Enzyme-assisted self-assembly under thermodynamic control

The production of functional molecular architectures through self-assembly is commonplace in biology, but despite advances^{1, 2, 3}, it is still a major challenge to achieve similar complexity in the laboratory. Self-assembled structures that are reproducible and virtually defect free are of interest for applications in three-dimensional cell culture^{4, 5}, templating⁶, biosensing⁷ and supramolecular electronics⁸. Here, we report the use of reversible enzyme-catalysed reactions to drive self-assembly. In this approach, the self-assembly of aromatic short peptide derivatives^{9, 10} provides a driving force that enables a protease enzyme to produce building blocks in a reversible and spatially confined manner. We demonstrate that this system combines three features: (i) self-correction—fully reversible self-assembly under thermodynamic control; (ii) component-selection—the ability to amplify the most stable molecular self-assembly structures in dynamic combinatorial libraries^{11, 12, 13}; and (iii) spatiotemporal confinement of nucleation and structure growth. Enzyme-assisted self-assembly therefore provides control in bottom-up fabrication of nanomaterials that could ultimately lead to functional nanostructures with enhanced complexities and fewer defects.

Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium : A review

Coronary heart disease (CHD) remains the greatest killer in the Western world, and although the death rate from CHD has been falling, the current increased prevalence of major risk factors including obesity and diabetes, suggests it is likely that CHD incidence will increase over the next 20 years. In conjunction with preventive strategies, major advances in the treatment of acute coronary syndromes and myocardial infarction have occurred over the past 20 years. In particular the ability to rapidly restore blood flow to the myocardium during heart attack, using interventional cardiologic or thrombolytic approaches has been a major step forward. Nevertheless, while 'reperfusion' is a major therapeutic aim, the process of ischemia followed by reperfusion is often followed by the activation of an injurious cascade. While the pathogenesis of ischemia-reperfusion is not completely understood, there is considerable evidence implicating reactive oxygen species (ROS) as an initial cause of the injury.

ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks, all potentially damaging to normal cellular function. ROS have been shown to be generated following routine clinical procedures such as coronary bypass surgery and thrombolysis, due to the unavoidable episode of ischemia-reperfusion. Furthermore, they have been associated with poor cardiac recovery post-ischemia, with recent studies supporting a role for them in infarction, necrosis, apoptosis, arrhythmogenesis and endothelial dysfunction following ischemia-reperfusion. In normal physiological condition, ROS production is usually homeostatically controlled by endogenous free radical scavengers such as superoxide dismutase, catalase, and the glutathione peroxidase and thioredoxin reductase systems. Accordingly, targeting the generation of ROS with various antioxidants has been shown to reduce injury following oxidative stress, and improve recovery from ischemia-reperfusion injury.

This review summarises the role of myocardial antioxidant enzymes in ischemia-reperfusion injury, particularly the glutathione peroxidase (GPX) and the thioredoxin reductase (TxnRed) systems. GPX and TxnRed are selenocysteine dependent enzymes, and their activity is known to be dependent upon an adequate supply of dietary selenium. Moreover, various studies suggest that the supply of selenium as a cofactor also regulates gene expression of these selenoproteins. As such, dietary selenium supplementation may provide a safe and convenient method for increasing antioxidant protection in aged individuals, particularly those at risk of ischemic heart disease, or in those undergoing clinical procedures involving transient periods of myocardial hypoxia.

Patient and practitioner compliance with silicone hydrogel and daily disposable lens replacement in Canada

Purpose: To assess current recommendations by optometrists for replacement frequency (RF) of silicone hydrogels (SH) and daily disposable (DD) contact lenses in Canada, determine rates of non-compliance with recommendations by both the optometrist and patient, and investigate reasons for non-compliance.

Methods: Survey packages were sent to optometrists in Canada who had agreed to participate. Patients completed survey questions regarding demographics and contact lens wearing patterns, including recommended and actual contact lens RF. Optometrists were asked to provide lens information and their recommendation for RF. Fifty-eight optometrists returned 654 surveys, of which 578 were eligible for analysis.

Results: Seventy percent of patients were female with a median age of 32 years. Lens type distribution was 18% DD, 35% two-week SH, and 47% one-month SH. Six percent were worn for extended wear. Daily wear median wearing time was 12 hours/day, a median of five days/week for DD, seven days/week for SH (two-week and one-month). Optometrists’ recommendations were non-compliant with the manufacturers’ recommended RF for 6% of DD, 35% of two week, and 2% of one-month patients. Patients were non-compliant with recommendations from both the manufacturer and optometrist for 12% of DD, 43% of two-week, and 31% of one-month lens wearers. The most common reason for non-compliance was forgetting which day to replace lenses. Fifty-six percent thought a reminder system would help with compliance. A higher proportion of compliant patients followed the RF because of confidence in their optometrist.

Conclusions: Optometrists generally recommended RFs consistent with manufacturers’ recommendations for DD and one-month SH lenses but often recommended longer intervals for two-week SH lenses. Patients were most compliant when wearing DD lenses and least compliant when wearing two-week SH lenses. Communication between the patient and optometrists concerning the risks of non-compliance, or initiating a reminder system might improve compliance.