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Promising biomaterials for facilitating regeneration should be tested in appropriate large animal models that better recapitulate human inflammatory and regenerative responses than rodent models. Previous studies have shown tyrosine-derived polycarbonates (TyrPC) are versatile biomaterials with a wide range of tissue engineering applications across multiple disciplines. The library of TyrPC has been well studied and consists of thousands of polymer compositions with tunable mechanical characteristics and degradation and resorption rates that are useful for the design of nerve guidance tubes (NGTs). NGTs made of different TyrPCs have been used in segmental nerve defect models in small animals. The current study is an extension of this work and evaluates the effects of NGTs made using two different TyrPC compositions in a porcine model of peripheral nerve injury and repair. We first evaluated a nondegradable TyrPC formulation in a 1 cm segmental nerve defect model in pigs, demonstrating proof-of-concept of chronic regenerative efficacy up to 6 months, at which time nerve/muscle electrophysiology and nerve morphometry were similar to those attained by an autograft repair control. Next, we characterized the acute regenerative response to a degradable TyrPC formulation using the same 1 cm segmental defect model. After 2 weeks in vivo , this TyrPC NGT was found to promote the deposition by host cells of pro-regenerative extracellular matrix (ECM) constituents (in particular collagen I, collagen III, collagen IV, laminin and fibronectin) at levels exceeding those deposited inside commercially available collagen-based NGTs. This corresponded with dense and rapid infiltration of host Schwann cells and axons into the lumen of the NGT and axonal crossing of the lesion into the distal nerve segment. These findings confirmed results reported previously in a mouse model and reveal that TyrPC NGTs were well tolerated in swine and facilitated host axon regeneration and Schwann cell infiltration in the acute phase across segmental defects - likely by eliciting a favorable neurotrophic ECM milieu. This regenerative response ultimately can contribute to functional recovery.

Aims: To evaluate erythropoietic response rates to oral iron over time in iron-deficient anemic patients with nondialysis-dependent chronic kidney disease (ND-CKD). Materials and methods: FIND-CKD was a 1-year, randomized, multicenter trial of iron therapy in patients with ND-CKD, anemia, and iron deficiency, without erythropoiesis-stimulating agent (ESA) therapy. Patients with active infection or C-reactive protein > 20 mg/L were excluded. In this post-hoc analysis, response was defined as >= 1 g/dL increase in hemoglobin (Hb) from baseline, before initiation of alternative anemia therapy (i.e., ESA, transfusion, or intravenous iron). Results: 308 patients received oral iron (200 mg elemental iron/day). Mean (SD) Hb at baseline was 10.4 (0.7) g/dL. At week 4, Hb data were available from 292 patients without alternative anemia therapy: 63/292 (21.6%) showed a response. Among the 229 nonresponders at week 4, 48.8% showed a cumulative response on >= 1 occasion by week 52 (11.1%, 19.9%, 25.9%, and 28.7% had a response at weeks 8, 12, 24, and 52, respectively), and 27.9% had received alternative iron therapy by week 52. Baseline levels of Hb, ferritin, and transferrin saturation were lower in responders than in nonresponders. Neither concomitant medication nor adherence (as assessed by medication count) was substantially different between early responders and nonresponders. Conclusion: Four weeks after starting oral iron therapy, only 21.6% of anemic patients with ND-CKD and iron deficiency showed an Hb increase of at least 1 g/dL. Among early nonresponders

BACKGROUNDOmega-3 fatty acids, such as those present in fish oil, have been reported to prolong life in myocardial infarction survivors. These fatty acids can decrease serum triglyceride concentrations, but so far the doses used in trials examining their effects on coronary end points have had only minimal triglyceride lowering effects.OBJECTIVETo examine the triglyceride lowering effectiveness, safety, and tolerability of Omacor, a concentrate of omega-3, long chain, polyunsaturated fatty acids from fish oil (84% of the total as opposed to an average of 35% in fish oil) over one year in patients with established coronary heart disease (CHD) and persisting hypertriglyceridaemia, despite receiving simvastatin in doses similar to those employed in the Scandinavian simvastatin survival study.SUBJECTS AND METHODS59 patients with CHD, receiving simvastatin 10–40 mg daily with serum triglycerides > 2.3 mmol/l, were randomised to receive Omacor 2 g twice a day or placebo for 24 weeks in a double blind trial. Forty six patients accepted the offer of active treatment for a further 24 weeks in an open phase of the trial.RESULTSThere was a sustained significant decrease in serum triglycerides by 20–30% (p CONCLUSIONOmacor was found to be a safe and effective means of lowering serum triglycerides over one year in patients with CHD and combined hyperlipidaemia, whose triglycerides remained elevated despite simvastatin treatment.

Cadmium (Cd) induced lipid peroxidation (LPO) and oxidative damage in various tissues by altering the antioxidant status of the cells. Rats were pretreated with vitamin E and/or Se, prior to Cd treatment to prepare the animals to withstand the oxidative assault. A Cd intoxication increased LPO in liver, kidney, and heart and diminished the activities of superoxide dismutase (SOD), catalase (CAT), total and Se-dependent glutathione peroxidase (GSH-Px) in these tissues. The Cd-induced LPO decreased and the antioxidant enzyme activity increased when animals were treated with vitamin F and/or Se prior to Cd intoxication. The animals treated with vitamin E and/or Se without Cd intoxication showed LPO and antioxidant enzyme activities comparable to control animals. The results show that Cd induces LPO and alters the antioxidant system in tissues, however, the presence of adequate vitamin E and/or Se ameliorates the oxidative effects of Cd.

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines. (C) 2014 Published by Elsevier Ireland Ltd.