Sex hormone binding globulin (SHBG) serum levels and insulin resistance in men on chronic hemodialysis.

BACKGROUND: In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance. METHODS: In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose. RESULTS: 27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other. CONCLUSIONS: Our findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.

Testosterone and dihydrotestosterone modulate the redox homeostasis of endothelium.

The predominance of cardiovascular diseases among men compared to premenopausal women has been attributed to testosterone, which is implicated in vascular remodeling. Molecular mechanisms underlying its role have not been clarified but oxidative stress-induced inflammation may be important. We therefore investigated in vitro the effects of testosterone and dihydrotestosterone, (a nonaromatized androgen), on redox homeostasis in absence (basal conditions) and after corticotropin-releasing hormone-induced pro-oxidant action in macroendothelial cells. More specifically, we explored their role on well-established antioxidant enzymes activity, namely endothelial nitric oxide synthase, superoxide dismutase, catalase, and glutathione. We observed that both androgens significantly increased the intracellular reactive oxygen species levels, endothelial nitric oxide synthase activity, nitric oxide concentration as well as superoxide dismutase activity and decreased catalase activity. These effects of Testosterone and DHT were reversed in the presence of the androgen receptor antagonist, flutamide. Moreover, testosterone and dihydrotestosterone similarly enhanced the stimulatory effect of corticotropin-releasing hormone on intracellular reactive oxygen species levels and superoxide dismutase activity but did not influence the inhibitory effect on endothelial nitric oxide synthase activity, nitric oxide release and catalase activity. Finally, androgens did not have a detectable effect on glutathione levels or the glutathione/glutathione plus glutathione disulfide ratio. Our results reveal that testosterone and DHT rise the intracellular redox threshold of the endothelial cell and increases NO synthesis. These findings suggest that the action of testosterone is affected by the redox status of the endothelium and help to explain its controversial effects on the cardiovascular system.

Isotopic Traceability (13C and 18O) of Greek Olive Oil.

In recent years, isotopic analysis has been proven a valuable tool for the determination of the origin of various materials. In this article, we studied the 18O and 13C isotopic values of 210 olive oil samples that were originated from different regions in Greece in order to verify how these values are affected by the climate regime. We observed that the δ18O isotopic values range from 19.2 ‱ to 25.2 ‱ and the δ13C values range from -32.7 ‱ to -28.3 ‱. These differences between the olive oils' isotopic values depended on the regional temperature, the meteoric water, and the distance from the sea. Furthermore, we studied the 13C isotopic values of biophenolic extracts, and we observed that they have same capability to differentiate the geographic origin. Finally, we compared the isotopic values of Greek olive oils with samples from Italy, and we concluded that there is a great dependence of oxygen isotopes on the climatic characteristics of the different geographical areas.

17-ß estradiol attenuates the pro-oxidant activity of corticotropin-releasing hormone in macroendothelial cells.

Corticotropin-releasing hormone, which is the predominant regulator of neuroendocrine responses to stress, attenuates inflammation through stimulation of glucocorticoid release. Enhanced corticotropin-releasing hormone expression has been detected in inflammatory cells of the vascular endothelium, where it acts as a local regulator of endothelial redox homeostasis. Estrogens have beneficial effects on endothelial integrity and function, though the mechanism underlying their antioxidative effect remains as yet largely unknown. We therefore investigated the effect of 17ß-estradiol on pro-oxidant action of corticotropin-releasing hormone in vitro in macroendothelial cells, and, more specifically, the role of 17ß-estradiol on corticotropin-releasing hormone-induced activities/release of the antioxidant enzymes namely, endothelial nitric oxide synthase, superoxide dismutase, catalase, and glutathione. We observed that 17ß-estradiol abolished the stimulatory effect of corticotropin-releasing hormone on intracellular reactive oxygen species levels and counteracted its inhibitory effect on endothelial nitric oxide synthase activity and nitric oxide release. In addition, 17ß-estradiol significantly induced superoxide dismutase and catalase activity, an effect that was not significantly influenced by corticotropin-releasing hormone. Finally, 17ß-estradiol significantly increased glutathione levels and the glutathione/glutathione + glutathione disulfide ratio, an action that was partially blocked by corticotropin-releasing hormone. Our results reveal that 17ß-estradiol counterbalances corticotropin-releasing hormone-mediated pro-inflammatory action and thereby maintains the physiological threshold of the endothelial cell redox environment. These observations may be of importance, considering the protective role of estrogen in the development of atherosclerosis.

Normal menstrual cycle steroid hormones variation does not affect the blood levels of total adiponectin and its multimer forms.

OBJECTIVE: Plasma total adiponectin reveals a sexual dimorphism indicating that gonadal steroids may be involved in its secretion and/or metabolism. However, results from previous reports are conflicting and data regarding the influence of ovarian steroids on adiponectin's multimer forms are scarce. The objective of the study was to assess if total adiponectin and its isoforms are affected by the changes of estradiol and progesterone during the normal menstrual cycle and the association of total adiponectin and its isoforms with the gonadal steroid levels. MATERIALS/METHODS: Quantitative determination of plasma adiponectin and its multimers was conducted in the three phases of an ovulatory cycle in 13 premenopausal women, in the follicular phase of 10 more premenopausal women, in 20 postmenopausal women and in 21 men. Moreover, serum levels of FSH, LH, prolactin, estradiol, progesterone, and testosterone, sex hormone binding globulin, glucose, and insulin were measured. RESULTS: The circulating levels of total adiponectin and its multimers were not affected by the normal variation of estradiol and progesterone across the ovulatory menstrual cycle. In the whole number of participants, the total adiponectin and high molecular weight adiponectin levels were significantly different between genders and associated positively with age and sex hormone binding globulin levels, and negatively with testosterone and progesterone levels and the waist/hip ratio. In the multiple logistic regression analysis, after adjustment for age, gender, and sex hormone binding globulin and progesterone levels, significant predictors of total adiponectin levels were the waist/hip ratio and testosterone levels, and of high molecular weight adiponectin the testosterone levels. CONCLUSIONS: Normal menstrual cycle ovarian steroids are not involved directly in the regulation of secretion and/or metabolism of total adiponectin and its multimers. Testosterone seems to be responsible for the adiponectin's sexual dimorphism.

Secondhand smoke exposure induces acutely airway acidification and oxidative stress.

Previous studies have shown that secondhand smoke induces lung function impairment and increases proinflammatory cytokines. The aim of the present study was to evaluate the acute effects of secondhand smoke on airway acidification and airway oxidative stress in never-smokers. In a randomized controlled cross-over trial, 18 young healthy never-smokers were assessed at baseline and 0, 30, 60, 120, 180 and 240 min after one-hour secondhand smoke exposure at bar/restaurant levels. Exhaled NO and CO measurements, exhaled breath condensate collection (for pH, H(2)O(2) and NO(2)(-)/NO(3)(-) measurements) and spirometry were performed at all time-points. Secondhand smoke exposure induced increases in serum cotinine and exhaled CO that persisted until 240 min. Exhaled breath condensate pH decreased immediately after exposure (p < 0.001) and returned to baseline by 180 min, whereas H(2)O(2) increased at 120 min and remained increased at 240 min (p = 0.001). No changes in exhaled NO and NO(2)/NO(3) were observed, while decreases in FEV(1) (p < 0.001) and FEV(1)/FVC (p < 0.001) were observed after exposure and returned to baseline by 180 min. A 1-h exposure to secondhand smoke induced airway acidification and increased airway oxidative stress, accompanied by significant impairment of lung function. Despite the reversal in EBC pH and lung function, airway oxidative stress remained increased 4 h after the exposure. Clinical trial registration number (EudraCT): 2009-013545-28.

Effect of CRH on NO bioavailability, ROS production and antioxidant defense systems in endothelial EAhy926 cells.

Local or 'Immune' Corticotropin-Releasing Hormone (CRH) is secreted in peripheral tissues and plays a direct immunomodulatory role as an endocrine or paracrine mediator of inflammation. The present study was undertaken to determine whether CRH affects the endothelial redox state. Accordingly, intracellular reactive oxygen species (ROS) content and peroxynitrite levels, endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) levels as well as catalase activity, superoxide dismutase (SOD) activity and glutathione (GSH) levels were measured in the presence or absence of selective CRH receptor-1 and CRH receptor-2 inhibitors in endothelial EAhy926 cells exposed in vitro in 10(-7) M CRH for 2 h. CRH acting through both receptors induced a significant increase of ROS content (p < 0.001), catalase activity (p < 0.001) and SOD activity (p < 0.001), accompanied by a simultaneous significant decrease of eNOS activity and NO levels (p < 0.001), as well as a significant increase in nitrotyrosine (peroxynitrite) levels (p < 0.05). The data indicate that CRH may act as a regulator of pro-inflammatory mechanisms inducing adaptation of endothelial cell function to local stress.

Serum nitrite and nitrate levels in children with obstructive sleep-disordered breathing.

BACKGROUND: Diminished nitric oxide (NO) levels have been reported in adults with obstructive sleep apnea but no data are available for children with obstructive sleep-disordered breathing (SDB). OBJECTIVES: To assess levels of serum NO metabolites in children with SDB and to explore the effects of NO metabolites, SDB and their interaction on blood pressure. METHODS: Morning nitrite, the sum of nitrite and nitrate (NO(x)), and the average of evening and morning blood pressure were assessed in children with SDB referred for polysomnography and in controls without SDB. RESULTS: Forty-three children with SDB (age: 5.8+/-2.1 years) had moderate-to-severe nocturnal hypoxemia (SpO(2) nadir: 85.6+/-4%), 54 subjects (6.6+/-2.7 years) had mild hypoxemia (SpO(2) nadir: 91.4+/-1.3%) and 20 subjects were controls free of SDB (6.7+/-3.7 years). Subjects with moderate-to-severe hypoxemia had significantly lower ln-transformed NO metabolites (1.4+/-0.7, nitrites; 2.6+/-0.5, NO(x)) compared to those with mild hypoxemia (1.9+/-0.8, nitrites; 3+/-0.6, NO(x)) and controls (2.2+/-0.7, nitrite; 3+/-0.6, NO(x); p<0.05). The effects of NO metabolites and SDB or their interaction on blood pressure were not significant (p>0.05). CONCLUSIONS: Moderate-to-severe hypoxemia accompanying SDB is associated with reduced concentrations of morning serum NO metabolites, but NO levels do not seem to affect blood pressure.

Increased oxidative stress indices in the blood of child swimmers.

The blood redox status of child athletes is compared with that of age-matched untrained individuals. In the present study, 17 swimmers (10.1 +/- 1.6 years) and 12 non-athletes (9.9 +/- 1.1 years) participated. Reduced glutathione (GSH) was lower by 37% in swimmers compared to non-athletes (P < 0.01), oxidized glutathione (GSSG) was not different and their ratio (GSH/GSSG) was lower by 43% in swimmers compared to non-athletes (P < 0.01). Thiobarbituric acid-reactive substances concentration was higher by 25% in swimmers compared to controls. Catalase exhibited a strong trend toward lower levels in swimmers (P = 0.08). Finally, total antioxidant capacity was found lower by 28% in swimmers compared to controls (P < 0.05). In conclusion, we report that children participating in swimming training exhibit increased oxidative stress and less antioxidant capacity compared to untrained counterparts and suggest that children may be more susceptible to oxidative stress induced by chronic exercise.