Sulfur in human crystallins

Molecular models of human gamma-crystallins and the 'alpha-crystallin domain' of human alphaA-crystallin have been built based on available related X-ray crystal structures. The accessibilities of the component cysteine, methionine and tryptophan side chains in the crystallin models have been calculated. The reactivities of these cysteines, which are oxidised in cataract, are assessed based on their known modifications and within the context of their location within the 3D models.     

Hypophosphatemic rickets and osteomalacia in polyostotic fibrous dysplasia

A 17 year-old girl with polyostotic fibrous dysplasia and hypophosphatemia had inappropriately low tubular reabsorption of phosphate. She had radiological evidence of rickets and osteomalacia. The patient showed clinical improvement after treatment with phosphate supplementation, active vitamin D (calcitriol) and alendronate. It is postulated that either a phosphaturic substance elaborated from the dysplastic bone or target-organ (kidney) unresponsiveness may interfere with phosphate reabsorption in the renal tubule.     

Neoral monitoring by limited sampling area under the concentration time curve in stable indian renal transplant recipients

The optimization of cyclosporine (CsA) immunosuppression remains a challenge because of the narrow therapeutic window and highly variable pharmacokinetics (PK). The highly variable PK were improved by the introduction of the current microemulsion preparation Neoral. However, the best clinical benefit of this CsA microemulsion can only be obtained by regular PK monitoring. During the past decade, various PK strategies have been proposed, such as C(0), C(2), level monitoring, abbreviated or limited sampling approach, and various prediction algorithms to replace the conventional area under the curve (AUC). In this study we evaluated the Neoral PK in stable Indian renal transplant recipients using a limited sampling approach. The C(0) (mean +/- SE) was 175 +/- 15 ng. mL(-1); C(max) 970 +/- 101 ng. mL(-1), and the AUC (0-4) 2734 +/- 258 ng. h. mL(-1). The C(0) showed a poor relationship to AUC (0-4) (r =.65) but high correlations were obtained with C(2) (r = 0.93) and C(3) (r =.96). Our finding suggest that stable Indian renal transplant recipients should either be monitored using C(2) or C(3).     

Recurrent bradycardia and delayed recovery in a neonate following repair of nasofrontal encephalocoele with holoprosencephaly and single cerebral ventricle

Holoprosencephaly and single cerebral ventricle are uncommon congenital anomalies that are associated with a high rate of perinatal mortality. We describe a neonate who developed recurrent bradycardia along with delayed recovery following frontal craniotomy for the repair of a nasofrontal encephalocoele associated with holoprosencephaly and a single cerebral ventricle. The neonate, however, recovered following elective ventilation. Etiopathogenesis and management of such complications are discussed.     

Familial keratoconus with cataract: linkage to the long arm of chromosome 15 and exclusion of candidate genes

PURPOSE: Keratoconus and cataract are common causes of visual morbidity. Both conditions show genetic predisposition. The purpose of this study was to map the disease locus in a large three-generation family affected by combined early-onset autosomal dominant anterior polar cataract and clinically severe keratoconus. Uniquely, in this family both disorders were present and fully penetrant in those affected. METHODS: Thirty members of the family were examined clinically on two occasions, at an interval of 5 years, to establish their phenotypes and determine the progression of the disease. Genomic DNA was extracted from blood samples of 16 affected and 14 unaffected individuals, and typed with more than 350 highly polymorphic microsatellite loci in a genome-wide linkage screen. Markers were amplified by PCR with fluorescently labeled primers and sized with an automated DNA analyser before calculation of lod scores. After linkage was established, several positional candidate genes were assessed by PCR-based DNA sequencing. RESULTS: The locus for keratoconus with cataract was mapped to a 6.5-Mb region of the long arm of chromosome 15, at 22.33-24.2 between CYP11A and D15S211. The positional and functional candidate genes CTSH, CRABP1, IREB2, and RASGRF1 were excluded as the cause of keratoconus with cataract in this family. CONCLUSIONS: This is the first report of a family with autosomal dominant inheritance of keratoconus in association with cataract. The causative gene maps to the long arm of chromosome 15 but has not yet been identified.     

Effect of hydrogen peroxide on amino acid concentrations in bovine retina and vitreous humor, ex vivo

In a previous study, we showed evidence that oxidative stress induced by hydrogen peroxide (H2O2) can inhibit the release of [3H]-D-aspartate from the bovine isolated retina, in vitro. The aim of the present study was to investigate the effect of H2O2 on glutamate and glycine levels in the bovine retina and vitreous humor, ex vivo. Furthermore, we examined whether inhibition of catalase activity with 3-amino-triazole had any effect on the concentrations of these amino acids in the posterior segment of the bovine eye. Whole eye organ cultures were prepared by incubating tissues in oxygenated Krebs solution at 37 masculine C for 30 min. After incubation, H2O2 (1-100 microM) or sterile distilled water was injected intravitreally into each eye. Thirty minutes after injection, the retina and vitreous humor were removed for analysis of glutamate and glycine by high performance liquid chromatography (HPLC) with fluorescence detection. Exogenously applied H2O2 (1-100 microM) caused a concentration-related decrease in both glutamate and glycine levels in the bovine retina. Furthermore, while H2O2 (1-10 microM) caused a concentration-dependent decrease in glycine levels in the vitreous humor, it had no significant effect on glutamate levels. The catalase inhibitor, 3-amino-triazole (10 mM), caused a significant reduction in both glutamate and glycine levels in the bovine retina, ex vivo. Likewise, 3-AT caused an attenuation in both glutamate and glycine concentration in the vitreous humor. We conclude that oxidative stress induced by H2O2 can alter the release and/or availability of amino acids in the posterior segment of bovine eyes.