Dose-response effects of sex hormone concentrations on body composition and adipokines in medically castrated healthy men administered graded doses of testosterone gel.

Objective: Serum sex steroid concentrations may alter body composition and glucose homoeostasis in men in a dose-response manner. We evaluated these end-points in healthy men rendered medically castrate through use of a gonadotrophin-releasing hormone antagonist (acyline) with incremental doses of exogenous testosterone (T) gel.

Design: Subjects (n=6-9 per group) were randomly assigned to injections of acyline every 2 weeks plus transdermal T gel (1.

Stable Intraprostatic Dihydrotestosterone in Healthy Medically Castrate Men Treated With Exogenous Testosterone.

Context: Concern exists that T replacement therapy (TRT) might increase the risk of prostate disease. There are limited data regarding the impact of TRT on prostate androgen concentrations.

Objective: Determine the dose-dependent effects of exogenous T administration on intraprostatic androgen concentrations.

The association of obesity with sex hormone-binding globulin is stronger than the association with ageing--implications for the interpretation of total testosterone measurements.

Objective: Total testosterone concentrations are influenced by sex hormone-binding globulin (SHBG) concentrations, which are decreased by obesity and increased with ageing. Therefore, we sought to understand and compare the associations of ageing and obesity with SHBG.

Design: We performed a retrospective, cross-sectional analysis of the associations of obesity and age on SHBG and testosterone measurements in men being evaluated for hypogonadism.

Androgens and prostate disease.

A growing body of literature has established the anabolic benefi ts of testosterone (T) therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy.

Cell biological approaches to investigate polyglutamine-expanded AR metabolism.

Spinal and bulbar muscular atrophy (SBMA) is a late-onset neurodegenerative disease caused by a polyglutamine expansion in the androgen receptor (AR). In vivo and in vitro studies have suggested that some steps of normal AR function and metabolism, such as hormone binding and nuclear translocation of the AR, are necessary for toxicity and aggregation of the mutant protein. Mutation of discreet functional domains of the AR and sites of posttranslational modification enable the detailed analysis of the role of AR function and metabolism in toxicity and aggregation of polyglutamine-expanded AR.

A mammalian melanopsin in the retina of a fresh water turtle, the red-eared slider (Trachemys scripta elegans).

A mammalian-like melanopsin (Opn4m) has been found in all major vertebrate classes except reptile. Since the pupillary light reflex (PLR) of the fresh water turtle takes between 5 and 10 min to achieve maximum constriction, and since photosensitive retinal ganglion cells (ipRGCs) in mammals use Opn4m to control their slow sustained pupil responses, we hypothesized that a Opn4m homolog exists in the retina of the turtle. To identify its presence, retinal tissue was dissected from seven turtles, and total RNA extracted.

Consensual pupillary light response in the red-eared slider turtle (Trachemys scripta elegans).

Purpose of this study was to determine if the turtle has a consensual pupillary light response (cPLR), and if so, to compare it to its direct pupillary light response (dPLR). One eye was illuminated with different intensities of light over a four log range while keeping the other eye in darkness. In the eye directly illuminated, pupil diameter was reduced by as much as approximately 31%.

Sympathetic influence on the pupillary light response in three red-eared slider turtles (Trachemys scripta elegans).

Objective: We investigated the effects of phenylephrine and its combination with vecuronium bromide on the iris of turtles to determine if the pupillary light response is affected by sympathetic innervation.

Animal Studied: Three red-eared slider turtles, Trachemys scripta elegans.

Procedure: Diameters of light-adapted pupils were tracked before and after topical application of drugs to eyes.

Do all of the neurologic diseases in patients with DNA repair gene mutations result from the accumulation of DNA damage?

The classic model for neurodegeneration due to mutations in DNA repair genes holds that DNA damage accumulates in the absence of repair, resulting in the death of neurons. This model was originally put forth to explain the dramatic loss of neurons observed in patients with xeroderma pigmentosum neurologic disease, and is likely to be valid for other neurodegenerative diseases due to mutations in DNA repair genes. However, in trichiothiodystrophy (TTD), Aicardi-Goutières syndrome (AGS), and Cockayne syndrome (CS), abnormal myelin is the most prominent neuropathological feature.

Inhibition of host kinase activity altered by the LMP2A signalosome-a therapeutic target for Epstein-Barr virus latency and associated disease.

Epstein-Barr virus (EBV) is a human herpesvirus that establishes a lifelong latent infection in the majority of the human population. The virus resides in a latent state in B lymphocytes and is associated with a variety of cancers in the human host. In normal individuals, latent infection with EBV typically poses no health risk, but upon immunosuppression, either following organ transplantation or HIV infection, malignancies and lymphoproliferative diseases can result.

The LMP2A signalosome--a therapeutic target for Epstein-Barr virus latency and associated disease.

Most adults are infected with Epstein-Barr virus (EBV), a virus that establishes a lifelong latent infection in B lymphocytes and is associated with a variety of cancers. In normal individuals, latent infection with EBV typically poses no health risk, but upon immunosuppression, either following organ transplantation or HIV infection, malignancies and lymphoproliferative diseases can result. We have utilized both transgenic mice and EBV transformed lymphoblastoid cell lines (LCLs) as models of EBV latent infection to explore the function of latent membrane protein 2A (LMP2A) of EBV.