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Biomedical subjects

Alberico Catapano

Publications and source records attributed to Alberico Catapano.

6 recordsLinked to original sources

Synthesis and biological evaluation of azido- and aziridino-hydroxyl-beta-lactams through stereo- and regioselective epoxide ring opening.

Two new classes of azido- and aziridino-hydroxyl-beta-lactam containing structures have been prepared by means of a stereo- and regioselective epoxide ring opening. The straightforwardness of the procedure makes this strategy useful for the synthesis of potentially bioactive compounds. Some selected examples showed promising activity in acyl CoA-cholesterol acyltransferase inhibition assays.

Azides↗

Lipid altering-efficacy of ezetimibe co-administered with simvastatin compared with rosuvastatin: a meta-analysis of pooled data from 14 clinical trials.

OBJECTIVE: Results of direct comparative studies between ezetimibe/simvastatin and rosuvastatin therapies have not been reported. Both of these treatment options offer significant reductions in LDL-C. To evaluate the lipid efficacy of each of these therapies relative to each other, a meta-analysis of data from 14 randomized, double-blind clinical trials that compared the effectiveness of two new options for cholesterol lowering was performed. DATA SOURCES: PubMed, EMBASE and BIOSIS databases were searched up to March 14, 2004. METHODS OF STUDY SELECTION: Efficacy results from clinical trials with the co-administration of ezetimibe 10 mg with simvastatin or with the ezetimibe/simvastatin combination product (ezetimibe/simvastatin 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg) were compared with efficacy results from clinical trials of rosuvastatin 5 mg, 10 mg, 20 mg, and 40 mg in patients with primary hypercholesterolemia. Trials in healthy patients, heterozygous familial hypercholesterolemia or combined hyperlipidemia, and pharmacokinetic trials were excluded. DATA EXTRACTION AND SYNTHESIS: This analysis used pooled data for LDL-C, HDL-C, non-HDL-C, triglycerides, total cholesterol, apolipoprotein (apo) A-I, and apo B for the two therapies at their lowest doses (ezetimibe/simvastatin 10/10 mg and rosuvastatin 5 mg) through their highest doses (ezetimibe/simvastatin 10/80 mg and rosuvastatin 40 mg), and estimated within-treatment percentage changes in these parameters. Percentage reductions from baseline in LDL-C for the pooled data were 46.2% and 41.8% for ezetimibe/simvastatin 10/10 mg and rosuvastatin 5 mg, respectively; 50.6% and 47.4% for ezetimibe/simvastatin 10/20 mg and rosuvastatin 10 mg, respectively; 55.9% and 52.1% for ezetimibe/simvastatin 10/40 mg and rosuvastatin 20 mg, respectively; and 59.7% and 58.5% for ezetimibe/simvastatin 10/80 mg and rosuvastatin 40 mg, respectively. CONCLUSIONS: The results of this meta-analysis suggest greater LDL-C lowering with ezetimibe/simvastatin compared with rosuvastatin. These results need to be confirmed in a head-to-head comparison of both therapies.

Anticholesteremic Agents↗

Inherited apolipoprotein A-V deficiency in severe hypertriglyceridemia.

OBJECTIVE: Mutations in LPL or APOC2 genes are recognized causes of inherited forms of severe hypertriglyceridemia. However, some hypertrigliceridemic patients do not have mutations in either of these genes. Because inactivation or hyperexpression of APOA5 gene, encoding apolipoprotein A-V (apoA-V), causes a marked increase or decrease of plasma triglycerides in mice, and because some common polymorphisms of this gene affect plasma triglycerides in humans, we have hypothesized that loss of function mutations in APOA5 gene might cause hypertriglyceridemia. METHODS AND RESULTS: We sequenced APOA5 gene in 10 hypertriglyceridemic patients in whom mutations in LPL and APOC2 genes had been excluded. One of them was found to be homozygous for a mutation in APOA5 gene (c.433 C>T, Q145X), predicted to generate a truncated apoA-V devoid of key functional domains. The plasma of this patient was found to activate LPL in vitro less efficiently than control plasma, thus suggesting that apoA-V might be an activator of LPL. Ten carriers of Q145X mutation were found in the patient's family; 5 of them had mild hypertriglyceridemia. CONCLUSIONS: As predicted from animal studies, apoA-V deficiency is associated with severe hypertriglyceridemia in humans. This observation suggests that apoA-V regulates the secretion and/or catabolism of triglyceride-rich lipoproteins. Mutations in APOA5 gene might be the cause of severe hypertriglyceridemia in subjects in whom mutations in LPL or APOC2 genes have been excluded. We detected a nonsense mutation in APOA5 gene (Q145X) in a boy with hyperchylomicronemia syndrome. This is the first observation of a complete apoA-V deficiency in humans.

Amino Acid Substitution↗

Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers.

The aim of our study was to evaluate the effect of a standardized formulation of a polyphenolic extract of grapes (Leucoselect-Phytosome [LP]) on low-density lipoprotein (LDL) susceptibility to oxidation in a group of heavy smokers. A randomized, double-blind, crossover study was undertaken in 24 healthy male heavy smokers, aged > or = 50 years. Enrolled subjects were given 2 capsules twice daily for 4 weeks (phase 1). Each capsule contained 75 mg of a grape procyanidin extracts and soy-phosphatidlcholine or placebo consisiting of 75 mg lactose and soy-phosphatidlcholine. A wash out period of 3 weeks was then followed by 4 weeks of the opposite treatment (phase 2). Blood samples were taken at baseline and at the end of each phase and assayed for plasma lipids and LDL susceptibility to oxidation. Compliance was good, and no adverse effects were recorded. Subjects did not show significant modification of total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C) and LDL-C during LP treatment. Among oxidative indices, thiobarbituric acid reactive substances (TBARS) concentration was significantly reduced in subjects taking LP (-14.7% +/- 21.1% v +5.0% +/- 18.1%, P <.01), and the lag phase prolonged (+15.4% +/- 24.4% v -0.1% +/- 16.0%, P <.05) compared with placebo and basal values. The antioxidant potential of grape seed extract polyphenols may prove effective in a model of oxidative stress (smoking); however more investigational data are needed before use in wider clinical settings.

Antioxidants↗

Effects of an automated electronic reminder in changing the antiplatelet drug-prescribing behavior among Italian general practitioners in diabetic patients: an intervention trial.

OBJECTIVE: To evaluate whether an electronic reminder integrated into a routine computer system increases the use of antiplatelet drugs for diabetic patients among Italian general practitioners (GPs). RESEARCH DESIGN AND METHODS: A randomized controlled trial was carried out among 300 GPs and their patients selected from the Health Search Database. Among these, 150 GPs (intervention group) received instructions to activate an electronic reminder plus a letter summarizing the beneficial effects of antiplatelet drugs in diabetic patients with at least one additional cardiovascular risk factor ("high risk"), whereas the other 150 GPs (control group) received only the letter. The electronic reminder, integrated into a standard software system for the management of the daily clinical practice, was displayed when every participating GP opened the medical record of diabetic patients aged > or =30 years. Only high-risk diabetic patients were included in the analysis. Patients were considered under antiplatelet treatment if they received two or more prescriptions at baseline and during the follow-up. RESULTS: We selected 15,343 high-risk diabetic patients, 7,313 belonging to GPs of the control group and 8,030 belonging to GPs of the intervention group. Overall, 1,672 patients (22.9%) of the control group and 1,886 (23.5%) patients of the intervention group received antiplatelet drugs at baseline (P = N.S.). At the end of the follow-up, the number of treated patients was significantly increased in the intervention group (odds ratio 1.99, 95% CI 1.79-2.22) versus the control group. The effect of the electronic reminder was more relevant among those patients with one or more cardiovascular risk factors but without previous cardiovascular diseases (CVDs), compared with those with CVDs. CONCLUSIONS: These findings provide evidence for the effect of an electronic reminder in affecting the prescriptive behavior of GPs.

Adult↗