Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy.

RAGE regulates immune cell infiltration and angiogenesis in choroidal neovascularization.

Purpose: RAGE regulates pro-inflammatory responses in diverse cells and tissues. This study has investigated if RAGE plays a role in immune cell mobilization and choroidal neovascular pathology that is associated with the neovascular form of age-related macular degeneration (nvAMD).

Methods: RAGE null (RAGE-/-) mice and age-matched wild type (WT) control mice underwent laser photocoagulation to generate choroidal neovascularization (CNV) lesions which were then analyzed for morphology, S100B immunoreactivity and inflammatory cell infiltration.

Upregulation of oxidative stress markers in human microvascular endothelial cells by complexes of serum albumin and digestion products of glycated casein.

The extent of absorption of dietary advanced glycation end products (AGEs) is not fully known. The possible physiological impact of these absorbed components on inflammatory processes has been studied little and was the aim of this investigation. Aqueous solutions of bovine casein and glucose were heated at 95 degrees C for 5 h to give AGE-casein (AGE-Cas).

Retinal endothelial cell apoptosis stimulates recruitment of endothelial progenitor cells.

Purpose: Bone marrow-derived endothelial progenitor cells (EPCs) contribute to vascular repair although it is uncertain how local endothelial cell apoptosis influences their reparative function. This study was conducted to determine how the presence of apoptotic bodies at sites of endothelial damage may influence participation of EPCs in retinal microvascular repair.

Methods: Microlesions of apoptotic cell death were created in monolayers of retinal microvascular endothelial cells (RMECs) by using the photodynamic drug verteporfin.

The role of advanced glycation end products in retinal ageing and disease.

The retina is exposed to a lifetime of potentially damaging environmental and physiological factors that make the component cells exquisitely sensitive to age-related processes. Retinal ageing is complex and a raft of abnormalities can accumulate in all layers of the retina. Some of this pathology serves as a sinister preamble to serious conditions such as age-related macular degeneration (AMD) which remains the leading cause of irreversible blindness in the Western world.

Advanced glycation end product (AGE) accumulation on Bruch's membrane: links to age-related RPE dysfunction.

Purpose: Advanced glycation end products (AGEs) accumulate during aging and have been observed in postmortem eyes within the retinal pigment epithelium (RPE), Bruch's membrane, and subcellular deposits (drusen). AGEs have been associated with age-related dysfunction of the RPE-in particular with development and progression to age-related macular degeneration (AMD). In the present study the impact of AGEs at the RPE-Bruch's membrane interface was evaluated, to establish how these modifications may contribute to age-related disease.

Advanced glycation as a basis for understanding retinal aging and noninvasive risk prediction.

The retina is exquisitely sensitive to age-related processes, and, in many cases, these can precipitate progressive and profound loss of vision. Many asymptomatic abnormalities that accrue in the outer retina as we get older can serve as a sinister preamble to age-related macular degeneration (AMD). This condition remains the leading cause of irreversible blindness in industrialized countries, but its precise pathogenesis has yet to be completely elucidated.

Advanced glycation of fibronectin impairs vascular repair by endothelial progenitor cells: implications for vasodegeneration in diabetic retinopathy.

Purpose: Vascular repair by marrow-derived endothelial progenitor cells (EPCs) is impaired during diabetes, although the precise mechanism of this dysfunction remains unknown. The hypothesis for the study was that progressive basement membrane (BM) modification by advanced glycation end products (AGEs) contributes to impairment of EPC reparative function after diabetes-related endothelial injury.

Methods: EPCs isolated from peripheral blood were characterized by immunocytochemistry and flow cytometry.

Inhibition of advanced glycation and absence of galectin-3 prevent blood-retinal barrier dysfunction during short-term diabetes.

Breakdown of the inner blood-retinal barrier (iBRB) occurs early in diabetes and is central to the development of sight-threatening diabetic macular edema (DME) as retinopathy progresses. In the current study, we examined how advanced glycation end products (AGEs) forming early in diabetes could modulate vasopermeability factor expression in the diabetic retina and alter inter-endothelial cell tight junction (TJ) integrity leading to iBRB dysfunction. We also investigated the potential for an AGE inhibitor to prevent this acute pathology and examined a role of the AGE-binding protein galectin-3 (Gal-3) in AGE-mediated cell retinal pathophysiology.

Distribution of the receptor for advanced glycation end products in the human male reproductive tract: prevalence in men with diabetes mellitus.

Background: Diabetics have a significantly higher percentage of sperm with nuclear DNA (nDNA) fragmentation and increased levels of advanced glycation end products (AGEs), in their testis, epididymis and sperm. As the receptor for AGEs (RAGE) is important to oxidative stress and cell dysfunction, we hypothesise, that it may be involved in sperm nDNA damage.

Methods: Immunohistochemistry was performed to determine the presence of RAGE in the human testis and epididymis.

Confocal Raman microscopy can quantify advanced glycation end product (AGE) modifications in Bruch's membrane leading to accurate, nondestructive prediction of ocular aging.

The modification of proteins by nonenzymatic glycation leading to accumulation of advanced glycation end products (AGEs) is a well-established phenomenon of aging. In the eyes of elderly patients, these adducts have been observed in retinal pigment epithelium (RPE), particularly within the underlying pentalaminar substrate known as Bruch's membrane. AGEs have also been localized to age-related subcellular deposits (drusen and basal laminar deposits) and are thought to play a pathogenic role in progression of the major sight-threatening condition known as age-related macular degeneration (AMD).

Managing a traumatic wound in a geriatric patient.

Clinical management of a wound in a geriatric patient requires an understanding of age-related changes in the skin and the knowledge to make appropriate treatment choices. This case study describes clinical assessment and management of a traumatic hip wound in a 75-year-old patient. In addition to addressing his nutritional status by providing supplements, topical wound care preparations, including papain-urea and castor oil/balsam of Peru/trypsin, were used as a conservative approach to address debridement and periwound skin concerns.

Propionibacterium acnes wound contamination at the time of spinal surgery.

Unlabelled: Bacteria of the normal skin microbiota such as Propionibacterium acnes and coagulase-negative staphylococci often are dismissed as contaminants when detected in clinical samples. Propionibacterium acnes is described as a cause of spinal infection and more recently has been linked to sciatica. To date no researchers formally have examined the incidence of bacterial wound contamination during spinal surgery.

Impaired retinal angiogenesis in diabetes: role of advanced glycation end products and galectin-3.

Suppression of angiogenesis during diabetes is a recognized phenomenon but is less appreciated within the context of diabetic retinopathy. The current study has investigated regulation of retinal angiogenesis by diabetic serum and determined if advanced glycation end products (AGEs) could modulate this response, possibly via AGE-receptor interactions. A novel in vitro model of retinal angiogenesis was developed and the ability of diabetic sera to regulate this process was quantified.

Propionibacterium acnes types I and II represent phylogenetically distinct groups.

Although two phenotypes of the opportunistic pathogen Propionibacterium acnes (types I and II) have been described, epidemiological investigations of their roles in different infections have not been widely reported. Using immunofluorescence microscopy with monoclonal antibodies (MAbs) QUBPa1 and QUBPa2, specific for types I and II, respectively, we investigated the prevalences of the two types among 132 P. acnes isolates.

Restorative Nursing Bladder Training program: recommending a strategy.

This article describes a Restorative Nursing Bladder Training program, a performance improvement initiative aimed at helping patients regain bladder control by postponing voiding, and then urinating according to a specific, individualized timetable. Data were collected on 14 patients who participated in the program from April 1999 through January 2001. Eight patients achieved a 100% reduction in incontinent episodes; 1 patient documented a 90% reduction; another patient attained an 85% reduction; 3 patients showed a 50% reduction; and 1 patient showed a 30% reduction.