Effects of different tube types on patient classification using current diabetes decision limits.

Unlabelled: Management of diabetes is a challenge starting in the pre-analytical phase with selecting the most appropriate glycolysis inhibitor. Study goal was to calculate the impact of tubes with different glycolysis inhibitors on the classification of the glycemic control of 157,415 consecutive hospital patients according to current WHO diabetes criteria.

Methods: Glucose and lactate were measured in parallel in samples from 68 healthy subjects collected and stored in different sample tubes from Sarstedt and Greiner.

A multi-step, dynamic allosteric model of testosterone's binding to sex hormone binding globulin.

Purpose: Circulating free testosterone (FT) levels have been used widely in the diagnosis and treatment of hypogonadism in men. Due to experimental complexities in FT measurements, the Endocrine Society has recommended the use of calculated FT (cFT) as an appropriate approach for estimating FT. We show here that the prevailing model of testosterone's binding to SHBG, which assumes that each SHBG dimer binds two testosterone molecules and that the two binding sites on SHBG have similar binding affinity is erroneous and provides FT values that differ substantially from those obtained using equilibrium dialysis.

Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction: a parallel, randomized trial.

Background: Erectile dysfunction and low testosterone levels frequently occur together.

Objective: To determine whether addition of testosterone to sildenafil therapy improves erectile response in men with erectile dysfunction and low testosterone levels.

Design: Randomized, double-blind, parallel, placebo-controlled trial.

Risk factors associated with cardiovascular events during testosterone administration in older men with mobility limitation.

Background: Testosterone in Older Men with Mobility Limitations Trial found an increased incidence of cardiovascular events in men randomized to testosterone, resulting in enrollment cessation by trial's Data and Safety Monitoring Board. We evaluated changes in gonadal hormones and markers of inflammation and coagulation to elucidate risk factors associated with cardiovascular events.

Methods: Men aged 65 years or more, with mobility limitation, total testosterone 100-350 ng/dL, or free testosterone less than 50 pg/mL, were randomized to placebo or 10 g testosterone gel daily for 6 months.

The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.

Background: Concerns about potential adverse effects of testosterone on prostate have motivated the development of selective androgen receptor modulators that display tissue-selective activation of androgenic signaling. LGD-4033, a novel nonsteroidal, oral selective androgen receptor modulator, binds androgen receptor with high affinity and selectivity. Objectives.

Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial.

Context: Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and androgenic alopecia, but the role of 5α-dihydrotestosterone (DHT) in mediating testosterone's effects on muscle, sexual function, erythropoiesis, and other androgen-dependent processes remains poorly understood.

Objective: To determine whether testosterone's effects on muscle mass, strength, sexual function, hematocrit level, prostate volume, sebum production, and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride (an inhibitor of 5α-reductase type 1 and 2).

Design, Setting, And Patients: The 5α-Reductase Trial was a randomized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010.

Genetic determinants of serum testosterone concentrations in men.

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl.

Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study.

Context: Many factors influence the concentration of circulating testosterone and its primary binding protein, SHBG. However, little is known about the genetic contribution to their circulating concentrations in women, and their heritability in women is not well established.

Objective: Our objective was to estimate the heritability of circulating total testosterone (TT), free testosterone (FT), and SHBG in women in families from the Framingham Heart Study.

Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation.

Context: Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation. Trial's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm. The changes in muscle performance and physical function were evaluated in relation to participant's perception of change.

Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts.

Context: Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men.

Methods: TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated.

Identification of serum biomarkers for aging and anabolic response.

Objective: With the progressive aging of the human population, there is an inexorable decline in muscle mass, strength and function. Anabolic supplementation with testosterone has been shown to effectively restore muscle mass in both young and elderly men. In this study, we were interested in identifying serum factors that change with age in two distinct age groups of healthy men, and whether these factors were affected by testosterone supplementation.

Dynamics of coregulator-induced conformational perturbations in androgen receptor ligand binding domain.

Androgen receptor (AR) coregulators modulate ligand-induced gene expression in a tissue specific manner. The molecular events that follow coactivator binding to AR and the mechanisms that govern the sequence-specific effects of AR coregulators are poorly understood. Using consensus coactivator sequence D11-FxxLF and biophysical techniques, we show that coactivator association is followed by conformational rearrangement in AR ligand binding domain (AR-LBD) that is enthalpically and entropically favorable with activation energy of 29.

Guanidinium chloride-induced spectral perturbations of 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid confound interpretation of data on molten globule states.

We describe limitations in the use of 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS) to examine unfolding intermediates associated with guanidinium chloride (GuHCl)-induced protein denaturation. Several studies have used alterations in fluorescence emission of bis-ANS to quantify the population of "molten globule" states. Our findings indicate that the observed changes in bis-ANS spectroscopic properties could originate from the interactions of bis-ANS and GuHCl and the aggregation of the dye at higher GuHCl concentrations.

Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis.

Context: The mechanisms by which testosterone increases hemoglobin and hematocrit are unknown.

Objective: The aim was to test the hypothesis that testosterone-induced increase in hematocrit is associated with suppression of the iron regulatory peptide hepcidin.

Participants: Healthy younger men (ages 19-35 yr; n = 53) and older men (ages 59-75 yr; n = 56) were studied.

Adverse events associated with testosterone administration.

Background: Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied.

Methods: Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.

Free testosterone levels are associated with mobility limitation and physical performance in community-dwelling men: the Framingham Offspring Study.

Context: Mobility limitation is associated with increased morbidity and mortality. The relationship between circulating testosterone and mobility limitation and physical performance is incompletely understood.

Objective: Our objective was to examine cross-sectional and prospective relations between baseline sex hormones and mobility limitations and physical performance in community-dwelling older men.

Kinetic and thermodynamic characterization of dihydrotestosterone-induced conformational perturbations in androgen receptor ligand-binding domain.

Ligand-induced conformational perturbations in androgen receptor (AR) are important in coactivator recruitment and transactivation. However, molecular rearrangements in AR ligand-binding domain (AR-LBD) associated with agonist binding and their kinetic and thermodynamic parameters are poorly understood. We used steady-state second-derivative absorption and emission spectroscopy, pressure and temperature perturbations, and 4,4'-bis-anilinonaphthalene 8-sulfonate (bis-ANS) partitioning to determine the kinetics and thermodynamics of the conformational changes in AR-LBD after dihydrotestosterone (DHT) binding.

Testosterone and growth hormone improve body composition and muscle performance in older men.

Context: Impairments in the pituitary-gonadal axis with aging are associated with loss of muscle mass and function and accumulation of upper body fat.

Objectives: We tested the hypothesis that physiological supplementation with testosterone and GH together improves body composition and muscle performance in older men.

Design, Setting, And Participants: One hundred twenty-two community-dwelling men 70.

The impact of assay quality and reference ranges on clinical decision making in the diagnosis of androgen disorders.

The Endocrine Society guideline on Androgen Deficiency in Men emphasized that accurate measurement of testosterone (T) levels is central to the diagnosis of androgen deficiency. Similarly, accurate measurements of testosterone levels are important in the diagnosis of androgen disorders in women and children. However, the accuracy of direct radioimmunoassays for the measurement of total T levels has been questioned, especially in the low range prevalent in women, children, and androgen deficient men.

Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects.

Objective: Experimental studies suggest that adipose inflammation is etiologically linked to obesity-induced systemic disease. Our goal was to characterize the state of inflammation in human fat in relation to vascular function and metabolic parameters in obese individuals.

Methods And Results: We collected subcutaneous abdominal fat in 77 obese subjects (BMI >or=30 kg/m(2)) and quantified adipose macrophage population using targeted immunohistochemistry.

Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss.

Testosterone increases fat-free mass (FFM) in men infected with human immunodeficiency virus (HIV), but its effects on muscle performance, physical function, mood, and quality of life are poorly understood. Sixty-one HIV-infected men with weight loss were randomized to receive weekly intramuscular injections of 300 mg of testosterone enanthate or placebo for 16 wk. The primary outcome of interest was physical function (walking speed, stair-climbing power, and load-carrying ability).

Spatio-temporal activation of cyclic AMP response element-binding protein, activity-regulated cytoskeletal-associated protein and brain-derived nerve growth factor: a mechanism for pontine-wave generator activation-dependent two-way active-avoidance memory processing in the rat.

The present study explored possible physiological and molecular mechanisms of pontine-wave (P-wave) generator activation-dependent memory processing in the rat using a two-way active-avoidance learning paradigm. The results show that learning training increased rapid eye movement sleep and activated brainstem cells in the P-wave generator. During this period, there was a time-dependent increase in phosphorylation of cAMP response element-binding protein (CREB) in the dorsal hippocampus and amygdala and increased synthesis of activity-regulated cytoskeletal-associated protein (Arc) in the dorsal hippocampus, amygdala, frontal cortex and occipital cortex.

Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice.

The cytotoxic effect of various concentrations of echitamine chloride was studied in HeLa, HepG2, HL60, KB and MCF-7 cell lines in-vitro and in mice bearing Ehrlich ascites carcinoma (EAC). Exposure of various cells to different concentrations of echitamine chloride resulted in a concentration-dependent cell killing, and KB cells were found to be most sensitive amongst all the cells evaluated. EAC mice treated with 1, 2, 4, 6, 8, 12 or 16 mg kg-1 echitamine chloride showed a dose-dependent elevation in the anti-tumour activity, as evident by increased number of survivors in comparison with the non-drug treated controls.

Neurotoxic lesions of phasic pontine-wave generator cells impair retention of 2-way active avoidance memory.

Study Objectives: The aim of this study was to test the hypothesis that the activation of pontine (P)-wave generator is critical for the posttraining rapid eye movement (REM) sleep-dependent memory processing.

Design: Ibotenic acid was microinjected (0.5 microg in 0.