Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men

CONTEXT: The development of a safe and effective reversible method of male contraception is still an unmet need. OBJECTIVE: Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone. DESIGN: Prospective multicentre study. SETTING: Ten study centers. PARTICIPANTS: Healthy men, aged 18-45 years, and their 18- to 38-year-old female partners, both without known fertility problems. INTERVENTION: Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks. MAIN OUTCOMES MEASURES: Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate. RESULTS: Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8-97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method). During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59-4.14). The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users (95% CI, 91.5-97.1). The most common adverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early. CONCLUSIONS: The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high

Styrene maleic acid recovers proteins from mammalian cells and tissues while avoiding significant cell death.

Detection of protein biomarkers is an important tool for medical diagnostics, typically exploiting concentration of particular biomarkers or biomarker release from tissues. We sought to establish whether proteins not normally released by living cells can be extracted without harming cells, with a view to extending this into biomarker harvest for medical diagnosis and other applications. Styrene maleic acid (SMA) is a polymer that extracts nanodiscs of biological membranes (containing membrane proteins) from cells. Hitherto it has been used to harvest SMA-lipid-membrane protein particles (SMALP) for biochemical study, by destroying the living cellular specimen. In this study, we applied SMA at low concentration to human primary cardiovascular cells and rat vascular tissue, to 'biopsy' cell proteins while avoiding significant reductions in cell viability. SMA at 6.25 parts per million harvested proteins from cells and tissues without causing significant release of cytosolic dye (calcein) or reduction in cell viability at 24 and 72 hours post-SMA (MTT assay). A wide range of proteins were recovered (20-200 kDa) and a number identified by mass spectrometry: this confirmed protein recovery from plasma membrane, intracellular membranes and cell cytosol without associated cell death. These data demonstrate the feasibility of non-lethally sampling proteins from cells, greatly extending our sampling capability, which could yield new physiological and/or pathological biomarkers

Quintic trigonometric Bézier curve with two shape parameters

The fifth degree of trigonometric Bézier curve called quintic with two shapes parameter is presented in this paper. Shape parameters provide more control on the shape of the curve compared to the ordinary Bézier curve. This technique is one of the crucial parts in constructing curves and surfaces because the presence of shape parameters will allow the curve to be more flexible without changing its control points. Furthermore, by changing the value of shape parameters, the curve still preserves its geometrical features thus makes it more convenient rather than altering the control points. But, to interpolate curves from one point to another or surface patches, we need to satisfy certain continuity constraints to ensure the smoothness not just parametrically but also geometrically

A quick guide to survey research

Many thanks for your interest in our article. We agree on the issue of multimodal surveys and, certainly, for non-responders, a multimodal survey is a good tool. The other points mentioned in your letter have already been covered in our article. Finally, we do not agree on the issue of surveys being time consuming but not expensive. Somebody is paying for the time

Synthesis and pharmacological studies of 1-<i>p</i>-nitrobenzoyl<b>-</b>3-(3-substituted-2-hydroxypropyloximino) indole-2,3-diones

258-261Sodium salt of 3-oximino indole-2,3-dione on reaction with epichlorohydrin in N,N'-dimeth ylformamide gives 3-(2,3-epoxypropyloximino) indole-2,3-dione 2. Compound 2 on reaction with diverse secondary amines yields corresponding Mannich bases 3a-e, which on benzoylation furnish 4a-e. The synthetic benzoyl derivatives of 4a-e have been screened for their pharmacological activities

Synthesis and biological evaluation of l-acetyl-3-(2-acetoxy-3-substituted propyloximino) indol-2(3<i>H</i>)-ones

971-9751-Acetyl 3-oximino-indol-2 (3H)-one 2 on reaction with epichlorohydrin in acetone gave l-acetyl-3-(2, 3-epoxy propyloximino) indol-2(3H)-one 3, which, on subsequent reaction with piperidine, pyrolidine, dicyclohexyl amine, diphenyl amine gave corresponding Mannich base 4, which on acetylation furnishes 5a-e. All these synthetic compounds 2, 3 and 5a-e are screened for their anti-microbial action, gross behavioral, toxicity, antagonism of tetrabenazine induced ptosis, inhibition of pentobarbitone-induced narcosis and effect on blood presure and respiration rate in suitable experimental models. Test compouds 2, 3 and 5a-e reduce MIC against B. substilis, E. coli, and C. albicans.Further, these compounds inhibit tetrabenazine induced ptosis in mice, of which except compound 2, all shows a ptosis score of 2 at the end of 150 and 210 min. In the test of inhibition of pentobarbitone induced narcosis all compounds except compound 2 possess a significant decrease in sleeping time. All test compounds inhibit the histamine-induced fall in blood pressure except compound 2. Test compounds 5a-e have a negligible skeletal muscle contraction effect when tested on frog's rectus abdominus muscl

Differential response of testis and serum gonadotropins to testosterone in rats treated with a gonadotropin releasing hormone antagonist or estradiol 17 beta

Adult rats treated with a GnRH antagonist (Ac D2Nal1, D4Cl Phe2, DTrp3, DArg6, DAla10 GnRH; code: 103-289-10, National Institutes of Health, USA) for 5 weeks (250 micrograms/kg b.w) showed multiple degrees of impairment and atrophy of the genital organs concomitant with decreased serum levels of testosterone, LH and FSH. Inhibition of spermatogenesis was characterized by germ cell degeneration and overall decline in different cell numbers and in particular, spermatids of any kind were completely absent. Testosterone supplementation (60 micrograms/rat/day, sc) to GnRH antagonist treated rats, for the same period, significantly elevated the weights of the sex organs, and the serum levels of hormones. Spermatogenesis was improved both qualitatively and quantitatively; albeit failed to be restored back to control levels. Treatment with estradiol 17 beta (1 microgram/rat/day) for 5 weeks had insignificant effect on spermatogenesis but the weights of the genital organs (seminal vesicles by 19% and ventral prostate by 40%) and the levels of serum hormones (LH by 24%, FSH 22% and testosterone by 25%) were otherwise reduced. Administration of testosterone either alone or in combination with estradiol 17 beta had only a marginal effect on spermatogenesis or on other reproductive parameters. The results indicate a positive shift in the response of the testis and serum levels of gonadotropins to testosterone supplementation in rats treated with either GnRH antagonist or estradiol 17 beta