Gönül Sultuybek

Association of PARP-1, NF-κB, NF-κBIA and IL-6, IL-1β and TNF-α with Graves Disease and Graves Ophthalmopathy

BACKGROUND Graves Disease (GD) is an autoimmune disorder affected by an interaction of multiple genes such as Nuclear Factor-κB (NF-κB), Nuclear Factor-κB Inhibitor (NF-κBIA), Poly (ADP-ribose) polymerase-1 (PARP-1) and cytokines like Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) and mostly accompanied by an ocular disorder, Graves Ophthalmopathy (GO). We hypothesize that there is a relationship between GD, GO, polymorphisms of inflammatory related genes and their association with cytokines, which may play important roles in autoimmune and inflammatory processes. SUBJECTS AND METHODS To confirm our hypothesis, we studied the polymorphisms and cytokine levels of 120 patients with GD and GO using PCR-RFLP and ELISA methods, respectively. RESULTS We found that patients with GG genotype and carriers of G allele of PARP-1 G1672A polymorphism are at risk in the group having GD (p=0.0007) while having GA genotype may be protective against the disease. PARP-1 C410T polymorphism was found to be associated with GO by increasing the risk by 1.7 times (p=0.004). Another risk factor for development of GO was the polymorphism of del/ins of NFkB1 gene (p=0.032) that increases the risk by 39%. Levels of cytokines were also elevated in patients with GD, but no association was found between levels of cytokines and the development of GO as there was no change in levels of cytokines. CONCLUSIONS We suggest that, PARP-1 and NFkB1 gene polymorphisms may be risk factors for developing Graves Disease and Ophthalmopathy.

The molecular markers of hemostatic activation on coronary artery disease

Endothelial cells, circulating platelets, and proteins of the coagulation and fibrinolytic systems are known to contribute to the hemostatic processes. Various molecular markers of hemostatic alteration are found in increased amounts in the circulation during the activation of this process. In this study, we investigated serum lipoprotein (a) and plasma platelet factor 4, beta-thromboglobulin, thrombin-anthithrombin complex, fibrinopeptid A, D-dimer, tissue plasminogen activator, tissue plasminogen activator inhibitor, and fibronectin levels in patients with coronary artery disease. The levels of all these markers were found to be significantly higher as compared to the control group. Our findings suggest that patients with coronary artery disease have greater blood coagulability than controls, and the use of molecular markers has become greatly important in clinical practice.

Effect of donor age on the susceptibility of erythrocytes and erthrocyte membranes to cumene hydroperoxide-induced oxidative stress

A comparative study on erythrocytes and erythrocyte membranes of healthy elderly and young adults was carried out to understand how the antioxidant defense capacity is effected by aging. The levels of endogenous malondialdehyde and Ca(2+)-ATPase activity were taken as indices of oxidative damage. In addition, chemiluminescence measurements were performed on intact erythrocytes. The susceptibility of these parameters to in vitro cumene hydroperoxide, under low oxidant level that does not induce hemolysis, was also taken as an age-related indicator of the endogenous peroxidative potential of the erythrocytes. Our data showed that the content of malondialdehyde and Ca(2+)-ATPase activity did not change with age. Furthermore, the susceptibility of intact erythrocytes to oxidative stress did not change in the elderly group. However, under the same conditions erythrocyte membranes were more susceptible to oxidative damage in the elderly than young adults. Our results also showed that antioxidant defenses were overwhelmed in intact erythrocytes of the elderly at high concentrations of cumene hydroperoxide.

Transport of glutathione conjugate in erythrocytes from aged subjects and susceptibility to oxidative stress following inhibition of the glutathione S-conjugate pump

The aim of the present study was to investigate the effect of donor aging on the glutathione conjugate transport in erythrocytes and whether it plays a role in the resistance to oxidative stress of the erythrocytes of aging subjects. In our comparative study on intact erythrocytes of healthy aging and young adults, in which 2,4-dinitrophenyl-S-glutathione (DNP-SG) was used as model glutathione S-conjugate, we found that the efflux of DNP-SG remained unchanged in the aged subjects. This result suggests that the detoxification function is maintained against the chemical stress employed in erythrocytes of aging subjects. In the assay conditions used, which were optimized to obtain maximal inhibition of glutathione S-conjugate transport, our results also indicated that the susceptibility of erythrocytes to in vitro lipid peroxidation generated by cumene hydroperoxide was enhanced by pretreatment with DNP-SG inhibitors in both age groups. However, the difference in susceptibility was not a function of aging. Further, the results suggested that inhibition of glutathione S-conjugate pump may impair cellular protection of the erythrocytes against oxidative damage.

Glucocorticoid receptors on mononuclear leukocytes in polycystic ovary syndrome

Objective. Many studies have suggested that there is a possible hormonal dysregulation of hypothalamic‐pituitary‐adrenal (HPA) axis and an increased cortisol clearance in patients with polycystic ovary syndrome (PCOS). Therefore in this study, we have examined the role of glucocorticoid receptor/s (GR) characteristics in the developing of these abnormalities in patients with PCOS. Method. For this purpose, the number and affinity of GR in peripheral mononuclear leukocytes (MNL) of 10 patients with PCOS and 10 healthy women (controls) were determined. Results. There were no significant differences in the number (6500±1001 sites/cell and 6352±1697 sites/cell, respectively; P>0.05) and affinity (3.93±0.89 nM and 4.49±0.71 nM, respectively; P>0.05) of GR between the PCOS patients and the controls. Conclusions. These results suggest that the alterations in the HPA axis and in the cortisol metabolism observed in PCOS are not related to GR deficiency.

Effect of acute hyperglycemia on potassium (86Rb+) permeability and plasma lipid peroxidation in subjects with normal glucose tolerance

Hyperglycemia is likely to be one of the important determinants of ion transport as it is known to induce oxidative stress and may thus enhance non-specific permeability of membranes. The aim of the present study was to evaluate the effects of an acute increase in glycemia on 86Rb+ (a marker for K+) influx and lipid peroxidation. We evaluated the 75-g oral glucose tolerance test (OGTT)-induced modification on 86Rb+ influx and plasma lipid peroxidation in 20 subjects with normal glucose tolerance (NGT). After 2-hour glucose loading, the levels of passive 86Rb+ influx and plasma lipid peroxidation were significantly increased, whereas the active influx of 86Rb+ was unchanged. The total and passive influx of 86Rb+ into erythrocytes was significantly correlated with the level of plasma lipid peroxidation. This study demonstrates that acute hyperglycemia induces an increase in the passive influx of 86Rb+ in subjects with NGT, suggesting that acute hyperglycemia may produce an oxidative stress in plasma. These changes may be among the earliest changes occurring in response to hyperglycemia.

PLASMA Lp(a) AND t-PA-PAI-1 COMPLEX LEVELS IN CORONARY HEART DISEASE

In this study we investigated serum Lp(a) and plasma t-PA-PAI-1 complex levels in patients with coronary heart disease (CHD). Serum total cholesterol, triglyceride, LDL and VDL cholesterol levels (p < 0.001) and HDL cholesterol levels (p < 0.01) in patients group were found to be significantly different from those in control group. The mean Lp(a) and t-PA-PAI-1 complex levels in patients with coronary heart disease were significantly higher as compared to control group (p < 0.001). This data indicate that the elevated levels of serum Lp(a) and plasma t-PA-PAI-1 complex may play an important role in the pathogenesis of coronary atherosclerosis.

Association of NFKB1A and microRNAs variations and the susceptibility to atherosclerosis

Atherosclerosis (AT) is a chronic immuno-inflammatory disease characterized by inflammatory mediators and immune activation in arterial wall. Although NF-

Glucocorticoid receptors in patients with congenital adrenal hyperplasia.

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