Advanced glycation end products and diabetic retinopathy

Diabetic retinopathy (DR) has a complex pathogenesis which is impacted by a raft of systemic abnormalities and tissue-specific alterations occurring in response to the diabetes milieu. Many pathogenic processes play key roles in retinal damage in diabetic patients. One such pathway is the formation and accumulation of advanced glycation endproducts (AGEs) and advanced lipoxidation end products (ALEs) which are relevant modifications with roles in the initiation and progression of pathology. In this review, AGE/ALE formation in the diabetic retina is discussed alongside their impact on retinal cell function. In addition, various inhibitors of the AGE-RAGE system and their therapeutic utility for DR will also be evaluated.

Middle Stone Age (MSA) site distributions in eastern Africa and their relationship to Quaternary environmental change, refugia and the evolution of Homo sapiens

This paper considers the evolution of Homo sapiens in eastern Africa in relation to refugia and bottlenecks around ~200 ka BP, at a macro scale. Middle Stone Age (MSA) lithics, site distributions and locations are analysed in relation to palaeovegetation maps of the last glacial/interglacial cycle, which are used as a proxy for earlier climate cycles. A ‘‘push and pull’’ model is then postulated for the spread of Homo sapiens out of refugia in eastern Africa, involving both volcanism (push) and habitat availability (pull). A date within OIS 5 is suggested for this expansion to other parts of the continent, and potentially further a?eld, contrary to a frequently proposed expansion within OIS 3. ©2008 Elsevier Ltd. All rights reserved.

On-line FTIR spectroscopic investigations of methanol oxidation in a direct methanol fuel cell

A real-time Fourier transform infrared spectroscopy (FTIRS) analysis of the products of methanol oxidation in a prototype direct-methanol fuel cell operating at high temperatures (150 to 185°C) is reported here. The methanol oxidation products on platinum black and platinum-ruthenium catalyst surfaces were determined as a function of the fuel cell operating temperature, current density, and methanol/water mole ratio. Neither formaldehyde nor formic acid was detected in anode exhaust gas at all cell operating conditions. The product distributions of methanol oxidation obtained by on-line FTIRS are consistent with our previous results obtained by on-line mass spectroscopy under similar conditions. With pure methanol in anode feed, methanaldimethylacetal was found to be the main product, methyl formate and CO were also found. However, when water was present in the anode feed, the main product was CO , and the formation of methanaldimethylacetal and methyl formate decreased significantly with increase of the water/methanol mole ratio. Increase of cell operating temperature enhanced the formation of CO and decreased the formation of methanaldimethylacetal and methyl formate. Pt/Ru catalyst is more active for methanol oxidation and has a higher selectivity toward CO formation than Pt-black. Nearly complete methanol oxidation, i.e., the product was almost exclusively CO , was achieved using a Pt/Ru catalyst and a water/methanol mole ratio of 2 or higher in the anode feed at a temperature of 185°C or above.

Substrates modified by advanced glycation end-products cause dysfunction and death in retinal pericytes by reducing survival signals mediated by platelet-derived growth factor

AIMS/HYPOTHESIS: Premature death of retinal pericytes is a pathophysiological hallmark of diabetic retinopathy. Among the mechanisms proposed for pericyte death is exposure to AGE, which accumulate during diabetes. The current study used an in vitro model, whereby retinal pericytes were exposed to AGE-modified substrate and the mechanisms underlying pericyte death explored. METHODS: Pericytes were isolated from bovine retinal capillaries and propagated on AGE-modified basement membrane (BM) extract or non-modified native BM. The extent of AGE modification was analysed. Proliferative responses of retinal pericytes propagated on AGE-modified BM were investigated using a 5-bromo-2-deoxy-uridine-based assay. The effect of extrinsically added platelet-derived growth factor (PDGF) isoforms on these proliferative responses was also analysed alongside mRNA expression of the PDGF receptors. Apoptotic death of retinal pericytes grown on AGE-modified BM was investigated using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling labelling, mitochondrial membrane depolarisation and by morphological assessment. We also measured both the ability of PDGF to reverse Akt dephosphorylation that was mediated by AGE-modified BM, and increased pericyte apoptosis. RESULTS: Retinal pericytes exposed to AGE-modified BM showed reduced proliferative responses in comparison to controls (p

Ion-acoustic supersolitons in plasmas with two-temperature electrons: Boltzmann and kappa distributions

Acoustic supersolitons arise when a plasma model is able to support three consecutive local extrema of the Sagdeev pseudopotential between the undisturbed conditions and an accessible root. This leads to a characteristic electric field signature, where a simple bipolar shape is enriched by subsidiary maxima. Large-amplitude nonlinear acoustic modes are investigated, using a pseudopotential approach, for plasmas containing two-temperature electrons having Boltzmann or kappa distributions, in the presence of cold fluid ions. The existence domains for positive supersolitons are derived in a methodological way, both for structure velocities and amplitudes, in terms of plasma compositional parameters. In addition, typical pseudopotentials, soliton, and electric field profiles have been given to illustrate that positive supersolitons can be found in the whole range of electron distributions from Maxwellian to a very hard nonthermal spectrum in kappa. However, it is found that the parameter ranges that support supersolitons vary significantly over the wide range of kappa considered. VC 2013 AIP Publishing LLC. [http://dx.doi.org/10.1063/1.4818888]