1,721,171 research outputs found

    [Red Yeast Rice, Monacolin K, and Pleiotropic Effects]

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    Riassunto. Gli estratti di riso rosso fermentato rappresen-tano un nutraceutico dalla comprovata azione ipocoleste-rolemizzante. La loro efficacia è proporzionale alla concen-trazione nell’estratto di monacolina K, che può raggiungere fino a 10 mg per dose quotidiana. L’assunzione quotidiana di monacolina K può quindi ridurre la colesterolemia LDL di circa il 15-25% già dopo 6-8 settimane di assunzione. All’azione sulla colesterolemia LDL coincide anche una ri-duzione di colesterolemia totale, colesterolemia non-HDL, livelli plasmatici di apolipoproteina B, proteina C-reattiva ad alta sensibilità e metalloproteinasi della matrice 2 e 9. Inoltre l’azione ipocolesterolemizzante si associa a miglio-ramento della funzionalità endoteliale e riduzione della velocità di onda di polso, entrambi marcatori strumentali di invecchiamento vascolare. Nonostante l’efficacia ipoco-lesterolemizzante e il meccanismo d’azione statino-simile, i rischi correlati all’assunzione di monacolina K al dosaggio di 10 mg sono minimi, e lievi mialgie possono essere pre-vedibili solo in pazienti fragili precedentemente intolleranti a dosaggi minimi di statina. In conclusione, il riso rosso fermentato titolato in monacolina K rappresenta un buon presidio terapeutico per la gestione di ipercolesterolemie moderate in pazienti con basso rischio cardiovascolare ag-giuntivo

    Uric acid and early prevention of vascular diseases: Women under the looking glass

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    The identification of new or emerging risk factors for cardiovascular disease is a non-stop challenge aimed at the early prevention of cardiovascular (CV) damage before is too late. Uric acid is the end-product of purine metabolism in superior primates and the Dalmatian dog and its deposition as sodium monourate crystals is responsible for gout and its complications. However, the possibility of damaging the articular tissue is only one of the possible negative effects of uric acid whose plasma concentration has been closely correlated with the incidence of CV and metabolic diseases with a significant increase in the risk of major CV events regardless of the presence of gout

    Triptans: the experience of a clinical pharmacologist in clinical practice

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    Despite the pharmacokinetic differences among triptans and the variety of ways of administration, the clinical differences in every day use of these drugs lack in an accepted decisional tree. In fact, there are a number of comparative trials showing conflicting results with regard to efficacy, onset of action, safety and recurrence incidence. That means that the patient’s preference probably is the main criterion for choosing one triptan vs. others. This point of view is probably correct considering also that the main cause of therapy failure is noncompliance. A good migraine care strategy requires a balance in what the patient views as satisfactory, a reasonable compromise between efficacy and tolerability, and a careful follow–up. Improvement in compliance should be the main and more immediate goal for the treatment of migraine attacks

    Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data.

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    INTRODUCTION: Cardiovascular (CV) diseases are the leading cause of death and disability in the developed countries. Lipid-lowering therapy is a cornerstone of the CV risk modification strategy. The first line treatment for hyperlipidemia is statins, which decrease low-density lipoprotein cholesterol (LDL-C) by 30-50% and proportionally reduce the CV events. However, they are not always enough to achieve LDL-C goals in many patients, and some patients are statin intolerant. For this reason, new powerful injectable lipid-lowering drugs have been developed. AREAS COVERED: The aim of this narrative review was to summarize the more recent clinical data on safety and tolerability of injectable lipid-lowering drugs. After an attentive literature search, the authors resumed here information on proprotein convertase subtilisin/kexin 9 inhibitors (evolocumab and alirocumab), small interfering RNA molecule inclisiran, antisense oligonucleotides (mipomersen, volanesorsen, ISIS 681257), and drugs targeting angiopoietin-like protein 3 (evinacumab, IONIS-ANGPTL3Rx). EXPERT OPINION: Injectable lipid-lowering therapy for patients at high risk for CV disease complications or with severe inherited hypercholesterolemias can be an important element of the available therapeutic armamentarium. Clinical data prove the favorable risk-benefit profile of evolocumab, alirocumab, and inclisiran. Mipomersen, volanesorsen, ISIS 681257, evinacumab, and IONIS-ANGPTL3Rx safety is currently less extensively studied, especially in patients with comorbidities and polypharmacotherapy

    Pharmacokinetic drug evaluation of ezetimibe + simvastatin for the treatment of hypercholesterolemia.

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    Introduction: Cholesterol lowering treatment is mainly based on statins eventually associated to adjunctive drugs of different class such as ezetimibe. In the present review, we analysed the pharmacokinetics, efficacy and safety of ezetimibe + simvastatin drug association. Areas covered: The bio-equivalence of ezetimibe and simvastatin when co-administrated in separate tablets or combined in a single pill is well documented. Ezetimibe is absorbed in small intestine, reaching peak plasma concentrations in 4–12 h, with a plasma half-life of 22 h. Simvastatin, ingested as a prodrug, is hydrolyzed in liver to its active beta-hydroxyacid metabolite, reaching peak plasma concentrations in 2–4 h, with a plasma half-life of approximately 5 h. The available evidence support the clinical efficacy of this drug combination, both in term of LDL-cholesterol reduction and cardiovascular risk decrease. Expert opinion: The synergistic action of these two drugs and the efficacy and safety extensively demonstrated of their association (in particular in the large IMProved Reduction of Outcomes: Vytorin Efficacy International Trial -IMPROVE-IT-) promote its clinical use, especially in subjects with high cardiovascular risk who need to optimize their LDL-Cholesterolemia, but also in patients who cannot tolerate high-dose of more powerful statins

    Nutraceutical approach to Non-alcoholic fatty liver disease (NAFLD): the available clinical evidence.

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    Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of Salvia milthiorriza, and probiotics. In conclusion, Silymarin, vitamin E and vitamin D, polyunsaturated fatty acids of the omega-3 series, coenzyme Q10, berberine and curcumin, if well dosed and administered for medium–long periods, and associated to lifestyle changes, could exert positive effects on NAFLD and NAFLD-related parameters. View Full-Tex

    Botanicals and phytochemicals active on cognitive decline: the clinical evidence.

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    Beyond the well-known effects on cognitive impairment of the Mediterranean diet, a number of studies have investigated the possible action on cognitive decline of different botanicals and phytochemicals, most of which are well-known anti-inflammatory or antioxidant agents with a good tolerability and safety profile. In particular, the current literature supports the use of Ginkgo biloba, resveratrol, epigallocatechin-3-gallate and l-theanine, Theobroma cacao, Bacopa monnieri, Crocus sativus and curcumin, which might have a positive impact on cognitive impairment used alone or in combination with other nutraceuticals or traditional drugs. Then, the aim of the present study was to review and comment the available evidence on botanicals and phytochemicals with a clinically demonstrable effect on cognitive decline. For this reason, we carefully reviewed studies published in English language from 1970 to April 2017 on botanicals and phytochemical claiming to show an effect on cognitive impairment in humans. Thus, the terms 'botanicals', 'dietary supplements', 'herbal drug', 'nutraceuticals', 'phytochemical', 'cognitive impairment', 'Alzheimer's disease', 'clinical trial', and 'humans', alone and in combinations, were incorporated into an electronic search strategy in both MEDLINE (National Library of Medicine, Bethesda, MD) and the Cochrane Register of Controlled Trials (The Cochrane Collaboration, Oxford, UK). As it emerges from this systematic review, the use of some phytochemicals and botanicals seems to be very promising in order to delay the onset and progression of neurodegenerative and other age-related diseases. However, further well-designed clinical research is certainly needed to finally confirm the efficacy and safety profile of these compounds

    Safety and tolerability of available urate-lowering drugs: a critical review

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    INTRODUCTION: Urate-lowering therapy (ULT) is the cornerstone of gout management, which is a widespread chronic illness characterized by hyperuricemia, arthropathy, tophus development, and urolithiasis. Since asymptomatic increased serum urate levels are associated with a higher risk of cardiovascular, renal and metabolic disorders, a larger use of ULTs in the general population is expected in the near future. AREAS COVERED: This review will focus on the safety and tolerability profile of the available urate-lowering drugs: xanthine oxidase inhibitors (XOIs), uricosuric agents and injectable uricases. EXPERT OPINION: Older drugs for ULT like allopurinol are well studied and extensively described from typical adverse effects (mild skin rash) to unusual fatal reactions, while febuxostat seems to be overall well tolerated. More evidence is required to define the safety profile of topiroxostat, arhalofenate, tranilast, and sulfinpyrazone. Furthermore, there are some unanswered questions about the pharmacological interactions of probenecid and the hepatotoxicity of benzbromarone. Despite a limited use in clinical practice, combination therapy with lesinurad or verinurad and XOI is not frequently accompanied by side effects. Rasburicase and pegloticase are usually well tolerated with some specific exceptions. Before prescribing UL drugs, physicians should take into account their safety profile tailoring the treatment on the patient characteristics

    Misinterpreting data in the era of COVID-19.

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    We read with interest the report by Wei et al. recently accepted for publication in the Journal.1 After retrospectively evaluating cholesterol serum levels of 597 patients affected by coronavirus disease 2019 (COVID-19) and 50 age- and sex-matched healthy subjects, authors conclude that patients with COVID-19 develop hypolipidemia when symptoms are mild and that hypolipidemia worsens with disease severity. In an attempt to support their interpretation of the research, authors also report some statistically significant correlations among serum lipid levels and inflammatory parameters

    Nephroprotective action of glycosaminoglycans: why the pharmacological properties of sulodexide might be reconsidered

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    A relatively large body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve biochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic reveals that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Moreover, angiotensin II inhibits heparan sulfate synthesis, while heparins modulate angiotensin II signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in diabetes patients. Sulodexide, a mixture of heparin and dermatan sulfate, appears to be a promising treatment for diabetic proteinuria partially resistant to renin-angiotensin system blocking agents. Sulodexide prevents heparan sulfate degradation, thus allowing reconstruction of heparan sulfate content and restoration of glomerular basement membrane ionic permselectivity. The antiproteinuric effect appears to be mainly related to the basal proteinuria and consequently to the duration of treatment in a relatively large number of small clinical trials. On the other hand, several sulodexide pharmacodynamic properties could improve the prognosis of chronic kidney disease patients, also independently from its antiproteinuric effect. However, sulodexide development as an antiproteinuric drug needs to be continued, in order to define which kind of patients could better respond to this treatment
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