Evaluation of Kisspeptin levels in prepubertal obese and overweight children: sexual dimorphism and modulation of antioxidant levels.

OBJECTIVE: Kisspeptin, neuropeptide involved in puberty beginning and regulation of pituitary-gonadal axis, has been shown to stimulate antioxidant defenses in murine models. Its levels are greater in females than males and also in obese prepubertal girls. Therefore, our aim was to evaluate sex-related differences in prepubertal obese patients and the relationships of Kisspeptin with metabolic/hormonal parameters. PATIENTS AND METHODS: We studied Kisspeptin concentrations in 54 children (22 males and 32 females, Tanner stage 1), 5-12 ys, classified according to Cole's criteria into 17 overweight and 37 obese; 25 normal-weight children, aged 6-12 years, were studied as controls. We evaluated metabolic (glucose and insulin levels after oral glucose load, total- LDL- HDL-cholesterol, triglycerides, uric acid) and hormonal (fT3, fT4, TSH, IGF-1, leptin) parameters. Moreover, total antioxidant capacity (TAC) was evaluated by spectrophotometric method, using the system H202-metmyoglobin-ABTS. Kisspeptin levels were measured by RIA. RESULTS: We did not find significant differences between obese and normal-weight children, but obese males presented significantly lower levels than females. Kisspeptin did not correlate with BMI, HOMA-IR, Insulin peak levels and TAC; a significant correlation was found between Kisspeptin and fT3 (r2=0.25; p=0.003) in the obese group; leptin levels, significantly greater in obese vs. overweight and control children, significantly correlated with TAC (r2=0.39; p=0.03). CONCLUSIONS: These data suggest that both hormones could modulate antioxidants, Kisspeptin indirectly via influence on thyroid hormones, and Leptin by a direct effect. This mechanism seems to be sex-related, not attributable to peripheral steroid levels. Further studies can clarify the complex interrelationship between central and peripheral Kisspeptin secretion and oxidative stress in children obesity.

Performance assessment of a fully automated electro-chemiluminescence immunoassay system for serum S100B protein.

The altered expression levels of S100 proteins can lead to four different categories of diseases: diseases of the heart and of the central nervous system, inflammatory disorders and cancer. Various studies have shown the lack of harmonization of the results obtained with different methods, mainly due to different performances and measurements of S100B. The purpose of this work was to compare quantitatively the fully automated Elecsys® immunoassay with the reference immunoenzimatic method CanAg® EIA for serum S100B protein. In the study serum samples were analyzed of 161 patients: 85 females (aged 22-83 years) and 76 males (aged 16-90 years), affected by oncological and non-oncological pathologies. Passing–Bablok regression was used to analyze the comparison between the assays; it showed a strong interassay correlation: r = 0.9350 (95% CI =0.9122 – 0.9520), with an intercept of 0.02063 (95% CI=-0.02850 – 0.01400) and a slope of 1.1125 (95% CI=1.0200 – 1.2417). Elecsys® S100 assay should be preferred to CanAg® S100 for better standardization, good reliability and precision but also with the aim to reduce costs and obtain results in a shorter time.

Oxidative stress as a possible mechanism underlying multi-hormonal deficiency in chronic heart failure.

OBJECTIVE: Chronic Heart Failure (CHF) is associated with multi-hormonal derangement depicting a prevalence of catabolic vs. anabolic axes. Moreover, thyroid adaption is characterized by the reduced conversion of thyroxine to the active hormone triiodothyronine. On the other hand, hormones modulate synthesis and utilization of antioxidant systems. Therefore, hormonal failure can cause unbalance between reactive radical species and the defenses, resulting in oxidative stress (OS). OS is well described in CHF, but the relationship with the hormonal picture is not entirely known. In the present review, we firstly analyze the mechanisms of ROS production in the heart, discussing animal and human studies, and focusing on new discovered protective mechanisms such as sirtuins and fibroblast growth factor 21 (FGF21). The second section is dedicated to the role of main anabolic axes influencing antioxidant systems. Finally, we present some data supporting the hypothesis that OS could be the link between hormonal derangement and clinical outcome of CHF.

Thyroid Function and its Implications in Oxidative Stress Influencing the Pathogenesis of Osteoporosis in Adults with Down Syndrome: A Cohort Study.

People with Down syndrome (DS) show lower bone mass density (BMD) and a higher prevalence of hypothyroidism compared to general population. Furthermore, DS is a well-known high oxidative stress (OS) condition because genes involved in OS map on chromosome 21. Thyroid function too is involved in OS. Since both thyroid function and OS lead to lower BMD and osteoporotic fractures, we have explored correlations among BMD, thyroid hormones, and parameters of OS in DS adults. A total of 105 DS patients (48 males; 21-71 years; mean BMI 28.88±7.12 kg/m(2)) were enrolled in a cohort study, 48 of them undergoing thyroid replacement therapy. We evaluated thyroid function, BMD, and total antioxidant capacity (TAC) in blood plasma. TAC was assayed by H2O2-metmyoglobin system, as source of radicals, and by the chromogenous ABTS, with a latency time (LAG) in the appearance of its cation ABTS+proportional to antioxidant concentration. BMD was evaluated with DEXA, using WHO criteria to classify osteoporosis. Low BMD was found in 83.78% of patients. TSH and LAG did not correlate with BMD. Nevertheless, LAG significantly correlates to Z-scores estimated at the lumbar spine (r(2)=0.558; p=0.03) in hypothyroid patients. Our data show that low TAC could be more associated with reduced BMD rather than TSH itself in DS patients and that the OS could have a role in the pathogenesis of osteoporosis regarding the hypothyroid subgroup.

Comparison of plasma antioxidant levels in middle-aged and old male with idiopatic osteoporosis: preliminary data.

OBJECTIVES: With the purpose of evaluating the role of oxidative stress (OS) in male idiopatic osteoporosis, we have evaluated plasma total antioxidant capacity (TAC) in patients classified according to age (< 65 or ≥ 65 yrs), with normal hormone values and in age-matched healthy control subjects. PATIENTS AND METHODS: TAC was evaluated with a colorimetric method, using the system metamyoglobin-H2O2 and the chromogen ABTS; the latency time (LAG, sec) in the appearance of ABTS radical species is proportional to antioxidant content of the system. RESULTS: We found slightly increased LAG values in middle-aged patients, compared with age-matched controls, probably expression of a compensatory mechanism to OS; on the contrary aged patients showed significantly lower LAG values in comparison with age-matched controls, suggesting a defective compensatory mechanism and, therefore, a risk for oxidative damage. CONCLUSIONS: OS could be a possible mechanism underlying male osteoporosis, both in middle-aged and aged patients, but compensatory mechanisms seem to be defective in the last group.

Estrogens as antioxidant modulators in human fertility.

Among treatments proposed for idiopathic male infertility, antiestrogens, like tamoxifen, play a possible role. On the other hand, oxidative stress is a mechanism well recognized for deleterious effects on spermatozoa function. After reviewing the literature on the effects of estrogens in modulation of antioxidant systems, in both sexes, and in different in vivo and in vitro models, we suggest, also on the basis of personal data, that a tamoxifen treatment could be active via an increase in seminal antioxidants.

Relationship between plasma antioxidants and thyroid hormones in chronic obstructive pulmonary disease.

BACKGROUND: A low-T3 syndrome is observed in chronic diseases, but its treatment is still debated. Chronic obstructive pulmonary disease (COPD) has not been conclusively studied under this aspect. COPD is a complex condition, which cannot be considered a lung-related disorder, but rather a systemic disease also associated to increased oxidative stress. We evaluated thyroid hormones and antioxidant systems, the lipophilic Coenzyme Q10 (CoQ10) and total antioxidant capacity (TAC) in COPD patients to reveal the presence of a low-T3 syndrome in COPD and investigate the correlation between thyroid hormones, lung function parameters and antioxidants. METHODS: We studied: 32 COPD patients and 45 controls, evaluating thyrotropin (TSH), free-triiodotyronine (fT3), free-tetraiodotyronine (fT4), CoQ10 (also corrected for cholesterol) and TAC. CoQ10 was assayed by HPLC; TAC by the metmyoglobin-ABTS method and expressed as latency time (LAG) in radical species appearance. RESULTS: We found significantly lower LAG values, fT3 and fT4 levels and significantly higher TSH in COPD patients vs. controls. LAG values significantly correlated with fT3 concentration. 12 out of 32 patients exhibited fT3 levels lower than normal range. So we divided COPD patients in 2 groups on the basis of the fT3 concentration (normal fT3 COPD and low fT3 COPD). We observed lower LAG values in normal fT3-COPD, compared to healthy subjects, with a further significant reduction in low fT3-COPD patients. Moreover higher TSH concentration was present in normal fT3-COPD, compared to healthy subjects, with a further significant increase in low fT3-COPD patients. CoQ10/cholesterol ratio was higher in low fT3-COPD vs. normal fT3-COPD, with a nearly significant difference. CONCLUSIONS: These data seem to indicate an increased oxidative stress in low fT3-COPD and a role of fT3 in modulating antioxidant systems. However low fT3 levels are joined to metabolic indexes of true hypothyroidism, suggesting that elevated CoQ10 expresses a reduced tissue utilization. These data might suggest the need of thyroid replacement therapy in such a condition.