-86.2 vs 40+/-15.3 pmol/ml per min, P<0.001). In monocytes, the percentage of CD10-positive circulating cells and the MFI in JIA were lower than in controls (11.6+/-5.2% vs 41.4+/-13%, P<0.001 and 18.1+/-7.5 vs 31.2+/-5.4, P<0.05, respectively). On synovial monocytes, the percentage of CD10-positive cells and the MFI were higher than on circulating monocytes (35.2+/-14.6% vs 9.1+/-2.4%, P<0.001 and 66.4+/-5.4 vs 22.8+/-14.7, P<0.001, respectively). CONCLUSIONS: The downregulation of CD10 expression in monocytes and the reduction in NEP activity may be linked to the enzyme's role in the control of peptides involved in the inflammation. The increased levels of NEP, MFI, and CD10-positive monocytes in synovial fluid, even though in plasma, might reflect a reactive effort to control synovial proliferation.

Arthritis, Juvenile↗
PubMed2003

Current Treatment Options in Raynaud's Phenomenon.

The treatment of Raynaud's phenomenon (RP) strictly depends on the severity of symptoms and on the presence of an underlying systemic disease. For this reason, any patient with RP should be carefully assessed for signs and symptoms that may herald an underlying disease. Primary RP can usually be managed with conservative nonpharmacologic lifestyle modifications (eg, avoidance of cold temperatures, tobacco, caffeine, and any drug interfering with vascular tone) and pharmacologic treatment added only if attacks are poorly controlled. Vasodilating drugs (eg, calcium channel blockers, angiotensin II receptor antagonists, topical nitrates, and prostanoids) are still the mainstay of medical therapy for RP. Anecdotal reports with different kinds of therapies appear regularly but always need evidence-based confirmation. In particular, antioxidant agents may be useful in limiting the progressive endothelial damage. Novel therapeutic tools interfering either with primary or secondary pathogenetic processes (ie, endothelial and peripheral nervous system dysfunction and smooth muscle cell hypertrophy) are awaited.

Journal Article↗
PubMed2003

Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis.

OBJECTIVE: To evaluate the coagulative/fibrinolytic cascade and the circulating markers of the endothelial injury in systemic sclerosis (SSc). METHOD: Plasma was obtained from 29 patients with SSc and tested for thrombin-antithrombin (TAT), fragments 1+2 (F1+2), dermatansulphate (DS), thrombomodulin (TM), lipoprotein (a) [Lp(a)], von Willebrand factor (vWF), tissue type plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimers, intercellular adhesion molecole-1 (ICAM-1), vascular cell adhesion molecule (VCAM), and E-selectin. The data were correlated with lung (forced vital capacity, diffusing lung capacity for carbon monoxide, vital capacity) and skin (skin score) involvement. RESULTS: Coagulation was significantly activated (increase in F1+2, P <.001; TAT, P <.01; and Lp(a), P <.05). TM was not significantly different from controls. vWF was significantly increased (P <.01), and its supranormal multimers increased in more than 50% of patients. DS was significantly increased in diffuse cutaneous SSc (P <.01). Fibrinolysis was impaired as shown by reduced D-dimers (P <.01) and decreased levels of PAI (P < 0.01). The markers of endothelial injury were also significantly elevated. DS correlated significantly with forced vital capacity (P <.01) and forced vital capacity ratio (P <.01). CONCLUSION: Injury to the endothelium reduces endothelial function, as suggested by impairment of fibrinolysis and activation of the coagulative pathway. The loss of the balance between fibrinolysis and coagulation contributes to vessel engulfment with fibrin and breakdown of vessel patency. The increase of circulating DS suggests that this factor may be a new marker of endothelial injury.

Adult↗
PubMed2002

Activin, a grape seed-derived proanthocyanidin extract, reduces plasma levels of oxidative stress and adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in systemic sclerosis.

This study evaluated whether a new generation antioxidant Activin derived from the grape seed proanthocyanidins, could reduce the induction of the adhesion molecules as a result of inflammatory response in the plasma of systemic sclerosis (SSc) patients. SSc patients were divided into two groups: one group was treated with Activin, a grape seed-derived proanthocyanidins, while the other group served as control. Patients were given Activin 100 mg/day orally for one month after which the blood samples were withdrawn from both groups of the patients. Blood was also taken from normal human volunteers. Plasma was obtained in fasting state between 8 to 9 A.M. from two groups of SSc patients and controls. Soluble adhesion molecules including ICAM-1, VCAM-1, E-selectin and P-selectin as well as malonaldehyde, a marker for oxidative stress, were measured. The results of our study demonstrated up-regulation of these soluble adhesion molecules except for P-selectin, in the plasma of the SSc patients compared to those obtained from human volunteers. Activin significantly attenuated the increased expression of these adhesion molecules. In addition, there was a significant increase in the amount of malondialdehyde formation in the plasma of the SSc patients, which was also attenuated by Activin. The results of this study demonstrated that Activin could reduce the inflammatory response and the oxidative stress developed in SSc patients.

Activins↗
PubMed2002

Angioedema and systemic sclerosis. A review of the literature.

We report a case of chronic idiopathic recurrent urticaria-angioedema and gastroesophageal reflux disease in a 35-years-old man, followed after 2 years by Raynaud's phenomenon and esophageal dysphagia, recurrent cough and dyspnoea, and after 4 years by systemic sclerosis. A review of the literature and possible correlated pathogenetic mechanisms are presented.

Adult↗
PubMed2002

Overlap syndromes.

Many connective tissue diseases share common signs and symptoms, which frequently makes the diagnosis of a specific rheumatic disease difficult. Rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis (DM), mixed connective tissue disease, and Sjögren's syndrome can present with similar clinical features, particularly during the first 12 months of symptoms. Overall, a rheumatic disease can appears in conjunction with features of one or more other connective tissue diseases, for example, patients can have a combination of rheumatoid arthritis and systemic lupus erythematosus ("rhupus"), or systemic sclerosis and polymyositis, defining an "overlap syndrome", where the diseases comply with the diagnosis criterias. Finally, when a person has symptoms of various connective tissue diseases without meeting the full criteria for any one of them, it is often called Undifferentiated Connective Tissue Disease.

Connective Tissue Diseases↗