Structure-property relationships of copolymers obtained by ring-opening polymerization of glycolide and epsilon-caprolactone. Part 2. Influence of composition and chain microstructure on the hydrolytic degradation

A series of glycolide/epsilon-caprolactone copolymers were compression molded and allowed to degrade in a pH 7.4 phosphate buffer at 37 degrees C. Degradation was monitored by various analytical techniques such as (1)H NMR, X-ray diffraction, DSC, CZE, ESI-MS, and inherent viscosity measurements. The results show that the degradation rate depends not only on the copolymer composition but also on its chain microstructure. Generally, copolymers with a higher C-G bond content or a higher degree of randomness exhibit higher degradation rates. Sequences with odd numbers of glycolyl units such as -CGC- and -CGGGC-, which result from the second mode transesterification, appear more resistant to hydrolysis. As a consequence, degradation residues obtained at the later stages of degradation are mainly composed of long glycolyl and caproyl sequences linked by -CGC- and -CGGGC- ones. The degradation rate of the copolymers depends also on the degree of crystallinity of each component which is related to the block length. The caproyl component can be preferentially degraded if it is in the amorphous state and the glycolyl component is semicrystalline.     

Kinetics of a nucleoside release from lactide-caprolactone and lactide-glycolide polymers in vitro

We assessed the rate of release of a model nucleoside (adenosine, 5%, w/w) from nine different lactide-glycolide or lactide-caprolactone polymers. The polymer discs were eluted every second day with an artificial cerebrospinal fluid at the elution rate roughly approximating the brain extracellular fluid formation rate. Adenosine in eluate samples was assayed by HPLC. Three polymers exhibited a relatively constant release of adenosine for over four weeks, resulting in micromolar concentrations of nucleoside in the eluate. This points to the necessity of further development of polymers of this types as intracerebral nucleoside delivery systems for local treatment of brain tumors.     

Financial ties and concordance between results and conclusions in meta-analyses: retrospective cohort study

Objective To determine whether financial ties to one drug company are associated with favourable results or conclusions in meta-analyses on antihypertensive drugs.Design Retrospective cohort study.Setting Meta-analyses published up to December 2004 that were not duplicates and evaluated the effects of antihypertensive drugs compared with any comparator on clinical end points in adults. Financial ties were categorised as one drug company compared with all others.Main outcome measures The main outcomes were the results and conclusions of meta-analyses, with both outcomes separately categorised as being favourable or not favourable towards the study drug. We also collected data on characteristics of meta-analyses that the literature suggested might be associated with favourable results or conclusions.Results 124 meta-analyses were included in the study, 49 (40%) of which had financial ties to one drug company. On univariate logistic regression analyses, meta-analyses of better methodological quality were more likely to have favourable results (odds ratio 1.16, 95% confidence interval 1.07 to 1.27). Although financial ties to one drug company were not associated with favourable results, such ties constituted the only characteristic significantly associated with favourable conclusions (4.09, 1.30 to 12.83). When controlling for other characteristics of meta-analyses in multiple logistic regression analyses, meta-analyses that had financial ties to one drug company remained more likely to report favourable conclusions (5.11, 1.54 to 16.92).Conclusion Meta-analyses on antihypertensive drugs and with financial ties to one drug company are not associated with favourable results but are associated with favourable conclusions.     

DELAYED URIC ACID ACCUMULATION IN PLASMA PROVIDES ADDITIONAL ANTI-OXIDANT PROTECTION AGAINST IRON-TRIGGERED OXIDATIVE STRESS AFTER A WINGATE TEST

Reactive oxygen species are produced during anaerobic exercise mostly by Fe ions released into plasma and endothelial/muscle xanthine oxidase activation that generates uric acid (UA) as the endpoint metabolite. Paradoxically, UA is considered a major antioxidant by virtue of being able to chelate pro-oxidative iron ions. This work aimed to evaluate the relationship between UA and plasma markers of oxidative stress following the exhaustive Wingate test. Plasma samples of 17 male undergraduate students were collected before, 5 and 60 min after maximal anaerobic effort for the measurement of total iron, haem iron, UA, ferric-reducing antioxidant activity in plasma (FRAP), and malondialdehyde (MDA, biomarker of lipoperoxidation). Iron and FRAP showed similar kinetics in plasma, demonstrating an adequate pro-/antioxidant balance immediately after exercise and during the recovery period (5–60 min). Slight variations of haem iron concentrations did not support a relevant contribution of rhabdomyolysis or haemolysis for iron overload following exercise. UA concentration did not vary immediately after exercise but rather increased 29% during the recovery period. Unaltered MDA levels were concomitantly measured. We propose that delayed UA accumulation in plasma is an auxiliary antioxidant response to post-exercise (iron-mediated) oxidative stress, and the high correlation between total UA and FRAP in plasma (R-Square = 0.636; p = 0.00582) supports this hypothesis.