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Leptin increases prostate cancer aggressiveness.
López Fontana, CM, Maselli, ME, Pérez Elizalde, RF, Di Milta Mónaco, NA, Uvilla Recupero, AL, López Laur, JD
Journal of physiology and biochemistry. 2011;(4):531-8
Abstract
Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.
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Effects of a daily mixed nutritional supplement on physical performance, body composition, and circulating anabolic hormones during 8 weeks of arduous military training.
Fortes, MB, Diment, BC, Greeves, JP, Casey, A, Izard, R, Walsh, NP
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2011;(6):967-75
Abstract
The aim of this work was to investigate the effect of a daily mixed nutritional supplement upon body composition, physical performance, and circulating anabolic hormones in soldiers undergoing arduous training. Thirty males received either a habitual diet alone (CON, n = 15) or with the addition of a daily mixed supplement (SUP, n = 15) of ∼5.1 MJ·d⁻¹ during 8 weeks of training. Body composition (DEXA), maximal dynamic lift strength (MDLS), and vertical jump (VJ) were assessed, and resting blood samples were collected before and after training. Blood analysis included insulin-like growth factors (IGF-1, IGF BP-1, and IGF BP-3), testosterone, and cortisol. There were no group differences at baseline. Body mass loss (mean ± SD) (CON 5.0 ± 2.3, SUP 1.6 ± 1.5 kg), lean mass loss (CON 2.0 ± 1.5, SUP 0.7 ± 1.5 kg), and fat mass loss (CON 3.0 ± 1.6, SUP 0.9 ± 1.8 kg) were significantly blunted by SUP. CON experienced significant decrements in MDLS (14%), VJ (10%), and explosive leg power (11%) that were prevented by SUP. Military training significantly reduced circulating IGF-1 (28%), testosterone (19%), and the testosterone:cortisol ratio (24%) with no effect of SUP. Circulating IGF BP-1 concentration and cortisol remained unchanged throughout, although SUP abolished the significant decrease in circulating IGF BP-3 (20%) on CON. In conclusion, a daily mixed nutritional supplement attenuated decreases in body mass and lean mass and prevented the decrease in physical performance during an arduous military training program.
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Elevated plasma concentration of asymmetric dimethylarginine that is reduced by single dose testosterone administration in idiopathic hypogonadotropic hypogonadism patients.
Cakir, E, Ozcan, O, Yaman, H, Akgul, EO, Bilgi, C, Erbil, MK, Yesilova, Z
The Journal of clinical endocrinology and metabolism. 2005;(3):1651-4
Abstract
Our aim was to investigate whether plasma l-arginine and asymmetric dimethylarginine (ADMA) concentrations and nitric oxide (NO) production are altered in male idiopathic hypogonadotropic hypogonadism (IHH) patients in the hypogonadal state and after single dose testosterone administration compared with those in control subjects. Eighteen newly diagnosed male patients with IHH and 20 healthy volunteer controls matched by age and body mass index were enrolled in the study. Single dose testosterone was administrated im. Initially, pretreatment blood samples were collected after overnight fasting. Posttreatment blood samples were drawn 10 d after the injection. ADMA, l-arginine, and NO were measured in pre- and posttreatment blood samples. The pretreatment ADMA and l-arginine levels were significantly higher, and plasma nitrite plus nitrate (NOx) levels were lower than those in the control group. After 10 d of treatment, ADMA and l-arginine levels were significantly reduced, and NOx levels were significantly increased. There was a significant positive correlation (P < 0.01) between ADMA and l-arginine and a negative correlation between ADMA and NOx levels in patients and controls. In conclusion, the patients with IHH showed elevated plasma ADMA levels associated with a reduction in NO production. Single dose parenteral T administration lowered ADMA concentrations and increased NO production to the control group values.
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Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men.
Olubodun, JO, Ochs, HR, von Moltke, LL, Roubenoff, R, Hesse, LM, Harmatz, JS, Shader, RI, Greenblatt, DJ
British journal of clinical pharmacology. 2003;(3):297-304
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Abstract
AIMS: The influence of ageing on the pharmacokinetics of zolpidem, an extensively prescribed hypnotic medication, was evaluated in healthy human volunteers. METHODS A series of 16 elderly (age: 61-85 years) and 24 young (age: 22-42 years) volunteers received single 5 mg oral doses of zolpidem tartrate. Serum zolpidem concentrations were determined by HPLC with fluorescence detection in samples drawn during 8 h after dosage. The effect of testosterone on zolpidem biotransformation was evaluated in vitro using human liver microsomes. Possible induction of CYP3A protein expression and function was studied in cultured human hepatocytes. RESULTS Among men, apparent oral clearance of zolpidem was decreased in elderly compared to young subjects (3.8 vs 11.0 ml min-1 kg-1, P < 0.01), Cmax was increased (93 vs 40 ng ml-1, P < 0.01), and half-life increased (2.7 vs 1.5 h, P < 0.03). Among women, zolpidem oral clearance was decreased in the elderly (3.0 vs 5.8 ml min-1 kg-1, P < 0.02), Cmax increased (108 vs 60 ng ml-1, P < 0.001), with no difference in t1/2 (2.3 vs 2.4 h). Among male subjects, free serum testosterone concentrations were lower in the elderly (10.5 vs 19.0 pg ml-1, P < 0.01), and were significantly correlated with zolpidem clearance (r2 = 0.46, P < 0.001). Multiple regression analysis indicated a greater relative contribution of serum testosterone than age to the oral clearance of zolpidem among men. In human liver microsomes, co-incubation of zolpidem (10 micro m) with varying concentrations of testosterone produced activation of biotransformation of zolpidem to its principal hydroxylated metabolite. Maximum activation was achieved at equimolar concentrations of testosterone (10 micro m). However, testosterone did not induce immunoactive CYP3A4 expression or catalytic function in cultured human hepatocytes. CONCLUSIONS The increased Cmax and lower oral clearance of zolpidem in the elderly are consistent with recommendations of lower clinical doses of zolpidem in the elderly. Our clinical and in vitro data both suggest that reduced free serum testosterone may have a modulatory role in age-dependent changes in zolpidem pharmacokinetics in men.