G. Prasanna

The Role of Glia, Mitochondria, and the Immune System in Glaucoma

Author(s): Tezel, Gulgun; Fourth ARVO/Pfizer Ophthalmics Research Institute Conference Working Group

A dual acting compound with latanoprost amide and nitric oxide releasing properties, shows ocular hypotensive effects in rabbits and dogs

The IOP lowering effects of NCX 139, a new chemical entity comprising latanoprost amide and a NO-donating moiety, were compared to those of the respective des-nitro analog in in vitro assays and in rabbit and dog models of ocular hypertension. The NO donor, molsidomine as well as the prostamide bimatoprost (Lumigan(®)) and the prostaglandin agonist, latanoprost (Xalatan(®)) were also investigated for comparison. NCX 139 but not its des-nitro analog resulted in NO-mediated vascular relaxant effect in pre-contracted rabbit aortic rings (EC(50)=0.70±0.06 μM; E(max)=80.6±2.9%). Like bimatoprost (IC(50)=3.07±1.3 μM) or latanoprost (IC(50)=0.48±0.15 μM), NCX 139 displaced (3)H-PGF2α binding on recombinant human prostaglandin-F (FP) receptors with an estimated potency of 0.77±0.13 μM. In transient ocular hypertensive rabbits, bimatoprost and latanoprost were not effective while molsidomine elicited a dose-dependent reduction of IOP confirming the responsiveness of rabbits to NO but not to FP receptor agonists. NCX 139 tested at a therapeutically relevant dose, significantly lowered IOP while the des-nitro analog was not effective (0.03% NCX 139, Δ(max)=-12.8±2.0 mmHg). In glaucomatous dogs, 0.03% NCX 139 decreased IOP to a greater extent compared to an equimolar dose of the respective des-nitro derivative (Δ(max)=-4.6±1.0 and -2.7±1.3 mmHg, respectively for NCX 139 and its des-nitro analog). Albeit with low potency, NCX 139 also resulted effective in normotensive dogs while it did not reduce IOP in normotensive rabbits. NCX 139, a compound targeting two different and important mechanisms, is endowed with ocular hypotensive effects more evident in hypertensive conditions which may be of interest in the search of more effective treatments for hypertensive glaucoma.

CDC Kerala 9: Effectiveness of Low Intensity Home Based Early Intervention for Autism Spectrum Disorder in India

ObjectiveTo validate effectiveness of low intensity, home based early intervention (EI) models in autism for countries with low disability resources.MethodsFifty-two toddlers and young children were assessed before and after intervention with Childhood Autism Rating Scale, Vineland Social Maturity Scale, and Receptive-Expressive Emergent Language Scale. Developmental and speech therapists helped mothers assemble low-cost training kits based on the developmental age of the child, gave initial training in the basic behavioral technique to address the three autism symptom clusters at home. Follow-up support was given either on a weekly, fortnightly or monthly basis. Most of the children were also placed in play-schools. Data was analyzed using appropriate bivariate and multivariate techniques.ResultsThere was statistical and clinical amelioration in the severity of autism, with acquisition of social skills and language skills (all P = 0.001) after intervention in children with mild to severe autism. Gender showed a trend in becoming a significant predictor for intervention response.ConclusionsLow-intensity, home-based EI can be effectively used in situations where there is paucity of disability resources in countries like India, especially in primary-care and community settings.

CDC Kerala 10: Diagnostic Accuracy of the Severity Scores for Childhood Autism Rating Scale in India

ObjectiveTo document the diagnostic accuracy of the Childhood Autism Scale (CARS) thresholds to identify mild, moderate and severe autism in India.MethodsThe CARS scores of 623 children, with and without autism were compared against the Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV-TR) for ASD diagnosis and clinical consensus between two developmental paediatricians as the reference standard for autism severity using the Receiver operating characteristics (ROC) curve analyses and contingency tables.ResultsThe CARS total score for mild, moderate and severe autism ranged from 30.5 to 35, 35.5–40 and ≥40.5 respectively in this study. The overall diagnostic accuracy of CARS total score in the mild range was moderate [AUC = 0.68 (95%CI = 0.62–0.88), z = 1.34; P = 0.18], moderate range was high [AUC = 0.90 (95%CI = 0.77–0.97), z = 8.62; P = 0.0001] and severe range was also high [AUC = 0.85 (95%CI = 0.77–0.90), z = 7.09; P = 0.0001].ConclusionsThere are validated severity scores for Childhood Autism Rating Scale for clinical and research use in India.