Irrespective of their clinical relevance, side effects cannot be considered a negligible problem in antihypertensive therapy. The aim of this trial was to evaluate the tolerability profile of ...lercanidipine with that of two other calcium antagonists (amlodipine and lacidipine) in elderly hypertensives.
In a multicenter, double-blind, parallel study 828 elderly (aged ≥60 years) hypertensives were randomized to lercanidipine 10 mg/day (
n = 420), amlodipine 5 mg/day (
n = 200), or lacidipine 2 mg/day (
n = 208) (ratio 2:1:1). If blood pressure (BP) control was unsatisfactory (systolic BP/diastolic BP ≥140/90 mm Hg), the dose of the double-blind medication was doubled and, as a further step, enalapril or atenolol (plus diuretic, if needed) was added. Patients were treated for an average of 12 months.
Amlodipine patients had significantly (
P < .001) higher rates of edema (19%) and of early study discontinuations due to edema (8.5%) compared with lercanidipine (9% and 2.1%) and lacidipine patients (4% and 1.4%). Similarly, edema-related symptoms (lower limb swelling and heaviness) occurred significantly (
P < .01) more often with amlodipine (50% and 45%, respectively) than with lercanidipine (35% and 33%) and lacidipine (34% and 31%). Most edema cases occurred in the first 6 months, a between-treatment difference being evident since beginning of treatment. Other drug-related adverse events did not differ between treatments. Blood pressure was equally and effectively reduced in the three groups.
The two lipophilic dihydropyridine calcium antagonists, lercanidipine and lacidipine, have an antihypertensive effect comparable to that of amlodipine, but a better tolerability profile.
GRK5 is a multifunctional protein that is able to move within the cell in response to various stimuli to regulate key intracellular signaling from receptor activation, on plasmamembrane, to gene ...transcription, in the nucleus. Thus, GRK5 is involved in the development and progression of several pathological conditions including cancer. Several reports underline the involvement of GRK5 in the regulation of tumor growth even if they appear controversial. Indeed, depending on its subcellular localization and on the type of cancer, GRK5 is able to both inhibit cancer progression, through the desensitization of GPCR and non GPCR-receptors (TSH, PGE2R, PDGFR), and induce tumor growth, acting on non-receptor substrates (p53, AUKA and NPM1). All these findings suggest that targeting GRK5 could be an useful anti-cancer strategy, for specific tumor types. In this review, we will discuss the different effects of this kinase in the induction and progression of tumorigenesis, the molecular mechanisms by which GRK5 exerts its effects, and the potential therapeutic strategies to modulate them.
Electrochemical hydrogen adsorption and desorption, and the state of adsorbed hydrogen (*H) on metal surfaces are of fundamental interest as well as practical importance for the hydrogen evolution ...reaction (HER) and electrochemical hydrogenation reactions including CO
2
and CO electroreduction. Here, we report a previously undiscovered phenomenon whereby *H desorbs as H
2
during an anodic potential sweep at potentials anodic of (more positive than) the equilibrium potential of
U
0
(H
2
/H
+
), hence at potentials where hydrogen desorption would be expected as H
+
. Using electrochemistry - online mass spectrometry, we observe, quantify, and characterize the phenomenon on two different materials in two different environments - Ru(0001) in acid and polycrystalline Cu in alkaline. For both Ru and Cu, the anodic H
2
formation seems to coincide with *OH adsorption, which would be consistent with a displacement mechanism. We propose that a high barrier for the Volmer step causes some of the displaced *H to desorb as H
2
(Tafel step) rather than the thermodynamically more favorable desorption as H
+
(Volmer step).
On important electrocatalysts including ruthenium and copper, increasing the potential pushes adsorbed hydrogen off as H
2
, an unexpected uphill desorption.
Endothelium-derived NO is formed from L-arginine by endothelial NO synthase (eNOS) encoded by the NOS 3 gene on chromosome 7. Because several studies have indicated that NO plays a key role in the ...development of the atherosclerotic process, we investigated whether common variants in the eNOS gene are associated with an increased risk of plaque on carotid arteries.
We studied 375 subjects attending the hypertension center of our institution to be screened for arterial hypertension. The examined subjects were classified according to the presence of carotid plaques (intima-media thickness >/=1.5 mm), and 2 intronic (CA and 27-bp repeats) polymorphisms and 1 exonic (Glu298Asp) polymorphism of the eNOS gene were explored.
Only the Glu298Asp polymorphism of eNOS was associated with the presence of carotid plaques (P:<0.05). In particular, there was an excess of homozygotes for the Asp298 variant among subjects with carotid plaques, whereas the number of subjects who had the Glu298 allele in exon 7 of the eNOS gene was equally distributed in both study groups. Interestingly, the risk of having carotid plaques was increased approximately 3 times in subjects who were homozygotic for the Asp298 variant compared with subjects who were homozygotic for the Glu298 variant and was independent of the other common risk factors (age, blood pressure, and smoking).
Homozygosity for Asp298, a common variant of the eNOS gene, is an independent risk factor for carotid atherosclerosis in this study population.
The treatment of in-stent restenosis (ISR) in the femoro-popliteal artery (FPA) is one of the major challenges of endovascular therapy, occurring in up to 40% of femoro-popliteal lesions treated with ...bare-metal stents within 1 year of treatment. Drug-eluting technologies, involving local delivery of paclitaxel, are providing a new paradigm for the treatment of ISR. Preliminary experience shows promising results compared to other techniques such as cutting balloon angioplasty and debulking strategies. Based on available data, drug-eluting balloons (DEBs) seem sufficient as stand-alone treatment of FPA-ISR. However, larger evidence from randomized studies is warranted to identify the clinical and/or anatomical setting in which they could fail.
High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, ...radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism.
Whether patients with hypertensive preclinical cardiovascular disease (CVD) are at higher risk of incident diabetes has never been studied.
We assessed incident diabetes in 4176 hypertensive ...non-diabetic patients (age 58.7 ± 8.9 years, 58% male) with ≥1 year follow-up (median: 3.57 years; inter-quartile range: 2.04-7.25). Left ventricular (LV) hypertrophy (LVH) was defined as LV mass index (LVMi) ≥51 g/m(2.7). Carotid atherosclerosis (CA) was defined as intima-media thickness >1.5 mm. During follow-up, diabetes developed in 393 patients (9.4%), more frequently in those with than without initial LVH or CA (odds ratio = 1.97 and 1.67, respectively; both P < 0.0001). In the Cox regression, the presence of either initial LVH or CA was associated with higher hazard of diabetes hazards ratio (HR) = 1.30 and 1.38, respectively; both P = 0.03, independently of the type and number of anti-hypertensive medications, initial systolic blood pressure (P < 0.001), body mass index, fasting glucose, family history of diabetes (all P < 0.0001), and therapy with β-blockers. The presence of one of the, or both, markers of preclinical CVD increased the chance of incident diabetes by 63 or 64%, respectively (both P < 0.002), independently of significant confounders, a result that was confirmed (HR = 1.70 or 1.93, respectively; both P < 0.0001) using ATPIII metabolic syndrome (HR = 2.73; P < 0.0001) in the Cox model.
Initial LVH and CA are significant predictors of new onset diabetes in a large population of treated hypertensive patients, independently of initial metabolic profile, anti-hypertensive therapy, and other significant covariates. This sequence may be attributable to risk factors common to preclinical CVD and diabetes, but a vascular origin of diabetes cannot be excluded.
The serine-threonine kinase Akt/PKB mediates stimuli from different classes of cardiomyocyte receptors, including the growth hormone/insulin like growth factor and the beta-adrenergic receptors. ...Whereas the growth-promoting and antiapoptotic properties of Akt activation are well established, little is known about the effects of Akt on myocardial contractility, intracellular calcium (Ca(2+)) handling, oxygen consumption, and beta-adrenergic pathway. To this aim, Sprague-Dawley rats were subjected to a wild-type Akt in vivo adenoviral gene transfer using a catheter-based technique combined with aortopulmonary crossclamping. Left ventricular (LV) contractility and intracellular Ca(2+) handling were evaluated in an isolated isovolumic buffer-perfused, aequorin-loaded whole heart preparations 10 days after the surgery. The Ca(2+)-force relationship was obtained under steady-state conditions in tetanized muscles. No significant hypertrophy was detected in adenovirus with wild-type Akt (Ad.Akt) versus controls rats (LV-to-body weight ratio 2.6+/-0.2 versus 2.7+/-0.1 mg/g, controls versus Ad.Akt, P, NS). LV contractility, measured as developed pressure, increased by 41% in Ad.Akt. This was accounted for by both more systolic Ca(2+) available to the contractile machinery (+19% versus controls) and by enhanced myofilament Ca(2+) responsiveness, documented by an increased maximal Ca(2+)-activated pressure (+19% versus controls) and a shift to the left of the Ca(2+)-force relationship. Such increased contractility was paralleled by a slight increase of myocardial oxygen consumption (14%), while titrated dose of dobutamine providing similar inotropic effect augmented oxygen consumption by 39% (P<0.01). Phospholamban, calsequestrin, and ryanodine receptor LV mRNA and protein content were not different among the study groups, while sarcoplasmic reticulum Ca(2+) ATPase protein levels were significantly increased in Ad.Akt rats. beta-Adrenergic receptor density, affinity, kinase-1 levels, and adenylyl cyclase activity were similar in the three animal groups. In conclusion, our results support an important role for Akt/PKB in the regulation of myocardial contractility and mechanoenergetics.
The impact of hypertension on left ventricular (LV) and vascular structure and the relation of left ventricular hypertrophy (LVH) with vascular changes in untreated essential hypertensives has not ...been fully explored. This study investigated the prevalence of structural abnormalities of LV and carotid arteries and their determinants in a large population of untreated, uncomplicated essential hypertensive patients. The Assessment of Prognostic Risk Observational Survey was a multicentre (44 centres) prospective study including 1142 untreated hypertensives classified as low or medium cardiovascular risk on the basis of the routine diagnostic work-up recommended by the 1999 World Health Organization/International Society of Hypertension guidelines. All patients underwent ultrasound examinations of the heart and carotid arteries. LVH and carotid structural changes were diagnosed when: (1) LV mass index exceeded 125 g/m(2) in men and 110 g/m(2) in women; (2) there was at least one plaque (focal thickening>1.3 mm) in any segment of either carotid artery or a diffuse common carotid intima-media thickness (IMT) (average of IMT>/=0.8 mm) was present. Overall, 1074 patients (504 women, mean age 48.1+/-11.4 years) completed the study with ultrasonographic examinations of good technical quality. The prevalences of LVH and LV concentric remodelling in the total population were 26.8 and 10.7%, respectively. Eccentric hypertrophy was more prevalent than concentric hypertrophy (15.2 vs 11.6%). One or more carotid plaques or thickening were present in 27.4% of the patients. A stepwise increase in IM thickness occurred from the lowest values in patients with normal cardiac mass and geometry (0.68 mm) to intermediate in those with LV remodelling (0.76 mm) and eccentric LVH (0.81 mm) and to the highest level in patients with concentric LVH (0.87 mm). Patients with LV concentric remodelling and concentric LVH had a significantly greater relative carotid wall thickness than those with normal geometry and eccentric LVH (0.25 and 0.26 vs 0.18 and 0.19, respectively, P<0.01). According to a multivariate analysis age, blood glucose, systolic BP and pulse pressure were the main independent predictors of LVH, while age, systolic BP and total cholesterol were the variables with the greatest impact on IM thickening. To conclude, this study shows that: (1) altered patterns of LV structure and geometry and carotid structural changes occur in a large fraction of patients with untreated essential hypertension; (2) there is a significant association between carotid wall thickening and LVH; (3) the probability of LVH or carotid thickening is significantly greater in elderly, in patients with higher systolic BP and in patients with associated metabolic risk factors.
Functional foods and cardiometabolic diseases Assmann, G; Buono, P; Daniele, A ...
Nutrition, metabolism, and cardiovascular diseases,
December 2014, Letnik:
24, Številka:
12
Journal Article
Recenzirano
Abstract 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 diet adopted 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.
PDF
