Browsing by Author "Turgan, N"
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Item β2-microglobulin and cystatin C in type 2 diabetesAksun, SA; Özmen, D; Özmen, B; Parildar, Z; Mutaf, I; Turgan, N; Habif, S; Kumanliogluc, K; Bayindir, OBackground: Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy (DN). This study was designed to demonstrate the clinical values of serum cystatin C (Cys C) and beta2-microglobulin in the assessment of renal function in type 2 diabetics by comparing them with the GFR, estimated from the uptake phase of 99 in technetium dimetiltriamino pentaacetic acid renogram (GFR-DTPA) and creatinine clearances. Materials and Methods: 68 type 2 diabetic patients with (urinary albumin excretions (UAE) 30-300 mg/24h) (n = 39) and without (UAE <30mg/24h) (n = 29) microalbuminuria and 32 controls were enrolled in the study. Serum Cys C, beta2-microglobulin, creatinine, urinary microalbumin levels, creatinine clearances and GFR-DTPA values were determined in all groups. Nonparametric ROC curves, using a cut-off GFR-DTPA of 60 mL/min/ 1.73 m(2), were obtained for these markers. Results: Serum Cys C, beta2-microglobulin, glucose and HbA1c concentrations were significantly higher in the group with diabetes compared to controls. In the patients with microalbuminuria, serum Cys C and glucose concentrations increased significantly in comparison to patients with normoalbuminuria, while no differences were observed for beta2-microglobulin levels. Serum creatinine concentrations, GFR-DTPA values and creatinine clearances were not different between both diabetic groups and controls. Cys C was positively correlated with beta2-microglobulin and creatinine and negatively with GFR values; beta2-microglobulin was also positively correlated with serum creatinine in microalbuminurics. A significant inverse correlation was found between beta2-microglobulin and GFR values in both microalbuminurics and normoalbuminurics. Conclusions: Increased Cys C and beta2-microglobulin in diabetics may be early indicators of incipient DN. The diagnostic accuracies of Cys C and beta2-microglobulin are superior to that of serum creatinine in distinguishing between mild and moderately reduced GFR.Item Impact of renal function or folate status on altered plasma homocysteine levels in hypothyroidismÖzmen, B; Özmen, D; Parildar, Z; Mutaf, I; Turgan, N; Bayindir, OHyperhomocysteinemia is an independent risk factor for coronary, peripheral and cerebrovascular diseases. Moderately elevated total homocysteine (tHcy) levels have been reported in patients with overt hypothyroidism. Plasma tHcy concentration is affected by several physiological factors and is elevated tinder conditions of impaired folate and cobalamin status and in renal failure. The aim of this Study was to assess plasma tHcy concentrations and to evaluate the role of potential determinants of plasma tHcy levels in hypothyroid patients. Fasting plasma tHcy, serum homocysteine-related vitamins folate and vitamin B-12, serum cystatin C (CysC) and creatinine, were determined in 22 hypothyroid patients and compared with 25 healthy control subjects. Creatinine clearance (CCr) was calculated using the Cockroft-Gault formula. Plasma tHcy levels were determined by HPLC with fluorescence detection and serum CysC by automated particle enhanced immunoturbidimetry. Plasma tHcy, creatinine levels were significantly higher, and serum CysC levels, and creatinine clearance values were lower in hypothyroid patients than in control subjects. Folate levels were lower in hypothyroidic group compared to the control group. There were no differences in vitamin 13, levels between hypothyroid and control groups. Positive correlation was noted between tHcy and creatinine levels in hypothyroid patients (r = 0.596); however, an inverse correlation was found between tHcy and folate levels (r = -0.705) in hypothyroid patients. In conclusion, tHcy was increased in hypothyroidism, and this increase was more strongly associated with changes in serum folate than in serum creatinine and CysC, suggesting an altered folate status.Item Association between homocysteinemia and renal function in patients with type 2 diabetes mellitusOzmen, B; Ozmen, D; Turgan, N; Habif, S; Mutaf, I; Bayindir, OHomocysteinemia is an independent risk factor for cardiovascular disease, but information on its association with type 2 diabetes and mild renal dysfunction is limited. Plasma total homocysteine (tHcy) concentration is partly determined by renal plasma clearance. Serum cystatin C (Cys C) concentration has been introduced as a marker of renal function, specifically as an indicator of glomerular filtration rate (GFR). The aim of this study was to explore the relationships among tHcy, creatinine clearance (Ccr), serum Cys C, and microalbuminuria in a population with type 2 diabetes. Fasting plasma tHcy, serum homocysteine-related vitamins (folate and vitamin B 12), serum Cys C, serum creatinine, urine microalbumin, and creatinine clearance were determined in 75 type 2 diabetic patients and 40 healthy control subjects. The patients were assigned to two groups based on urinary albumin excretion (UAE): normoalbuminuric (NAU, UAE <30 mg/24 hr, n = 35) and microalbuminuric (MAU, UAE 30-300 mg/24 hr, n = 40). Ccr was calculated using the Cockroft-Gault formula. Plasma Hcy levels were determined by HPLC with fluorescence detection and serum Cys C by automated particle enhanced immunoturbidimetry. Plasma tHcy levels were significantly higher in normoalbuminuric and microalbuminuric patients than in controls (10.64+/-0.53, 13.29+/-0.78, 6.91+/-0.37 mmol/L, respectively). Serum Cys C levels in microalbuminuric diabetics were higher than in normoalbuminurics and controls (1.36+/-0.06, 1.12+/-0.04, 1.10+/-0.06 mg/L, respectively). Positive correlations were noted between tHcy and Cys C levels in normoalbuminuric and microalbuminuric diabetics (r = 0.72, r = 0.64, respectively). Homocysteine and creatinine concentrations were correlated in both diabetic groups (r = 0.89, r = 0.93, NAU and MAU, respectively). Elevated plasma total homocysteine concentrations in type 2 diabetics suggest an association between homocysteinemia and deterioration of renal function, evidenced by increased serum creatinine and Cys C, Ccr, and microalbuminuria. These findings implicate homocysteinemia in the relationship between diabetic nephropathy and cardiovascular complications of diabetes.Item Histological Investigation of Experimentally Induced Diabetes Effects on the Distribution of Transforming Growth Factor (TGFβ), Nuclear Factor Kappa B (Nf-κB), Heat Schock 90β (Hsp90β) and E-cadherin Proteins in Testicular TissueToros, P; Oltulu, F; Tuglu, I; Uysal, A; Özçinar, E; Turgan, N; Rouhrazi, H; Aktug, HDiabetes is a metabolic disorder characterized by high blood sugar levels and it causes complications in many systems, including the reproductive system. As a result of diabetic conditions, one of the mechanisms that can cause repression of reproductive activity is testicular oxidant stress. The identification of diabetes on the cell signaling molecules axis is still under discussion. The aim of this study was to detennine the effect of Transfonning Growth Factor (TGF beta), Nuclear Factor kappa B (NF-kappa B), Heat-schock 90 beta (HSP90 beta) signal pathways and E-cadherin cell adhesion molecule on infertility in diabetic rat testicular tissue. In our study, includes histological, molecular and biochemical analysis of testicular tissue removed at the end of the 2 weeks experiment period. A total of 14 adult male rats were divided as control and diabetes. No intervention was given to 7 male rats in the control group. For the diabetic group, 7 male rats were injected by intraperitoneal with a single dose of 55 mg/kg streptozotocin (STZ). TGF beta, NF-kappa B, HSP90 beta and E-cadherin proteins were immunohistochemically studied to investigate possible tissue damage, inflanunatoly process, cell stabilization and integrity due to diabetes. In order to determine oxidant stress, lipid peroxidation product malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GPx) analyzes were performed. Fibrosis, inflammatory changes and loss of spermatogenetic series are prominent findings in the diabetic group. On analysis of all the samples with immunostaining, in the diabetic group, TGF beta and NF-kappa B inununoexpression significantly increased, while Hsp90 beta and E-cadherin immunoexpression significantly decreased compared with control groups. Experimental diabetes was found to cause fibrosis, inflammation, disrupting cell adhesion and stabilization in testicular tissue. These results suggest that cellular therapy studies are needed for possible damage.Item Age and gender dependent alterations in the activities of glutathione related enzymes in healthy subjectsHabif, S; Mutaf, I; Turgan, N; Onur, E; Duman, C; Özmen, D; Bayindir, OObjectives: Oxidative stress as a result of increased free radical production is implicated in the pathogenesis of several diseases. Specific antioxidant enzymes have a crucial role in the prevention of these deleterious effects. Since the activities of these enzymes differ significantly in different populations and seem to be affected by various environmental factors, in this study we aimed to determine the reference values of glutathione related antioxidant enzyme activities in the erythrocytes of healthy subjects and to investigate the possible variations as a function of age and gender in a healthy Turkish Mediterranean population. Design and methods: 130 healthy subjects (12-90 yr, 82 females, 48 males) were divided into six different age groups. Erythrocyte glutathione peroxidase (GSH-PX), glutathione reductase (GR) and glutathione-s-transferase (GST) activities were measured on a Hitachi 704 autoanalyser by the modification of previously described manual UV spectrophotometric methods. Results: No significant differences were observed in erythrocyte GSH-PX, GR and GST activities between different age groups. Overall, GST activities were significantly higher in females compared with males (8.08 +/- 1.39, 6.88 +/- 1.51 U/g Hb respectively, mean +/- SD, p < 0.001). A significant positive correlation between GSH-PX and GR activities was observed (r = 0.49, p < 0.001). Conclusion: The results of this study suggested that the activities of GSH-PX, GR and GST did not depend. GST activities overall were higher in females. The reference values that we obtained were different than the previous reports. This situation implies that each population should determine its own reference values and should investigate the influence of environmental factors and life style habits on the activities of these enzymes that constitute a major part of the antioxidant defense system in the human organism. (C) 2002 The Canadian Society of Clinical Chemists. All rights reserved.Item Effects of defibrotide on aorta and brain malondialdehyde and antioxidants in cholesterol-induced atherosclerotic rabbitsAydemir, EO; Duman, C; Çelik, HA; Turgan, N; Uysal, A; Mutaf, I; Habif, S; Özmen, D; Nisli, N; Bayindir, OThe effects of a high-cholesterol diet in the presence and absence of defibrotide, a single-stranded polydeoxyribonucleotide compound, on the lipid peroxidation product malondialdehyde, endogenous antioxidant enzymes catalase, glutathione peroxidase, and the antioxidant thiol compound GSH were investigated. Forty male New Zeland white rabbits were divided into four groups each consisting of 10 rabbits. Group I received a regular rabbit chow diet and group II 1% cholesterol plus regular chow, group III was given defibrotide (60 mg/kg per day p.o. in water) and was fed with regular chow, and group IV received defibrotide plus 1% cholesterol for 9 weeks. Blood cholesterol and malondialdehyde, catalase, glutathione peroxidase, and GSH were determined before starting the experimental diet regimen (basal). After 9 weeks, the same parameters were determined in blood, aorta, and brain tissues (end -experiment). Aortic tissue was examined under a light microscope for morphological alterations indicative of atherosclerosis. The increase in serum total cholesterol was greater in group II than group IV. Plasma malondialdehyde in group II was higher than in group III. Brain malondialdehyde in group II was higher than all other groups, and aortic malondialdehyde in this group was higher than group I and III. Serum catalase activity decreased in group II and increased in group III, compared with basal values. Brain catalase activity in group I was higher than group II, and aorta catalase in group IV was higher than in group I and III. Blood glutathione peroxidase activity in group III and IV was higher than basal. GSH concentrations decreased significantly in the cholesterol-fed groups (group II and IV). Histological alterations in the cholesterol-fed groups were mon pronounced in group II. The increased levels of malondialdehyde in plasma, aorta, and brain tissue of group II suggest a role of oxygen foe radicals in the pathogenesis of cholesterol-induced atherosclerosis. The higher malondialdehyde values in the brain tissues of animals in group II compared with group IV suggest a protective role of defibrotide in the brain against lipid peroxidation in the oxidant stress of cholesterol-induced atherosclerosis. Increased catalase activities in the blood and aortic tissues and increased glutathione peroxidase activities in the blood of rabbits receiving defibrotide suggest an induction of these antioxidant enzyme activities by defibrotide. These results imply that anti-atherosclerotic, anti-ischemic effects of this drug may be due to the beneficial effects on the oxidant-antioxidant balance of various tissues.Item Immunoexpressions of embryonic and nonembryonic stem cell markers (Nanog, Thy-1, c-kit) and cellular connections (connexin 43 and occludin) on testicular tissue in thyrotoxicosis rat modelOltulu, F; Aktug, H; Uysal, A; Turgan, N; Oktem, G; Erbas, O; Yavasoglu, NUK; Yavasoglu, AIn this study, possible thyrotoxicosis-related histological changes in testicular tissues of rats with experimentally induced thyrotoxicosis model were evaluated on cellular connections and stem cell markers. Two experimental groups, thyrotoxicosis and control, each consisting of eight animals were used. Rats in the thyrotoxicosis group were injected intraperitoneally with 3,3,5-triiodo-l-thyronine (50 mu g/100 g body weight/day) for 10 days. At the end of the study, animals in both groups were anesthetized, and blood samples were collected for biochemical analyses. Their testes were dissected out and histological procedure was conducted to perform further histochemical, immunohistochemical analyses and tissue expression analysis by real-time polymerase chain reaction. Expression of the stem cell markers such as c-kit and Thy-1 significantly decreased in the testes of the thyrotoxicosis group compared with the control group; however, Nanog expression was not detected in any of the groups. Similarly, connexin 43 and occludin expressions were also found to be significantly lower in the thyrotoxicosis group. These results on cellular connections are supported with the tissue expression analysis. Our findings are indicative of supporting microenvironmental tissue decay rather than parenchyma damage, which has been actually ignored in the literature. In conclusion, experimental thyrotoxicosis model may have adverse effects on the cell junctional complexes, cell-cell interactions, and pluripotency capacity.Item Serum and urinary nitric oxide in Type 2 diabetes with or without microalbuminuria - Relation to glomerular hyperfiltrationAksun, SA; Özmen, B; Özmen, D; Parildar, Z; Senol, B; Habif, S; Mutaf, I; Turgan, N; Bayindir, OBackground: Glomerular hyperfiltration is considered as one of the pathophysiological mechanisms for the development of diabetic nephropathy. Oxidative stress is enhanced in patients with diabetes mellitus. Reportedly, nitric oxide (NO) might be involved in the pathogenesis of hyperfiltration. We investigated the relationship between hyperfiltration and NO system, and malondialdehyde (MDA) levels in Type 2 diabetics with/without microalbuminuria. Methods: In 39 microalbuminuric, 29 normoalbuminuric Type 2 diabetic patients and 32 healthy controls, serum creatinine, nitrite, nitrate, urinary microalbumin, nitrite, nitrate, plasma MDA and estimated glomerular filtration rate (EGFR) values, calculated according to the Cockcroft and Gault formula, were recorded. Results: Serum and urine NO levels were higher in both microalbuminurics and normoalbuminurics than controls. There were no significant differences in EGFR between groups. However, hyperfiltration was determined in 31% of normoalbuminurics and 20% of microalbuminurics. Serum and urine NO levels were higher in patients with hyperfiltration. Plasma MDA levels were significantly elevated in both microalbuminurics and normoalbuminurics when compared with controls. Serum glucose and microalbuminuria were positively correlated in microalbuminuric diabetics. Serum NO levels were also positively correlated with EGFR in both normoalbuminurics and microalbuminurics. HbA1c levels were positively correlated with both urinary albumin excretion and plasma MDA levels in normoalbuminuric diabetics. Conclusion: Hyperglycemia is associated with an increased NO biosynthesis and lipid peroxidation. Increased oxidative stress may contribute to the high NO levels in Type 2 diabetes. Furthermore, the high NO levels may lead to hyperfiltration and hyperperfusion, which in turn leads to an increase in urinary albumin excretion and thus causes progression of nephropathy in early Type 2 diabetes. (C) 2003 Elsevier Inc. All rights reserved.