Oral administration of polyphenolic compounds from cognac decreases ADP-induced platelet aggregation and reduces chronotropic effect of isoprenaline in rats

This study sought to evaluate whether consumption of polyphenol extract from Cognac (CPC) modulates platelet activation and cardiovascular reactivity in rats. Male Wistar rats were treated daily for 4 weeks by intra-gastric gavage receiving CPC at 80 mg/kg/day or vehicle (5 % glucose). Platelet adhesion and aggregation in response to different activators were assessed. Cardiac and vascular reactivity in response to various agonists as well as NO measurement by electron paramagnetic resonance technique were investigated in isolated heart and thoracic aorta. Oral administration of CPC decreased platelet aggregation induced by ADP but not by collagen. CPC did not affect adhesion to collagen. The chronotropic but not the inotropic response to isoprenaline was reduced without alteration of NO production in hearts from CPC-treated rats. CPC treatment did not affect ex vivo relaxation to acetylcholine nor NO content of rat aorta. CPC did not significantly alter the response to phenylephrine in aorta despite the participation of endothelial vasoconstrictor products. In summary, chronic treatment with CPC has no impact on ex vivo vascular and cardiac reactivity; however, it reduced heart work and platelet aggregation. These data suggest the existence of compounds in Cognac that may decrease the risk of coronary thrombosis and protect against some cardiac diseases

Annexin A1 Released in Extracellular Vesicles by Pancreatic Cancer Cells Activates Components of the Tumor Microenvironment, through Interaction with the Formyl-Peptide Receptors

Pancreatic cancer (PC) is one of the most aggressive cancers in the world. Several extracellular factors are involved in its development and metastasis to distant organs. In PC, the protein Annexin A1 (ANXA1) appears to be overexpressed and may be identified as an oncogenic factor, also because it is a component in tumor-deriving extracellular vesicles (EVs). Indeed, these microvesicles are known to nourish the tumor microenvironment. Once we evaluated the autocrine role of ANXA1-containing EVs on PC MIA PaCa-2 cells and their pro-angiogenic action, we investigated the ANXA1 paracrine effect on stromal cells like fibroblasts and endothelial ones. Concerning the analysis of fibroblasts, cell migration/invasion, cytoskeleton remodeling, and the different expression of specific protein markers, all features of the cell switching into myofibroblasts, were assessed after administration of wild type more than ANXA1 Knock-Out EVs. Interestingly, we demonstrated a mechanism by which the ANXA1-EVs complex can stimulate the activation of formyl peptide receptors (FPRs), triggering mesenchymal switches and cell motility on both fibroblasts and endothelial cells. Therefore, we highlighted the importance of ANXA1/EVs-FPR axes in PC progression as a vehicle of intercommunication tumor cells-stroma, suggesting a specific potential prognostic/diagnostic role of ANXA1, whether in soluble form or even if EVs are captured in PC

Platelet aggregation is affected by nitrosothiols in patients with chronic hepatitis: in vivo and in vitro studies

AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-6 in patients with chronic hepatitis C (CH). METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo, S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts 150000/microL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen

Argas (Persicargas) persicus (Oken, 1818) (Ixodida: Argasidae) in Sicily with considerations about its Italian and West-Mediterranean distribution.

Recently, in the province of Trapani (Western Sicily), some overwintering specimens of the argasid tick Argas (Persicargas) persicus (Oken, 1818) were observed and collected. Morphological and genetic analysis were utilized in order to reach a definitive identification. The species was found in two semi-natural sites where, having been found repeatedly, its presence does not appear accidental. Moreover the characteristics of the Sicilian findings seem to exclude a human-induced spread. This record, the first regarding Sicily and South Italy, is discussed together with the previous doubtful citations for Italy. These findings revalue not only all the old citations for Italy but also the hypothesis that the Mediterranean distribution of this argasid is of a natural origin

Transannular patching is a valid alternative for tetralogy of Fallot and complete atrioventricular septal defect repair

Objective: We report our experience with repair of tetralogy of Fallot associated with complete atrioventricular septal defect, addressing in particular the need for a pulmonary valve in the right ventricular outflow tract. Methods: Between 1992 and 2006, 33 children with tetralogy of Fallot and complete atrioventricular septal defect were admitted; 26 had Down’s syndrome (79%). Thirty-two children had complete repair (18 primary, 14 staged); of the 15 who received initial palliation, 1 died before complete repair. Right ventricular outflow tract obstruction was relieved by transannular patch in 14 cases (42%), infundibular patch with preservation of the pulmonary valve in 7 (21%), and right ventricle–to–pulmonary artery conduit in 11 (33%). Results: There were no hospital deaths. Actuarial survival was 96% 3.9% at 5 years and 85.9 1.1% at 10 years. Multivariate analysis showed that type of relief of right ventricular outflow tract obstruction did not influence survival (P ¼ .16), nor did the choice to use a valved conduit (P ¼ .82). Primary correction (P ¼ .05) and lower weight at repair (P ¼ .05) were associated with higher probability of survival. Mean follow-up was 69.3 5.9 months (range 0.2–282 months). There were 2 late deaths. Overall freedom from reoperation was 69% at 5 years and 38%at 10 years. Right ventricular outflow tract reconstruction without use of a valved conduit allowed a significantly higher freedom from reinterventions (P<.05). Conclusions: Tetralogy of Fallot associated with complete atrioventricular septal defect can be corrected at low risk with favorable intermediate survival. Use of right ventricle–to–pulmonary artery conduit can be avoided in two thirds of patients with no impact on survival, possibly improving overall freedom from reintervention

Transannular patching is a valid alternative for tetralogy of Fallot and complete atrioventricular septal defect repair

Objective: We report our experience with repair of tetralogy of Fallot associated with complete atrioventricular septal defect, addressing in particular the need for a pulmonary valve in the right ventricular outflow tract. Methods: Between 1992 and 2006, 33 children with tetralogy of Fallot and complete atrioventricular septal defect were admitted; 26 had Down’s syndrome (79%). Thirty-two children had complete repair (18 primary, 14 staged); of the 15 who received initial palliation, 1 died before complete repair. Right ventricular outflow tract obstruction was relieved by transannular patch in 14 cases (42%), infundibular patch with preservation of the pulmonary valve in 7 (21%), and right ventricle–to–pulmonary artery conduit in 11 (33%). Results: There were no hospital deaths. Actuarial survival was 96% 3.9% at 5 years and 85.9 1.1% at 10 years. Multivariate analysis showed that type of relief of right ventricular outflow tract obstruction did not influence survival (P ¼ .16), nor did the choice to use a valved conduit (P ¼ .82). Primary correction (P ¼ .05) and lower weight at repair (P ¼ .05) were associated with higher probability of survival. Mean follow-up was 69.3 5.9 months (range 0.2–282 months). There were 2 late deaths. Overall freedom from reoperation was 69% at 5 years and 38%at 10 years. Right ventricular outflow tract reconstruction without use of a valved conduit allowed a significantly higher freedom from reinterventions (P<.05). Conclusions: Tetralogy of Fallot associated with complete atrioventricular septal defect can be corrected at low risk with favorable intermediate survival. Use of right ventricle–to–pulmonary artery conduit can be avoided in two thirds of patients with no impact on survival, possibly improving overall freedom from reintervention

SIRT1 activity in peripheral blood mononuclear cells correlates with altered lung function in patients with chronic obstructive pulmonary disease

Background. Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD). Expression of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease. Methods. We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS). Results. The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS &gt; HS &gt; COPD). TOS levels were significantly lower in HnS than in smoke-associated subjects (COPD and HS), while TEAC levels were progressively lower according (HnS &gt; HS &gt; COPD). In COPD patients, SIRT1 activity, but not protein levels, correlated significantly with both lung function parameters (FEV1/FVC and FEV1) and TEAC. Conclusions. These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD

The anti-ageing molecule sirt1 mediates beneficial effects of cardiac rehabilitation

Background An exercise-based Cardiac Rehabilitation Programme (CRP) is established as adjuvant therapy in heart failure (HF), nevertheless it is underutilized, especially in the elderly. While the functional and hemodynamic effects of CRP are well known, its underlying molecular mechanisms have not been fully clarified. The present study aims to evaluate the effects of a well-structured 4-week CRP in patients with stable HF from a molecular point of view. Results A prospective longitudinal observational study was conducted on patients consecutively admitted to cardiac rehabilitation. In fifty elderly HF patients with preserved ejection fraction (HFpEF), levels of sirtuin 1 (Sirt1) in peripheral blood mononuclear cells (PBMCs) and of its targets, the antioxidants catalase (Cat) and superoxide dismutase (SOD) in serum were measured before (Patients, P) and at the end of the CRP (Rehabilitated Patients, RP), showing a rise of their activities after rehabilitation. Endothelial cells (ECs) were conditioned with serum from P and RP, and oxidative stress was induced using hydrogen peroxide. An increase of Sirt1 and Cat activity was detected in RP-conditioned ECs in both the absence and presence of oxidative stress, together with a decrease of senescence, an effect not observed during Sirt1 and Cat inhibition. Conclusions In addition to the improvement in functional and hemodynamic parameters, a supervised exercise-based CRP increases Sirt1 activity and stimulates a systemic antioxidant defence in elderly HFpEF patients. Moreover, CRP produces antioxidant and anti-senescent effects in human endothelial cells mediated, at least in part, by Sirt1 and its target Cat