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Biomedical subjects

G Chandrasekhar

Publications and source records attributed to G Chandrasekhar.

6 recordsLinked to original sources

Rational selection of structurally diverse natural product scaffolds with favorable ADME properties for drug discovery.

Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules.

Alkaloids↗

Applying the recent clinical trials on primary open angle glaucoma: the developing world perspective.

Recent clinical trials have provided scientific guidelines for the treatment of ocular hypertension and primary open angle glaucoma. The developing world need to apply these trials in a sensible and cost effective manner. The number needed to treat (NNT) attempts to tailor treatment to the individual patient. The NNT for the average ocular hypertensive is 20. Those with intraocular pressure > or =26 mm Hg have an NNT of 6. Restricting treatment to those with lower central corneal thickness and or high cup disc ratios can further lower NNT and make treatment more cost effective. The NNT for the average patient with early POAG is 5. Targeting those at higher risk for progression, (bilateral POAG, higher IOP and or pseudo-exfoliation) can further reduce NNT. As far as the modality of treatment is concerned, provided quality can be ensured, collaborative initial glaucoma treatment study (CIGTS) could be interpreted to justify primary surgery in the developing world context. Population attributable risk percentage (PAR), a measure that reflects the public health importance of a disease was used to extrapolate results to the overall population. Ocular hypertension has an "effective" PAR of 8.5%, a value not considered high enough to warrant public health intervention. POAG had an "effective" PAR of 16%, perhaps high enough to be considered a public health problem and justify inclusion as a target disease in the Vision 2020 program. However the logistics and opportunity costs of diagnosis and treatment would probably prevent inclusion of POAG in public health budgets of most developing countries.

Developing Countries↗

Bronchial hyperresponsiveness in patients with sarcoidosis.

OBJECTIVE: To study bronchial hyperresponsiveness (BHR) in patients with sarcoidosis. METHODS: Twenty freshly diagnosed patients with sarcoidosis were evaluated. Progressively increasing concentrations of methacholine were administered using a standard five-breath dosimeter protocol, and spirometry performed after each challenge. BHR was expressed as PC20 (provocating concentration of methacholine resulting in 20% fall in forced expiratory volume in first second). All patients were nonsmokers, had no other concurrent cardiopulmonary disease, and were not on any specific treatment for sarcoidosis. RESULTS: Borderline (PC20 4.0-16.0 mg/mL), mild (PC20 1.0-4.0 mg/mL) and moderate to severe (PC20 <1.0 mg/mL) BHR was documented in three (15%), one (5%) and five (25%) patients respectively. Patients with BHR were similar to those having normal reactivity in terms of age, gender, disease duration and results of pulmonary function testing. All patients with endobronchial disease had BHR. CONCLUSION: BHR may be seen in several patients of sarcoidosis and could possibly contribute to decline in lung function.

Adult↗

Humphrey visual field and frequency doubling perimetry in the diagnosis of early glaucoma.

PURPOSE: To compare Humphrey Visual Field Analyzer (HVF) and Frequency Doubling Perimetry (FDP) testing in the diagnosis of early glaucoma. METHODS: We performed HVF (24-2 standard full threshold) and FDP (N-30) evaluations in 34 consecutive patients with early primary glaucoma and 96 normal subjects. Early glaucoma was defined on the basis of disc changes of glaucoma; the mean deviation on white-on-white perimetry had to be no worse than 6 decibels. Glaucomatous optic neuropathy was defined as a combination of cup-disc asymmetry of more than 0.2, notching, excavation, thinning or pallor of superior or inferior neuroretinal rims, retinal nerve fibre layer defects of the wedge or diffuse type and neuroretinal rim haemorrhage. Both the glaucoma patients and normal subjects had vision better than 6/9 with correction. They had no media opacities other than early nuclear sclerosis and no fundus pathology. Further, normal subjects were free of systemic diseases known to affect the retina or optic nerve. The sensitivity and specificity of HVF and FDP were calculated. RESULTS: There were 44 eligible eyes among the 34 subjects. The glaucomatous disc findings included notch (n=8), pallor (n=21), thinning (n=23) and haemorrhage (n=1) of the neuroretinal rim. The sensitivity and the specificity of the HVF were 52.3% and 57.3% respectively. The sensitivity and the specificity of FDP were 65.9% and 61.5% respectively. CONCLUSION: The difference between FDP and HVF in the diagnosis of early glaucoma is not marked.

Adult↗

The role of artificial drainage devices in glaucoma surgery.

The use of artificial drainage devices (ADDs) or "setons" in glaucoma surgery is generally restricted to patients with refractory glaucoma at high risk for failure from conventional filtration surgery. ADDs, both valved and nonvalved are currently available in this country. Recently, some of these devices have been propogated as primary treatment even for primary glaucomas. This article examines the role of ADDs in the modern management of the glaucomas. Specific indications for ADDs and methods to reduce the complication of overfiltration are discussed. The use of antimitotics, such as 5-fluorouracil or mitomycin, with traditional filtration has decreased the indications for ADDs. The literature and our experience confirm that currently there is no role for use of ADDs as a primary procedure in most glaucomas.

Animals↗

Ultrasonic evaluation of retinoblastoma.

Seventeen children presenting with leucocoria were subjected to complete investigations. Careful A and B mode ultrasonography allowed us to make the correct diagnosis of retinoblastoma in 11 eyes of 9 patients, which was confirmed by histopathology or by response to radiotherapy. The diagnosis of retinoblastoma was not missed ultrasonographically in any of the eyes studied. The "V/W" configuration and absence of vascular pulsations on A mode; the "mixed" pattern and absence of choroidal excavation and orbital shadowing on B mode were found to be essential echographic features in characterizing the tumor and in differentiating it from other conditions including vitreous hemorrhage. The ultrasonographic features of early extraocular extension of retinoblastoma are discussed. Careful ultrasonic evaluation of leucocoria would seem to be invaluable in obviating the possibility of misdiagnosis in such problematic cases.

Child, Preschool↗