Search results for "MIB"

Ezetimibe alone or in combination with simvastatin increases small, dense low-density lipoproteins in healthy men: a randomized trial

2010

Aims The predominance of small dense low-density lipoproteins (sdLDLs) has been associated with increased cardiovascular risk. The effect of ezetimibe on LDL subfraction distribution has not been fully elucidated. This study assessed by gradient gel electrophoresis the effects of ezetimibe alone, simvastatin alone, and their combination on sdLDL subfraction distribution. Methods and results A single-centre, randomized, parallel three-group open-label study was performed in 72 healthy men with a baseline LDL-cholesterol (LDL-C) concentration of 111 ± 30 mg/dL (2.9 ± 0.8 mmol/L). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24), or their combination ( n = …

Cataracts and statins. A disproportionality analysis using data from VigiBase.

2019

The basis of the association between statin use and cataract has been explored using the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) through January 2019. The reporting odds ratios (RORs) as a measure of disproportionality for reported cataracts and individual statins have been calculated. Subgroup analyses according statin lipophilicity, sex, and age groups have been performed. Moreover, RORs have been calculated for non-statin lipid lowering drugs. An increased disproportionality have been found for most individual statins lovastatin: [ROR: 14.80, 95% confidence interval (CI): 13.30, 16.46)], atorvastatin (ROR: 3…

Antisense lipoprotein[a] therapy: State-of-the-art and future perspectives

2020

Several lines of evidence now attest that lipoprotein[a] (Lp[a]) is a significant risk factor for many cardiovascular disorders. This enigmatic lipoprotein, composed of a single copy of apolipoprotein B (apoB) and apolipoprotein[a] (apo [a]), expresses peculiar metabolism, virtually independent from lifestyle interventions. Several therapeutic options have hence been proposed for lowering elevated Lp[a] values, with or without concomitant effect on low density lipoprotein (LDL) particles, mostly encompassing statins, ezetimibe, nicotinic acid, lipoprotein apheresis, and anti-PCSK9 monoclonal antibodies. Since all these medical treatments have some technical and clinical drawbacks, a novel s…

Vascular effects of diet supplementation with plant sterols.

2008

Objectives The purpose of this study was to evaluate vascular effects of diet supplementation with plant sterol esters (PSE). Background Plant sterol esters are used as food supplements to reduce cholesterol levels. Their effects on endothelial function, stroke, or atherogenesis are not known. Methods In mice, plasma sterol concentrations were correlated with endothelial function, cerebral lesion size, and atherosclerosis. Plasma and tissue sterol concentrations were measured by gas-liquid chromatography-mass spectrometry in 82 consecutive patients with aortic stenosis. Results Compared with those fed with normal chow (NC), wild-type mice fed with NC supplemented with 2% PSE showed increase…

The efficacy and safety of ezetimibe/simvastatin combination compared with intensified lipid-lowering treatment strategies in diabetic subjects with …

2012

Aims The objective was to assess the consistency of effect of switching to ezetimibe/simvastatin 10/20 mg versus doubling the baseline statin dose (to simvastatin 40 mg or atorvastatin 20 mg) or switching to rosuvastatin 10 mg across subgroups of subjects with (n = 617) and without (n = 191) metabolic syndrome (MetS). Methods This was a post hoc analysis of a randomized, double-blind, 6-week study of adults 18–79 years with cardiovascular disease and diabetes mellitus with low-density lipoprotein cholesterol (LDL-C) ≥70 and ≤160 mg/dl. The percent change in LDL-C and other lipids was estimated within each subgroup separately. Safety and tolerability were assessed. Results In subjects with M…

Coronary artery disease: Risk stratification and patient selection for more aggressive secondary prevention.

2017

In patients with stable coronary artery disease, clinical outcomes are predominantly characterized by the consequences of atherosclerosis on the myocardium, but also by complications of atherosclerosis, notably recurrent acute coronary syndrome or stroke. Secondary prevention therapy is therefore key in this patient population. Intensification of secondary prevention therapy is possible, at the price of a therapeutic risk or a high cost, therefore justifying careful selection of patients with a high residual risk and low therapeutic risk. Two lines of therapy can be intensified, independently of each other, namely anti-thrombotics and lipid-lowering agents. Intensification of anti-thromboti…

Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells

2017

AbstractHepatocellular carcinoma (HCC) is one of the common malignancies and is an increasingly important cause of cancer death worldwide. Surgery, chemotherapy, and radiation therapy extend the 5-year survival limit in HCC patients by only 6%. Therefore, there is a need to develop new therapeutic approaches for the treatment of this disease. The orally bioavailable proteasome inhibitor MLN2238 (ixazomib) has been demonstrated to have anticancer activity. In the present study, we investigated the preclinical therapeutic efficacy of MLN2238 in HCC cells through in vitro and in vivo models, and examined its molecular mechanisms of action. MLN2238 inhibited cell viability in human HCC cells He…

Development of peptidomimetic boronates as proteasome inhibitors.

2013

Abstract Proteasome inhibition has emerged over the past decade as an effective therapeutic approach for the treatment of hematologic malignancies. It is a multicatalytic complex, whose proteolytic activity relies in three types of subunits: chymotrypsin-like (β5), trypsin-like (β2) and caspase-like (β1). Most important for the development of effective antitumor agents is the inhibition of the β5 subunits. In this context, the dipeptide boronate bortezomib (Velcade ® ) represents the first proteasome inhibitor approved by the FDA and the lead compound in drug discovery. This paper describes the synthesis and biological evaluation of a series of conformationally constrained pseudopeptide bor…

Use of intrapleural bortezomib in myelomatous pleural effusion [1]

2007

The cervical fracture as first symptom of multiple myeloma: A case report

2017

Introduction: Multiple Myeloma (MM) is a clonal disorder characterized by proliferation and accumulation of malignant plasma cells in the bone marrow. Bone disease occurs in approximately 80% of patients with newly diagnosed MM. The cervical spine is the least common site of disease involvement. Case presentation: A 60-year-old female patient was referred to the Department of Neurosurgery for bone pain. A magnetic resonance imaging (MRI) scan showed a pathological fracture of the sixth cervical vertebra (C6). The laboratory tests and the bone marrow examination led to a diagnosis of IgA χ MM (Durie Salmon stage IIIA). The patient underwent a cervical arthrodesis and started systemic Bortez…