1,721,302 research outputs found
Results of the Heart Protection Study: Can we still assume a class effect?
No full textStatins share several common features including the mechanism of action, i.e. inhibition of HMG-CoA reductase, as well as LDL-cholesterol (LDL-C) and triglyceride lowering properties. However, statins show minor differences in chemical structure, lipophilicity that could translate into a different pharmacological properties. For example, simvastatin exerted a more favorable effect on HDL-C levels than did atorvastatin when higher doses of the two drugs were compared. Finally, the major considerations to chose between statins for CVD patient therapy include clinical benefits and safety (i.e. evidence-based medicine). Primary prevention trials with pravastatins and lovastatin and secondary prevention trials with pravastatin, fluvastatin and simvastatin have established the clinical benefits of statins. In addition, HPS study was designed to investigate the benefits of simvastatin 40 mg in a broad range of patients at high risk for heart disease including women, the elderly and those with a history of hearth attacks, diabetes, hypertension or vascular disease. The results show the ability of simvastatin to reduce all causes of mortality, vascular death and cardiovascular morbidity. The trial also confirms the safety of simvastatin 40 mg although 60% of patients were receiving additional pharmacological treatment. In summary, it appears that statins are not the same and the choice of the more appropriate statin in high-risk patients should be driven by the evidence-based medicine both in terms of safety and efficacy
Calcium antagonists and intimal cell proliferation in atherogenesis
No full textSmooth muscle cell (SMC) migration and initimal proliferation are major events in the formation of the atherosclerotic lesions. Among other processes, calcium may participate in atherogenesis by affecting SMC proliferation. Calcium antagonists, which possess antiatherosclerotic properties in animal models, are effective in inhibiting SMC proliferation. This effect has been demonstrated both in vitro in cell culture and in vivo in balloon-catheterised rats and rabbits. Such an effect, indicates a possible mechanism involved in the antiatherosclerotic activity elicited by this category of drugs
A new generation of calcium antagonists and their role in atherosclerosis
No full textnew generation of calcium antagonists is being developed in an attempt to improve the already widespread therapeutic applications of this class of drugs. In this report the effect of these new calcium antagonists on those processes involved in atherogenesis that occur in the cellular component of the arterial wall is reviewed. The new generation of calcium antagonists appears to possess many of the antiatherosclerotic properties demonstrated by their prototypes. Moreover, these new compounds may have unique mechanisms of action and may be more potent than their first-generation counterpart
Focus on anti-atherosclerotic therapy
No full textCalcium antagonists (CA) exert an anti-atherosclerotic effect in cholesterol-fed rabbits through reduction of cholesterol accumulation in the arterial wall. Further studies in our Institute indicate that verapamil-like compounds and diltiazem stimulate receptor-mediated LDL uptake by human fibroblasts in culture, while nifedipine-like compounds and flunarizine are inactive. Verapamil and diltiazem stimulated LDL-receptor activity also in cells from a heterozygous FH patient, while they were inactive in a receptor defective homozygous FH patient. A basic group needs to be present on the CA molecule to modulate the LDL receptor expression. Preliminary data in our laboratory suggest that some CA can achieve concentrations in the aortic wall likely to exert effects on LDL receptors. This stimulatory activity may improve lipid metabolism in the arterial wall
Dal farmaco di ricerca al farmaco equivalente.
No full textCaratteristiche dello sviluppo e criticità di impiego dei farmaci generici in rapporto ai farmaci originali in precedenza coperti da brevett
Nonlinear Schrödinger-Poisson systems in dimension two: The zero mass case
No full textWe provide an existence result for a Schrödinger-Poisson system in gradient form, set in the whole plane, in the case of zero mass. Since the setting is limiting for the Sobolev embedding, we admit nonlinearities with subcritical or critical growth in the sense of Trudinger-Moser. In particular, the absence of the mass term requires a nonstandard functional framework, based on homogeneous Sobolev spaces. These features, combined with the logarithmic behaviour of the kernel of the Poisson equation, make the analysis delicate, since standard variational tools cannot be applied. The system is solved by considering the corresponding logarithmic Choquard equation. The existence of a mountain pass-type solution is established by means of a careful analysis of appropriate Cerami sequences, whose boundedness is ensured through a nonstandard variational method, suggested by the subtle nature of the functional geometry involved. As a key tool in our estimates, we also introduce a logarithmic weighted Trudinger–Moser inequality, along with a related Cao-type inequality, both of which hold in our functional setting and are, we believe, of independent interest
Automatic averaging in the vibrational control of nonlinear systems
No full textVibrational control is a non classical technique proposing the utilisation of zero mean parametric vibrations for shaping the response of a linear or nonlinear dynamic system. Several theoretical results on vibrational control are available in literature. In the case of nonlinear systems computational difficulties arise and theoretical results cannot easily be applied. A new averaging technique, based on the Taylor series expansion of the nonlinear system, is proposed in order to overcome such difficultie
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