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Background Pentraxin-3 (PTX-3) is involved in acute immunological responses and it is a pro-inflammatory protein and a novel biomarker of inflammatory diseases. It is demonstrated that PTX-3 is higher in cerebrospinal fluid (CSF) of aggressive Multiple Sclerosis (MS). Metabolomics, the identification of small endogenous molecules, offers a molecular profile of MS. Glatiramer acetate (GA) is a widely used treatment for (MS) but its mechanism of action is not completely defined. The aim of our study is to analyze PTX-3 and metabolomic profile in MS patients compared to controls and to investigate the effect of GA on PXT-3 and metabolic molecules during treatment in responder and not responder MS patients. Methods 28 unrelated MS patients and 27 age-and sex-matched controls were recruited. In serum, PTX-3 levels were measured by ELISA and Metabolomic panel was evaluated trough Nuclear Magnetic Resonance (NMR). According to clinical practice patients started GA treatment; PTX-3 and metabolomic identification were performed before and during treatment. Responders to treatment were identified if no evidence of instrumental, clinical relapses and disability progression (NEDA) occurred during follow up. Results Serum PTX-3 levels were higher in MS patients compared to matched controls (7,85 ± 2,19 vs 6,20 ± 1,63 ng/ml) (p = 0,03); metabolomic evaluation shows higher levels of lactate and lower levels of valine, tyrosine and tryptophan in MS patients compared to controls. During therapy, PTX-3 levels have been reduced statistically significant (p = 0,001) at six months and one year of treatment. After one year, of the twenty patients that completed the study, 55% were considered fully responders to treatment; in these patients the mean reduction of PTX-3 at one year was higher respect to not responders (−3,82 ± 1,24 ng/ml vs −2,32 ± 1,03 ng/ml p = 0,02) and we observed a higher reduction of lactate, tyrosine and hypoxanthine and an increase of hydroxyproline and ADP as well as of three oxidative phosphorylation markers, citrulline, ornithine and tryptophan approaching the metabolic profile of healthy subjects. Discussion and conclusions We demonstrated a metabolomic imbalance with mitochondrial dysfunction detected by higher levels of lactate and lower levels of tryptophan, tyrosine and valine in MS patients compared to healthy controls. The reduction of PTX-3 levels and the restoring of mitochondrial function, reducing oxidative stress by GA, allows to identify responder patients. Further and larger studies are needed to understand the predictive role of PTX-3 and metabolomic pattern in the identification of responder patients to GA.

Information on subcortical ischaemic changes (SIC) in young hypertensive patients is scarce. We evaluated the frequency of SIC at magnetic resonance imaging (MRI), the possible effect on cognition of these patients, and the role of plasma markers known as indicators of endothelial and haemostatic activation. Inclusion criteria were age

The aim of this study was to evaluate the relation between erectile dysfunction and endothelial functions, coagulation activation, peripheral and autonomic neuropathy in men with Type II (non-insulin-dependent) diabetes mellitus. We studied 30 Type II diabetic patients with symptomatic erectile dysfunction and 30 potent diabetic patients matched for age and disease. Endothelial functions were assessed with the l-arginine test, plasma thrombomodulin and cell adhesion molecules circulating concentrations. Haemostasis was evaluated with markers of thrombin activation and fibrinolysis. Quantitative sensory testing (vibratory, warming, and heat-pain thresholds), cardiovascular reflex tests and 24-h blood pressure monitoring were used to assess peripheral or autonomic neuropathy. Mean erectile score and HbA1 c were 10.5 ± 5.8 and 8.3 ± 1.6 % in patients with erectile dysfunction, and 24.0 ± 0.7 and 6.8 ± 1.4 % in those without erectile dysfunction, respectively (p < 0.001); there was a significant relation between HbA1 c and erectile function score in patients with erectile dysfunction (r = –0.45, p = 0.02). The decrease in blood pressure and platelet aggregation in response to l-arginine was lower (p < 0.05–0.02) in patients with erectile dysfunction, whereas soluble thrombomodulin, P-selectin and intercellular cell ahhesion molecule-1 concentrations were higher (p < 0.05–0.02). Indices of coagulation activation (F1 + 2 and d-dimers) and reduced fibrinolysis (PAI-1) were also found to be higher in erectile dysfunction patients. Heat-pain and warm perception thresholds, as well as cardiovascular reflex tests, were most commonly abnormal in patients with erectile dysfunction (p < 0.05). In multivariate analysis, HbA1 c, MBP response to l-arginine, P-selectin, indices of coagulation, and quantitative sensory testing were independent predictors of erectile function score. Erectile dysfunction in diabetic men correlates with endothelial dysfunction. A reduced nitric oxide activity might provide a unifying explanation. [Diabetologia (2001) 44: 1155–1160]

Objectives: Iloprost, an analogue of prostacy- clin, is often utilised in subjects with diabetes mellitus complicated by macroangiopathy. Methods: The eects of iloprost infusion on plasminogen activator inhibitor type-1 (PAI-1), glucometabolic con- trol and cardiovascular equilibrium in patients with type-2 diabetes mellitus and peripheral arterial occlusive disease were investigated. Thirteen (7 men/6 women) normal-weight, normotensive and non-smoker type-2 diabetic patients (63.8 3.4 years, mean SD) with peripheral arterial occlusive disease, stage-II according to Fontaine classi®cation, were enrolled. Eight (four men/four women) patients underwent three study de- signs, each separated by a 1-week interval: study I, in- fusion of iloprost (3 ng kgA1 minA1 for 5 h) for 1 day alone (short-term treatment); study II, infusion of saline (for 5 h) for 1 day (control treatment); study III, infu- sion of iloprost (3 ng kgA1 minA1 for 5 h) over a period of 28 days (long-term treatment). The remaining ®ve (three men/two women) patients underwent study IV only, infusion of saline over a period of 28 days (placebo treatment). Plasma levels of glucose, plasminogen, PAI-1 activity and ®brinogen, blood pressure and heart rate were determined in all studies, while plasma insulin levels, blood HbA1c, walking distance and Winsor index only in studies III and IV. Results: Both short- and long-term treatments with ilo- prost signi®cantly reduced PAI-1 activity (baseline vs end: 17.4 1.9 AU/ml vs 15.0 1.6 AU/ml, P < 0.02; 20.5 7.6 AU/ml vs 7.9 2.1 AU/ml, P < 0.002,respectively). Long-term treatment with iloprost signi®- cantly increased walking distance (baseline vs end: 32541m vs 49652m, P

Summary The objective of the study was to investigate the activity and antigen levels of u-PA in non-insulin dependent diabetes mellitus (NIDDM) patients, and their changes after venous stasis. A cross-sectional case-control study was carried out in the out-patient diabetology clinical unit of the General Hospital in Pescara, Italy. Fifty-nine unselected NIDDM patients (23 females and 36 males; mean age 63±10, with diabetes definition by WHO criteria) were studied. A group of 50 subjects, age matched (age 58±9, 42 males, 8 females), without a history of diabetes, were consecutively recruited among healthy relatives of patients admitted to the hospital for surgical interventions to serve as a control group. The levels of both u-PA activity (scu-PA) and antigen (u-PA Ag) were significantly lower in NIDDM patients compared to controls. In contrast, t-PA, PAI-1 antigen and PAI activity levels were increased in NIDDM patients. There was no change in u-PA levels (both activity and antigen) after venous stasis, while t-PA levels were significantly increased. There was no difference in u-PA (both activity and antigen) and in t-PA levels between male and female patients. However, fibrinogen levels were lower and PAI-1, both antigen and activity, was higher in men than in women. No difference was found between patients with and without macrovascular complications in the parametres studied. Besides changes in t-PA and PAI-1 levels, NIDDM is also characterized by a decrease in u-PA activity and antigen levels. Such impairment of the fibrinolytic system, together with the increase in fibrinogen levels, could contribute to the prothrombotic condition peculiar to these patients.

SummaryThe contribution of Helicobacter pylori (HP) infection to the risk of myocardial infarction was evaluated. The role of fibrinogen and its genetic control as a possibile mechanism by which HP may influence myocardial infarction risk was explored in this context. A case-control study was performed in 101 patients with myocardial infarction and in 101 controls.HP infection was associated with an increased risk of myocardial infarction independently for confounding variables (OR 4.1, CI95: 1.8-9.4). HP infection was significantly associated with higher levels of fibrinogen, both in cases and in controls. Furthermore, there was an additive effect of HP infection and B2 allele of BclI fibrinogen poly-morphism in increasing fibrinogen levels. HP infection showed a stronger effect on the risk of myocardial infarction in B2 allele carriers (OR 7.6, CI95: 1.8-31.6) as compared to subjects carrying the B1B1 genotype (OR 3.3, CI95: 1.2-9.2).We showed that a previous HP infection is a risk factor for myocardial infarction. An increase in fibrinogen levels is a possible mechanism by which HP may act. Concomitant conditions, like a genetic predisposition in increasing fibrinogen levels, seem to further increase the effect of HP on myocardial infarction risk.