Marina Marino

L41Q polymorphism of the G protein coupled receptor kinase 5 is associated with left ventricular apical ballooning syndrome.

Altered response to acute catecholamine increase in the synaptic cleft is considered to be the mechanism underlying transient left ventricular apical ballooning syndrome (LVABS). –3 Cardiac adrenergic receptors (ARs) of the b1 and b2 subtypes activate myocytes by coupling to the Ga subunit of the heterotrimeric Gs protein, but on the other hand they also promote G protein coupled receptor kinase (GRK)-mediated phosphorylation of bAR with the intent to shut-off signalling. The impact on cardiac function of genetic variants of molecules involved in the intracellular pathways of bAR signalling has been extensively investigated. –8

Resveratrol Improves Vascular Function in Patients With Hypertension and Dyslipidemia by Modulating NO Metabolism

Epidemiological studies have demonstrated that the Mediterranean diet, which is rich in resveratrol, is associated with a significantly reduced risk of cardiovascular disease. However, the molecular mechanisms that underlie the beneficial effects of resveratrol on cardiovascular function remain incompletely understood. Therefore, we set out to identify the molecular target(s) mediating the protective action of resveratrol on vascular function. To this end, we performed vascular reactivity studies to evaluate the effects of resveratrol on superior thyroid artery obtained from 59 patients with hypertension and dyslipidemia. We found that resveratrol evoked vasorelaxation and reduced endothelial dysfunction through the modulation of NO metabolism via (1) an 5′ adenosine monophosphate–activated protein kinase–mediated increase in endothelial NO synthase activity; (2) a rise in tetrahydrobiopterin levels, which also increases endothelial NO synthase activity; and (3) attenuation of vascular oxidative stress, brought about by overexpression of manganese superoxide dismutase via an nuclear factor erythroid–derived 2-like 2–dependent mechanism. The effects of resveratrol on acetylcholine vasorelaxation were also tested in vessels from patients with nonhypertensive nondyslipidemia undergoing thyroid surgery. In this setting, resveratrol failed to exert any effect. Thus, our finding that resveratrol reduces endothelial dysfunction, an early pathophysiological feature and independent predictor of poor prognosis in most forms of cardiovascular disease, supports the concept that the risk of vascular events could be further reduced by adherence to a set of dietary and behavioral guidelines.

Blood biomarkers role in acute ischemic stroke patients: higher is worse or better?

BackgroundThrombolytic therapy (TT) for acute ischemic stroke (AIS) can provoke bleeding’s complication depending on the ischemic lesion (IL) dimension. Inflammation involved in the setting of acute ischaemic stroke, is associated with infarct size. We aimed to study the independent correlation and association between clinical panel of routinely identified biomarkers, including inflammatory parameters, and cerebral IL dimension and site.ResultsWe evaluated eleven biomarkers in 105 unrelated patients during their hospitalization after acute stroke event. Our data indicate a significant association of: a) confluent IL size with 4th quartile of Erythrocyte Sedimentation Rate (ESR) (OR = 5.250; 95% CI, 1.002 to 27.514) and an independent correlation with sex; b) confluent IL size with 3rd quartile of fibrinogen (OR = 5.5; 95% CI, 1.027 to 29.451); c) confluent IL size with 3rd quartile of platelets (OR= 0.059; 95% CI, 0.003 to 1.175) and independent correlation with sex; d) smaller IL size (OR = 5.25; 95% CI, 1.351 to 20.396) with 3rd quartile of albumin levels and nodular and parenchimal IL size with 2nd (OR = 0.227; 95% CI, 0.053 to 0.981), 3rd (OR = 0.164; 95% CI, 0.038 to 0.711) and 4th (OR = 0.205; 95% CI, 0.048 to 0.870) quartiles albumin levels; e) smaller IL size with 3rd quartile triglycerides (TG) levels (OR = 9; 95% CI, 2.487 to 32.567) and an independent correlation with anterior location. Smaller IL size, anterior AIS turned out to be independently correlated with high serum albumin levels. Finally, high INR and PTT values were associated with worse NIHSS clinical outcomes in contrast to that observed with higher albumin level.ConclusionsWe provide evidence of routine biomarkers levels correlation with acute IL size, independently of age and sex. In addition, we highlight the importance of differentiation of biomarkers normal interval levels for further improvement not only of the clinical decision making but also in post-acute clinical outcome management.

Persistence and adherence to antihypertensive treatment in relation to initial prescription: diuretics versus other classes of antihypertensive drugs.

Background: The use of thiazide diuretics in the treatment of hypertension is widely considered as a first-line treatment, given the efficacy and low cost of this class of drugs. This indication is not unanimous, because thiazides can cause metabolic alterations, and other side effects that reduce compliance and persistence on treatment. Objectives: In a multicentre, open-label randomized study we compared adherence and persistence to therapy of chlortalidone versus other treatments, as a first-line antihypertensive therapy. Methods: Ninety-two general practitioners (GPs) recruited 2409 hypertensive patients with indication to antihypertensive therapy, who were randomized in two arms to start treatment with chlortalidone (12.5–25 mg daily) or any other single medications (excluding thiazides). The patients have been followed for at least 2 years. Result: Patients receiving diuretic therapy as first-line antihypertensive treatment, modified antihypertensive treatment regimen more often than the others (79.1 versus 43.9%; &khgr;2 < 0.0001). Patients starting with diuretics received greater number of drugs, compared to patients starting with different antihypertensive therapy (1.55 versus 1.4 antihypertensive drugs; P < 0.0001), but achieved the same blood pressure (BP) control during the follow-up. No differences were observed in persistence and adherence to treatment between the two groups. Conclusion: Our results demonstrate that the recommendation to start antihypertensive therapy with diuretics, when no compelling indications are present, is not supported by the evidence that this strategy produces more rapid and better control of BP.

Retrospective Analysis of Coagulation Factor II Receptor (F2R) Sequence Variation and Coronary Heart Disease in Hypertensive Patients

Objectives—The purpose of this study was to evaluate the role of genetic variants within the coagulation factor II receptor (F2R) in the occurrence of coronary heart disease (CHD). Methods and Results—Four SNPs (−1738 G/A, 2860 G/A, 2930 T/C, and 9113 C/A) and an ins/del polymorphism −506-/GGCCGCGGGAAGC (D/I), replicating a consensus sequence for Ets-1 transcription factor, and their related haplotypes were tested for association to CHD in 1600 hypertensive patients divided in 2 groups according to presence (cases, n=559) and absence (controls, n=1041) of CHD. Allele I at −506 locus was associated with increased risk of CHD under additive, dominant, and recessive models of inheritance (all P<0.01). Three haplotypes carrying I allele were consistently associated with an increased risk of CHD (all P<0.05). Patients homozygous for the C allele at the 2930 locus also showed an increased risk of CHD (P<0.05). To test the functionality of −506 locus, nuclear extracts were incubated with −506D and −506I sequences by EMSA and F2R promoter activity (F2R-A) were assessed in HUVECs transfected with vectors carrying −506D and −506I sequences and exposed to hypoxia. Presence of the −506I sequence was associated with a 26% reduction of affinity binding to nuclear proteins and to blunted F2R-A in response to hypoxia as compared with the −506D sequence (all P<0.05). Conclusions—F2R genetic variants may influence the natural history of CHD in patients at high risk of cardiovascular events.

Study of the effects of a diet supplemented with active components on lipid and glycemic profiles

OBJECTIVES Currently, there are numerous studies on risk factors for cardiovascular disease and the potential for functional foods to bring benefits or improve peoples health. However, most of these studies are conducted with middle-aged individuals. The aim of this study was to evaluate the effects of supplementing a typical diet with some functional components, which are substances that when consumed in small quantities can improve peoples welfare. METHODS The participants in this study were young; slightly overweight; had normal glucose tolerance; and had lipid values indicating dyslipidemia or close dyslipidemia. Following a 4-wk run-in phase, participants followed either a diet containing foods enriched with ω-3 fatty acids, β-glucans, phytosterols, and vitamin E or an isoenergetic diet without the active components. Sixteen individuals (age range 20 to 37 y) were randomly assigned to one of two groups. At the end of treatment, while fasting, plasma concentrations of triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol were measured. Furthermore, blood glucose was evaluated after fasting and after a meal enriched with β-glucans. RESULTS There was a statistically significant reduction (α < 0.05) across the lipid profile. A meal rich in β-glucans produced a glycemic response significantly lower than the nonenriched meal. CONCLUSION The dietary supplements used in this work, based on the integration of functional components into the usual diet of the population, have proved effective in reducing peak levels of postprandial glucose and the risk for dyslipidemia. Therefore, these functional components proved a valuable aid in the prevention of cardiovascular diseases and metabolic disorders.

A Parallel Implementation of a Potential Reduction Algorithm for Box-Constrained Quadratic Programming

In this paper we describe a parallel version of the potential reduction algorithm for MIMD distributed memory machines, in which the computational kernels arising at each step of the algorithm are concurrently performed by using standard parallel software environments. This approach is shown to be very effective, in contrast to what happens in the active set strategies where the linear algebra computational kernels represent a serious drawback to an effective parallel implementation. The computational results show the effectiveness of our approach.

Rac1 Modulates Endothelial Function and Platelet Aggregation in Diabetes Mellitus

Background Vascular complications and abnormal platelet function contribute to morbidity and mortality in diabetes mellitus. We hypothesized that the Rho‐related GTPase protein, Rac1, can influence both endothelial and platelet function and might represent a potential novel therapeutic target in diabetes mellitus. Methods and Results We used both in vitro and ex vivo approaches to test the effects of pharmacological inhibition of Rac1 during hyperglycemic condition. We evaluated the effect of NSC23766, a pharmacological inhibitor of Rac1, on vascular function in diabetic mice and platelet aggregation in diabetic subjects. We demonstrated that the administration of NSC23766 protects from hyperglycemia‐induced endothelial dysfunction, restoring NO levels, and reduces oxidative stress generated by nicotinamide adenine dinucleotide phosphate oxidase. Mechanistically, we identified Rho‐associated coiled‐coil serine/threonine kinase‐1 as a downstream target of Rac1. Moreover, we reported that during hyperglycemic conditions, human platelets showed hyperactivation of Rac1 and impaired NO release, which were both partially restored after NSC23766 treatment. Finally, we characterized the antiplatelet effect of NSC23766 during hyperglycemic conditions, demonstrating the additional role of Rac1 inhibition in reducing platelet aggregation in diabetic patients treated with common antiplatelet drugs. Conclusions Our data suggest that the pharmacological inhibition of Rac1 could represent a novel therapeutic strategy to reduce endothelial dysfunction and platelet hyperaggregation in diabetes mellitus.

From Histogram Data to Model Data Analysis

The aim of this work is to propose a new approach for dealing with histogram data in symbolic data analysis framework. The idea is to approximate histogram data using B-spline functions in order to synthetize the information within data trough some characteristic function parameters. This parameters will be the new data that could be, subsequently, analyzed with methodologies of multidimensional data analysis.

New food approaches to reduce and/or eliminate increased gastric acidity related to gastroesophageal pathologies

OBJECTIVE Gastroesophageal reflux disease is very common in industrialized countries and rapidly and significantly increasing even in developing countries. The approach in this study is one not commonly found to date in the scientific literature. To assess the ability of reduced-carbohydrate diets and foods that are enriched with acid potential of hydrogen (pH; lemon and tomato) to quickly and exponentially reduce symptoms that are related to conditions such as gastritis and gastroesophageal reflux and unrelated to Helicobacter pylori. METHODS After the administration of an anamnestic test, 130 patients were selected including 73 women and 57 men, 21 to 67 y, and with a gastritis diagnosis for 92 patients (56 women, 36 men) and reflux gastritis for 38 patients (17 women, 21 men). Study participants followed three dietary treatments in succession. Each treatment lasted 2 wk and treatments were separated by 2 wk of washout. The patients followed a diet that consisted primarily of proteins and fats and included the exponential reduction of glycides (simple and complex). In addition, the treatment provided for the daily intake of the juice of two lemons and approximately 100 g of fresh orange tomato without seeds eaten either raw or cooked and peeled. RESULTS During treatment and at the end of 2 wk of treatment, the patients reported significant improvements including an almost total disappearance of symptoms that were related to the disease in question. CONCLUSIONS This study shows that a carbohydrate-free diet and/or highly hypoglycidal diet that is enriched with acid pH foods appears to lead to a decrease in the pH of the gastric contents, thus inhibiting the further production of hydrochloric acid with a reduction or disappearance of heartburn symptoms that are typical of gastroesophageal diseases.