Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive.

The novel androgen, dimethandrolone (DMA) has both androgenic and progestational activities, properties that may maximize gonadotropin suppression. We assessed the pharmacokinetics of dimethandrolone undecanoate (DMAU), an orally bioavailable, longer acting ester of DMA, for male contraceptive development. Our objective was to examine the safety and pharmacokinetics of single, escalating doses of DMAU (powder in capsule formulation) administered orally with or without food in healthy men.

An update on male hypogonadism therapy.

Introduction: Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy.

Areas Covered: Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks.

Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR.

Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D2) caused more adenomas in Apc(Min/+) mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D2 (PGD2) binds to the prostaglandin D2 receptor known as PTGDR (or DP1).

A tortuous proximal urethra in urorectal septum malformation sequence?

We observed a newborn boy with urorectal septum malformation sequence. Anomalies of the genitalia and rectum were present. He expired on the first day of life, due to severe lung hypoplasia.

Exposure to prenatal life events stress is associated with masculinized play behavior in girls.

Previous research has shown that prenatal exposure to endocrine-disrupting chemicals can alter children's neurodevelopment, including sex-typed behavior, and that it can do so in different ways in males and females. Non-chemical exposures, including psychosocial stress, may disrupt the prenatal hormonal milieu as well. To date, only one published study has prospectively examined the relationship between exposure to prenatal stress and gender-specific play behavior during childhood, finding masculinized play behavior in girls who experienced high prenatal life events stress, but no associations in boys.

Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort.

Objectives: Autosomal recessive long QT syndrome (LQTS), or Jervell and Lange-Nielsen syndrome (JLNS), can be associated with sensorineural hearing loss. We aimed to explore newborn hearing screening combined with electrocardiograms (ECGs) for early JLNS detection.

Study Design: In California, we conducted statewide, prospective ECG screening of children ≤ 6 years of age with unilateral or bilateral, severe or profound, sensorineural or mixed hearing loss.

Testosterone replacement ameliorates nonalcoholic fatty liver disease in castrated male rats.

Nonalcoholic fatty liver disease is common in developed countries and is associated with obesity, metabolic syndrome, and type 2 diabetes. T deficiency is a risk factor for developing these metabolic deficiencies, but its role in hepatic steatosis has not been well studied. We investigated the effects of T on the pathogenesis of hepatic steatosis in rats fed a high-fat diet (HFD).

Characteristics associated with suppression of spermatogenesis in a male hormonal contraceptive trial using testosterone and Nestorone(®) gels.

Development of a male hormonal contraceptive has been challenging ascribable to the failure to adequately suppress spermatogenesis in 5-10% of men. Methods to identify incomplete suppressors early in treatment might identify men most responsive to male hormonal contraceptives. We hypothesized that serum hormone and gonadotropin concentrations after 4 weeks of transdermal treatment with testosterone and Nestorone in a contraceptive trial would be associated with suppression of sperm concentrations to <1 million/mL after 24 weeks.

A multicenter, open-label, observational study of testosterone gel (1%) in the treatment of adolescent boys with klinefelter syndrome or anorchia.

Purpose: To assess the safety and clinical outcomes of 6-month treatment with testosterone gel 1% therapy in adolescent boys with primary hypogonadism resulting from Klinefelter syndrome (KS) or anorchia.

Methods: This was a subgroup analysis of a multicenter, open-label study of adolescent boys (N = 86) with delayed puberty who received .5-5.

Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease.

Objectives: Accelerated cardiovascular morbidity and mortality occur in patients with rheumatoid arthritis (RA). We evaluated the presence, burden and compositional differences of coronary plaque in patients with RA without symptoms or diagnosis of coronary artery disease (CAD) compared against controls.

Methods: One hundred and fifty patients with RA and 150 matched controls underwent 64-slice CT angiography (CTA) for evaluation of coronary plaque.

Functional role of progestin and the progesterone receptor in the suppression of spermatogenesis in rodents.

Synthetic progestins such as levonorgestrel (LNG) are used in combination with testosterone (T) in male contraceptive clinical trials to suppress gonadotropins secretion, but whether progestins have additional direct effects on the testis are not known. This study aimed to examine the effect of a potent progestin, (LNG), alone or in combination with testosterone (T) on spermatogenesis in adult rats, and to evaluate the functional role of the progesterone receptors (PRs) in the testis. In comparison with a low dose of LNG treatment in adult rats for 4 weeks, T and T + LNG treatment decreased testicular sperm count to 64.

Use of cardiac CT angiography imaging in an epidemiology study - the Methodology of the Multicenter AIDS Cohort Study cardiovascular disease substudy.

Objective: The methodology for use of cardiac CT angiography (CTA) in low risk populations is not well defined. In order to present a reference for future studies, we present CTA methodology that is being used in an epidemiology study- the Multicenter AIDS Cohort Study (MACS).

Methods: The Multicenter AIDS Cohort Study (MACS) is an on-going multicenter prospective, observational cohort study.

Xanthine oxidase does not contribute to apoptosis after brain hypoxia-ischemia in immature rabbits.

Background. The mechanisms involving the initiation of apoptosis after brain hypoxia-ischemia through caspase activation are not fully defined. Oxygen free radicals may be an important mediator of caspase initiation with reactive oxygen species generated by xanthine oxidase (XO) being one potential source.

Implications of sleep restriction and recovery on metabolic outcomes.

Context: Alongside the growing epidemics of obesity and diabetes mellitus, chronic partial sleep restriction is also increasingly common in modern society, and the metabolic implications of this have not been fully illustrated as yet. Whether recovery sleep is sufficient to offset these detriments is an area of ongoing research.

Objective: This review seeks to summarize the relevant epidemiological and experimental data in the areas of altered metabolic consequences of both shortened sleep and subsequent recovery sleep.

Dietary fat modulates the testosterone pharmacokinetics of a new self-emulsifying formulation of oral testosterone undecanoate in hypogonadal men.

This study investigates the effect of dietary fat on the testosterone (T) pharmacokinetics in hypogonadal men following administration of a self-emulsifying capsule formulation of oral T undecanoate (TU). In an open-label, 2-center, 5-way crossover study, a single oral dose of TU containing 300-mg equivalents of T (maximum anticipated human dose per administration) was administered to 16 hypogonadal men with a washout period of at least 5 days between doses. All participants were randomized to receive the TU capsules fasting or 30 minutes after an approximately 800-calorie meal containing 10%, 20%, 30%, or 50% fat.

Fungal cell wall vaccines: an update.

This discussion is intended to be an overview of current advances in the development of fungal cell wall vaccines with an emphasis on Candida; it is not a comprehensive historical review of all fungal cell wall vaccines. Selected, more recent, innovative strategies for developing fungal vaccines will be highlighted. Both scientific and logistical obstacles related to the development of, and clinical use of, fungal vaccines will be discussed.

Hematopoietic prostaglandin D synthase (HPGDS): a high stability, Val187Ile isoenzyme common among African Americans and its relationship to risk for colorectal cancer.

Intestinal tumors in Apc(Min/+) mice are suppressed by over-production of HPGDS, which is a glutathione transferase that forms prostaglandin D(2) (PGD(2)). We characterized naturally occurring HPGDS isoenzymes, to see if HPGDS variation is associated with human colorectal cancer risk. We used DNA heteroduplex analysis and sequencing to identify HPGDS variants among healthy individuals.

High dietary niacin may increase prostaglandin formation but does not increase tumor formation in ApcMin/+ mice.

High doses of niacin (nicotinic acid) used to treat dyslipidemias cause flushing, due to high levels of prostaglandin D(2) (PGD(2)). GPR109A, a G-protein coupled receptor, triggers the flushing in the skin. In addition to boosting PGD(2), niacin binding to GPR109A activates the entire prostanoid cascade.

Efficacy and safety of the 2% formulation of testosterone topical solution applied to the axillae in androgen-deficient men.

Objectives: Testosterone replacement therapy in hypogonadal men relieves symptoms and restores serum testosterone levels to the physiological range. In this study, we assessed the safety, pharmacokinetics, and efficacy of the 2% formulation of testosterone topical solution applied daily to the axillae.

Design And Patients: An open-label trial was conducted in testosterone-deficient men who started on a daily dose of 60 mg of testosterone.

Male hormonal contraception: potential risks and benefits.

An effective, safe, reversible, and acceptable method of contraception is an important component of reproductive health and provides the opportunity of shared responsibility for family planning for both partners. Female hormonal contraceptives have been proven to be safe, reversible, available and widely acceptable by different populations. In contrast, male hormonal contraception, despite significant progress showing contraceptive efficacy comparable to female hormonal methods during last three decades, has not yet led to an approved product.

Reexamination of pharmacokinetics of oral testosterone undecanoate in hypogonadal men with a new self-emulsifying formulation.

Many hypogonadal men prefer oral testosterone (T) treatment. Oral T undecanoate (TU) is available in many countries, but not in the United States. We aimed to assess the pharmacokinetics of oral TU in a new self-emulsifying drug delivery system formulation.

Does ethnicity matter in male hormonal contraceptive efficacy?

The development of male hormonal contraception has progressed significantly during the last three decades. The ultimate goal is to produce an effective, safe and reversible male method of contraception that are within reach of and can be used by all men globally. This review aims to outline the recent developments in male hormonal contraception with special emphasis on how ethnicity influences acceptability, extent of sperm suppression, and rate of recovery of spermatogenesis.

Insights into the pathogenesis of XXY phenotype from comparison of the clinical syndrome with an experimental XXY mouse model.

Klinefelter syndrome (47, XXY male) is the most common sex chromosome disorder in men. To study the underlying mechanisms of XXY phenotypes and design specific and novel therapeutic regimens for KS men, an experimental mouse model (41, XXY) was established. This manuscript compares the phenotypes of XXY men and mice and discusses the possible contributions of low androgen levels and extra X chromosome genes to the XXY phenotypes.