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.

Alterations in hearing function of patients with glucose disorders.

OBJECTIVE: To study the prevalence of hearing impairment in patients with various glucose disorders. PATIENTS AND METHODS: A total of 499 individuals were studied, 51 patients with type 1 (TIDM), 188 patients with type 2 diabetes mellitus (T2DM), 39 patients with impaired fasting glucose (IFG), and 221 controls. Measurements were performed, blood was drawn, and a relevant questionnaire was completed. Ηearing function was assessed by pure-tone audiometry (PTA) and distortion product otoacustic emissions (DPOAEs). RESULTS: Patients with impaired glucose metabolism (IGM: T2DM or IFG) compared to controls had a higher percentage of abnormal PTA and DPOAEs for both the right (70.2 vs. 56.9% and 40.4 vs. 24.2%, respectively, p < 0.001) and the left (74.1 vs. 59.3% and 47.5 vs. 25.4%, respectively, p < 0.001) ear. Patients with TIDM had similar levels for the left ear (54.9 vs. 59.3% and 27.5 vs. 25.4%, respectively, p > 0.05) and lower levels for the right ear (35.3 vs. 56.9% and 13.7 vs. 24.2%, respectively, p < 0.001 and p = 0.044) percentages of abnormal PTA and DPOAEs compared to controls. Logistic regression analysis indicated that independent parameters for abnormal DPOAEs in one or both ears are age, male gender, exposure to noisy environments, and the presence of IGM. CONCLUSIONS: Hearing impairment was more prevalent in patients with IGM compared to healthy controls, as assessed by PTA and DPOAEs. Age, male gender, and exposure to noise are other factors that can independently affect hearing ability. Physicians should bear in mind possible defects in hearing ability when dealing with such patients.

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.

Prevalence and determinants of type 2 diabetes mellitus in a Greek adult population.

The prevalence of diabetes mellitus (DM) is increasing worldwide reaching epidemic proportions. The aim of the present study was to estimate the prevalence of DM in Thessaly, a large region of Central Greece, and to extrapolate our results to the population of the entire country. A random sample of 805 adults (421 females and 384 men) living in Thessaly, aged 18-80 years, was surveyed. After completing a questionnaire about health status and a thorough physical examination, a blood sample was obtained from each participant for biochemical analysis. Participants with fasting glucose levels between 100-125 mg/dl underwent an oral glucose tolerance test (OGTT). A second survey was also conducted, via telephone call-interviews, in a randomly selected sample age- and sex-stratified to the country's adult population in order to extrapolate the DM data from Thessaly to the whole country. The frequency of DM based on patient history and fasting blood glucose levels was 6.96%, comparable to that observed in the telephone-based nationwide survey (7.38%, p=0.669). However, after the OGTT an additional 3.72% of the population had undiagnosed DM, increasing DM prevalence to 10.68% (age adjusted 11.77%). The prevalence of pre-diabetes was 8.70%, with impaired fasting glucose at 5.84% and impaired glucose tolerance at 2.86%. The prevalence of DM was significantly higher in men (14.58%) than in women (7.13%, p<0.001), increased with age in both sexes and was more prevalent in hypertensive (p<0.001) and obese subjects (p=0.001) and in those living in rural areas (p=0.003). In the multiple logistic regression analysis, significant predictors of pre-diabetes and DM together were age, homeostasis model of assessment of insulin resistance (HOMA-IR), alcohol consumption and educational status, whereas those of DM alone were age, HOMA-IR and triglycerides. Extrapolating our data to the whole country, the age-adjusted prevalence of DM was estimated at 11.97% (men 13.98%, women 9.25%), clearly indicating a major public health problem.

Associations of estrogen receptor alpha and Beta gene polymorphisms with lipid levels and insulin resistance in men.

OBJECTIVE: The association of four single nucleotide polymorphisms in estrogen receptor alpha (ESR1) and beta (ESR2) genes with lipid levels and insulin resistance in men. DESIGN AND METHODS: Lipids, glucose, insulin and HOMA-IR were determined, in a population-based, cross-sectional, cohort of 170 apparently healthy middle-aged Greek men, along with body mass index (BMI), waist circumference (WC) and percentage of body fat content (%fat). Genotyping of ESR1 for PvuII and XbaI and ESR2 for RsaI and AluI polymorphisms was performed. RESULTS: Associations of AluI with LDL-Chol (mean ± SD, aa 4.3 ± 1.1 vs. Aa 3.7 ± 1.0 and ΑΑ 4.2 ± 1.1, p = 0.023) and RsaI with HOMA-IR [median (IQR), RR 1.55 (0.88-2.49) vs. Rr/rr 1.69 (0.72-2.29), p = 0.032] were found. Synergistic effects of RsaI and AluI of ESR2 gene on LDL-Chol levels, %fat and WC, as well as a synergistic effect of both ESR1 and ESR2 genes on levels of TChol (p = 0.01) and LDL-Chol (p = 0.027) were also shown. These findings remained significant after adjustment for potential confounders. Significant independent associations of PvuII with %fat (mean ± SD, pp 24.6 ± 5.3 vs Pp 22.4 ± 5.2 and PP 21.2 ± 6.7, p = 0.044), and RsaI with %fat (RR 22.6 ± 5.5 vs. Rr/rr 25.2 ± 6.3, p = 0.015) and WC (mean ± SD, RR 97.4 ± 10.4 vs. Rr/rr 102.6 ± 12.6, p = 0.013) were found. Synergistic effects on %fat, between the ESR1 polymorphisms (p = 0.004), between the ESR2 polymorphisms and among all four ESR polymorphisms studied were also present. CONCLUSIONS: ESR2 is associated with LDL-Chol levels and HOMA-IR in men independently of confounders. Body fat is affected by both genes. Furthermore, a synergistic effect of ESR1 and ESR2 on TChol, LDL-Chol and %fat, was shown.

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.

Increased primary autoimmune thyroid diseases and thyroid antibodies in sarcoidosis: evidence for an under-recognised extrathoracic involvement in sarcoidosis?

OBJECTIVE AND DESIGN: Sarcoidosis has been associated with thyroid diseases. However, until today no definite conclusions have been drawn. We aimed to assess the frequency of thyroid disorders and the levels of thyroid hormones and thyroid antibodies in 68 sarcoidosis patients and 75 controls. Additionally, we performed ultrasonography and fine-needle aspiration. RESULTS: In this prospective case control study conducted in the University Hospital of Larissa, Greece, overt thyroid disease was present in 29.4% of patients and 16.1% of patients presented clinical autoimmune thyroid disease. Sarcoidosis patients had a significantly higher frequency of serological autoimmunity. Female patients had significantly increased frequency of positive TSH receptor antibodies (TRAbs) and antithyroid peroxidase antibodies (TPOAbs) when compared to gender-matched controls (40% vs 0%, p<0.001, and 28.8% vs 11.86%, p=0.029, respectively). The hypoechoic pattern of the thyroid was more frequent in female patients vs controls (p<0.001). Male patients had a higher frequency of TRAbs and hypoechoic pattern of the thyroid gland (43.4% vs 0%, p=0.002, and 39.1% vs 6.25%, p=0.021, respectively). Indices of thyroid autoimmune disease were significantly more frequent in sarcoidosis patients vs gender-matched controls. Increased TPOAbs were significantly associated with clinical autoimmune disease in sarcoidosis. CONCLUSIONS: Overall, the findings derived from this study suggest that thyroid disorders are frequent in sarcoidosis. This association may potentially be the result of increased thyroid antibodies.

High rates of obesity prevalence in adults living in central Greece: data from the ARGOS study.

OBJECTIVE: To investigate the prevalence of obesity in adults of a large region of Central Greece. DESIGN: The target group was adults aged 18 to 79 years who were residents of the region of Thessaly for at least one year. A sample of 852 individuals stratified for sex and age were included. Each subject underwent a thorough physical examination and body mass index (BMI) was calculated from body weight and height. Waist and hip circumferences as well as body fat content were additionally measured. RESULTS: Mean (SD) BMI for the total population was 27.5+/-5.5 and was significantly higher in males than in females (28.2+/-4.4 vs. 26.9+/-6.2, p<0.001). The overall prevalence of obesity was 26.6% distributed equally between men (27.8%) and women (25.6%), whereas prevalence of overweight was 39.4% with male predominance (50.8% vs. 29.3%, p<0.001). Morbid obesity (MO) was found in 3.5% with female predominance. The prevalence of central obesity, using waist circumference cut-off points (>102cm for men, >88cm for women), was comparable in males (40.4%) and females (35.3%). There was a positive association between obesity, central obesity, and age. The prevalence of overweight (19.5%) and obesity (9.4%) in the age-range of 18-29 years almost doubled in the next decade of age and attained the highest value, respectively, in the age-range of 50 to 59 (48.2%), and of 60 to 70 years group (38.9%). CONCLUSIONS: The rates of overweight and obesity in the population of Thessaly are relatively high with overweight being more prominent in males than in females, whereas MO was higher in females compared to males.

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.

Amelioration of cardiovascular risk factors with partial biochemical control of acromegaly.

OBJECTIVE: Complete remission of acromegaly is associated with favourable changes in cardiovascular risk parameters. We evaluated the effects of suboptimal therapy on haemodynamic, metabolic, inflammatory and coagulation cardiovascular risk indices. DESIGN AND METHODS: Eighteen acromegalic patients on somatostatin analogues, with incomplete biochemical control, were evaluated at diagnosis and 6 months after treatment and compared to 15 healthy age- and body mass index (BMI)-matched controls. Measurements of blood pressure, GH, IGF-I, glucose, insulin, glycated haemoglobin (HbA1c), lipids, apolipoprotein A1 (apoA1), apoB, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA) and circulating thrombomodulin were performed in all study participants, followed by an oral glucose tolerance test (OGTT). Insulin sensitivity (IS) was expressed by the Matsuda index (OGTT(ISI)). RESULTS: Partial control of acromegaly resulted in a significant reduction in systolic and diastolic blood pressure, glucose, insulin, HbA1c, total (T-C) and low density lipoprotein cholesterol (LDL-C) and triglyceride levels, and a significant increase in apoA1, high density lipoprotein cholesterol (HDL-C) and OGTT(ISI) compared to pretreatment levels. Plasma fibrinogen and PAI-1 levels fell significantly [respectively (mean +/- SEM), 11.04 +/- 0.41 vs. 10.12 +/- 0.34 micromol/l, P = 0.003 and 9.6 +/- 1.97 vs. 6.55 +/- 1.89 microg/l, P < 0.001]. However, a marked reduction in tPA [median (IQR) 5.1 (2.5-15) vs. 3.4 (2.4-8.6) microg/l, P = 0.031] and an increase in hs-CRP [median (IQR) 0.05 (0.03-0.11) vs. 0.1 (0.06-0.23) mg/l, P < 0.001] were also noted. On treatment, acromegalic patients were comparable to controls, except for OGTT(ISI), lipoprotein(a) [Lp(a)], fibrinogen and tPA and HDL-C levels. Thrombomodulin and apoB levels were not affected by treatment. CONCLUSIONS: Partial control in disease activity following somatostatin analogues results in significant improvement in a considerable number of cardiovascular risk markers in acromegaly.

Multivitamins and phospholipids complex protects the hepatic cells from androgenic-anabolic-steroids-induced toxicity.

INTRODUCTION: Androgenic-anabolic-steroids (AAS)-induced hepatotoxicity typically occurs with C-17 alkylated oral agents abused by exercising individuals at clinically recommended doses. Injectable compounds appear to have the same risk for hepatotoxicity, but are applied in doses three to six times higher than clinically recommended. AAS users occasionally try to avoid the well-known hepatotoxic effects associated with the abuse of a multitude of AAS agents, by using the pharmaceutical agent compound N a phospholipid/vitamin preparation. PRIMARY OBJECTIVE: The investigation of the actual hepatoprotective effect of compound N against AAS-induced toxicity. METHODOLOGY: This was an observational cohort study of 320 athletes; 160 were AAS users and the other 160 were not abusing any substances. Of the 160 users, 44 were using AAS and compound N (group A), and 116 were using solely AAS (group B). The 160 athletes abstaining from substances abuse acted as controls (group C). All athletes were tested for alterations in serum levels of hepatic enzymes. Enzyme levels before the study's onset and after the end of the 8-week AAS regimes were compared among the three groups, in order to delineate the hepatoprotective effect of compound N. RESULTS: Prior to our research all groups showed normal values in all enzymes except creatine kinase (CK). After the 8-week period, CK levels were slightly lower in group A, but without variation in Groups B and C; -Glutamyl Transferase (GT) levels remained normal. Groups A and C had no elevations in any of the enzymes, except CK, while in group B all enzymes' values were elevated above the normal range. The only factor differentiating AAS users in group A from those in group B was the use of compound N, thus the results being suggestive of the compound's detoxification effect. The severity of AAS abuse was positively associated with the degree of changes ( values) in all measured enzymes except GT and CK. CONCLUSIONS: Previous suggestions that serum hepatic enzyme elevations in exercising AAS abusers are connected to muscle fiber damage rather than the abuse itself, are contradicted by our results. Since all AAS abusing athletes were prone to exhibit elevations in enzymes' values, the mean values of group A were to be similar to those observed in group B, exceeding normal values. The group hepatic enzyme values of group B were significantly higher than the group C (control). Notably, group A did not have any statistically significant difference in the hepatic enzyme values compared to group C. The effect of exercise on these enzymes' elevations was ruled out by the comparability of training regimens and AAS toxicity was correlated to the severity of AAS abuse.

Prevalence of coeliac disease in the adult population of central Greece.

OBJECTIVES: Recent studies from several countries have shown that coeliac disease (CD) is increasingly being diagnosed in adults, as the availability of new, accurate serologic tests has made screening in the general population possible. No data exist regarding the prevalence of CD in Greece. The aim of this study was the implementation of a serologic screening procedure for CD in the adult general population of Thessaly, an area of central Greece, using a novel diagnostic algorithm. METHODS: The study included 2230 participants (1226 women, 1004 men, median age 46 years, range 18-80 years), selected by systematic random sampling, from the adult general population of Thessaly. All the serum samples were tested for total immunoglobulin A (IgA)-serum levels, to exclude IgA deficiency. Samples with total IgA within the normal range were tested for IgA antibodies against native human-tissue transglutaminase (anti-tTG); samples that were anti-tTG positive were tested for IgA antiendomysial antibodies (EmA). Samples from participants with selective IgA deficiency were examined for IgG antigliadin antibodies. Participants who were EmA-positive or antigliadin antibody-positive were referred for intestinal biopsy and human leucocyte antigen (HLA) typing. RESULTS: No participant with selective IgA deficiency was detected. Four individuals tested positive for EmA, all of whom were biopsy-proven coeliacs. Therefore, the CD prevalence in this general population sample is 1 : 558 or 1.8 per 1000 (SE 0.13). The four new patients with abnormal histology (two men, two women) were aged between 18 and 35 years. Two of them were considered to be asymptomatic and two presented with a subclinical course. All four had the heterodimer HLA-DQ2. CONCLUSIONS: This first serological screening study for CD in Greece has demonstrated that CD prevalence in Thessaly is among the lowest reported in Europe.

Methylenetetrahydrofolate reductase gene polymorphism as a risk factor for diabetic nephropathy: a meta-analysis.

Investigations into the association between diabetic nephropathy (DN) and MTHFR C677T gene polymorphism in several case-control studies has yielded contradictory results. To shed light on these inconclusive findings, a meta-analysis of all available studies relating the C677T polymorphism to the risk of developing DN was conducted. The PubMed database was searched, and case-control studies investigating the association between MTHFR C677T gene polymorphism and DN were included in the meta-analysis. The meta-analysis included 15 studies, of which 8 involved Caucasians and 5 East Asians; 11 studies involved subjects with type 2 diabetes and 4 with type 1 diabetes. The main analysis (all studies) revealed significant heterogeneity between the studies (P(Q)<0.01) and a marginal association between the 677T allele and the risk of developing DN; the random effects (RE) pooled odds ratio (OR) was 1.30 (1.03-1.64). However, the sensitivity analysis (exclusion of studies not in Hardy-Weinberg equilibrium) produced non-significant results. The recessive model derived significant results in main analysis [fixed effects (FE) OR=1.32 (1.10-1.58), P(Q)=0.27], and in type 2 diabetes [FE OR=1.30 (1.06-1.60), P(Q)=0.38]. The additive model produced significant association in main analysis [RE OR=1.65 (1.13-2.42), P(Q)<0.01] in Caucasians [FE OR=1.48 (1.11-1.98), P(Q)=0.17] and in type 2 diabetes [RE OR=1.65 (1.03-2.67), P(Q)<0.01]. However, sensitivity analysis diminished the significant results in type 2 diabetes. There is no differential magnitude of effect in large versus small studies. In conclusion, although there is some evidence of association between MTHFR C677T gene polymorphism and DN, the above findings reinforce the need for further and more rigorous association studies.

Psychiatric and hostility factors related to use of anabolic steroids in monozygotic twins.

INTRODUCTION: Anabolic androgenic steroids (AAS) are derived by chemical manipulation of the testosterone molecule. The specified category of drugs produces anabolic, androgenic and psycho-active effects including elevated aggressive, hostile, violent and anti social behavior. OBJECTIVE: The objective of this case report observational study was to evaluate the possible psychological consequences of AS use in the twin user of each pair, compared with the non-user twin. METHODOLOGY: We studied two pairs of male monozygotic twins: one pair 24 years old and the other 31 years old, with absolute genome and phenotype similarity. One of the twins of each pair used AAS while the other did not. Both pairs lived in Hellenic provincial towns and followed a common training and nutrition regime. The psychometric instruments used were the Symptoms Check List-90 (SCL-90) and the Hostility and Direction of Hostility Questionnaire (HDHQ). The psychometric evaluations took place within a time interval of 6 months. RESULTS: The study found high levels of aggressiveness, hostility, anxiety and paranoid ideation in the twins who used AS. The non-user twins showed no deviation from their initial status. CONCLUSION: The use of AAS induced several important psychiatric changes in monozygotic twins which were not present in the twin who did not use AAS.

Psychiatric side effects induced by supraphysiological doses of combinations of anabolic steroids correlate to the severity of abuse.

OBJECTIVE: The objective of our study was to evaluate the psychological consequences of real-world AAS use in athletes abusing such agents, in comparison with a placebo and control group of comparable athletes, while correlating the severity of abuse with the side effects observed. The hypothesis tested by the study was that the use of AAS induces a wide range of psychological side effects whose impact and emergence is dependent upon the severity of the abuse. DESIGN: The study includes a substantial group of AAS abusing athletes and two more groups demographically similar to the first, one composed of athletes not using any substance and a placebo group. All athletes were stratified according to the severity of AAS abuse. Psychometric instruments were applied to all athletes in specific time intervals, dependent to the AAS abusers' regimens, providing us with a final psychological profile that was to be compared to the pre-study profile. All results were comparable (within and between groups) for statistically significant differences and correlated to the severity of the abuse. Homogeneity of all groups was safeguarded by random doping controls, monitoring of drug levels and analysis of all self obtained drugs by method of liquid chromatography/mass spectrometry. All athletes were provided with a common exercise and dietary regime, so common training and nutritional conditions were achieved. METHODS: We studied a cohort of 320 body-building, amateur and recreational athletes, of whom 160 were active users of AAS (group C), 80 users administering placebo drugs (group B) and 80 not abusing any substance (Group A). Group C athletes were stratified according to AAS abuse parameters, thus providing us with three subgroups of "light, medium and heavy abuse". Athletes of groups A and B were included in a "no abuse" subgroup. The psychometric instruments used were the Symptoms Check List-90 (SCL-90) and the Hostility and Direction of Hostility Questionnaire (HDHQ). The psychometric evaluations took place within a time interval of 13 months. Statistical analysis was performed by using the Mann-Whitney/Wilcoxon two-sample non-parametric test (Kruskal-Wallis test for two groups) for data that were not normally distributed and Linear regression analysis was used to ascertain the correlation between severity of use and escalation of side effects. RESULTS: The study showed a statistically significant increase in all psychometric subscales recorded in group C, and no statistically significant difference in group C and A. There was a significant increase in the scorings of group C for all subscales of SCL-90 and HDHQ. Correlation of abuse severity and side effects showed that there was a statistical significant increase in Delta values of all SCL-90 and HDHQ subscales that escalated from light abuse to medium and heavy abuse/consumption patterns. CONCLUSIONS: The results of the study suggest that the wide range of psychiatric side effects induced by the use of AAS is correlated to the severity of abuse and the force of these side effects intensifies as the abuse escalates.

BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and the risk of osteoporosis: a meta-analysis.

A meta-analysis regarding BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and their associations with osteoporosis in females is reported. The meta-analysis involved 14, seven, seven and three studies for BsmI, TaqI, ApaI and FokI polymorphisms, respectively. The studies were association studies with osteoporotic cases and controls free of osteoporosis that provided the genotype distribution of individual cases and controls. For the BsmI polymorphism, the allele contrast b vs. B showed heterogeneity among studies (p< 0.01, I2> 50%) and the random effects (RE) pooled odds ratio (OR) was non-significant: 0.94 [95% confidence interval (CI) 0.63-1.38]. Caucasians, postmenopausal cases and studies with WHO diagnostic criteria showed no association under any genetic contrast. However, in East Asians, the OR for the dominant model [fixed effects OR=0.14 (95% CI 0.04-0.50) and RE OR=0.16 (95% CI 0.03-0.84)] was significant, indicating prevention. Overall, for the TaqI, ApaI and FokI polymorphisms, the allele contrast showed heterogeneity and the pooled RE ORs were non-significant [OR=1.06 (95% CI 0.71-1.60), OR=0.99 (95% CI 0.72-1.37) and OR=1.17 (95% CI 0.76-1.80), respectively]. The allele contrast for Caucasians, East Asians, postmenopausal cases and studies with WHO diagnostic criteria showed no association for TaqI, ApaI, and FokI. The allele contrast of homozygotes, and the recessive and dominant models the results followed the same pattern as the allele contrast. Therefore, the relationship between the VDR polymorphisms and osteoporosis remains an unresolved issue and other probable genetic-environmental risk factors interacting with the above polymorphisms should be investigated.

Effect of 4 weeks of basic military training on peripheral blood leucocytes and urinary excretion of catecholamines and cortisol.

In this study, we assessed the effects of a 4 week basic military physical training programme for male recruits of the Hellenic Air Force on the number and distribution of circulating immune cells and adrenergic and adrenocortical hormonal responses. One group of recruits (exercised, n = 48) participated in moderate intermittent physical exercise, whereas a second group (non-exercised controls, n = 9) performed only light work in the barracks. Both groups participated in the same non-physical, classroom-type training and testing. Military training by the exercised group resulted in significant increases in CD4+ T-lymphocytes, renal cortisol excretion and the urinary noradrenaline/adrenaline ratio, together with reductions in neutrophils and the neutrophil/lymphocyte ratio. In the exercised group, the urinary noradrenaline/adrenaline ratio correlated positively with the training-induced changes in CD4+ T-lymphocytes and negatively with changes in the neutrophil/lymphocyte ratio. No significant relationship was found between training-induced increases in cortisol excretion and any of the peripheral blood cell alterations. Our results indicate that 4 weeks of military training consisting of intermittent moderate exercise resulted in a significant increase in CD4+ T-lymphocytes and reduction in neutrophils. These changes were probably driven by alterations in hormonal status, including the significant impact of sympathetic nervous system activation.

Metabolic control of diabetes is associated with an improved response of diabetic retinopathy to panretinal photocoagulation.

OBJECTIVE: To study the influence of glycemic control and the presence of microalbuminuria on the initial response to panretinal photocoagulation (PRP) in patients with a high-risk proliferative diabetic retinopathy (PDR). RESEARCH DESIGN AND METHODS: This was a prospective cohort study with a two-by-two factorial design. We used full-scattered PRP to treat 115 eyes of type 2 diabetic patients who have high-risk PDR. HbA1c (A1C) and albumin levels in 24-h urine were constantly monitored during the pre-enrollment, treatment, and posttreatment periods. At a follow-up visit 12 weeks after the last PRP session, the fundus was examined for characteristics of regression from high-risk PDR and the response to PRP was determined to be successful or unsuccessful. The eyes were categorized into four groups based on average A1C levels and the presence or absence of microalbuminuria. The data were analyzed using a logistic regression model. Our statistical analysis determined the probability of achieving a satisfactory response to PRP in association with A1C levels and the presence or absence of microalbuminuria. RESULTS: Of the 115 eyes examined, 65 (56.5%) had a successful initial response to PRP and 50 (43.5%) did not. The probability of a satisfactory response to PRP was related to A1C levels (P < 0.05) but not to microalbuminuria and its interaction with hemoglobin glycosylation (P > or = 0.05). CONCLUSIONS: Low levels of hemoglobin glycosylation (A1C <8%) during the pretreatment, treatment, and posttreatment periods are associated with a regression of proliferative diabetic retinopathy after PRP.

Circulating adhesion molecules levels in type 2 diabetes mellitus and hypertension.

BACKGROUND: Risk factors for atherosclerosis such as hypertension, type 2 diabetes, obesity and dyslipidemia affect endothelial function and stimulate adhesion molecules expression. The aim of the study was to examine endothelial activation in type 2 diabetes and hypertension as indicated by adhesion molecule levels and further to investigate whether the coexistence of the above conditions has a different effect. METHODS: Serum levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured in 17 hypertensive type 2 diabetic patients (DM-HY), 32 normotensive type 2 diabetic patients (DM), 11 hypertensive nondiabetic patients (HY) and 15 healthy subjects. RESULTS: In diabetic patients (either DM-HY or DM), soluble E-selectin levels were significantly increased compared to healthy subjects (p<0.001). In HY patients, both sE-selectin (66.44+/-71.59 vs. 29.42+/-15.56 ng/ml, p=0.033) and sVCAM-1 (1529+/-433.33 vs. 1027+/-243.56 ng/ml, p=0.03) levels were found significantly higher compared to healthy subjects (p<0.05). The coexistence of diabetes and hypertension (DM-HY) did not have an additive effect on circulating adhesion molecules levels compared with the levels observed in either diabetes or hypertension. Systolic and diastolic blood pressure (BP) were independent factors correlated respectively with sE-selectin and sVCAM-1 levels (R=0.454, p=0.034 and R=0.578, p=0.005) in nondiabetic subjects (hypertensive and normotensive). CONCLUSIONS: Type 2 diabetes mellitus and hypertension induce endothelial activation as indicated by elevated levels of soluble adhesion molecules. This effect is not different when comorbidity is present.