The visual complications of Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder affecting middle-aged and elderly people. The disorder is of particular interest to Optometrists because it is associated with a range of visual problems including defects in eye movement and pupillary function. This article reviews the visual complications of PD and the pathological changes in the eye and brain which may explain these symptoms.

Local and systemic delivery of a novel group of inhibitors of transglutaminase enzyme: A potential approach for treating of catheter-related complications and liver fibrosis

The present thesis investigates targeted (locally and systemically) delivery of a novel group of inhibitors of enzyme transglutaminases (TGs). TGs are a widely distributed group of enzymes that catalyse the formation of isopeptide bonds between the y-carboxamide group of protein-bound glutamines and the a-amino group of protein-bound lysines or polyamines. The first group of the novel inhibitors tested were the tluorescently labelled inhibitors of Factor XIIIa (FXIIIa). These small, non-toxic inhibitors have the potential to prevent stabilisation of thrombi by FXIIIa and consequently increase the natural rate of thrombolysis, in addition it reduces staphylococcal colonisation of catheters by inhibiting their FXIIIa¬mediated cross-linking to blood clot proteins on the central venous catheter (CVCs) surface. The aim of this work was to incorporate the FXIIIa inhibitor either within coating of polyurethane (PU) catheters or to integrate it into silicone catheters, so as to reduce the incidence of thrombotic occlusion and associated bacterial infection in CVCs. The initial work focused on the incorporation of FXIIIa inhibitors within polymeric coatings of PU catheters. After defining the key characteristics desired for an effective polymeric-coating, polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA) or their combination were studies as polymers of choice for coating of the catheters_ The coating was conducted by dip-coating method in a polymer solution containing the inhibitor. Upon incubation of the inhibitor-and polymer-coated strips in buffer, PVP was dissolved instantly, generating fast and significant drug release, whilst PLGA did not dissolve, yielding a slow and an insufficient amount of drug release. Nevertheless, the drug release profile was enhanced upon employing a blend solution of PVP and PLGA. The second part of the study was to incorporate the FXIIIa inhibitor into a silicone elastomer; results demonstrated that FXIIIa inhibitor can be incorporated and released from silicone by using citric acid (CA) and sodium bicarbonate (SB) as additives and the drug release rate can be controlled by the amount of incorporated additives in the silicone matrix. Furthermore, it was deemed that the inhibitor was still biologically active subsequent to being released from the silicone elastomer strips. Morphological analysis confirmed the formation of channels and cracks inside the specimens upon the addition of CA and SB. Nevertheless, the tensile strength, in addition to Young's modulus of silicone elastomer strips, decreased constantly with an increasing amount of amalgamated CA/ SB in the formulations. According to our results, incorporation of FXIIIa inhibitor into catheters and other medical implant devices could offer new perspectives in preventing bio-material associated infections and thrombosis. The use of tissue transglutaminase (T02) inhibitor for treating of liver fibrosis was also investigated. Liver fibrosis is characterized by increased synthesis and decreased degradation of the extracellular matrix (ECM). Transglutaminase-mediated covalent cross-linking is involved in the stabilization of ECM in human liver fibrosis. Thus, TG2 inhibitors may be used to counteract the decreased degradation of the ECM. The potential of a liposome based drug delivery system for site specific delivery of the fluorescent TG2 inhibitor into the liver was investigated; results indicated that the TG2 inhibitor can be successfully integrated into liposomes and delivered to the liver, therefore demonstrating that liposomes can be employed for site-specific delivery of TG2 inhibitors into the liver and TG2 inhibitor incorporating liposomes could offer a new approach in treating liver fibrosis and its end stage disease cirrhosis.

New insights into the etiology of preeclampsia:identification of key elusive factors for the vascular complications

The incidence of preeclampsia is reduced by a third in smokers, but not in snuff users. Soluble Flt-1 (sFlt-1) and soluble endoglin (sEng) are increased prior to the clinical onset of preeclampsia. Animals exposed to high circulating levels of sFlt-1 and sEng elicit severe preeclampsia-like symptoms. Smokers have reduced circulating sFlt-1 and cigarette smoke extract decreases sFlt-1 release from placental villous explants. An anti-inflammatory enzyme, heme oxygenase-1 (HO-1) and its metabolite carbon monoxide (CO), inhibit sFlt-1 and sEng release. Women with preeclampsia exhale less CO than women with normal pregnancies and HO expression decreases as the severity of preeclampsia increases. In contrast, sFlt-1 levels increase with increasing severity. More importantly, chorionic villous sampling from women at eleven weeks gestation shows that HO-1 mRNA expression is decreased in women who go on to develop preeclampsia. Collectively, these facts provide compelling evidence to support the proposition that the pathogenesis of preeclampsia is largely due to loss of HO activity. This results in an increase in inflammation and excessive elevation of the two key anti-angiogenic factors responsible for the clinical signs of preeclampsia. These findings provide strong evidence for a protective role of HO-1 in pregnancy and identify HO as a target for the treatment of preeclampsia. The cardiovascular drugs, statins, stimulate HO-1 expression and inhibit sFlt-1 release in vivo and in vitro, thus, they have the potential to ameliorate early onset preeclampsia. The StAmP trial is underway to address this and if positive, its outcome will lead to the very first therapeutic intervention to prolong affected pregnancies.

Metformin:effects on micro and macrovascular complications in type 2 diabetes

Introduction: The antihyperglycaemic agent metformin is widely used in the treatment of type 2 diabetes. Data from the UK Prospective Diabetes Study and retrospective analyses of large healthcare databases concur that metformin reduces the incidence of myocardial infarction and increases survival in these patients. This apparently vasoprotective effect appears to be independent of the blood glucose-lowering efficacy. Effects of metformin: Metformin has long been known to reduce the development of atherosclerotic lesions in animal models, and clinical studies have shown the drug to reduce surrogate measures such as carotid intima-media thickness. The anti-atherogenic effects of metformin include reductions in insulin resistance, hyperinsulinaemia and obesity. There may be modest favourable effects against dyslipidaemia, reductions in pro-inflammatory cytokines and monocyte adhesion molecules, and improved glycation status, benefiting endothelial function in the macro- and micro-vasculature. Additionally metformin exerts anti-thrombotic effects, contributing to overall reductions in athero-thrombotic risk in type 2 diabetic patients. © 2008 Springer Science+Business Media, LLC.

Pregnancy complications in hyperemesis-affected pregnancy:a large hospital database study

Objective: Vomiting in pregnancy is a common condition affecting 80% of pregnant women. Hyperemesis is at one end of the spectrum, seen in 0.5–2% of the pregnant population. Known factors such as nulliparity, younger age and high body mass indexare associated with an increased risk of this condition in the first trimester. Late pregnancy complications attributable to hyperemesis, the pathogenesis of which is poorly understood, have not been studied in large population-based studies in the United Kingdom. The objective of this study was to determine a plausible association between hyperemesis and pregnancy complications,such as pregnancy-related hypertension, gestational diabetes and liver problems in pregnancy, and the rates of elective (ElCS) and emergency caesarean section (EmCS). Methods: Using a database based on ICD-10 classification, anonymised data of admissions to a large multi-ethnic hospital in Manchester, UK between 2000 and 2012 were examined.Notwithstanding the obvious limitations with hospital database-based research, this large volume of datasets allows powerful studies of disease trends and complications.Results Between 2000 and 2012, 156 507 women aged 45 or under were admitted to hospital. Of these, 1111 women were coded for hyperemesis (0.4%). A greater proportion of women with hyperemesis than without hyperemesis were coded forhypertensive disorders in pregnancy such as pregnancy-induced hypertension, pre-eclampsia and eclampsia (2.7% vs 1.5%;P=0.001). The proportion of gestational diabetes and liver disorders in pregnancy was similar for both groups (diabetes:0.5% vs. 0.4%; P=0.945, liver disorders: 0.2% vs. 0.1%;P=0.662). Hyperemesis patients had a higher proportion of elective and emergency caesarean sections compared with the non-hyperemesis group (ElCS: 3.3% vs. 2%; P=0.002, EmCS: 5% vs.3%; P=0.00). Conclusions: There was a higher rate of emergency and elective caesarean section in women with hyperemesis, which could reflect the higher prevalence of pregnancy-related hypertensive disorders(but not diabetes or liver disorders) in this group. The factors contributing to the higher prevalence of hypertensive disorders arenot known, but these findings lead us to question whether there is a similar pathogenesis in the development of both the conditions and hence whether further study in this area is warranted.