Ercan Sivasli

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.

Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism.

Abstract.There is great evidence in recent years that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. The present study was performed to assess the changes in red blood cells thiobarbituric acid-reactive substances (TBARS) levels, and superoxide dismutase (SOD), catalase (CAT), adenosine deaminase (ADA) and xanthine oxidase (XO) activities in patients with autism (n = 27) compared to age- and sex-matched normal controls (n = 26). In the autistic group, increased TBARS levels (p < 0.001) and XO (p < 0.001) and SOD (p < 0.001) activity, decreased CAT (p < 0.001) activity and unchanged ADA activity were detected. It is proposed that antioxidant status may be changed in autism and this new situation may induce lipid peroxidation. These findings indicated a possible role of increased oxidative stress and altered enzymatic antioxidants, both of which may be relevant to the pathophysiology of autism.

Significance of Serotonin Transporter Gene 5-HTTLPR and Variable Number of Tandem Repeat Polymorphism in Attention Deficit Hyperactivity Disorder

The purpose of this study was to evaluate the relationship between attention deficit hyperactivity disorder (ADHD) and polymorphism of the two regions of the 5-HTT gene [variable number of tandem repeats (VNTR) and 5-HTTLRR] in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 71 patients with ADHD and 128 healthy controls. The 5-HTTLPR S/S genotype was significantly lower in the patients than in the controls (p = 0.018). Homozygous and heterozygous L variant predominated in the ADHD group. But the VNTR STin2.12/12 genotype was significantly less found in the patients than in the controls (p = 0.001). There was no significant difference between the frequency of the short (S), long, 10, and 12 alleles of both groups. The lack of an S/S variant of 5-HTTLPR polymorphism of the STin2.12/12 variant of VNTR polymorphism appears to be associated with an increased risk of ADHD.

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.

No Evidence for an Association between the T102C and 1438 G/A Polymorphisms of the Serotonin 2A Receptor Gene in Attention Deficit/Hyperactivity Disorder in a Turkish Population

Disturbances in the serotonergic neurotransmission system have been implicated in the etiology of attenion deficit/hyperactivity disorder (ADHD). As the importance of genetic factors is well established, genes encoding for proteins of the serotonergic pathway are important candidates to unravel the underlying genetic contribution. We previously demonstrated that the polymorphisms of the serotonin transporter gene promoter and regions of variable number of tandem repeats were involved in the pathogenesis of ADHD. The purpose of this study was to examine the relationship between ADHD and two polymorphisms (T102C and 1438 G/A) in the 5-HT2A gene in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 70 patients with ADHD and in 100 healthy controls. There was no significant difference between the frequencies of the T, C, G and A alleles of both groups. No association was found between the studied polymorphisms of the 5-HT2A gene and ADHD in this sample consisting of Turkish children. Overall, our results suggest that the investigated 5-HT2A polymorphisms are not major susceptibility factors in the etiology of ADHD.

Adrenomedullin and total nitrite levels in children with Henoch-Schönlein purpura

Nitric oxide (NO) is synthesized from endothelium and has an important role in the control of vascular tonus. Adrenomedullin (AM) is a potent vasodilator, and cytoprotective peptide is produced not only in adrenal medulla, but also in the vascular smooth muscle and endothelial cells. To investigate the endothelial synthesis of AM and NO, and endothelial injury in Henoch-Schönlein purpura (HSP), we measured their levels in 16 children with HSP, who were evaluated during the acute and remission phases, and compared with 12 healthy controls. Plasma AM levels (pmol/ml) were significantly higher in acute phase children (46.87±11.49) than in those in remission (35.59±12.39, p<0.01) and controls (30.70±9.12, p<0.001). Similarly, plasma total nitrite levels (μmol/l) were higher in acute phase patients (47.50±12.30) than in those in remission (35.94±10.08, p<0.005) and controls (34.56±11.51, p<0.05). Urinary excretion of AM (pmol/mg creatinine) was higher in acute phase patients (53.85±23.22) than in remission patients (29.97±9.33, p<0.01) and controls (37.43±15.78, p<0.05). Patients had increased urinary nitrite excretion (μmol/mg creatinine) in acute phase (2.39±1.18) compared to those in remission (1.53±0.90, p<0.05) and controls (1.05±0.61, p<0.005). There was no significant difference between remission phase and controls in AM and nitrite levels (p>0.05). This study concluded that AM and NO may have a role in the immunoinflammatory process of HSP, especially in the active stage, although whether this perpetuates, or protects against, further vascular injury is not clear. Further studies are needed to clearly establish the roles of AM and NO in the pathogenesis of HSP.

PREVALENCE AND HEMATOLOGICAL CHARACTERISTICS OF β-THALASSEMIA TRAIT IN GAZIANTEP URBAN AREA, TURKEY

Thalassemia is one of the most common hereditary disorders in the Mediterranean region and studies have shown that the prevalence of β-thalassemia trait is high in the southern part of Turkey. Gaziantep is a city located near this region and, therefore, the authors investigated the prevalence and hematological characteristics of the β-thalassemia traits in primary school students in Gaziantep. Sixty primary schools were selected from a list of all primary schools using a systematic sampling method. Data were collected by a face-to-face questionnaire. Osmotic fragility testing (OFT) using single-tube 0.36% NaCl solution was used for the screening of β-thalassemia. Students who were positive in regard to OFT went through a series of testing, including a complete blood count, serum ferritin levels, serum iron, and hemoglobin electroforesis. Chi-square test was used in statistical analysis. Of the 2439 students enrolled to the study from the selected 60 classrooms, 1353 (55.5%) were male and 1086 (44.5%) were female. The OFT was positive in 115 (4.7%) of the participants. CEA and confirmatory HPLC results of the students who were positive OFT indicated that 70 (60.8%) had normal results, 33(28.7%) showed high HbA2 levels, 7 (6.1%) showed high HbA2 and HbF levels, 5(5.2%) showed high HbA2 and Fe-deficiency anemia, and none showed increased HbF levels. The overall prevalence of β-thalassemia trait was 1.84%. No gender differentials and highest rates among the Kahramanmaras (3.5%) and Sanliurfa (1.7%) born students were the other significant findings of this study. Implementation of a routine carrier-screening program offering genetic counseling, prenatal diagnosis, and selective termination of affected fetuses would be a wise approach to eliminate this disease from the region.

Endothelial NOS gene Glu298Asp polymorphism in preterm neonates with respiratory distress syndrome

Respiratory Distress Syndrome (RDS) due to prematurity is one of the most important causes of morbidity and mortality in Neonatal Intensive Care Units. According to few studies in recent years, endothelial nitric oxide synthase (eNOS) gene polymorphisms are found to be partially responsible for liability to RDS. The purpose of this study was to determine the association between eNOS gene polymorphism and RDS in preterm neonates.

Protective effects of Y-27632 on hypoxia/reoxygenation-induced intestinal injury in newborn rats

BACKGROUND/PURPOSE Necrotizing enterocolitis (NEC) is a major cause of mortality in neonates and is associated with a disruption in the protective intestinal barrier. The precise cause of NEC is elusive. However, ischemia/reperfusion injury of the intestine has been considered a major contributing factor. We examined the role of Y-27632, a selective Rho-kinase inhibitor, on a hypoxia/reoxygenation (H/R)-induced intestinal injury of newborn rat pups. METHODS Hypoxia/reoxygenation was achieved by placing rat pups in an airtight chamber aerated with 95% N(2) + 5% CO(2) for 10 minutes followed by 10-minute 100% oxygen. Forty newborn rat pups were randomly allocated into 4 groups. Group 1 served as untreated controls. The pups in group 2 were subjected to H/R only. In groups 3 and 4, the rats were treated with intraperitoneal injection of 0.3 and 3 mg kg(-1) day(-1) of Y-27632 for 5 days following H/R, respectively. The pups were killed 6 days following the H/R injury. Intestine specimens were evaluated for histopathology and biochemical investigation. RESULTS The microscopic lesions in H/R rat pups were virtually the same as those seen in neonatal NEC, with severe destruction of villi and crypts. Hypoxia/reoxygenation resulted in significant elevation in malondialdehyde levels, but decreased tissue nitric oxide levels (P < .05). Protective effects of Y-27632 on H/R-induced intestinal injury of newborn rat pups were observed with a significant decrease in the intestinal injury score, suppression in malondialdehyde levels, and increase in nitric oxide levels (P < .05). CONCLUSIONS In this experimental study, Y-27632 significantly attenuated H/R-induced intestinal injury. These findings indicate that inhibition of Rho-kinase may offer a novel therapeutic approach in the treatment of NEC.

Otogenic cerebral venous infarction: a rare complication of acute otitis media.

A case of cerebral venous infarction (CVI) as a complication of acute otitis media (AOM) was presented in a 16-month-old male patient. The patient admitted with AOM in the right ear, ipsilateral facial paralysis and contralateral hemiplegia. Computerized tomography of the brain showed low density areas involving both the cortex and subcortical white matter in the right frontoparietal region, and there were patchy and multifocal enhancing areas with intravenous contrast enhancement. These findings disclosed the diagnosis of venous infarctions involving the superficial cortical veins on the right side. Complete recovery was achieved with 2 weeks of sulbactam-ampicilline, amikacin and prednisolone treatment. Although it is rather rare, CVI should also be remembered among the otogenic intracranial complications.