Atorvastatin versus Bezafibrate in Mixed Hyperlipidaemia : Randomised Clinical Trial of Efficacy and Safety (the ATOMIX Study)

OBJECTIVE: Combined hyperlipidaemia is a common and highly atherogenic lipid phenotype with multiple lipoprotein abnormalities that are difficult to normalise with single-drug therapy. The ATOMIX multicentre, controlled clinical trial compared the efficacy and safety of atorvastatin and bezafibrate in patients with diet-resistant combined hyperlipidaemia. PATIENTS AND STUDY DESIGN: Following a 6-week placebo run-in period, 138 patients received atorvastatin 10mg or bezafibrate 400mg once daily in a randomised, double-blind, placebo-controlled trial. To meet predefined low-density lipoprotein-cholesterol (LDL-C) target levels, atorvastatin dosages were increased to 20mg or 40mg once daily after 8 and 16 weeks, respectively. RESULTS: After 52 weeks, atorvastatin achieved greater reductions in LDL-C than bezafibrate (percentage decrease 35 vs 5; p < 0.0001), while bezafibrate achieved greater reductions in triglyceride than atorvastatin (percentage decrease 33 vs 21; p < 0.05) and greater increases in high-density lipoprotein-cholesterol (HDL-C) [percentage increase 28 vs 17; p < 0.01 ]. Target LDL-C levels (according to global risk) were attained in 62% of atorvastatin recipients and 6% of bezafibrate recipients, and triglyceride levels <200 mg/dL were achieved in 52% and 60% of patients, respectively. In patients with normal baseline HDL-C, bezafibrate was superior to atorvastatin for raising HDL-C, while in those with baseline HDL-C <35 mg/dL, the two drugs raised HDL-C to a similar extent after adjustment for baseline values. Both drugs were well tolerated. CONCLUSION: The results show that atorvastatin has an overall better efficacy than bezafibrate in concomitantly reaching LDL-C and triglyceride target levels in combined hyperlipidaemia, thus supporting its use as monotherapy in patients with this lipid phenotype

Fatty acid signature analysis confirms foraging resources of a globally endangered Mediterranean seabird species: calibration test and application to the wild

Tissue fatty acid signatures (FAS) can complement traditional methods of studying seabird diets. Although plasma lipid FAS are known to indicate dietary changes qualitatively, here we test whether they can be used to determine the proportions of different dietary items in a quantitative manner.2. Captive herring gulls (Larus argentatus) were fed North Atlantic plaice Pleuronectes platessa (demersal species made available to wild seabirds by fisheries) and herring Clupea harengus (pelagic fish often found naturally in their diet) with different mixing ratios (0%, 10%, 20% and 50% herring).3. Major fatty acids did not indicate diet, but several minor components in plasma, for example, 14 : 0, 18 : 3n-3, 18 : 4n-3 and C20-22 monounsaturated fatty acids (MUFA), showed good correlations with diet composition. Different fatty acids were incorporated from diet into plasma lipids with different calibration coefficients.4. Together with dose-dependent but inefficient (low calibration coefficient) transfer of 22 : 1n-11 (a major fatty acid of herring) to the plasma FAS of the gulls, the percentages of potential chain shortening products of 22 : 1n-11, that is, 20 : 1n-11, 18 : 1n-11 and 16 : 1n-11 increased with increasing proportion of herring in the diet. Notably, the dietary supply of these fatty acids itself did not change. Thus the metabolic products of certain dietary fatty acids can reflect the amount of their dietary precursors in a quantitative way.5. Despite the fact that many major fatty acids in FAS of seabird plasma are greatly modified by endogenous metabolism, several minor components of FAS (in this experiment 14 : 0, branched chain 17 : 0, 18 : 1n-7, 18 : 3n-3, 18 : 4n-3, C20-22 MUFA with their chain shortening products, and 22 : 4n-6) that can be accurately and reliably quantified by gas chromatography, vary proportionally to diet composition, allowing their use for monitoring temporal and spatial differences in seabird diet

Pathology in practice

4 páginas.Funded by CEU Universidad Cardenal Herrera (IDOC-1610). Analyses were performed with a slide scanner purchased with European Union funds (FEDER Programme: PO FEDER 2007-2013)

Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN-01.

Retinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor RB1 VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway. Thus, we reasoned that VCN-01 could provide targeted therapeutic activity against even chemoresistant retinoblastoma. In vitro, VCN-01 effectively killed patient-derived retinoblastoma models. In mice, intravitreous administration of VCN-01 in retinoblastoma xenografts induced tumor necrosis, improved ocular survival compared with standard-of-care chemotherapy, and prevented micrometastatic dissemination into the brain. In juvenile immunocompetent rabbits, VCN-01 did not replicate in retinas, induced minor local side effects, and only leaked slightly and for a short time into the blood. Initial phase 1 data in patients showed the feasibility of the administration of intravitreous VCN-01 and resulted in antitumor activity in retinoblastoma vitreous seeds and evidence of viral replication markers in tumor cells. The treatment caused local vitreous inflammation but no systemic complications. Thus, oncolytic adenoviruses targeting RB1 might provide a tumor-selective and chemotherapy-independent treatment option for retinoblastoma