Goncagül Haklar

Reactive Oxygen Species Production by the Spermatozoa of Patients With Idiopathic Infertility: Relationship to Seminal Plasma Antioxidants

PURPOSE We attempted to determine reactive oxygen species production by the spermatozoa of patients with idiopathic infertility and healthy donors, and observe whether increased production was due to decreased seminal plasma reactive oxygen species scavengers. MATERIALS AND METHODS Reactive oxygen species production by spermatozoa and seminal plasma antioxidants was assayed in 18 patients with idiopathic infertility and 10 controls. Reactive oxygen species formation and seminal plasma antioxidants were measured by luminol and lucigenin dependent chemoluminescence, and enzymatic methods, respectively. RESULTS Higher reactive oxygen species production was observed in 16 of the 18 patients (88.8%, p < 0.0001 versus controls). Seminal plasma superoxide dismutase, catalase, glutathione peroxidase and total sulfhydryl group levels in infertile patients were significantly lower than in controls. CONCLUSIONS Decreased seminal plasma antioxidant activity and increased reactive oxygen species production can be responsible for idiopathic male infertility.

Different kinds of reactive oxygen and nitrogen species were detected in colon and breast tumors

Several studies have shown the involvement of reactive oxygen species (ROS; O2*-, hypochlorite, hydroxyl radical, hydrogen peroxide) in carcinogenesis. With certain pathologies, nitric oxide (NO) is formed and can interact with superoxide radical (O2*-) resulting in the propagation of the highly reactive species, peroxynitrite. In order to study the molecular mechanisms underlying the ability of reactive oxygen and nitrogen species (RONS) to mediate carcinogenesis, we have measured ROS, NO, and peroxynitrite content of cancerous tissues obtained from colon and breast carcinoma cases by chemiluminescence technique. All ROS were significantly increased in cancerous colon tissues with hypochlorite making the most important contribution and suggesting the role of inflammatory cells. NO was also increased and the peroxynitrite concentration was higher in cancerous samples. For breast carcinoma cases, only O2*- was significantly increased. Hypochlorite was not detected excluding the contribution of inflammatory cells. NO concentrations were not significantly different, therefore, ROS might originate by change in the redox state of the tissue.

Estrogens ameliorate remote organ inflammation induced by burn injury in rats

Abstract.Objective and design: The present study was designed to investigate the role of sex steroids in burn-induced remote organ injury.¶Material or subjects: Male Wistar albino rats were given burn trauma (n=39), and underwent castration or sham operation at 2 h following the burn injury.¶Treatment: Rats were injected sc with either 17β estradiol benzoate (E2, 10 mg/kg) or an androgen receptor blocker cyproterone acetate (CPA, 25 mg/kg) or vehicle, immediately after burn and at 12 h.¶Methods: At 24 h of burn insult, rats were decapitated. Blood samples for RIA of testosterone, estradiol and tumor necrosis factor (TNF)-α and the tissue samples for myeloperoxidase activitiy (MPO) were taken. ANOVA students t test was used for statistical analysis.¶Results: Castration, antiandrogen and E2 treatments increased plasma estradiol levels and depressed burn-induced elevation in serum TNF-α levels. In the liver and lung, burn-induced increase in MPO was reduced by E2 and castration, while CPA was effective in reducing neutrophil infiltration only in the liver.¶Conclusion: We propose that treatment with estrogens or antiandrogens might be applicable in clinical situations to ameliorate systemic inflammation induced by burn.

Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients

Objective Disturbed endothelial function is closely associated with hyperinsulinaemia and insulin resistance in essential hypertension. The aims of this study were: 1) to evaluate whether the two alternative drugs, angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II (Ang II) antagonists, had comparable effects on glucose metabolism and endothelial function. 2) to determine whether they improve endothelial dysfunction through modulating insulin resistance and oxidative stress. Study design and methods Study design and methods Essential hypertensive patients were randomised into two groups: Twelve (nine patients in final analysis) patients were given enalapril (enalapril group), and twelve (nine patients in final analysis) were given losartan (losartan group). Twelve sex- and age-matched normotensive volunteers were included as controls. Before and after six months of treatment, endothelial function, insulin sensitivity and lipid peroxidation (TBARs) and NO metabolites (NOx) were evaluated. Results Endothelial function, measured as flow mediated dilatation (FMD), was improved in both of the treatment groups (p=0.0001). Calculated insulin sensitivity index also improved in the enalapril-treated group (p=0.05) but not in the losartan-treated group, compared with baseline levels. TBARS values decreased significantly in the enalapril group compared with baseline levels (p<0.001). FMD was positively correlated with insulin sensitivity index (r=0.32, p<0.05) and NOx levels (r=0.39, p=0.01) and negatively correlated with TBARS levels (r=-0.53, p=0.0002) in hypertensive patients. Conclusion Inhibition of the renin-angiotensin system, either with ACE inhibitors or AT1-receptor blockers improves endothelial dysfunction. ACE inhibition has prominent effects on improving insulin sensitivity and decreasing oxidative stress in essential hypertensive patients.

Serum IGF-I and IGFBP-3 levels of Turkish children during childhood and adolescence: establishment of reference ranges with emphasis on puberty.

Aims/Methods: We established age- and sex-related reference ranges for serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in 807 healthy Turkish children (428 boys, 379 girls), and constructed a model for calculation of standard deviation scores of IGF-I and IGFBP-3 according to age, sex and pubertal stage. Results: Serum IGF-I and IGFBP-3 concentrations tended to be higher in girls compared to boys of the same ages, but the differences were statistically significant only in pubertal ages (9–14 years) for IGF-I and only in prepubertal ages for IGFBP-3 (6–8 years) (p < 0.05). Peak IGF-I concentrations were observed earlier in girls than boys (14 vs. 15 years, Tanner stage IV vs. V) starting to decline thereafter. IGFBP-3 levels peaked at age 13 and at Tanner stage IV in both sexes with a subsequent fall. Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal stage followed by a rapid increase in IGF-I in the early pubertal stages. A relatively steeper increase in IGF-I but not in IGFBP-3 levels was observed at age 10–11 years in girls and at 12–13 years in boys which preceded the reported age of pubertal growth spurt. At late pubertal stages, both IGF-I and IGFBP-3 either did not change or decreased by increasing age. Interrelationships between growth factors and anthropometric measurements have been described, and the physiologic consequences of these have been discussed in detail. Conclusions: Differences in the pattern of IGF-I and IGFBP-3 in the present paper and those reported in other studies emphasize the importance of locally established reference ranges. Establishment of this reference data and a standard deviation score prediction model based on age, sex and puberty will enhance the diagnostic power and utility of IGF-I and IGFBP-3 in evaluating growth disorders in our population.

Effect of Mitochondrial Electron Transport Chain Inhibitors on Superoxide Radical Generation in Rat Hippocampal and Striatal Slices

In this study, we have compared the generation of superoxide radical in rat hippocampal and striatal slices in the presence of specific mitochondrial electron transport chain (ETC) inhibitors (complexes I and III) under control and depolarization conditions [incubation in artificial cerebrospinal fluid (ACSF) or depolarizing ACSF (dACSF), respectively]. Superoxide radical generation was increased in both ACSF- and dACSF-incubated hippocampal and striatal slices when rotenone and antimycin A were added to the incubation medium. The increase in superoxide radical was dependent on the concentration of ETC inhibitors under control, but not depolarization conditions. Rotenone was found to be more effective than antimycin A in producing superoxide radical from hippocampal and striatal slices. Our results also showed that hippocampal slices were more sensitive to ETC inhibitors compared with striatal slices. Thus, different regions of the brain seem to differ in their capacity to generate free radicals and vulnerability to oxidative stress conditions. This difference should be considered in developing therapeutic modalities against oxidative stress-related disorders and neurodegeneration.

Evaluation of oxidant stress in chronic hemodialysis patients: use of different parameters

Patients with chronic renal failure, particularly those undergoing regular dialysis treatment (RDT) are candidates for free radical damage. It is difficult to quantitate free radicals because of their short half-lives and reactive nature. Therefore, indirect methods measuring products of lipid peroxidation and protein oxidation are preferred. The present study displays a profile of lipid peroxidation and protein oxidation parameters, which are more sensitive and specific than the widely used method measuring thiobarbituric acid reactive substances (TBARS), adapted to the plasma and erythrocyte samples of RDT patients. We have observed increased levels of plasma and erythrocyte lipid peroxidation and also demonstrated increased protein oxidation in erythrocyte membranes of RDT patients.

Effect of zinc supplementation on growth hormone secretion, IGF-I, IGFBP-3, somatomedin generation, alkaline phosphatase, osteocalcin and growth in prepubertal children with idiopathic short stature

Controversy exists about the effect of zinc on growth and the GH-IGF system. Zinc supplementation has been shown to stimulate linear growth in zinc-deficient children. However the mechanism of this effect has not been well characterized. Furthermore, the effect of zinc supplementation on non-zinc-deficient short children is unknown. We investigated the effect of zinc supplementation on endogenous GH secretion, serum IGF-I and IGFBP-3 concentrations, IGF-I and IGFBP-3 generation in response to exogenous GH, bone formation markers, and linear growth of non-zinc-deficient children with idiopathic short stature. We analyzed prospectively serum zinc, IGF-I, IGFBP-3, alkaline phosphatase, osteocalcin, and GH response to clonidine test, and performed a somatomedin generation test before and 6 weeks after zinc supplementation in 22 (16 M, 6 F) prepubertal children with idiopathic short stature. Serum IGF-I increased from 67.4+/-70.6 to 98.2+/-77.3 ng/ml (p <0.001), IGFBP-3 from 2326+/-770 to 2758+/-826 ng/ml (p <0.001), alkaline phosphatase from 525+/-136 to 666+/-197 U/l (p <0.0001), and osteocalcin from 16.8+/-10.6 to 25.8+/-12.8 ng/ml (p <0.05) after zinc supplementation despite there being no difference in GH response to clonidine after zinc supplementation (peak GH 11.6+/-6.9 vs 13.4+/-7.8 ng/ml, GH area under the curve during clonidine test 689+/-395 vs 761+/-468, NS). Percent change in IGF-I and IGFBP-3 during the somatomedin generation test was not significantly affected by zinc supplementation (118% vs 136% and 57% vs 44%, respectively). There was no significant correlation between percentage increase in zinc levels and percentage increase in parameters tested. Height SDS or weight SDS did not improve significantly in 17 patients who continued on zinc supplementation for at least 6 months (6-12 months) (-2.59 vs -2.53 SDS and -1.80 vs -1.67 SDS, respectively). Zinc supplementation increased basal IGF-I, IGFBP-3, alkaline phosphatase and osteocalcin without changing GH response to clonidine. Zinc supplementation did not affect sensitivity to exogenous GH as tested by IGF-I and IGFBP-3 generation test. These results suggest a direct stimulatory effect of zinc on serum IGF-IGFBP-3, alkaline phosphatase and osteocalcin. Despite improvements in the above parameters, zinc supplementation to children with idiopathic short stature with normal serum zinc levels did not significantly change height or weight SDS during 6-12 months follow-up.

OXYGEN RADICALS AND NITRIC OXIDE IN RAT MESENTERIC ISCHAEMIA-REPERFUSION: MODULATION BY L-ARGININE AND NG-NITRO-L-ARGININE METHYL ESTER

1. The aims of the present study were to detect changes in superoxide anion (O2−), nitric oxide (NO) and other reactive oxygen species (ROS) directly by measurement of chemilumin‐escence (CL) and to investigate the role of L‐arginine, a nitric oxide synthase (NOS) substrate, and NG‐nitro‐L ‐arginine methyl ester (L‐NAME), a NOS inhibitor, together with their molecular enantiomers D‐arginine and D‐NAME, in a rat mesenteric ischaemia‐reperfusion (I/R) model.

Height, Weight, IGF-I, IGFBP-3 and Thyroid Functions in Prepubertal Children with Attention Deficit Hyperactivity Disorder: Effect of Methylphenidate Treatment

Objective: To investigate if there are any disease-related or methylphenidate-induced aberrations in growth parameters, growth hormone insulin-like growth factor (IGF)-I, IGFBP-3 axis and the thyroid function tests in children with attention deficit hyperactivity disorder (ADHD). Methods: Newly diagnosed and untreated prepubertal children with ADHD were longitudinally followed before and approximately every 4 months after methylphenidate treatment for up to 16 months. Height SDS, weight SDS, BMI SDS, serum GH, IGF-I, IGFBP-3, T4, free T4, T3, and TSH were measured at each visit. Results: All of the examined parameters were within normal limits for age before treatment. Methylphenidate treatment did not significantly affect SDS of height, weight, BMI, IGF-I and IGFBP-3 in the long run. Serum T4 and free T4 levels showed modest reductions within normal limits in a time-dependent manner. Conclusions: Prepubertal children with ADHD had normal height, weight, BMI, serum IGF-I and IGFBP-3 and thyroid functions. Methylphenidate treatment had no sustained effects on growth parameters, IGF-I and IGFBP-3 during the follow-up period of this study. However, it caused a mild decrease in total and free T4 which may warrant further monitoring.