Abstract-Endothelial progenitor cells (EPCs) seem to be a promising tool for cell therapy of acute myocardial infarction, but their nature is still unclear. We show here that EPCs obtainable from peripheral blood (PB) derive from the adhesion-related selection in culture of a subset of CD14ϩ cells, which, when assessed by the highly-sensitive antibody-conjugated magnetofluorescent liposomes (ACMFL) technique, were found to express CD34. These CD14ϩCD34 low cells represented a variable proportion at individual level of CD14ϩ cells, ranging from 0.6% to 8.5% of all peripheral-blood leukocytes, and constituted the dominant population among circulating KDRϩ cells. By using the ACMFL technique, virtually all CD14ϩ cells present in the bone marrow were found to be CD14ϩCD34 low double-positive cells. EPCs, as well as purified circulating CD14ϩCD34 low cells, exhibited high expression of embryonic stem cell (SC) markers Nanog and Oct-4, which were downregulated in a STAT3-independent manner when they differentiated into endothelial cells (ECs) [1][2][3] Indeed, these cells have been successfully used to repair tissue damage in both murine experimental models 3-5 and in preliminary trials performed in humans experiencing acute myocardial infarction. 4,5 EPC populations are usually derived from peripheral blood mononuclear cells (PBMNCs) cultured in presence of vascular endothelial growth factor (VEGF), and identified as a population of adherent cells expressing both acLDL and Ulexlectin. However, controversy exists with respect to the true nature and origin of circulating EPCs. Although it is well known that CD34ϩ, or CD133ϩ progenitors, purified by the immunomagnetic technique and cultured in the presence of VEGF, can generate endothelial cells (ECs) and exhibit revascularization properties in vivo, 1-7 these cells represent a very small subset of PBMNCs, ranging from 0.02% to 0.1%.Thus, the recovery of a sufficient number of these cells for therapeutic treatments usually requires the mobilization of bone marrow (BM)-derived CD34ϩ or CD133ϩ populations by administration of granulocyte colony-stimulating factor (G-CSF); 5,7 however, this treatment has been questioned, because of the high risk of adverse events in subjects with vascular disorders. 8 On the other hand, adherence-related selection of cultured PBMNCs allows for the recovery of a number of EPCs sufficient for therapeutic treatments, suggesting that EPCs can also originate from circulating populations other than CD34ϩ or CD133ϩ progenitors. 1-5 Accordingly, conventional cytofluorimetric techniques of PBMNCs-derived EPCs have shown that these cells consist of a population sharing monocytic and EC markers, but not the classic stem cell (SC) markers CD34 and CD133. [1][2][3][4][5]9,10 Thus, the precise nature of cells effective in clinical trials 4,5 remains unclear. In this study, we demonstrate that PBMNC-derived EPCs appear to be CD14ϩ by using the conventional cytofluorimetric technique, but virtually all of them were also found to express low levels of su...

The use of pioglitazone does not appear to be harmful in terms of cardiovascular events and all-cause deaths.

No abstract

This study was designed to assess the antimicrobial effect and tolerability of a single dose of a photo-activated gel containing RLP068 in the treatment for infected foot ulcers in subjects with diabetes. A randomized, double-blind, parallel series, placebo-controlled phase IIa trial was performed with three concentrations of RLP068 (0.10, 0.30, and 0.50 %), measuring total and pathogen microbial load on Day 1 (before and 1 h after topical gel application and photoactivation with 689 nm red light), on Days 3, 8, and 15, as add-on to systemic treatment with amoxicillin and clavulanic acid. Blood samples were also drawn 1, 2, and 48 h after administration for the assessment of systemic drug absorption. The trial was performed on 62 patients aged ≥18 years, with type 1 or type 2 diabetes and infected foot ulcer, with an area of 2-15 cm(2) and a maximum diameter ≤4.6 cm. A dose-dependent reduction in total microbial load was observed (-1.92 ± 1.21, -2.94 ± 1.60, and -3.00 ± 1.82 LogCFU/ml for 0.10, 0.30, and 0.50 % RPL068 vs. -1.00 ± 1.02 LogCFU/ml with placebo) immediately after illumination, with a progressive fading of the effect during follow-up. No safety issues emerged from the analysis of adverse events. Systemic absorption of RLP068 was negligible. Photodynamic antimicrobial treatment with RLP068 of infected diabetic foot ulcers is well tolerated and produces a significant reduction in germ load. Further clinical trials are needed to verify the efficacy of this approach as add-on to systemic antibiotic treatment.

No abstract

Objective: To evaluate dietary habits and lifestyle of Italian subjects, to provide current data on adequacy of the nutritional guidelines and recommendations especially in relation to primary prevention of cardiovascular diseases and to assess the influence of dietary habits on lipid profile and homocysteine levels. Design: Cross-sectional. Setting: Population-based study. Subjects: A sample of 520 clinically healthy subjects (211 males, 309 females) with a mean age of 46 y, living in Florence area, Italy. Interventions: Dietary pattern was assessed by trained dietitians through a semiquantitative food questionnaire. Fasting blood samples were drawn for assessment of lipid profile, homocysteine and circulating vitamins. Results: Contribution from total fats was over 30% in about 70% of subjects and intake of saturated fatty acids (SFA) was above the recommended values in at least 40% of the study population. Furthermore, almost the whole (99.6%) population reported low intake of polyunsaturated fatty acids (PUFA). High levels of total cholesterol were present in over 40% of the study population, whereas abnormal values of LDL-cholesterol were observed in about 30%. High levels of homocysteine were found in 11.7% of the study population. An extremely high percentage of subjects reported low intake of vitamins, especially with regard to folic acid (89%), vitamin B 6 (70.1%) and vitamin E (99.6%). In a multiple linear regression model, circulating levels of vitamin B 12 and folic acid, and intake of alcohol and vitamin C resulted in being independently associated with homocysteine plasma levels. Conclusions: In a typical Mediterranean country, general outlines of Mediterranean diet are not completely followed, especially concerning total fats, SFA, PUFA and vitamins' intake.

The aim of this study was to determine the presence of organization of atrial activation processes during atrial fibrillation (AF) by assessing whether the activation sequences are wholly random or are governed by deterministic mechanisms. We performed both linear and nonlinear analyses based on the cross correlation function (CCF) and recurrence plot quantification (RPQ), respectively. Recurrence plots were quantified by three variables: percent recurrence (PR), percent determinism (PD), and entropy of recurrences (ER). We recorded bipolar intra-atrial electrograms in two atrial sites during chronic AF in 19 informed subjects, following two protocols. In one, both recording sites were in the right atrium; in the other protocol, one site was in the right atrium, the other one in the left atrium. We extracted 19 episodes of type I AF (Wells' classification). RPQ detected transient recurrent patterns in all the episodes, while CCF was significant only in ten episodes. Surrogate data analysis, based on a cross-phase randomization procedure, decreased PR, PD, and ER values. The detection of spatiotemporal recurrent patterns together with the surrogate data results indicate that during AF a certain degree of local organization exists, likely caused by deterministic mechanisms of activation.

Background and Purpose-To evaluate preliminarily efficacy and safety of intravenous tirofiban combined with mechanical clot disruption and urokinase in patients with stroke attributable to major cerebral artery occlusion. Methods-Eleven consecutive patients with stroke attributable to acute occlusion of a major cerebral artery were treated with an intravenous bolus injection of the platelet glycoprotein IIb/IIIa antagonist tirofiban combined with heparin and by endovascular procedures including mechanical thrombolysis and locally delivered urokinase. Of the 11 cases, 9 involved angioplasty and 2 only microcatheter and microguidewire manipulation. Results-There were 7 patients with internal carotid or middle cerebral artery occlusion treated within 6 hours and 4 patients with basilar artery occlusion treated within 12 hours of symptom onset. Median National Institutes of Health Stroke Scale (NIHSS) score on admission was 20. After the interventional procedure, vessel recanalization was partial (thrombolysis in myocardial infarction grade flow 2 [TIMI 2]) in 7 patients and absent or insufficient in 4 patients. Twenty-four hours after the procedure, all the patients but 1 improved substantially, and on control angiography, the occluded vessel was totally patent (TIMI 3) in 10 of the 11 patients. One patient with partial recanalization did not improve and died 3 months later from pulmonary embolism. Neither a symptomatic intracerebral hemorrhage nor systemic bleedings requiring blood transfusion occurred in any patient. At discharge, median NIHSS score was 2. The 3-month outcome was excellent in 8 patients (modified Rankin Scale [mRS] 0 to 1), good in 2 patients (mRS 2), and poor in 1 patient (mRS 6). Conclusions-The combination of intravenous tirofiban with intra-arterial mechanical clot disruption and urokinase may be successful in reopening an occluded major cerebral vessel without increasing the hemorrhagic risk and with good functional outcome. This strategy cannot be recommended as the systematic treatment of stroke attributable to major cerebral artery occlusion until tested in a controlled study design. (Stroke. 2005;36:2154-2158.)