Implication of glutathione S-transferase M1 and T1 polymorphisms in the development of senile cataract among Egyptians

Cataract, or opacification of the lens, is one of the most common causes of loss of useful vision among Egyptians. Currently, surgery is the only approach for the treatment of cataract and the etiology of age-related changes in the lens is not fully understood. Oxidative damage and genetic factors have a major role in the development of age related cataract. Glutathione is the most abundant non-protein intracellular thiol, with multiple roles as antioxidant agent, and the glutathione S-transferases [GSTs] are group of polymorphic enzymes that are important in protection against oxidative damage, as they dethiolate protein-S-S-glutathione in the human lens. The study aimed to determine the effect of genetic polyorphisms of Glutathione S-transferases M1 and T1 on the risk of senile cataract in Egyptian population. Using a multiplex polymerase chain reaction [PCR], the GSTM1 and GSTT1 gene polymorphisms were evaluated in 53 Egyptian patients with senile cataract and in 73 otherwise healthy control group with matched age and sex distribution. Serum GST activity, the level of Malondiableyde [a lipid peroxidation product] and the blood level of reduced glutathione [GSH] were estimated. The frequency of the GSTM1 positive individuals among the senile cataract group was significantly higher than in controls [57 vs 37%] with odds ratio 2.22 95% CI:1.08-4.573; p=0.029]. The risk among the GSTM1 positive individuals of developing senile caaract was even higher in female subjects: 68% of females were GSTM1 positive in the cataract group while only 38% of females had GSTM1 positive genotype in controls [OR=3.4; 95% CI: 1.284-9.067; p=0.012]. combination of "GSTM1 positive and GSTT1 positive" genotypes [OR = 2.16; 95% CI: 0998-4.68; P=0.049]. However the combination of "GSTM1 null, GSTT1 positive" was found to be protective from the development of senile cataract [OR=0.47; 95% CI: 0.22-0.99; p=0.045]. The study also showed significantly deceased serum level of GST and reduced glutathione [GSH] and increased level of malondialdehyde [MDA] in senile cataract patients relative to controls [p>0.001]. The present study suggests that the GSTM1 positive genotype and the combined "GSTM1 positive/GSTT1 positive" genotype may be associated with increased risk of development of senile cataract. However the "GSTM1 null/GSTT1 positive" genotype was found to be protective from the development of cataract in the Egyptian population. The correlation between polymorphic GSTs with the other cataractogenic genetic and environmental factors is highly complicated so, the study also, suggests that when evaluating the role of a particular GST gene in any disease susceptibility, the whole pattern of different biotransformation enzymes should be taken into account as much as possible. The importance to further evaluate this matter is related to the possibility of developing diagnostic tool for predicting, by non-invasive genotype analysis, the inter-individual susceptibility to the disease

Role of lipid peroxidation and protein glycation in non diabetic pediatric nephrotic syndrome

In recent years, it has been proposed that nephrotic syndrome is a consequence of oxidative damage. Oxygen free radicals [OFRs] can bring about severe metabolic dysfunctions, including peroxidation of membrane lipids. Lipid peroxidation has also been reported to promote the process of protein glycation. This study was performed to evaluate the role of lipid peroxidation presented by serum Malondialdahydefructos [MDA] on protein glycation presented by level of fructosamine and the role of hypercholesterolemia in pathogenesis of nephrotic syndrome. Fifteen children with nephrotic syndrome during relapse and 12 age and sex matched healthy controls were enrolled for this study. Serum MDA, fructosamine, fasting glucose and serum cholesterol were analyzed in both groups. Serum MDA and fructosamine levels were found to be increased in nephrotic syndrome patients when compared with controls. Correlation analysis showed a significant positive correlation between fructosamine and MDA, as well as between serum cholesterol and MDA. Also a positive correlation was detected between both MDA and cholesterol with proteinuria in nephrotic syndrome patients. Present data point to a possible involvement of MDA in the glycation of proteins in non-diabetic nephrotic syndrome patients, and provide support for the potential use of an antioxidant therapy in these patients

Combination of a cyclooxygenase inhibitor and a nitric oxide synthase inhibitor in the treatment of experimental uveitis

Multiple factors and mediators interact to modulate the inflammatory process. In the present study, roles of nitric oxide [NO] and prostagl and in E[2] [PGE[2]] together with their simultaneous inhibition are investigated in a model of induced anterior uveitis in rabbits. Six groups of animals served as controls. Anterior uveitis was induced in 4 groups by intravitreal injection of 10 micro l complete Freund's adjuvant. One group was left untreated and the other three groups were treated three times daily for 14 days with N[G]-nitro-L-arginine methyl ester [L-NAME] 0.1% eye drops or with diclofenac 0.1% eye drops or with both drugs. Severity of uveitis was evaluated by clinical scoring at days 2, 7 and 14. On day 14, biochemical analysis of aqueous humor samples was performed for total proteins, albumin, nitrite and PGE[2]- Histopathological examination for iris and ciliary body was also done. Induction of uveitis caused elevation of clinical scores, elevation of the biochemically analyzed parameters and severe inflammatory signs by pathological examination. On day 14, both individual drugs and combination treatment produced significant decrease in intensity of uveitis compared to untreated animal model by all methods of evaluation. Combination treatment produced more reduction in clinical scores, more reduction in levels of total proteins, albumin and PGE[2] and also better histopathological picture compared to individual drug treatment. It can be concluded that both NO and PGE[2] are involved in the pathogenesis of Freund's adjuvant induced uveitis. Inhibition of production of both of them can improve the management of uveitis

Taurine level and field changes in different hereditary types of retinitis pigmentosa

This study was performed to detect if there is a correlation between various hereditary subtypes, taurine level and field indices. This correlation may help in the accurate diagnosis and management of different hereditary subtypes of retinitis pigmentosa cases. The study included 28 patients with retinitis pigmentosa [16 males and 12 females] and 25 controls with matched age and sex distribution. All patients and controls were subjected to clinical evaluation that included personal and family history taking, informative pedigree construction and full clinical examination to exclude the associated genetic syndromes. Field changes were detected in both eyes of 22 RP patients using Humphrey field analyzer 640 utilizing the 24-2 program. All patients and ten of the controls were examined for plasma taurine level by amino acid analyzer [Lc 3000 Eppendorf Biotronik]. A statistical analysis was done using statistical package for social science [SPSS] program. The results showed that taurine level can help in the diagnosis of different hereditary subtypes of retinitis pigmentosa, especially simplex cases that has no definite inheritance. This will improve the genetic counseling for RP families. Taurine can also be considered as a marker for the degree of severity of visual field affection in retinitis pigmentosa cases