Savas Guzel

Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis.

OBJECTIVES To investigate lipid, protein, DNA oxidation and antioxidant status in blood and synovial fluid of rheumatoid arthritis (RA) patients and to determine the importance of oxidative stress parameters in reflecting disease activity. DESIGN AND METHODS 20 RA patients and 15 healthy controls were included. Lipid peroxidation (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxide, and conjugated diene), protein oxidation (carbonyl and thiol), DNA oxidation (8-OHdG) and antioxidant status markers (glutathione (GSH), glutathione peroxidase (GSH Px), superoxide dismutase (CuZn SOD), and catalase) were determined in blood and synovial fluid. RESULTS TBARS (p<0.001), lipid hydroperoxide (p<0.001), conjugated diene (p<0.001), carbonyl (p<0.001) and 8-OHdG (p<0.01) levels were significantly higher; thiol (p<0.01) and GSH levels (p<0.01) and GSH Px (p<0.001) and CuZn SOD (p<0.01) activities were significantly lower in blood of RA patients. TBARS (p<0.001), lipid hydroperoxide (p<0.001), conjugated diene (p<0.01), carbonyl (p<0.001) and 8-OHdG (p<0.05) levels were significantly higher, catalase activity (p<0.001) significantly lower in synovial fluid of RA patients. CONCLUSIONS Increased lipid, protein and DNA oxidation markers and impaired antioxidant status confirm the role of oxidative stress in the pathogenesis of RA. Lipid peroxidation markers can serve as surrogate markers for disease activity.

Relationship between levels of brain-derived neurotrophic factor and metabolic parameters in patients with type 2 diabetes mellitus.

Background and Aim. Studies have suggested that brain-derived neurotrophic factor (BDNF) plays a role in glucose and lipid metabolism and inflammation. The aim of this study was to evaluate the relationship between serum BDNF levels and various metabolic parameters and inflammatory markers in patients with type 2 diabetes mellitus (T2DM). Materials and Methods. The study included 88 T2DM patients and 33 healthy controls. Fasting blood samples were obtained from the patients and the control group. The serum levels of BDNF were measured with an ELISA kit. The current paper introduces a receiver-operating characteristic (ROC) generalization curve to identify cut-off for the BDNF values in type 2 diabetes patients. Results. The serum levels of BDNF were significantly higher in T2DM patients than in the healthy controls (206.81 ± 107.32 pg/mL versus 130.84 ± 59.81 pg/mL; P < 0.001). They showed a positive correlation with the homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.28; P < 0.05), the triglyceride level (r = 0.265; P < 0.05), and white blood cell (WBC) count (r = 0.35; P < 0.001). In logistic regression analysis, age (P < 0.05), body mass index (BMI) (P < 0.05), C-reactive protein (CRP) (P < 0.05), and BDNF (P < 0.01) were independently associated with T2DM. In ROC curve analysis, BDNF cut-off was 137. Conclusion. The serum BDNF level was higher in patients with T2DM. The BDNF had a cut-off value of 137. The findings suggest that BDNF may contribute to glucose and lipid metabolism and inflammation.

Osteoprotegerin, leptin and IL-6: Association with silent myocardial ischemia in type 2 diabetes mellitus

Background: Diabetic patients often exhibit severe, asymptomatic coronary artery disease (CAD). The relationship between osteoprotegerin (OPG), inflammatory markers and silent myocardial ischemia remains to be elucidated. Methods: We recruited 45 type 2 diabetic patients and 33 healthy controls and assessed them for silent myocardial ischemia (SMI) by myocardial perfusion imaging. Patient blood was tested for OPG, IL-6 and leptin concentrations. Results: OPG, leptin and IL-6 levels were found significantly elevated in diabetic patients (p < 0.001, p < 0.01, p < 0.05). Based on our classification of presence/absence of SMI in our diabetic group, we found that there was a significant association between SMI and the biomarkers IL-6 (p < 0.001), leptin (p < 0.001) and OPG (p < 0.05). In multivariate regression analyses, OPG was found to be significantly related to diabetes mellitus and to SMI. Age, sex and smoking increased the association between OPG and SMI. Conclusion: High OPG, leptin and IL-6 levels are associated with the presence and severity of SMI in type 2 diabetic patients.

Is subclinical hypothyroidism contributing dyslipidemia and insulin resistance in women with polycystic ovary syndrome

We aimed to analyze lipid parameters and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance test (IGT) in subclinical hypothyroidism (SCH) women with and without polycystic ovary syndrome (PCOS). 20 patients with PCOS and SCH consisted of Group I and 39 patients with PCOS and normal thyroid function consisted of Group II and 53 healthy women with normal thyroid function consisted of Group III. Triglyceride levels were 143.26 ± 99.86 mg/dL in group 1 and 88.56 ± 37.56 mg/dL in group 2 and 83.71 ± 31.94 mg/dL in group 3 which were statistically significant. Total cholesterol, HDL- cholesterol, LDL-cholesterol were found similar between the groups. Fasting insulin levels were 12.45 ± 8.62 µU/mL in group 1 and 8.60 ± 5.35 µU/mL in group 2 and 7.04 ± 3.55 µU/mL in group 3 which were statistically significant (P = 0.027). HOMA-IR were 2.92 ± 2.34 in group 1 and 1.95 ± 1.52 in group 2 and 1.60 ± 0.86 in group 3 which were statistically significant (P = 0.046). This study showed that women with PCOS and subclinical hypothyroidism should be evaluated for dyslipidemia and Insulin resistance.

Association of Pb, Cd, and Se Concentrations and Oxidative Damage-Related Markers in Different Grades of Prostate Carcinoma

Prostate cancer is known to be affected by the heavy metal levels and oxidative damage of the body, yet there are very few studies which look into the way it occurs. The aim of this study was to determine whether blood and tissue lead (Pb), cadmium (Cd), and selenium (Se) levels are associated with oxidative damage in the context of prostate cancer progression and development. Seventy-nine patients comprising 25 patients with benign prostatic hypertrophy (BPH), 23 patients with malignant prostatic carcinoma (malign Ca), 16 patients with low-grade prostatic intraepithelial neoplasia (LGPIN), and 15 patients with high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosed on the basis of their clinical profile, transrectal ultrasonography, and histopathology were included in this study. Cd and Pb levels in whole blood were found to be increased in patients with HGPIN compared with the BPH group; also, the levels of Cd in whole blood and tissue were found to be increasing in patients with malign Ca, unlike BPH patients. Moreover, the levels of malondialdehyde (MDA) in plasma and tissue were significantly increased in malign Ca, LGPIN, and HGPIN than those in BPH. However, the levels of tissue Pb were found to be decreasing in BPH, unlike the malign Ca and HGPIN patients, and the levels of tissue protein carbonyls in malign Ca were significantly lower than those in HGPIN. The levels of tissue reduced glutathione (GSH) in malign Ca were significantly lower than those in BPH. Additionally, the levels of Se in serum and tissue in LGPIN were significantly lower than those in BPH. The serum Se levels in HGPIN were also significantly lower than those in BPH and malign Ca groups. Furthermore, the concentrations of serum Se in LGPIN were significantly lower than those in malign Ca. From the Pearson correlation analysis, there were significant positive correlations between tissue Cd and MDA levels in malign Ca, LGPIN, and HGPIN and between the tissue Pb and tissue MDA and protein carbonyl levels in malign Ca. Blood Pb and tissue Pb were also significantly positively correlated with plasma MDA and protein carbonyl levels in malign Ca. In addition, blood Pb was significantly positively correlated with tissue MDA and protein carbonyl levels in malign Ca, and a significant positive correlation was also found between blood Cd and plasma protein carbonyls and tissue MDA in LGPIN. We observed that altered prooxidant–antioxidant balance and heavy metal levels may lead to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis. These findings indicate that changes in the levels of Pb, Cd, Se, MDA, protein carbonyls, and GSH in the blood and/or tissue are related to the prostatic carcinoma development and progression, although triggering one of the mentioned changes is unknown; therefore, further study is required to determine the exact steps of the process and clarify the roles of different substances in order to obtain a more detailed explanation of the phenomenon.

Indices Used in Differentiation of Thalassemia Trait from Iron Deficiency Anemia in Pediatric Population: Are They Reliable?

Background: Iron deficiency (IDA) and beta thalassemia trait (TT) are the most common causes of hypochromia and microcytosis. Many indices have been defined to quickly discriminate these similar entities via parameters obtained from automated blood cell analyzers. However, studies in the pediatric age group are scarce and their results are controversial. Methods: We calculated eight discrimination indices [Mentzer Index (MI), England and Fraser Index (E&F), Srivastava Index (S), Green and King Index (G&K), Shine and Lal Index (S&L), red blood cell (RBC) count, RBC distribution width, and red blood cell distribution width Index (RDWI)] in 100 patients. We calculated sensitivity (SENS), specificity (SPEC), positive and negative predictive value (PPV and NPV), and Youdens Index (YI) of each discrimination index. Results: None of the discrimination indices showed a SENS and SPEC of 100%. The highest SENS was obtained with S&L (87.1%), while the highest SPEC was obtained with E&F formula (100%). The highest YI value was obtained with E&F formula (58.1%). Conclusion: In our study, none of the formulas appears reliable in discriminating between TT and IDA patients. The evaluation of iron status and measurement of hemoglobin A2 (HbA2) remain the most reliable investigations to differentiate between TT and IDA patients.

Erratum: Interleukin-33, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 in myocardial infarction

Background/Aims Acute coronary syndrome (ACS) is characterized by increased inflammatory processes and endothelial activation. We investigated the association between ACS and inflammatory mediators and matrix-degrading enzymes. Methods We prospectively enrolled 55 consecutive patients with ACS: 25 with unstable angina (UA) and 30 with non-ST elevated myocardial infarction (NSTEMI). For comparison, 25 age- and sex-matched subjects with no significant coronary artery stenosis were included as the control group. Peripheral serum levels of interleukin (IL)-33, matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP-1, and C-reactive protein (CRP) were measured on admission, and at 12, 24, 48, and 72 hours after the initial evaluation. Results Compared to serum levels in the control group, serum levels of IL-33 decreased in the NSTEMI group (p < 0.05), and levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 increased in the UA group (p < 0.01, p < 0.05, respectively) and NSTEMI group (p < 0.05, p < 0.05, respectively). IL-33 levels were significantly lower on admission than at 12 hours after the initial evaluation (p < 0.05). IL-33 levels were negatively correlated with MMP-9 levels (r = -0.461, p < 0.05) and CRP levels (r = -0.441, p < 0.05). Conclusions Elevated levels of MMP-9, TIMP-1, and decreased levels of IL-33 play a role in the development and progression of ACS.

Protective effect of infliximab on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation

OBJECTIVE The aim of this study was to investigate the effect of infliximab on experimentally induced ovarian ischemia/reperfusion injury (IRi). STUDY DESIGN A total of 42 female rats were equally divided into 6 experimental groups; group 1: sham operation, group 2: 3-h ischemia, group 3 and 4: 3-h ischemia, 3-h reperfusion, group 5 and 6: 3-h ischemia, 24h reperfusion. In group 4 and group 6, 30 min before reperfusion, infliximab was administered intraperitoneally at a dose of 5mg/kg. Bilateral ovaries were removed for histopathologic and biochemical analysis. Serum MDA (sMDA), tissue MDA (tMDA), serum NO (sNO), tissue NO (tNO) and serum catalase concentrations were analyzed. Tissue damage of ovarian tissue was scored by histological examination. RESULTS The infliximab administration significantly lowered the sNO, tNO and sMDA concentrations in group 4 compared to group 3 (p=0.041, p=0.025 and p=0.035, respectively). sNO, tNO and sMDA concentrations were also lower in group 6 when compared to group 5, but this differences were not significant (p>0.05). On the other hand, tMDA concentrations were lower in infliximab-applied groups when compared to ischemia/reperfusion groups (group 3 vs. 4 and 5 vs. 6) (p=0.045 and p=0.048, respectively). Moreover, histopathologic tissue damage scores in infliximab administration groups were significantly lower than in ischemia/reperfusion groups (p<0.001). CONCLUSION Infliximab attenuates I/R-induced ovarian tissue injury in rats subjected to ischemia/reperfusion.

Association Between Serum Fetuin-A levels, Carotid Artery Stiffness, and Intima–Media Thickness in Patients With Normotensive Obstructive Sleep Apnea Syndrome

Increased carotid intima–media thickness (cIMT) and stiffness, reflecting subclinical atherosclerosis, are associated with obstructive sleep apnea syndrome (OSAS). The relationship between serum fetuin-A, which inhibits ectopic calcification, and atherosclerosis is unclear. Therefore, we investigated the association between serum fetuin-A levels and carotid artery stiffness and cIMT in patients with normotensive OSAS (n = 50) and non-OSAS controls (n = 38). Compared with controls, there were lower fetuin-A levels (59.4 ± 6.5 vs 68.2 ± 5.8 ng/mL, P = .029), higher mean cIMT (0.73 ± 0.2 vs 0.63 ± 0.3 mm, P < .001), and greater stiffness (β) index (7.45 ± 0.9 vs 5.2 ± 0.7, P = .001) in the OSAS group. The cIMT and stiffness (β) index were inversely correlated with fetuin-A levels (r = −.324, P = .033; r = −.466, P < .001, respectively) and positively correlated with apnea hypopnea index (r = .498, P < .001; r = .422, P = .001, respectively) in the OSAS group. Decreased serum fetuin-A levels were associated with subclinical carotid atherosclerosis in patients with normotensive OSAS.

Visfatin, Leptin, and TNF-α: Interrelated Adipokines in Insulin-Resistant Clinical and Subclinical Hypothyroidism

Purpose. This study is designed to evaluate the interrelationships among adipokines—visfatin, leptin, and tumor necrosis factor-α (TNF-α)— and insulin resistance (IR) in overt (n = 40) and subclinic hypothyroid (n = 25) patients and compare our findings with sex and body mass index-matched healthy controls (n = 25). Methods. Serum visfatin, leptin, and TNF-α levels were measured by enzyme-linked immunosorbent assay and C-reactive protein by immunoturbidimetry. Thyroid status (TSH, FT3, FT4) and lipid status (triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol) parameters were measured. IR was determined by homeostatic model assessment (HOMA-IR) and McAuley (McA) indices. Results. HOMA-IR (p < 0.05) and McA indices (p < 0.01) revealed the presence of IR in overt hypothyroid patients. C-reactive protein, TNF-α, leptin, and visfatin levels were significantly higher (p < 0.01, p < 0.01, p < 0.001, and p < 0.001) in overt hypothyroid patients than euthyroid control group. Subclinic hypothyroid patients were observed to have significantly higher leptin and visfatin levels (p < 0.05) than euthyroid control group. In overt hypothyroid patients, we found plasma visfatin to be significantly positively correlated with HOMA-IR index (r = 0.336, p < 0.05) and body mass index (r = 0.445, p < 0.01) and negatively correlated with McA index (r = –0.574, p < 0.01). Conclusion. This study demonstrates the presence of IR in overt hypothyroid patients by HOMA and McA indices. Increased levels of visfatin, leptin, and TNF-α in overt and subclinic hypothyroid patients and the correlations among these adipokines highlighten their crucial role in the IR-associated disorders.