Mehmet Tarakcioglu

Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism

BACKGROUND There is evidence that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. Although it has not been investigated yet, several recent studies proposed that nitric oxide (NO) and other parameters related to oxidative stress may have a pathophysiological role in autism. METHODS We assessed the changes in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and thiobarbituric acid-reactive substances (TBARS) levels in plasma as well as NO levels in red blood cells (RBC) in patients with autism (n=27) compared to age- and sex-matched normal controls (n=30). RESULTS In the autistic group, increased RBC NO levels (p<0.0001) and plasma GSH-Px activity (p<0.0001) and unchanged plasma TBARS levels and SOD activity were detected. CONCLUSIONS These findings indicate a possible role of increased oxidative stress and altered enzymatic antioxidants, both of which may be relevant to the pathophysiology of autism.

Pediatric urolithiasis--evaluation of risk factors in 95 children.

Objective: Pediatric urolithiasis is a rarely encountered pathology, except in endemic areas such as Turkey. As a recurrent pathology which may reveal functional as well and morphologic changes in the urinary tract, metabolic and environmental factors, in addition to urogenital abnormalities, should be evaluated thoroughly in each patient. In this prospective study, the patient and family histories of 95 children with stone disease were evaluated, together with serum and urine risk factors. Material and Methods: Between 1996 and 2001, 95 children (25 females, 70 males; mean age 7.3 years; age range 0.6-15 years) referred to our department with urolithiasis were evaluated. All patients were investigated with respect to stone localization, associated abnormalities, urinary tract infection (UTI), positive family history and serum and urine risk factors. In addition to standard risk factors (hypocitraturia, hypercalciuria, hyperoxaluria, hyperuricosuria, hypomagnesuria), diet and 24-h urine volume were also assessed in all children. Children with cystinuria were excluded from the study. Results: Stone size ranged from 0.3 to 3.3 r cm, with an average value of 2.0 r cm. The localization of the stones was classified as unilateral single stone in 37 patients, multiple unilateral stones in six and bilateral multiple stones in 27. Hypocitraturia was the commonest risk factor detected in our patients. A positive family history was present in 51 cases (54%). In addition, UTI was present in 59 cases (62%) and 67 cases had a previous history of recurrent UTI. Associated urogenital abnormality was detected in nine cases (9.4%). There were significant correlations between stone size and urinary citrate excretion ( p r < r 0.05) and between the presence of UTI and urinary phosphate excretion ( r r = r 0.59, p r = r 0.047). Treatments used were open surgery in seven (7.3%) cases, extracorporeal shock-wave lithotripsy in 39 (41%) and endoscopic surgery in 20 (21%). Following these procedures, 39 (41%) patients were completely stone-free, 11 (11%) had residual stones (<5 r mm in diameter) and 12 (14.8%) passed the stone(s) spontaneously. During follow-up, regrowth was seen in four (4.2%) patients and stone recurrence was noted in a further four (4.2%). Conclusions: In addition to stone removal, treatment of pediatric urolithiasis requires a thorough metabolic and environmental evaluation of all patients on an individual basis. Obstructive pathologies have to be corrected immediately and apparent metabolic abnormalities should also be treated. Children with a positive family history should be followed carefully with respect to stone recurrence. Urine volume increases in parallel with body mass index and medical therapeutic agents which increase urine citrate levels should be encouraged.

Serum IL-1β, sIL-2R, IL-6, IL-8 and TNF-α in schizophrenic patients, relation with symptomatology and responsiveness to risperidone treatment

Activation of the inflammatory response system and varied levels of cytokines in acute schizophrenia have been suggested by recent studies. Psychopharmacologic agents can differentially effect cytokine production, which suggests that therapeutic function of neuroleptics may involve immunomodulation. The present study was carried out to examine: (i) serum concentrations of interleukin (IL)-1beta, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8 and tumour necrosis factor (TNF)-alpha in schizophrenic patients; (ii) their relation with psychopathological assessment; and (iii) the relation of the initial cytokine levels with responsiveness to risperidone therapy. Thirty-four drug-free schizophrenic patients with acute exacerbation and 23 age- and gender-matched healthy controls were recruited for this study. Psychopathological assessments at admission and throughout risperidone treatment for 60 days were recorded. Serum cytokine concentrations were determined with chemilumunescence assays. According to our results, serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha concentrations adjusted for age, gender, body mass index and smoking were no different in patients with schizophrenia and controls and among subtypes of schizophrenia. However, the initial TNF-alpha concentrations had a significant effect on Brief Psychiatric Rating Scale and Scale Assessment of Positive Symptoms scores. The initial cytokine concentrations of the patients responsive to risperidone were not significantly different from those of non-responsive patients. The present study demonstrates that plasma levels of IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha adjusted for confounding factors are not altered in drug-free schizophrenic patients at acute exacerbation. We suggest that, if cytokine production is altered in schizophrenia, these alterations may not be detectable in systemic circulation. According to our results, the therapeutic effect of risperidone is not related to basal levels of the aforementioned cytokines. However, serum TNF-alpha may contribute to symptomatology in schizophrenia

Mediators of inflammation in children with type I diabetes mellitus: cytokines in type I diabetic children

OBJECTIVES Recent evidence favors primary role of cellular autoimmunity and its humoral mediators in pathogenesis and following Type I diabetes mellitus (DM). The present study was carried out to investigate serum concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha in children with type I DM. Potential role of lipid metabolism, glycemic control, body mass index (BMI) and disease duration were evaluated. DESIGN AND METHODS Thirty-five children with type I DM and 30 age and gender matched nondiabetic controls were recruited for this study. RESULTS Circulating IL-8 levels were elevated in children with type I DM (12.7 +/- 1.7 pg/mL) compared with nondiabetic controls (5.5 +/- 0.3 pg/mL) and the difference remained significant after adjustment for cofactors and covariates (p: 0.033). Although statistically insignificant serum CRP concentrations were slightly higher in diabetic children (p: 0.075). Serum TNF-alpha and IL-6 levels were comparable in diabetic and nondiabetic groups. However newly diagnosed (<1 yr) cases had higher TNF-alpha and IL-6 levels compared to cases with longer standing DM. In diabetic children BMI was independently associated with an increase in serum IL-8 levels. Serum CRP, lipids, apolipoproteins and glycemic control were not significant predictors of cytokine concentrations in children with type I DM. CONCLUSION Circulating levels of IL-8 were elevated and were correlated with BMI in children with type I DM, hinting perhaps at adipose tissue as a site of production. Elevated systemic IL-6 and TNF-alpha were limited to newly diagnosed cases suggesting activation of the inflammatory immune response system at early stages of the disease.

Serum prolidase activity as a marker of osteoporosis in type 2 diabetes mellitus.

OBJECTIVES Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation This study aimed to evaluate serum prolidase activity and urinary deoxypyridinoline cross links in type 2 diabetic subjects with and without osteoporosis assessed by bone mineral density. DESIGN AND METHODS Seventy-five patients (54 F/21 M) with type 2 DM and 43 age and gender matched healthy subjects (30 F/13 M) were recruited for this study. Serum prolidase activity was assessed with colorimetric determination. Urinary deoxypyridinoline (Dpy) was determined with electrochemiluminesence immunoassay. RESULTS Serum prolidase activity was significantly lower in patients with type 2 DM than in the healthy controls (mean +/- SEM; 43.3 +/- 1.4 U/L and 53.3 +/- 2.2 U/L respectively, p: 0.000). Non osteoporotic diabetic patients had lower serum prolidase activity (median: 25th-75th percentiles; 39.5: 30.3-50.5 U/L) than osteoporotic diabetic patients (50.0: 41.8-56.3 U/L, p: 0.030) and healthy controls (52.0: 43.0-58.0 U/L, p: 0.004). Urinary Dpy excretion was not different between osteoporotic and nonosteoporotic diabetic patients. However it was lower in both diabetic groups than the healthy controls. We did not observe a statistically significant difference between the serum prolidase activity of dislipidemic/normolipidemic, hypertensive/normotensive, obese/nonobese, insulin/OAD treated, poorly/well-controlled patients and patients with/without diabetic nephropathy and retinopathy (p > 0.05). CONCLUSION This study shows a significant decrease in serum prolidase activity in patients affected with type 2 DM, which may be interpreted as evidence of decreased bone resorption. Our data also suggest that serum prolidase activity may be a better marker of osteoporosis in diabetic state than Dpy.

Pro-inflammatory cytokines in Turkish children with protein-energy malnutrition.

BACKGROUND: Protein-energy malnutrition (PEM) results from food insufficiency as well as from poor social and economic conditions. Development of PEM is due to insufficient nutrition. Children with PEM lose their resistance to infections because of a disordered immune system. It has been reported that the changes occurring in mediators referred to as cytokines in the immune system may be indicators of the disorders associated with PEM. AIMS: To determine the concentrations of pro-inflammatory cytokines in children with PEM, and to find out whether there was an association with the clinical presentation of PEM. METHODS: The levels of serum total protein, albumin, tumour necrosis factor-alpha, and interleukin-6 were measured in 25 patients with PEM and in 18 healthy children as a control group. PEM was divided into two groups as kwashiorkor and marasmus. The kwashiorkor group consisted of 15 children and the marasmus group consisted of 10 children. RESULTS: Levels of serum total protein and albumin of the kwashiorkor group were significantly lower than both the marasmus group and controls (p < 0.05). In view of tumour necrosis factor-alpha levels, there was no difference between groups (p > 0.05). While levels of interleukin-6 in both the marasmus group and the kwashiorkor group were significantly higher compared with controls (p < 0.05), there was no significant difference between the groups of marasmus and kwashiorkor (p > 0.05). CONCLUSIONS: It was observed that the inflammatory response had increased in children with malnutrition.

Acute effect of hemodialysis on serum levels of the proinflammatory cytokines

Chronic inflammation is a common feature of end-stage renal disease, which carries a heightened risk of atherosclerosis and other co-morbid conditions. Dialysis treatment per se can bring additional risk factors for inflammation, such as increased risk of local graft and fistula infections, impure dialysate or bio-incompatible membranes. Our study was designed to determine whether a hemodialysis session leads to an acute substantial alteration in the plasma levels of the proinflammatory cytokines interleukin (IL)-6, IL-1beta and tumor necrosis factor (TNF)-alpha, the T-lymphocyte activation factor soluble IL-2 receptor (sIL-2R), and an inflammation mediator and chemotactic granulocyte factor, IL-8, in end-stage renal disease patients receiving chronic intermittent HD. In this study, 21 (12 male/nine female) patients undergoing chronic hemodialysis were enrolled. The acute effect of a hemodialysis session on serum cytokine concentrations was assessed by comparison of pre-hemodialysis and post-hemodialysis determinations. Serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha levels were determined with chemiluminescence enzyme immunometric assays. A significant difference was not observed for IL-1beta, IL-6, TNF-alpha, and sIL-2R concentrations in pre-hemodialysis and post-hemodialysis specimens (p>0.05). Serum median (25th-75th percentiles) IL-8 concentration was 69.4 (34.9-110.3) pg/ml before hemodialysis, and decreased to 31.5 (18.0-78.8) pg/ml following hemodialysis (p: 0.006). Clearance of IL-8 increased by 0.47+/-0.08 pg/ml for each unit increase in pre-dialysis IL-8 (p<0.001) and decreased by 5.63+/-2.59 pg/ml for each unit increase in pre-dialysis urea mmol/l (p<0.05). In conclusion, the results of our study demonstrate that a hemodialysis session markedly decreases IL-8 concentration, which is significantly affected by pre-dialysis concentrations, indicating that removal of IL-8 is a concentration gradient-dependent action, but does not change the serum levels of IL-1beta, sIL-2R, IL-6, and TNF-alpha, underlining importance of the structural characteristics of the molecules.

Effects of periodontal therapy on disease activity and systemic inflammation in rheumatoid arthritis patients

OBJECTIVE This observational prospective cohort study aimed to evaluate the effects of non-surgical periodontal treatment on clinical periodontal measurements and systemic inflammatory mediator levels in low or moderate to highly active rheumatoid arthritis (RA) patients with chronic periodontitis. SUBJECTS AND METHODS Rheumatoid arthritis activity was assessed with disease activity score test (DAS28). Thirty patients with RA with moderate to high disease activity (DAS28 ≥ 3.2) and chronic periodontitis (MHDA group) and thirty patients with RA with low disease activity (DAS28 < 3.2) and chronic periodontitis (LDA group) were enrolled in the study. The patients were monitored at the beginning and 3 months after undergoing periodontal therapy. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α) levels in serum, DAS28 and periodontal parameters were evaluated. RESULTS Erythrocyte sedimentation rate, CRP, TNF-α levels in serum, DAS28 and periodontal parameters exhibited similar and significant reduction 3 months after the non-surgical periodontal treatment. CONCLUSION Non-surgical periodontal treatment may prove beneficial in reducing RA severity as measured by ESR, CRP, TNF-α levels in serum and DAS28 in low or moderate to highly active RA patients with chronic periodontitis.

Serum CA 125 Levels in Patients with Chronic Heart Failure and Accompanying Pleural Fluid

Malignant and nonmalignant serosal fluids have been found to be associated with high serum levels of CA 125, suggesting that the presence of fluid in the serosal cavities may stimulate its release. In this study, we investigated the relationship between serum CA 125 levels and the presence of pleural fluid in patients with chronic heart failure (CHF). We performed a clinical study in 36 patients with CHF with and without pleural fluid. Patients with CHF were divided into two groups based on the presence of fluid in the pleural cavity. Group 1 included 18 CHF patients (6 females, 12 males) with pleural fluid. Group 2 consisted of 18 CHF patients (7 females, 11 males) without pleural fluid. The control group consisted of 30 healthy volunteers (12 females, 18 males). The serum CA 125 level was determined in all groups. Serum CA 125 levels were found to be 100.0 ± 129.4 U/ml in CHF patients with pleural fluids, whereas they were 36.5 ± 35.2 U/ml in CHF patients without pleural fluid and 8.9 ± 6.1 U/ml in the control group. Significantly high serum CA 125 levels were found in CHF patients with pleural fluids (p < 0.05) when compared with both CHF patients without pleural fluid and the control group. There was also a statistically significant difference in CA 125 levels between patients without pleural fluid and the control group (p < 0.05). We concluded that serum CA 125 levels should be interpreted with caution in patients with CHF in the presence of pleural fluid. Invasive procedures to define the etiology of elevated serum CA 125 levels may be unnecessary in this patient group.

Low-dose and short-term cyclosporine treatment in patients with chronic idiopathic urticaria: A clinical and immunological evaluation

The present study aimed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin (CsA) treatment in patients with severe chronic idiopathic urticaria (CIU) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU. Twenty‐seven CIU patients and 24 healthy control subjects were included in the study. The autologous serum skin test (ASST) for autoantibodies and urticaria activity scoring (UAS) were measured for the evaluation of the clinical severity and the response to therapy, and the serum levels of interleukin (IL)‐6, IL‐8, IL‐2 receptor, IL‐1β, tumor necrosis factor (TNF)‐α and IL‐5 were measured. The mean UAS score was 32.07 ± 7.05 and 6.22 ± 3.84 before and after CsA treatment, respectively. The serum IL‐2 receptor, TNF‐α and IL‐5 levels of patients before CsA treatment were statistically higher than those of the control group (P = 0.001), and after 4 weeks of CsA therapy the mean IL‐2R, TNF‐α and IL‐5 levels were significantly decreased. The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients. Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting.