URINARY MARKERS OF OXIDATIVE DNA DAMAGE IN TYPE 1 DIABETIC CHILDREN: RELATION TO MICROVASCULAR COMPLICATIONS

  Objective: Type 1 diabetes mellitus (T1DM) is a widespread metabolic disease, which frequently carries with it a significant impact on human health. Oxidative damage and tissue inflammation have been claimed to be a typical pathogenic component for the progression of diabetic complications. We aim in this study to explore the relation of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) (as a marker of nucleic acid oxidation) to microvascular complications in T1DM.Methods: A case–control study, enrolling 45 T1DM children and an equivalent number of healthy subjects, was performed. Full clinical examination and anthropometric measurement were performed to all subjects. Urinary assessment for 8-oxodG and albumin was done in addition to blood sampling for lipid profile and glycated Hb (HbA1c) assay. Complete ocular examination for assessment of diabetic retinopathy (DR) was also done.Results: Levels of urinary 8-oxodG, serum cholesterol, triglycerides, and low-density lipoprotein in cases were significantly higher than non-diabetics; these levels were likewise higher in uncontrolled T1DM patients in comparison with well-controlled T1DM subjects. Urinary 8-oxodG and HbA1c were significantly higher in diabetic patients with albuminuria and DR compared to patients without complications. Significant positive correlation was found between 8-oxodG with HbA1c (r=0.8, p<0.01), diastolic blood pressure (DBP) (r=0.4, p=0.02), and cholesterol (r=0.4, p=0.05).Conclusion: Urinary 8-oxodG was found to be a reliable marker for assessing oxidative DNA damage in T1DM and can be used in the determination of microvascular complications related to diabetes

Catching the therapeutic window of opportunity in early initial-onset Vogt�Koyanagi�Harada uveitis can cure the disease

Purpose: Vogt�Koyanagi�Harada (VKH) disease is a primary autoimmune granulomatous choroiditis that begins in the choroidal stroma. The aim of this review was to gather a body of evidence for the concept of a window of therapeutic opportunity, defined as a time interval following initial-onset disease during which adequate treatment will substantially modify the disease outcome and possibly even lead to cure, similar to what has been described for rheumatoid arthritis. Methods: We reviewed the literature and consulted leading experts in VKH disease to determine the consensus for the notion of a therapeutic window of opportunity in VKH disease. Results: We found a substantial body of evidence in the literature that a therapeutic window of opportunity exists for initial-onset acute uveitis associated with VKH disease. The disease outcome can be substantially improved if dual systemic steroidal and non-steroidal immunosuppressants are given within 2�3 weeks of the onset of initial VKH disease, avoiding evolution to chronic disease and development of �sunset glow fundus.� Several studies additionally report series in which the disease could be cured, using such an approach. Conclusions: There is substantial evidence for a therapeutic window of opportunity in initial-onset acute VKH disease. Timely and adequate treatment led to substantial improvement of disease outcome and prevented chronic evolution and �sunset glow fundus,� and very early treatment led to the cure after discontinuation of therapy in several series, likely due to the fact that the choroid is the sole origin of inflammation in VKH disease. © 2018 The Author(s

Stromal Cell-Derived Factor 1 Polymorphism in Retinal Vein Occlusion

BACKGROUND: Stromal cell-derived factor 1 (SDF1) has crucial role in the regulation of angiogenesis and ocular neovascularisation (NV). The purpose of this study was to evaluate the association between SDF1-3'G(801)A polymorphism and NV complications of retinal vein occlusion (RVO). METHODS: 130 patients with RVO (median age: 69.0, range 35-93 years; male/female- 58/72; 55 patients had central RVO, 75 patients had branch RVO) were enrolled in this study. In the RVO group, 40 (30.8%) patients were diagnosed with NV complications of RVO and 90 (69.2%) patients without NVs. The median follow up period was 40.3 months (range: 18-57 months). The SDF1-3'G(801)A polymorphism was detected by PCR-RFLP. Allelic prevalence was related to reference values obtained in the control group consisted of 125 randomly selected, age and gender matched, unrelated volunteers (median age: 68.0, range 36-95 years; male/female- 53/72). Statistical analysis of the allele and genotype differences between groups (RVO patients vs controls; RVO patients with NV vs RVO patients without NV) was determined by chi-squared test. P value of <0.05 was considered statistically significant. RESULTS: Hardy-Weinberg criteria was fulfilled in all groups. The SDF1-3'G(801)A allele and genotype frequencies of RVO patients were similar to controls (SDF1-3'A allele: 22.3% vs 20.8%; SDF1-3'(801)AA: 5.4% vs 4.8%, SDF1-3'(801)GG: 60.8% vs 63.2%). The frequency of SDF1-3'(801)AA and SDF1-3'(801)GA genotypes, as well as the SDF1-3'(801)A allele frequency were higher in RVO patients with NV versus in patients without NV complication (SDF1-3'(801)AA+AG genotypes: 57.5% vs 31.1%, p = 0.008; SDF1-3'(801)A allele: 35.0% vs 16.7%, p = 0.002) or versus controls (SDF1-3'(801)AA+AG genotypes 57.5% vs 36.8%, p = 0.021; SDF1-3'(801)A allele: 35.0% vs 20.8% p = 0.01). Carrying of SDF1-3'(801)A allele increased the risk of neovascularisation complications of RVO by 2.69 (OR, 95% CI = 1.47-4.93). CONCLUSION: These findings suggest that carrying SDF1-3'(801)A allele plays a role in the development of neovascular complications in retinal vein occlusion

The Development of an Age-Structured Model for Trachoma Transmission Dynamics, Pathogenesis and Control

Trachoma is the worldwide leading infectious cause of blindness and is due to repeated conjunctival infection with Chlamydia trachomatis bacteria. The effects of control interventions on population levels of infection and active disease can be promptly measured, but the effects on severe ocular disease outcomes require long-term monitoring. We present a mathematical model of trachoma transmission and disease to predict the impact of interventions on blinding trachoma. The model is based on the concept of multiple re-infections leading to progressive scarring of the eye and the potentially blinding disease sequelae. It includes aspects of trachoma natural history such as an increasing rate of recovery from infection, and a decreasing chlamydial load with subsequent infections. The model reproduces key features of trachoma epidemiology such as the age-profile of infection prevalence; a shift in the prevalence peak toward younger ages in higher-transmission environments; and a rising profile of the prevalence of the severe sequelae (scarring, trichiasis), as well as estimates of the number of infections experienced before these sequelae appear. The model can be used to examine the outcomes of various control strategies on infection and disease and can help to plan treatment interventions for different endemic settings

Ocular Application of the Kinin B1 Receptor Antagonist LF22-0542 Inhibits Retinal Inflammation and Oxidative Stress in Streptozotocin-Diabetic Rats

Purpose: Kinin B1 receptor (B1R) is upregulated in retina of Streptozotocin (STZ)-diabetic rats and contributes to vasodilation of retinal microvessels and breakdown of the blood-retinal barrier. Systemic treatment with B 1R antagonists reversed the increased retinal plasma extravasation in STZ rats. The present study aims at determining whether ocular application of a water soluble B1R antagonist could reverse diabetes-induced retinal inflammation and oxidative stress. Methods: Wistar rats were made diabetic with STZ (65 mg/kg, i.p.) and 7 days later, they received one eye drop application of LF22-0542 (1 % in saline) twice a day for a 7 day-period. The impact was determined on retinal vascular permeability (Evans blue exudation), leukostasis (leukocyte infiltration using Fluorescein-isothiocyanate (FITC)-coupled Concanavalin A lectin), retinal mRNA levels (by qRT-PCR) of inflammatory (B1R, iNOS, COX-2, ICAM-1, VEGF-A, VEGF receptor type 2, IL-1b and HIF-1a) and anti-inflammatory (B2R, eNOS) markers and retinal level of superoxide anion (dihydroethidium staining). Results: Retinal plasma extravasation, leukostasis and mRNA levels of B 1R, iNOS, COX-2, VEGF receptor type 2, IL-1b and HIF-1a were significantly increased in diabetic retinae compared to control rats. All these abnormalities were reversed to control values in diabetic rats treated with LF22-0542. B1R antagonist also significantly inhibited the increased production of superoxide anion in diabetic retinae. Conclusion: B1R displays a pathological role in the early stage of diabetes by increasing oxidative stress and proinflammator