Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and plasma concentrations of asymmetric dimethylarginine in Turkish pre-eclamptic women without fetal growth retardation.

AIMS: Pre-eclampsia (PE) is a leading cause of maternal death worldwide, affecting 3 to 5% of all pregnancies. We analyzed the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and asymmetric dimethylarginine (ADMA) in 55 Turkish patients with PE without fetal growth retardation (FGR) and in 54 healthy pregnant women. METHODS: Restriction fragment length polymorphism analysis of Glu298Asp of the endothelial nitric oxide synthase gene was evaluated by amplification of genomic DNA isolated from whole blood followed by digestion with the restriction enzyme Frio. PE was defined according to the Working Group(2000) criteria as high blood pressure (>or=140/90 mmHg after 20 weeks of gestation) and proteinuria (>300 mg/24 h). We excluded the women with FGR Serum arginine, with only ADMA and symmetric dimethylarginine (SDMA) levels measured by high-performance liquid chromatography. RESULTS: Genotypes were defined as GG, GT and TT according to the presence of the G and T alleles. In this case-control study, we did not find any significant difference in either the genotypic distribution or allelic frequency of Glu298Asp gene polymorphism between the pre-eclamptic patients and healthy pregnant women. Serum ADMA, arginine and SDMA levels were higher in patients with PE compared with healthy pregnant women (respectively, P < 0.0001, P < 0.0001, P < 0.0001). CONCLUSIONS: The results suggested a lack of association between the Glu298Asp gene polymorphism and pre-eclampsia without FGR in the Turkish population. But elevated ADMA and SDMA levels suggest that ADMA has a role in the pathogenesis of PE.

eNOS Glu298Asp Polymorphism and Endothelial Dysfunction in Patients with and without End-stage Renal Disease.

BACKGROUND: Chronic kidney diseases are known to influence nitric oxide metabolites (NOx) and asymmetric dimethylarginine (ADMA), though the exact mechanism is still poorly understood. AIMS: The purpose of the present study was to examine eNOS Glu298Asp gene polymorphism, plasma NOx and ADMA concentration in subjects with and without End-stage Renal Disease. STUDY DESIGN: Case-control study. METHODS: In this study, genotype distributions of Glu-298Asp in exon 7 of the eNOS gene polymorphisms in 130 hemodialysis and 64 peritoneal dialysis patients were compared with 92 controls. NOx was measured by using the Griess reaction while arginine, ADMA and SDMA measurements were performed by HPLC. Genotyping for eNOS Glu298Asp polymorphism was detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: When the genotype frequencies of TT and GT genes were compared between both groups, there was no detected statistically important difference, even-though a TT genotype frequency was 27 (20.8%) versus 17 (26.6%), GT heterozygote genotype frequency was 52 (40%) versus 22 (34.4%), and GG homozygote genotype frequency was 51 (39.2%) versus 25 (39.1%), respectively (p>0.05). NOx, SDMA and ADMA concentrations were significantly elevated in subjects with hemodialysis patients as compared to their corresponding controls. Whereas nitrite was found to be significantly decreased in the patient with peritoneal dialysis. CONCLUSION: Not observed any connection between the Glu298Asp polymorphism in the eNOS gene and end-stage Renal Diseases in our study population under different dialysis treatments. However, higher ADMA and SDMA concentrations in subjects with ESRD support the existing hypothesis that NOx overproduction affects endothelial dysfunction. Thus, the reduction of ADMA and SDMA concentrations might play a protective role in ESRD patients.

The impact of octreotide in experimental proliferative vitreoretinopathy.

AIMS: This study aims to investigate the effects of intravitreal octreotide on the growth factors, which have significant roles in the pathogenesis of proliferative vitreoretinopathy (PVR). SETTINGS AND DESIGN: An experimental trial. MATERIALS AND METHODS: 21 guinea pigs were randomly assigned to form 3 groups each including 7 animals. In group 1 (the control group), 0.2 ml saline solution was applied intravitreally in a location of 1.5 mm behind the limbus. In group 2 (the sham group), 0.07 IU dispase in 0.1 ml and 0.1 ml saline solution were applied via the same route. The guinea pigs in group 3 (the treatment group) were applied 0.07 IU dispase in 0.1 ml and 1 mg octreotide in 0.1 ml via the same route. Octreotide injection was applied twice during the period of 10 weeks of the experiment. At the end of the 10 weeks, eyes were enucleated and retinal homogenates were prepared. The platelet derivated growth factor (PDGF), insulin-like growth factor (IGF 1) and transforming growth factor (TGF ß) levels in homogenized retina tissue were measured by Enzyme Linked-Immuno-Sorbent Assay (ELISA) method. STATISTICAL ANALYSIS USED: Kruskal-Wallis variance analysis and Mann-Whitney U test. RESULTS: In the treatment group, a significant decrease was observed in retinal PDGF levels (P < 0.01) while decreases in TGF ß and IGF 1 levels were not found to be significant (P > 0.05). CONCLUSIONS: Intravitreally applied octreotide at a dose of 1 mg has a highly strong effect on PDGF. This study suggests that intravitreal octreotide may suppress PVR development and that octreotide may merit investigation for PVR prophylaxis.