Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans

OBJECTIVES: The goal of this study was to test the hypothesis that NCX-4016 may have broader anti-inflammatory and antithrombotic effects as well as better gastric tolerability than aspirin in humans. BACKGROUND: NCX-4016 is an aspirin derivative containing a nitric oxide-releasing moiety that prevents platelet activation and modulates tissue factor (TF) expression and cytokine release from lipopolysaccharide (LPS)-stimulated monocytes. METHODS: This was a blind-observer, placebo-controlled, parallel-group study in which 48 healthy subjects were randomized to receive NCX-4016 800 mg twice a day, NCX-4016 800 mg twice a day plus aspirin 325 mg, aspirin 325 mg, or placebo for 21 days. RESULTS: Similar to aspirin alone, NCX-4016 effectively inhibited platelet aggregation induced by 0.6 mmol/ arachidonic acid, clot-stimulated thromboxane (TX) B2 generation in whole blood, and urinary excretion of 11-dehydro-TXB2. Unlike aspirin alone, the administration of NCX-4016 significantly inhibited TF expression in monocytes stimulated ex vivo with 10 micromol/l LPS (determined by flow-cytometry analysis of TF on CD14 positive cells). NCX-4016 also inhibited the rapid TF expression induced in monocytes by a proteinase activated receptor agonist (thrombin receptor activator protein, 2 micromol/l) as well as LPS-induced expression of CD11b . Ex vivo, release of MCP-1 and interleukin-6 were significantly inhibited by NCX-4016, but not by aspirin. NCX-4016 was not associated with gastric damage, and significantly reduced gastric injury when co-administered with aspirin, although both drugs reduced gastric PGE2 production to the same extent. CONCLUSIONS: NCX-4016 is equally effective as aspirin in inhibiting cyclooxygenase activity. However, NCX-4016 causes less gastric damage and prevents monocyte activation. Larger multicenter trials are warranted to establish clinical efficacy and safety of NCX-4016.     

Survival after aortic valve replacement for aortic stenosis: does left ventricular mass regression have a clinical correlate?

AIM: The effects of post-operative left ventricular mass regression (LVMR) on clinical outcome after aortic valve surgery remains to be established. This study was intended to establish the impact of patient characteristics on post-operative survival in patients referred for aortic valve replacement (AVR), with particular regard to LVMR. METHODS AND RESULTS: Two hundred and sixty consecutive cases submitted to aortic valve replacement for valvular stenosis were prospectively followed for a mean of 28+/-9 months. Baseline, characteristics and extent of LVMR were tested for association with survival by uni- and multivariable analysis. Ten deaths occurred during hospital stay and 52 during out-of-hospital follow-up. Mean left ventricular mass decreased from 190+/-43 to 158+/-70 g/m2 (P<0.001). Older age, advanced functional class, hypertension, reduced left ventricle ejection fraction, and high pre-operative left ventricular mass index were associated with reduced survival. Overall the extent of LVMR did not influence the clinical results, while only early (<6 months) LVMR was weakly associated with mid-term outcome. CONCLUSION: Survival after aortic valve surgery is mainly determined by the pre-operative functional cardiac and systemic status. The extent of LVMR does not correlate with clinical outcome, whereas aggressive treatment of hypertension may improve post-operative survival.     

The plasma59Fe clearance curve in man

Summary Studies of⁵⁹Fe clearance from the plasma are used for obtaining a quantitative measure of erythropoiesis. However, there are many difficulties associated with a good definition and a valid analysis of the plasma⁵⁹Fe clearance curve. The low plasma activity, plasma iron variation, and traces of haemolysis are factors which make the measurement of the curve difficult. All these problems were examined in the present work. Liquid scintillation counting allows a more accurate assay of plasma⁵⁹Fe activity than conventional gamma counting. Plasma iron fluctuations may affect tracer kinetics but adjustment of plasma activity for plasma iron variation (expressing⁵⁹Fe activity per unit mass of iron) does not appear a satisfactory procedure for overcoming this difficulty. The removal of haemoglobin from plasma samples is a necessary procedure to avoid contamination by [⁵⁹Fe] haemoglobin. Fitting three exponentials to the plasma⁵⁹Fe clearance curve does not yield satisfactory results in some cases. A better prediction of the clearance curve in most cases can be obtained by means of a more refined mathematical model.The research was supported by C.N.R. Contract No. 78.00513.86 within the Special Project on Biomedical Engineering.     

Diagnostic Accuracy of a Bedside Screening Tool for Dysphagia (BSTD) in Acute Stroke Patients

Background and purposean estimated 40-80% of acute ischemic stroke patients have dysphagia and about 14% develop stroke-associated pneumonia. However, it may be difficult to detect swallowing problems at admission. Moreover, there might not be an on-duty specialist skilled in the diagnosis of this condition. This study aimed at developing a user-friendly bedside examination to identify the risk of dysphagia in stroke patients at hospital admission.Methodsa diagnostic accuracy study was carried out to assess the concurrent validity of a simple Bedside Screening Tool for Dysphagia (BSTD) in acute stroke. All the consecutive stroke patients admitted between January and April 2018 were enrolled. Sensitivity, specificity, positive (PPV), negative predictive values (NPV) and the Cohen K concordance index scores, reported by nurses and speech-pathologists, were assessed.Resultsa total of 67/120 patients (55.8%) were male; overall average age was 67.4 (range 45-91) and 80.8% of the whole population had a history of ischemic stroke. The nursing staff identified 33.3% of dysphagia cases at admission and the speech pathologists 30%. The Cohen K was 0.92 (optimal concordance when K was > 0.8), sensitivity was 100%, specificity 95.2%, PPV 90% and NPV 100%.Conclusionsour BSTD had a 100% negative predictive value, indicating that this screening test is very useful in ruling out/confirming dysphagia in acute stroke patients     

Synergistic potential of 1α,25-dihydroxyvitamin D3 and calcium–aluminate–chitosan scaffolds with dental pulp cells

Clinical Oral Investigations - This study aimed to develop a porous chitosan–calcium–aluminate scaffold (CH-AlCa) in combination with a bioactive dosage of 1α,25-dihydroxyvitamin...     

Spontaneous platelet aggregation in type IIB Tampa von Willebrand disease is inhibited by the 52/48-kDa fragment of normal von Willebrand factor, which contains the GPIb binding domain

The association of Type IIB von Willebrand disease (vWD) with chronic persistent thrombocytopenia and spontaneous platelet aggregation has recently been recognized. It has been shown that IIB von Willebrand factor (vWF) can initiate platelet aggregation by binding to the platelet glycoprotein (GP) lb receptor and inducing exposure of the GpIIb/IIIa fibrinogen receptor. In this study we demonstrate the increased binding of Type IIB Tampa vWF with normal platelets when compared with nonthrombocytopenic Type IIB vWF. Studies further demonstrate that spontaneous platelet aggregation initiated by IIB Tampa vWF can be blocked by a 52/48-kDa fragment of normal vWF, which contains the binding domain.