Abstract Background and aims The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic ...syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes. Methods and results A total of 2429 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) <60 ml/min/1.73 m2 or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women). The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03–1.18; P = 0.0060; OR 1.28, 95% CI 1.15–1.42; P < 0.0001). These associations were stronger in patients without diabetes and with normal renal function. Conclusions Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk.
Abstract
Objective Insulin protects cardiomyocytes from apoptosis. Insulin resistance usually refers to a defect in the ability of insulin to stimulate glucose uptake. It is unknown, however, whether ...or not insulin resistance compromises the cell-protective effect of the hormone. Caspases are a family of cysteine proteases that regulate apoptosis. We explored the effects of insulin resistance on hypoxia-induced caspase-3 activation in cardiomyocytes.
Methods Experiments were performed in cultured neonatal rat cardiomyocytes. Insulin resistance was induced by treating cardiac myocytes with isoproterenol, a β-adrenergic receptor agonist.
Results Twelve hours of hypoxia-induced caspase-3 cleavage, which was inhibited by treatment with insulin, while pre-treatment with isoproterenol abolished the insulin effect. Hypoxia-induced cleavage of caspase-3 was mediated by p38 mitogen-activated protein kinase (MAPK). Insulin inhibited hypoxia-induced phosphorylation of p38 through MAPK phosphatase-1 (MKP-1). Insulin-induced MKP-1 expression was mediated by extracellular signal-regulated protein kinases (ERK) 1/2, c-Jun NH2-terminal kinases (JNK) MAPK, and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. Isoproterenol stimulation failed to induce expression of MKP-1; moreover, insulin resistance induced by long-term β-adrenergic stimulation inhibited insulin-evoked expression of MKP-1 by impairing insulin-induced phosphorylation of both ERK1/2 and JNK without affecting Akt kinase activity. Furthermore, concomitant activation of Akt, ERK 1/2, and JNK was required for insulin to exert its protective effect against the hypoxia-induced cleavage of caspase-3.
Conclusions The results of this study lead to the conclusions that, in cardiac myocytes, antiapoptotic signals induced by insulin are mediated by more than one signaling pathway, and that long-term β-adrenergic receptor stimulation impairing some of these pathways affects the cytoprotective action of insulin.
p53 is a transcription factor with tumour suppressor properties, which is able to induce mitochondrial apoptosis independently of its transcriptional activity. We recently synthesised two new ...compounds (ISA27 and SM13), which block p53-MDM2 interaction and induce apoptosis in p53 wild-type (WT) tumour cells. The aim of this study was to verify the effectiveness of these compounds in tumours carrying a mutated form of p53 gene with no transcriptional activity.
In vitro we evaluated the effectiveness of our compounds in cancer cell lines carrying WT, mutated and null p53 gene. In vivo study was performed in Balb/c nude mice and the mitochondrial-dependent apoptotic signalling was evaluated by western blot.
Both ISA27 and SM13 reduced cell proliferation and induced apoptosis in vitro in cells carrying either p53 WT or mutated gene, suggesting that its effect is independent from p53 transcriptional activity. On the contrary, SM13 had no effect in a p53 null cell line. In vivo, ISA27 and SM13 induced cancer cell death in a dose-dependent manner through the activation of the mitochondrial-dependent death signalling in p53-mutated cells. In vivo, SM13 reduced tumour growth.
Our study proposes SM13 as anticancer compound to use for the treatment of p53-dependent tumours, even in the absence of p53 transcriptional activity.
Electrochemical reactions play an increasingly important role in sustainable energy conversion and chemical synthesis. Better understanding of catalytic mechanisms at electrode surfaces is thus ...important for the transition to a clean-energy economy, but is hindered by the difficulty of real-time detection of reaction products and intermediates during electrochemistry experiments. Herein, we present a new type of electrochemistry – mass spectrometry (EC-MS) based on a versatile gas inlet to vacuum fabricated onto a silicon microchip, and compare it to established techniques with focus on sensitivity, time response, and mass transport. The inlet system is able to capture reactant molecules directly from an electrode surface and pass them on to a mass spectrometer on a sub-second time scale with 100% collection efficiency for quantitative analysis with unprecedented sensitivity. The high sensitivity and fast time-response, coupled with well-characterized mass transport of both reactants and products in this setup enables sub-turnover resolution for analysis of electrochemical reactions. The technology and concepts presented here can serve as a platform to improve in-situ mass spectrometry in electrochemistry as well as other fields.
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The efficient partial oxidation of hydrocarbons to valuable chemicals without formation of CO 2 is one of the great challenges in heterogeneous catalysis. The ever-decreasing cost of renewable ...electricity and the superior control over reactivity qualify electrochemistry as a particularly attractive means of addressing this challenge. Yet, to date, little is known about the factors regulating hydrocarbon oxidation at the atomic level. A relevant showcase reaction is propene electro-oxidation to key industrial commodity chemicals, such as acrolein, acrylic acid and propylene oxide. In this study, we investigate the partial electrochemical oxidation of propene on high-surface area Pd electrodes using a combination of electrochemical measurements, advanced product characterization and theoretical modeling. We report a new reaction product, propylene glycol, and high selectivity towards acrolein. We further identify key reaction intermediates and propose a mechanism dictated by the surface coverage of organic species formed in situ , where stable reactant adsorption at low coverage determines the selectivity towards allylic oxidation at high coverage. Our fundamental findings enable advances in partial hydrocarbon oxidation reactions by highlighting atomic surface structuring as the key to selective and versatile electrochemical catalyst design.
Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and ...dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional dietadopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health.
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