Cellular and molecular pathology of age-related macular degeneration: Potential role for proteoglycans

Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch's membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD

Who is more vulnerable to death from extremely cold temperatures? A case-only approach in Hong Kong with a temperate climate

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Platelet-derived growth factor-stimulated versican synthesis but not glycosaminoglycan elongation in vascular smooth muscle is mediated via Akt phosphorylation

Proteoglycans are associated with the initiation of atherosclerosis due to their binding of apolipoproteins on lipid particles leading to retention in the vessel wall. The signaling pathways through which growth factors regulate the synthesis and structure of proteoglycans are potential therapeutic targets. Platelet-derived growth factor (PDGF) is present in atherosclerotic plaques and activates phosphorylation of the serine/threonine kinase Akt. We have investigated the role of Akt in the signaling pathways for proteoglycan core protein expression and elongation of glycosaminoglycan chains on proteoglycans secreted by human vascular smooth muscle cells. The pharmacological inhibitor of Akt phosphorylation, SN30978, blocked PDGF stimulated phosphorylation of Akt. SN30978 caused concentration dependent inhibition of PDGF stimulated radiosulfate incorporation into secreted proteoglycans and the response was blocked by the PDGF receptor antagonists Ki11502 and imatinib. Analysis of the size of the biglycan molecules by SDS-PAGE showed that PDGF increased the apparent size of biglycan but this effect on glycosaminoglycan chain elongation was blocked by Ki11502 but not by SN30978. PDGF also stimulated total protein core protein synthesis assessed as 35S-methionine/cysteine incorporation and specifically the expression of versican mRNA. Both of these responses were blocked by SN30978. This data shows that PDGF-stimulated proteoglycan core protein synthesis but not glycosaminoglycan chain elongation is mediated via Akt phosphorylation. These data identify potential pathways for the development of agents which can pharmacologically regulate individual components of the synthesis of proteoglycans

Effect modifications of smoking on risk of mortality associated with influenza

BACKGROUND AND AIMS: Influenza is well known to cause heavy disease burden in both temperate and tropical/subtropical regions. Although smoking has been found to increase susceptibility to influenza infection, its role in modifying the mortality risk associated with influenza remains unexplored. This study examined the effect modifications of cigarette smoking on influenza-associated mortality in a cohort of older …postprin

Effect of lifestyle factors on risk of mortality associated with influenza in elderly people

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Generation Y and sparkling wines: a cross-cultural perspective

The aim of this study was to investigate and compare the engagement of Generation Y consumers with champagne and sparkling wine across five Anglophone countries. A qualitative approach was adopted using focus groups with young consumers, including images and wine tasting as projective stimuli. There were significant trans-cultural similarities between consumption behaviour (sparkling wine is a women’s drink, and a separate category from still wine, and that they will ‘grow into’ drinking it) but also noticeable differences (responses to images and colours varied substantially, as did attitudes to price and the particular status of champagne). Research into the behaviour of Generation Y as a cohort needs to take account of cultural as much as generational context. However, as a qualitative study the findings need further quantitative validation. Marketers cannot view Generation Y as a single group; even within countries marketing strategies may need to be refined depending on where a product is being sold

Relationship between serum testosterone and fracture risk in men: a comparison of RIA and LC-MS/MS

BACKGROUND: Serum testosterone can be measured byLC-MS/MS and RIA. We investigated whether the testosterone–fracture relationship was affected by the method of measurement. METHODS: We measured total testosterone (TT) by LCMS/MS (TTLC-MS/MS) and RIA (TTRIA) in serum samples collected from 602 men whose incident fractures had been continuously ascertained by x-ray reports from 1989 to 2010. We measured bone mineral density (BMD) by dual-energy x-ray absorptiometry. The association between TT and fracture risk was assessed by the Cox proportional hazards model, taking into account the effect of age and BMD. CONCLUSIONS: The concordance between LC-MS/MS and RIA in the measurement of serum TT was moderate. Moreover, the magnitude of association between testosterone and fracture risk in older men was largely unaffected by the method of measurement. © 2015 American Association for Clinical Chemistr

Is exercise protective against influenza-associated mortality?

Background: Little is known about the effect of physical exercise on influenza-associated mortality. Methods and Findings: We collected information about exercise habits and other lifestyle, and socioeconomic and demographic status, the underlying cause of death of 24,656 adults (21% aged 30-64, 79% aged 65 or above who died in 1998 in Hong Kong, and the weekly proportion of specimens positive for influenza A (H3N1 and H1N1) and B isolation during the same period. We assessed the excess risks (ER) of influenza-associated mortality due to all-natural causes, cardiovascular diseases, or respiratory disease among different levels of exercise: never/seldom (less than once per month), low/moderate (once per month to three times per week), and frequent (four times or more per week) by Poisson regression. We also assessed the differences in ER between exercise groups by case-only logistic regression. For all the mortality outcomes under study in relation to each 10% increase in weekly proportion of specimens positive for influenza A+B, never/seldom exercise (as reference) was associated with 5.8% to 8.5% excess risks (ER) of mortality (P<0.0001), while low/moderate exercise was associated with ER which were 4.2% to 6.4% lower than those of the reference (P<0.001 for all-natural causes; P=0.001 for cardiovascular; and P=0.07 for respiratory mortality). Frequent exercise was not different from the reference (change in ER -0.8% to 1.7%, P=0.30 to 0.73). Conclusion: When compared with never or seldom exercise, exercising at low to moderate frequency is beneficial with lower influenza-associated mortality. © 2008 Wong et al.published_or_final_versio

Authors’ Reply to “Training and Supporting Residents, for All Family Medicine Practice Settings.”

TO THE EDITOR: We appreciate Dr Wu’s comments and agree wholeheartedly that meeting community needs and negotiating relationships are essential skills for all family physicians. The need for these skills is amplified in the intimacy of the rural environment, as physicians navigate daily life amongst patients at grocery stores, restaurants, schools, and social gatherings

Effect of influenza on cardiorespiratory and all-cause mortality in Hong Kong, Singapore and Guangzhou.

1. Using a common modelling approach, mortality attributable to influenza was higher in the two subtropical cities Guangzhou and Hong Kong than in the tropical city Singapore. 2. The virus activity appeared more synchronised in subtropical cities, whereas seasonality of influenza tended to be less marked in the tropical city. 3. High temperature was associated with increased mortality after influenza infection in Hong Kong, whereas relative humidity was an effect modifier for influenza in Guangzhou. No effect modification was found for Singapore. 4. Seasonal and environmental factors probably play a more important role than socioeconomic factors in regulating seasonality and disease burden of influenza. Further studies are needed in identifying the mechanism behind the regulatory role of environmental factors.published_or_final_versio