Why one size doesn\u2019t fit all \u2013 Case of Italy

The European Solidarity Manifesto is a proposal of controlled dismantling of the Eurozone aimed at minimizing the cost of the breakup while maintaining solidarity links among Euro Member State

Zofenopril and incidence of cough: a review of published and unpublished data.

open2noOBJECTIVE: Cough is a typical side effect of angiotensin-converting enzyme (ACE) inhibitors, though its frequency quantitatively varies among the different compounds. Data on the incidence of cough with the lipophilic third-generation ACE inhibitor zofenopril are scanty and never systematically analyzed. The purpose of this paper is to give an overview on the epidemiology, pathophysiology, and treatment of ACE inhibitor-induced cough and to assess the incidence of cough induced by zofenopril treatment. METHODS: Published and unpublished data from randomized and postmarketing zofenopril trials were merged together and analyzed. RESULTS: Twenty-three studies including 5794 hypertensive patients and three studies including 1455 postmyocardial infarction patients exposed for a median follow-up time of 3 months to zofenopril at doses of 7.5-60 mg once-daily were analyzed. The incidence of zofenopril-induced cough was 2.6% (range 0%-4.2%): 2.4% in the hypertension trials (2.4% in the double-blind randomized studies and 2.4% in the open-label postmarketing studies) and 3.6% in the doubleblind randomized postmyocardial infarction trials. Zofenopril-induced cough was generally of a mild to moderate intensity, occurred significantly (P < 0.001) more frequently in the first 3-6 months of treatment (3.0% vs 0.2% 9-12 months), and always resolved or improved upon therapy discontinuation. Zofenopril doses of 30 mg and 60 mg resulted in significantly (P = 0.042) greater rate of cough (2.1% and 2.6%, respectively) than doses of 7.5 mg and 15 mg (0.4% and 0.7%, respectively). In direct comparison trials (enalapril and lisinopril), incidence of cough was not significantly different between zofenopril and other ACE inhibitors (2.4% vs 2.7%). CONCLUSION: Evidence from a limited number of studies indicates a relatively low incidence of zofenopril-induced cough. Large head-to-head comparison studies versus different ACE inhibitors are needed to highlight possible differences between zofenopril and other ACE inhibitors in the incidence of cough.openOmboni S.; Borghi C.Omboni S.; Borghi C

Nanomanufacturing of titania interfaces with controlled structural and functional properties by supersonic cluster beam deposition

Great emphasis is placed on the development of integrated approaches for the synthesis and the characterization of ad hoc nanostructured platforms, to be used as templates with controlled morphology and chemical properties for the investigation of specific phenomena of great relevance for technological applications in interdisciplinary fields such as biotechnology, medicine and advanced materials. Here we discuss the crucial role and the advantages of thin film deposition strategies based on cluster-assembling from supersonic cluster beams. We select cluster-assembled nanostructured titania (ns-TiO2) as a case study to demonstrate that accurate control over morphological parameters can be routinely achieved, and consequently over several relevant interfacial properties and phenomena, like surface charging in a liquid electrolyte, and proteins and nanoparticles adsorption

Personalized medicine—a modern approach for the diagnosis and management of hypertension

The main goal of treating hypertension is to reduce blood pressure to physiological levels and thereby prevent risk of cardiovascular disease and hypertension-associated target organ damage. Despite reductions in major risk factors and the availability of a plethora of effective antihypertensive drugs, the control of blood pressure to target values is still poor due to multiple factors including apparent drug resistance and lack of adherence. An explanation for this problem is related to the current reductionist and ‘trial-and-error’ approach in the management of hypertension, as we may oversimplify the complex nature of the disease and not pay enough attention to the heterogeneity of the pathophysiology and clinical presentation of the disorder. Taking into account specific risk factors, genetic phenotype, pharmacokinetic characteristics, and other particular features unique to each patient, would allow a personalized approach to managing the disease. Personalized medicine therefore represents the tailoring of medical approach and treatment to the individual characteristics of each patient and is expected to become the paradigm of future healthcare. The advancement of systems biology research and the rapid development of high-throughput technologies, as well as the characterization of different –omics, have contributed to a shift in modern biological and medical research from traditional hypothesis-driven designs toward data-driven studies and have facilitated the evolution of personalized or precision medicine for chronic diseases such as hypertension

Is it time to implement a standardized oral glucose and fat load test to detect high risk patients? Probably not yet

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a possible role for hydrochlorothiazide hctz as enhancer of zofenopril activity at the tissue level

Background: Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic has proven to be effective in the treatment of hypertension with or without end-organ damage. Discussion: The mechanism of action of such a combination therapy may involve a opposite effect on the renin-angiotensinaldosterone system (RAAS) with possible "functional" synergistic effects. Indeed, while diuretics can initially reduce intravascular volume leading to an activation of the RAA system with consequent vasoconstriction and salt and water retention, the concomitant presence of an ACE inhibitor may prevent such a counterregulatory response on neurohumoral system. This creates the conditions for the achievement of a maximal antihypertensive effect for both the ACE inhibitor and the diuretic. In recent years, however, experimental evidence has suggested that in addition to the above described mechanism of action, which is common to all the combinations of ACE-inhibitors and diuretics, it can be possible to identify some additional and peculiar mechanisms involving some selected drugs. Such additional mechanisms would be essentially related to some differences in the pharmacokinetic profiles of ACE inhibitors. In particular, the extent of lipophilicity could play an important role in membrane penetration and tissue accumulation and has been correlated with the overall ACE-inibitory activity of various compounds, eg., tissue ACE inhibitory activity could increase with the increase of lipophilicity. For instance, in rats with myocardial infarction, volume depletion induced by concomitant administration of HCTZ can increase the tissue levels of zofenoprilat (the active metabolite of zofenopril, an highly lipophilic ACE inhibitor), but not those of the highly hydrophilic lisinopril. An interesting hypothesis is that associating HCTZ to a highly lipophilic ACE inhibitor translates into peculiar clinical profiles, therefore we suggest further studies on this matter. Conclusion: Experimental models have shown that hydrochlorothiazide (HCTZ) could act like a "tissue levels enhancer" of lipophilic ACE-inhibitors, eg., can increase tissue concentrations of zofenoprilat (active metabolite of zofenopril, an highly lipophilic compound), and consequently induce an enhancement of its tissue ACE inhibition. On the basis of available experimental data, we suggest a peculiar interaction between zofenopril and HCTZ, i.e., HCTZ could act as a "tissue levels enhancer" of zofenopril. This hypothesis, if confirmed, could imply a relevant therapeutic advantage for the treatment of arterial hypertension