A novel protein C inhibitor gene mutation in pediatric stroke patients after bone marrow transplantation.

Protein C inhibitor is a heparin dependent serine protease inhibitor found in human plasma, urine and other body fluids. It was originally identified as an inhibitor of activated protein C. Stroke is an important cause of morbidity and mortality in the pediatric age group. In this study we analyzed the protein C inhibitor gene mutations in Turkish pediatric stroke patients. We found a missense mutation of G to A at nucleotide 6760 in exon 2, resulting in a transition serine to asparagine (p.Ser188Asp) and in a child and his father and also we found same alteration in exon 2 in an another pediatric stroke case following bone marrow transplantation.

Two new mutations at ERGIC-53 gene in a Turkish family.

Combined factor V and factor VIII deficiency (F5F8D) is a rare autosomal recessive coagulation disorder associated with plasma levels of coagulation factors V and VIII approximately 5% to 30% normal. Combined factor V and factor VIII deficiency is caused by mutations in ERGIC-53 (LMAN1) gene. ERGIC-53 and multiple coagulation factor deficiency 2 (MCFD2) form a protein complex that functions as a cargo receptor transport FV and FVIII from the endoplasmic reticulum to the Golgi. The aim of this study was to determine the mutations of ERGIC-53 (endoplasmic reticulum [ER] to the ER-Golgi intermediate compartment) gene and combined F5F8D in a family. In this study, we analyzed a patient in a Turkish family with combined F5F8D. We found a nonsense mutation of C to T at nucleotide 202 in exon 9, resulting in a transition of arginine to stop codon, and in 1 child, we found a timine deletion in exon 4 in ERGIC-53 gene.

The effects of Ankaferd® Blood Stopper on transcription factors in HUVEC and the erythrocyte protein profile.

OBJECTIVE: Ankaferd® Blood Stopper (ABS) is an herbal extract that has historically been used as a hemostatic agent in traditional Turkish medicine. ABS is comprised of a standardized herbal mixture of T. vulgaris, G. glabra, V. vinifera, A. officinarum, and U. dioica. ABS's basic mechanism of action is the formation of an encapsulated protein web, which represents the focal point for vital erythrocyte masses. The hemostatic effects of ABS have been observed in vitro and in vivo. ABS was registered as a hemostatic agent for external hemorrhages and dental bleeding following phase I randomized, double-blind crossover placebo-controlled clinical research, and safety and efficacy reports. In terms of the potential use of ABS, transcription factors may be novel factors that play a role in the hemostatic and other pleiotropic effects of ABS. METHODS: Hence, the present study aimed to investigate the effects of ABS on endothelium, and possible transcription factor changes in HUVEC (human umbilical vein endothelial cells) and the erythrocyte membrane profile. ABS (5 µL and 50 µL) was administered to HUVEC (in 75 cm2; ~75% fullness) for 5 min and 15 min. RESULTS: ABS caused significant increases in the level of activation of the following transcription factors; AP2, AR, CRE/ATF1, CREB, E2F1-5, E2F6, EGR, GATA, HNF-1, ISRE, Myc-Max, NF-1, NFkB, p53, PPAR, SMAD 2/3, SP1, TRE/AP1, and YY1. Following erythrocyte membrane isolation, protein complexes were undissolved, but denatured. The protein complex formed was resistant to heat and detergent. Trypsin and sonication were used in order to break this complex; the complex dissolved and erythrocyte membrane proteins were released in SDS-PAGE. CONCLUSION: ABS established a very fast and solid protein web, and increased the level of transcription factor activation. Therefore the cellular effects of ABS could be related to different intracellular biological pathways.

Association of methylenetetrahydrofolate reductase C677T and cystathionine ß-synthase polymorphisms in cardiovascular disease in the algerian population.

AIM: Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and cystathionine ß-synthase (CBS) genes, involved in the intracellular metabolism of homcysteine, can result in hyperhomocysteinemia. The objective of this study was to evaluate prevalence estimates of MTHFR C677T and the CBS insertion of 68-bp (844ins68) polymorphisms among individuals with cardiovascular disease (CVD). METHODS: In total, 131 patients (61 men and 70 women) were hospitalized in the Cardiology Department in CHU of Sétif, Algeria. The control group included 147 apparently healthy adults (82 women and 65 men). The genetic analysis of the MTHFR C677T polymorphism was performed by real-time polymerase chain reaction on a Light Cycler; the CBS genotype was analyzed by polymerase chain reaction in a thermal cycler. RESULTS: The frequency of the TT genotype was 16.1% in the patient group and 14.3% in the control group. The CT genotype constituted 43.5% and 40.1% in the patient group and the control group, respectively. There was no significant difference in the occurrence of the TT genotype between the studied groups. The frequency of C677T/MTHFR in male and female patients was 16.4% and 15.7% for the TT genotype, respectively. There was no significant difference in T allele frequencies between sexes. However, the frequency of C677T homozygotes in the patients was higher in men with CVD than that in corresponding control subjects (40.2% vs. 29.2%), but the difference was not statistically significant. The coexistence of the MTHFR 677TT genotype and the common CBS 844ins68 variant was lower among patients. CONCLUSIONS: The MTHFR C677T and CBS 844ins68 variants tested in this study, individually or combined, are not associated with CVD in the Algerian population.