Oxidative stress in diabetic patients with retinopathy

Background: Diabetes mellitus (DM) is known to induce oxidative stress along with deranging various metabolisms; one of the late complications of diabetes mellitus is diabetic retinopathy, which is a leading cause of acquired blindness. Poor glycemic control and oxidative stress have been attributed to the development of complications like diabetic retinopathy. The aim of this study was to analyze and correlate oxidative stress marker, Malondialdehyde (MDA), and antioxidants (erythrocyte glutathione, vitamin C) along with glycosylated hemoglobin (HbA1c) and fasting blood sugar (FBS) in diabetic patients with and without retinopathy.Materials and Methods: The study population comprised of 50 type 2 diabetics with retinopathy as Group 1 (G1) and 50 type 2 diabetics without retinopathy as Group 2 (G2) in the age group 40-70 years as patients, and 50 ageand gender-matched healthy individuals as controls, Group 3 (G3). FBS, HbA1c MDA, glutathione in erythrocytes, and vitamin C were assayed. Results were analyzed using SPSS 11.0, Mann–Whitney U-test, and Pearson correlation coefficient.Results: Mean FBS (mg/dl) were 194.04 ± 48.52 (G1), 181.24 ± 50.05 (G2), and 92.20 ± 9.19 (G3) (P < 0.001). Mean values of MDA were 6.65 ± 0.30 (G1), 4.63 ± 0.56 (G2), and 3.90 ± 0.34 (G3) (P < 0.001). The mean reduced glutathione (GSH) levels were (mg/g of Hb) 6.10 ± 1.41 (G1), 6.44 ± 1.53 (G2), and 13.09 ± 2.49 (G3) (P < 0.001). The mean vitamin C levels (mg/dl) were 0.70 ± 0.24 (G1), 0.87 ± 0.29 (G2), and 1.25 ± 0.27 (G3) (P < 0.001).Conclusion: Estimation of HbA1c, MDA, GSH in erythrocytes, and vitamin C levels can contribute to determine the extent of oxidative stress in diabetes and help in effective control and prevention of the onset and progression of diabetic retinopathy.Keywords: Diabetic retinopathy, glycosylated hemoglobin,  malondialdehyde, reduced glutathione, vitamin

Empirical relation between energy and angular deviation of muons transmitted through thick slabs

739-743To facilitate detection of materials of high atomic number buried inside materials of low atomic number using cosmic ray muons, Monte Carlo simulations have been carried out and an empirical relation has been developed to correlate energy with the most probable angular deviation of transported muons through slabs of different materials. This empirical relation describes the correlation between the energy distribution and the distribution of angular deviation of muons passing through slabs of different materials and of different thickness, and is expected to be useful in the field of cosmic ray muon radiography

Oxidative stress sensitizes retinal pigmented epithelial (RPE) cells to complement-mediated injury in a natural antibody-, lectin pathway-, and phospholipid epitope-dependent manner.

International audienceUncontrolled activation of the alternative complement pathway (AP) is thought to be associated with age-related macular degeneration. Previously, we have shown that in retinal pigmented epithelial (RPE) monolayers, oxidative stress reduced complement inhibition on the cell surface, resulting in sublytic complement activation and loss of transepithelial resistance (TER), but the potential ligand and pathway involved are unknown. ARPE-19 cells were grown as monolayers on transwell plates, and sublytic complement activation was induced with H2O2 and normal human serum. TER deteriorated rapidly in H2O2-exposed monolayers upon adding normal human serum. Although the effect required AP activation, AP was not sufficient, because elimination of MASP, but not C1q, prevented TER reduction. Reconstitution experiments to unravel essential components of the lectin pathway (LP) showed that both ficolin and mannan-binding lectin can activate the LP through natural IgM antibodies (IgM-C2) that recognize phospholipid cell surface modifications on oxidatively stressed RPE cells. The same epitopes were found on human primary embryonic RPE monolayers. Likewise, mouse laser-induced choroidal neovascularization, an injury that involves LP activation, could be increased in antibody-deficient rag1(-/-) mice using the phospholipid-specific IgM-C2. In summary, using a combination of depletion and reconstitution strategies, we have shown that the LP is required to initiate the complement cascade following natural antibody recognition of neoepitopes, which is then further amplified by the AP. LP activation is triggered by IgM bound to phospholipids. Taken together, we have defined novel mechanisms of complement activation in oxidatively stressed RPE, linking molecular events involved in age-related macular degeneration, including the presence of natural antibodies and neoepitopes

Synthesis of a Novel Quinoline Derivative, 2-(2-Methylquinolin-4- ylamino)-N-phenylacetamide—A Potential Antileishmanial Agent

Some novel quinoline derivatives were prepared and tested for antileishmanial activity. 2-(2-Methylquinolin-4-ylamino)- N-phenylacetamide (2) was found to be significantly more active than the standard antileishmanial drug sodium antimony gluconate (SAG) in reducing the parasite load both in the spleen and liver at a much lower concentration in hamster models. The results suggest that the compound could be exploited as an antileishmanial drug. # 2002 Elsevier Science Ltd. All rights reserved

Retinal Pre-Conditioning by CD59a Knockout Protects against Light-Induced Photoreceptor Degeneration

<div><p>Complement dysregulation plays a key role in the pathogenesis of age-related macular degeneration (AMD), but the specific mechanisms are incompletely understood. Complement also potentiates retinal degeneration in the murine light damage model. To test the retinal function of CD59a, a complement inhibitor, CD59a knockout (KO) mice were used for light damage (LD) experiments. Retinal degeneration and function were compared in WT versus KO mice following light damage. Gene expression changes, endoplasmic reticulum (ER) stress, and glial cell activation were also compared. At baseline, the ERG responses and rhodopsin levels were lower in CD59aKO compared to wild-type (WT) mice. Following LD, the ERG responses were better preserved in CD59aKO compared to WT mice. Correspondingly, the number of photoreceptors was higher in CD59aKO retinas than WT controls after LD. Under normal light conditions, CD59aKO mice had higher levels than WT for GFAP immunostaining in Müller cells, mRNA and protein levels of two ER-stress markers, and neurotrophic factors. The reduction in photon capture, together with the neurotrophic factor upregulation, may explain the structural and functional protection against LD in the CD59aKO.</p></div

Photomicrographs of plastic sections of WT and CD59aKO retinas, and quantification of ONL nuclei.

<p>Histology of mouse retinas showing thinning of the ONL (white brackets) and IS/OS in post-LD WT retinas, while CD59aKO retinas showed less thinning of the ONL and IS/OS (A). Plot of the number of nuclei per column in the ONL. In WT retinas on both the Balb/c and C57BL/6 background, there was a significant decrease of ONL thickness across all sampled retinal regions (a-d) comparing non-light- damaged (NLD) (black line in B and C) and LD (green line in B and C). However, there was a smaller reduction of ONL thickness comparing NLD (blue line in B and C) and LD CD59aKO retinas (red line in B and C). Data are expressed as means ± SD. N = 4. *<i>P</i><0.01, and significance markings refer to overall differences between groups across all four retinal regions (a-d).</p