Significance of vitronectin and PAI-1 activity levels in carotid artery disease: comparison of symptomatic and asymptomatic patients.

AIM: Carotid atherosclerosis one of the main risk factors for ischemic stroke. Acute thrombosis after atherosclerotic plaque disruption is a major complication of primary atherosclerosis, leading to acute ischemic syndromes and atherosclerotic progression. PAI-1 is the most important and most rapidly acting physiological inhibitor of tissue-type (t-PA) and urokinase type (u-PA) plasminogen activators. Active PAI-1 form spontaneously converts to the latent with a half-life of ~1 h. Complex formation with vitronectin increases half life of PAI-1 by two- to four-folds. Thus, this inhibitor function of PAI-1 facilitated by Vn that binds the inhibitor and may regulate its activity by the stabilizing the active PAI-1 conformation. In addition, PAI-1/VN complexes may effect vascular structure and function. However, the exact role of these complexes in vascular remodelling are not completely clear. The aim of the present study was determining, correlating and comparing the plasma vitronectin, t-PA and PAI-1 activity levels in asymptomatic and symptomatic patients with carotid artery plaque. METHODS: A total of 37 carotid artery disease patients were included in this study. Blood samples were obtained from Cerrahpasa Medical School, Department of Heart and Vessel Surgery, University of Istanbul. Plasma vitronectin, tPA and PAI-1 activity levels were determined by ELISA. RESULTS: We found plasma PAI-1 activity levels were elevated in the asymptomatic group as compared with symptomatic group (P=0.038). We have also found a positive correlation between PAI-1 activity and vitronectin levels in symptomatic group (r=0.399, P=0.039). CONCLUSION: Decreased PAI-1 activity levels correlate with vitronectin in the symptomatic group; a) may be the consequence a compensatory mechanisms (due to possibilty in increased fibrinolytic activity and decreased vascular remodelling) against disease progression. b) or may be also cause progression of disease by increase of vascular remodelling.

The importance of circulating levels of salusin-α, salusin-ß, and heregulin-ß1 in atherosclerotic coronary arterial disease.

OBJECTIVE: The relationship between the severity of atherosclerotic coronary artery disease (CAD) and circulating levels of salusin-α, salusin-ß and heregulin-ß1 has been investigated. In addition, the relationship with these peptides and high sensitive C-reactive protein (hsCRP) has been investigated. METHODS: The study was conducted on 55 volunteers who had normal coronary angiography (CAG) as the control group, 35 volunteers with the degree of coronary artery stenosis below 50% in CA as the non-critical stenosis group, 37 volunteers with narrowing of one coronary artery above 50% as single vessel group and 41 volunteers with narrowing of more than one coronary artery above 50% as multi-vessel group. One hundred and thirteen volunteers have been included to CAD group. RESULTS: There was no statistically significant difference in serum salusin-α levels between groups. Serum salusin-ß ve hsCRP levels were significantly lower in control group compared to other groups and CAD group. There was no statistically significant difference in salusin-ß and salusin-α levels in reciprocal comparison of other groups other than heregulin-ß1 levels. Heregulin-ß1 levels were significantly lower in 'non-critical occlusion' and 'multiple artery occlusion' groups compared to control group. Heregulin-ß1 levels in 'single artery occlusion' group were significantly higher than control, 'non-critical occlusion' and 'multiple artery occlusion' groups. CONCLUSION: Salusin-α levels does not indicate any significant differences between any groups in our study however the relationship of salusin-α with salusin- ß and heregulin-ß1 levels drives to cogitate that these peptides can be used as biomarkers and therapeutic approaches in CAD. We think that these peptides will be used in laboratories routinely in future in addition to hsCRP for CAD.

Relationship between DNA damage and total antioxidant capacity in patients with glioblastoma multiforme.

AIMS: To assess oxidative DNA damage and total antioxidant capacity (TAC) in glioblastoma multiforme (GBM) and to compare the results with normal brain tissues. MATERIALS AND METHODS: Oxidative DNA damage and TAC were evaluated in GBM tissues extracted from 26 patients and in normal brain tissues of 15 subjects who underwent autopsy within the first 4h of death. Oxidative DNA damage was assessed by measuring 8-hydroxy-2-deoxyguanosine (8-OH-dG) using the 8-OH-dG enzyme immunoassay kit, a quantitative assay for 8-OH-dG, and TAC was analysed using the ImAnOx colorimetric test system for the determination of antioxidative capacity. The results were compared between two groups and any correlation between 8-OH-dG and TAC was sought. RESULTS: The median level of TAC in GBM (121.5 nmol/g wet tissue) was remarkably lower than that in normal brain tissue (298 nmol/g wet tissue). The difference was statistically significant (P=0.00001). In contrast, oxidative DNA damage was significantly higher in patients with GBM (74.9 ng/g wet tissue) than in controls (34.71 ng/g wet tissue). Again, the difference was statistically significant (P=0.00001). We also found a negative correlation between oxidative DNA damage and TAC (P<0.001). CONCLUSIONS: These findings indicate that the degree of oxidative DNA damage is increased and TAC is decreased in GBM. Oxidative DNA damage is correlated with the levels of TAC.

Icodextrin and Seprafilm do not interfere with colonic anastomosis in rats.

BACKGROUND: Physical barriers and instilled solutions have been studied to prevent intra-abdominal adhesions. However, undesirable side effects of these substances on the healing of intestinal anastomoses may limit their use. This study was designed to compare the effects of antiadhesives on the healing of colonic anastomosis in rats. METHODS: Sixty female Sprague-Dawley rats were divided into 3 groups of 20. The animals received isotonic saline and 7.5% icodextrin, intraperitoneally after standard left colonic anastomosis. In group 3, Seprafilm was wrapped around the anastomosis and also laid over the abdominal viscera. Half of the animals from each group were killed on postoperative day (POD) 4 and the remaining half on POD 21. Adhesion scoring, bursting pressure and tissue hydroxyproline measurements and histopathological assessment were performed. RESULTS: Mean hydroxyproline levels were significantly higher in groups receiving icodextrin and Seprafilm compared with the control group, whereas mean bursting pressures were significantly higher in the group that received icodextrin (p < 0.05). Intraperitoneal administration of icodextrin resulted in significant reduction of adhesion formation on POD 21 (p < 0.05). CONCLUSIONS: Seprafilm does not prevent formation of adhesions as much as icodextrin does, but its effect on the healing of colonic anastomoses is similar.

Relation between Endothelial Nitric Oxide Synthase Genotypes and Oxidative Stress Markers in Larynx Cancer.

Nitric oxide synthase (eNOS/NOS3) is responsible for the endothelial synthesis of nitric oxide (NO(•)). G894T polymorphism leads to the amino acid substitution from Glu298Asp that causes lower NOS3 activity and basal NO(•) production in NOS3 894T (298Asp) allele carriers compared with the GG homozygotes. NO(•) acts as an antioxidant protecting against Fenton's reaction which generates highly reactive hydroxyl radicals. Allelic variation of NOS3 may influence an individual's risk of laryngeal cancer (LC). In the current study we have examined the possible relationship between NOS3 G894T genotypes and various systemic oxidative damage markers such as protein carbonyl, advanced oxidation protein products, Cu, Zn-superoxide dismutase, thiol group fractions, and lipid hydroperoxides in LC patients. Genotyping was carried out by PCR-RFLP. In LC patients with TT genotype, Cu, Zn-superoxide dismutase activities and nonprotein thiol levels were significantly higher than the controls. In patients with GT and GG genotype, high levels of lipid hydroperoxides showed statistical significance when compared to controls. Our results indicate a potential relationship among G894T polymorphism of NOS3, and impaired redox homeostasis. Further studies are required to determine the role of NOS3 gene polymorphism and impaired plasma redox homeostasis.