Extraction of phenolic compounds from 'Aglianico' and 'Uva di Troia' grape skins and seeds in model solutions: Influence of ethanol and maceration time

The effect of increasing concentration of ethanol (0, 4, 7.5 and 13 %) and contact time (respectively 1, 4, 7 and 10 days) on the extraction of phenolics from berry skins and seeds of the grape, Vitis vinifera 'Aglianico' and 'Uva di Troia', were examined. Two assays of post-fermentative maceration in two hydroalcoholic solutions at 11 and 13 % ethanol, were also performed. Chromatic properties and phenolics of medium were analyzed by HPLC and spectrophotometric methods. The extraction of total phenolics, anthocyanins, proanthocyanidins, and vanilline reactive flavans (VRF) from berry skins reached the maximum on the 4th day of maceration. Quercetin and gallic acid were gradually extracted from grape skins. The maximum release of flavan-3-ols from the skins was achieved on the first day of maceration. Total phenolics, tannins and VRF were gradually extracted from seeds. During the postfermentative maceration, higher the content of ethanol, higher the extraction of total polyphenols and tannins from 'Uva di Troia' skins and the extraction of total polyphenols and tannins from 'Aglianico' seeds. These results clearly indicate that the grape cultivar mainly influences the release of phenolic compounds from the solid parts of berry to the must especially during postfermentative maceration.

Expert consensus document: A 'diamond' approach to personalized treatment of angina.

In clinical guidelines, drugs for symptomatic angina are classified as being first choice (β-blockers, calcium-channel blockers, short-acting nitrates) or second choice (ivabradine, nicorandil, ranolazine, trimetazidine), with the recommendation to reserve second-choice medications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. No direct comparisons between first-choice and second-choice treatments have demonstrated the superiority of one group of drugs over the other. Meta-analyses show that all antianginal drugs have similar efficacy in reducing symptoms, but provide no evidence for improvement in survival. The newer, second-choice drugs have more evidence-based clinical data that are more contemporary than is available for traditional first-choice drugs. Considering some drugs, but not others, to be first choice is, therefore, difficult. Moreover, double or triple therapy is often needed to control angina. Patients with angina can have several comorbidities, and symptoms can result from various underlying pathophysiologies. Some agents, in addition to having antianginal effects, have properties that could be useful depending on the comorbidities present and the mechanisms of angina, but the guidelines do not provide recommendations on the optimal combinations of drugs. In this Consensus Statement, we propose an individualized approach to angina treatment, which takes into consideration the patient, their comorbidities, and the underlying mechanism of disease

REAL-WORLD ITALIAN EXPERIENCE OF POMALIDOMIDE IN RELAPSED-REFRACTORY MYELOMA: RETROSPECTIVE MULTICENTER STUDY BY THE RETE EMATOLOGICA PUGLIESE AND BASILICATA

Background: The POM+LoDEX combination was approved for patients with RRMM who have received at least two prior therapies including lenalidomide and bortezomib. Aims: We report here retrospective analysis of 94 patients with RRMM treated with POM+LoDEX as salvage therapy at 12 hematological centers in the Puglia and Basilicata Network to describe the outcomes and toxicities in a daily practice setting outside clinical trials. Methods: From January 2016 to September 2018, 94 patients (60 F and 34 M) were treated in our haematogical Institutions. Sixty-three patients of them (67%) had relapsed MM and 31 patients (33%) MM refractory to two or more previous treatment lines. The median age was 73 years (range 42–86). Twenty-four patients (23,3%) had EMD. Patients received a median 3 previous lines of therapy. The last treatment received was bortezomib-based regimens in 29% of patients, lenalidomide-based regimens in 50% of patients, and bendamustine containing regimen in 18% of patients. Results: The median number of cycles administered was 5 (range 1–27). The ORR was 51%. Higher ORR was recorded in the patient group with relapsed MM compared to those with refractory disease (p < 0.05). There were no statistically significant differences in terms of response between patients who had received two or more previous lines of therapy (p NS) and between patients aged over or under 70 years (p 0.25). After median follow-up of 9.5 months, median TTP and median OS in the ITT population were respectively, 10 months (range 7–17) and 16 months (range 11–24). The median TTP was significantly longer in patients who achieved the haematological response (p < 0.001) and in patients aged >70 years (p 0.03). The median OS was significantly longer for fit patients (p 0.03). The “disease status’’, the “prior exposure to lenalidomide-based strategies’’, the “number of previous lines of therapy’’ did not influence the TTP and the OS. Multivariate analysis of median TTP identified the “high LDH levels’’ as negative variable (p < 0.001) and the “age >70 years’’ as positive prognostic factor (p < 0.001). Multivariate analysis of median OS identified the “frailty score’’ and confirmed “high LDH levels’’ as statistically significant variables (p < 0.001). Median TTNT was 30 months (range 18–30). Neutropenia was the most common hematologic adverse event and occurred in 32% of patients. The most frequent grade 3–4 non-haematologic toxicities were fatigue (6%) and infections (4%). Summary/Conclusion: POM+LoDEX resulted in a longer OS and TTP compared to data reported from clinical trials. This advantage was observed mainly in elderly patients and in those with haematologic response and the outcome benefit remained consistent regardless of number of prior and last therapy received. The good toxicity profile and the all-oral administration of POM+LoDEX make this combination a recommended therapeutic opportunity also in older patients and should be recommended mainly in patients living far from the hospital

Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with in-stent restenosis in patients undergoing coronary stenting

Previously undiagnosed diabetes, impaired glucose tolerance, and insulin resistance are common in patients with acute myocardial infarction and coronary heart disease (CHD) and might be involved in early restenosis after stent implantation. To evaluate whether markers of insulin resistance syndrome, including leptin, and endothelial dysfunction are related to increased rate of early restenosis, we studied nondiabetic patients with CHD after successful coronary stenting

Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and β-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy.</p> <p>Methods</p> <p>A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00841139">NCT00841139</a></p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN2887836">ISRCTN2887836</a></p

The diagnostic accuracy of pharmacological stress echocardiography for the assessment of coronary artery disease: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>Recent American Heart Association/American College of Cardiology guidelines state that "dobutamine stress echo has substantially higher sensitivity than vasodilator stress echo for detection of coronary artery stenosis" while the European Society of Cardiology guidelines and the European Association of Echocardiography recommendations conclude that "the two tests have very similar applications". Who is right?</p> <p>Aim</p> <p>To evaluate the diagnostic accuracy of dobutamine versus dipyridamole stress echocardiography through an evidence-based approach.</p> <p>Methods</p> <p>From PubMed search, we identified all papers with coronary angiographic verification and head-to-head comparison of dobutamine stress echo (40 mcg/kg/min ± atropine) versus dipyridamole stress echo performed with state-of-the art protocols (either 0.84 mg/kg in 10' plus atropine, or 0.84 mg/kg in 6' without atropine). A total of 5 papers have been found. Pooled weight meta-analysis was performed.</p> <p>Results</p> <p>the 5 analyzed papers recruited 435 patients, 299 with and 136 without angiographically assessed coronary artery disease (quantitatively assessed stenosis > 50%). Dipyridamole and dobutamine showed similar accuracy (87%, 95% confidence intervals, CI, 83–90, vs. 84%, CI, 80–88, p = 0.48), sensitivity (85%, CI 80–89, vs. 86%, CI 78–91, p = 0.81) and specificity (89%, CI 82–94 vs. 86%, CI 75–89, p = 0.15).</p> <p>Conclusion</p> <p>When state-of-the art protocols are considered, dipyridamole and dobutamine stress echo have similar accuracy, specificity and – most importantly – sensitivity for detection of CAD. European recommendations concluding that "<it>dobutamine and vasodilators (at appropriately high doses) are equally potent ischemic stressors for inducing wall motion abnormalities in presence of a critical coronary artery stenosis</it>" are evidence-based.</p

Transthoracic coronary flow reserve and dobutamine derived myocardial function: a 6-month evaluation after successful coronary angioplasty

After percutaneous transluminal coronary angioplasty (PTCA), stress-echocardiography and gated single photon emission computerized tomography (g-SPECT) are usually performed but both tools have technical limitations. The present study evaluated results of PTCA of left anterior descending artery (LAD) six months after PTCA, by combining transthoracic Doppler coronary flow reserve (CFR) and color Tissue Doppler (C-TD) dobutamine stress. Six months after PTCA of LAD, 24 men, free of angiographic evidence of restenosis, underwent standard Doppler-echocardiography, transthoracic CFR of distal LAD (hyperemic to basal diastolic coronary flow ratio) and C-TD at rest and during dobutamine stress to quantify myocardial systolic (S(m)) and diastolic (E(m )and A(m), E(m)/A(m )ratio) peak velocities in middle posterior septum. Patients with myocardial infarction, coronary stenosis of non-LAD territory and heart failure were excluded. According to dipyridamole g-SPECT, 13 patients had normal perfusion and 11 with perfusion defects. The 2 groups were comparable for age, wall motion score index (WMSI) and C-TD at rest. However, patients with perfusion defects had lower CFR (2.11 ± 0.4 versus 2.87 ± 0.6, p < 0.002) and septal S(m )at high-dose dobutamine (p < 0.01), with higher WMSI (p < 0.05) and stress-echo positivity of LAD territory in 5/11 patients. In the overall population, CFR was related negatively to high-dobutamine WMSI (r = -0.50, p < 0.01) and positively to high-dobutamine S(m )of middle septum (r = 0.55, p < 0.005). In conclusion, even in absence of epicardial coronary restenosis, stress perfusion imaging reflects a physiologic impairment in coronary microcirculation function whose magnitude is associated with the degree of regional functional impairment detectable by C-TD