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Biomedical subjects

S Bhasin

Publications and source records attributed to S Bhasin.

122 records · Page 7Linked to original sources

Testosterone dose-dependency of sexual and nonsexual behaviors in the gonadotropin-releasing hormone antagonist-treated male rat.

The testosterone dose-dependency of several mating and nonmating behaviors was examined in the male rat, chemically castrated with a GnRH antagonist analog. Graded doses of testosterone enanthate (TE) were given to male rats to reinstate behaviors abolished by GnRH antagonist treatment. GnRH antagonist treatment alone markedly lowered serum LH, FSH and T concentrations and ventral prostate and testis weights. Open field behaviors were not significantly affected by GnRH antagonist treatment or castration. Scent-marking behavior was markedly suppressed by both castration and GnRH antagonist and restored by the lowest dose of TE (0.05 mg). All measures of male sexual behavior were impaired by GnRH antagonist treatment and castration and restored by the lowest dose of TE (0.05 mg). The doses of TE required to restore normal ventral prostate weights and testis weights were higher than those required to maintain scent marking and mating behaviors. No direct behavioral effects of the GnRH antagonist, other than those that can be explained by GnRH antagonist-induced suppression of testosterone were observed. The finding that sexual and nonsexual behaviors in the male rat have different testosterone requirements from those maintaining spermatogenesis and fertility may have significant implications for contraception.

Animals↗

Process evaluation of pulse polio immunisation in Delhi.

The aim of the study was to assess the functional aspects and the staffing at Pulse Polio immunisations posts. Interns and medical students conducted the survey in eighty seven pulse polio immunisation posts scattered all over National Capital Territory of Delhi on 18th January 1997. A pre-tested structured format containing information pertaining to dose utilisation and staffing was filled. Number of children given pulse polio was on an average 459.2 per immunisation post (474.7 rural, 516.35 slums and 435.0 urban). Average number of neonates (below one month) per immunisation post given polio drops was 5.1 (1.1%). The break-up for rural area, slums and urban area was 3.0 (0.63%), 6.7 (1.30%) and 4.9 (1.13%) respectively. By 12 pm, 67.8% and by 2 pm 88.7% of the doses had been administered. Staffing at most of the immunisation posts was adequate for all categories of staff except doctors (0.48 per booth).

Developing Countries↗

Testosterone increases TRH biosynthesis in epididymis but not heart of zinc-deficient rats.

Enzymes responsible for the posttranslational processing of precursor proteins to form alpha-amidated peptide hormones require the availability of several cofactors, including zinc, copper, and ascorbic acid. For this reason, we studied the effects of 6 weeks of a zinc-deficient diet (ZD1; 1 microgram zinc per g diet), pair-feeding (PF), and marginal zinc deficiency (ZD6; 6 micrograms zinc per g diet) compared to a control diet (36 micrograms/g zinc) on the conversion of prepro-TRH to TRH in epididymides, testes, prostate, pancreas, and heart of young adult, male Sprague-Dawley rats. In the epididymis, severe zinc deficiency (ZD1 diet) reduced TRH and TRH-like peptides to undetectable levels. In ZD6 animals, TRH was selectively inhibited 80%, while pair-feeding increased all of these peptide levels compared to controls. A similar effect of zinc deficiency on the TRH precursor peptides was observed. A quantitative loss of TRH from the testes of ZD1 was also observed. Zinc deficiency results in a substantial reduction in body weight and testosterone production in male rats. Exogenous testosterone (T) supplementation of ZD1 rats resulted in a selective increase in the TRH concentration of the epididymis but not of the heart. The change in steady-state levels of TRH precursor peptides in the hearts of the ZD1+T rats was consistent with a reduction in the activity of the zinc-dependent carboxypeptidase H enzyme. We conclude that severe zinc deficiency inhibits TRH biosynthesis in reproductive tissues of the male rat due to the combined effects of hypogonadism and inhibition of the zinc-dependent carboxypeptidase H.

Amino Acid Sequence↗

Can androgen therapy replete lean body mass and improve muscle function in wasting associated with human immunodeficiency virus infection?

A significant number of men who are infected with the human immunodeficiency virus (HIV) have low testosterone levels. Androgen deficiency in HIV-infected patients is associated with decreased muscle mass and function, and adverse disease outcome. Administration of replacement doses of testosterone to healthy hypogonadal men augments lean body mass, muscle size, and maximal voluntary strength. Recent studies have shown that physiologic testosterone replacement in HIV-infected men with weight loss who have low testosterone levels can also increase muscle mass and effort-dependent strength. However, further studies are needed to determine whether androgen therapy can improve physical function and health-related outcomes in HIV-infected men.

Androgens↗

Serum dihydrotestosterone and testosterone concentrations in human immunodeficiency virus-infected men with and without weight loss.

Weight loss is an important determinant of disease outcome in human immunodeficiency virus (HIV)-infected men. Others have suggested that a defect in dihydrotestosterone (DHT) generation contributes to weight loss in HIV-infected men. To determine whether DHT levels correlate with weight loss independently of changes in testosterone levels, we prospectively measured serum total- and free-testosterone and DHT levels in 148 consecutive HIV-infected men and 42 healthy men. Thirty-one percent of HIV-infected men had serum testosterone levels less than 275 ng/dL, the lower limit of the normal male range; of these, 81% had normal or low LH and FSH levels (hypogonadotropic), and 19% had elevated LH and FSH levels (hypergonadotropic). Overall, serum testosterone, free-testosterone, and DHT levels were lower in HIV-infected men than in healthy men, but serum DHT-to-testosterone ratios were not significantly different between the two groups. Serum total- and free-testosterone levels were lower in HIV-infected men who had lost 5 lb or more of weight in the preceding 12 months than in those who had not lost any weight. Serum DHT levels and DHT-to-testosterone ratios did not differ between those who had lost weight and those who had not. Serum testosterone and free-testosterone levels, but not DHT levels, correlated with weight change and with Karnofsky performance status. We also performed a retrospective analysis of data from a previous study in which HIV-infected men with serum testosterone levels less than 400 ng/dL had been treated with placebo or testosterone patches designed to nominally release 5 mg testosterone over 24 hours. Serum testosterone-to-DHT ratios did not change after testosterone treatment. Changes in fat-free mass were correlated with changes in both serum testosterone (r = 0.42, P = 0.018) and DHT (r = 0.35, P = 0.049) levels. Serum total- testosterone and DHT levels were highly correlated with one another, and when the change in serum testosterone was taken into account, serum DHT levels no longer showed a significant correlation with change in fat-free mass. We conclude that DHT levels are lower in HIV-infected men than in healthy men but that neither DHT levels nor DHT-to-testosterone ratios correlate with weight loss. During testosterone treatment, serum DHT levels increase proportionately, but the increments in serum testosterone correlate with the change in fat-free mass. Our data do not support the hypothesis that a defect in DHT generation contributes to weight loss in HIV-infected men independently of changes in testosterone levels; it is possible that such a defect might exist in HIV-infected men with more severe weight loss.

Adolescent↗

Tuberculous mediastinitis: a rare presentation.

Granulomatous mediastinitis is a rare condition, and tuberculosis and fungal infections are the most important causes of this potentially lethal condition. Tuberculous mediastinitis usually presents with fever, cough, dyspnoea and rarely, florid features of obstruction to intra-thoracic structures are seen. A case of tuberculous mediastinitis presenting as a suprasternal lump, a rare presentation, is described here.

Granuloma↗

Follicle-stimulating hormone (FSH) escape during chronic gonadotropin-releasing hormone (GnRH) agonist and testosterone treatment.

Observations that serum follicle-stimulating hormone (FSH) levels begin to rise after initial suppression during chronic gonadotropin-releasing hormone (GnRH) agonist treatment of men with prostate cancer had led to speculation that FSH escape might in part account for the failure of GnRH agonist analogs to completely suppress spermatogenesis in normal eugonadal men. However, previous studies in healthy young men failed to report FSH escape during GnRH agonist treatment for up to 16 weeks. We considered the possibility that this may have been due to the insensitivity of the FSH assays. Accordingly, using highly sensitive and specific two-site directed fluorometric assays and a sustained-release GnRH agonist formulation, we reexamined the issue of whether serum FSH levels rise after initial suppression during chronic GnRH agonist treatment. Two groups of healthy normal men, 19-50 years of age, received 7.5 mg of a long-acting GnRH agonist microcapsule formulation (Lupron Depot; TAP Pharmaceutical Company, North Chicago, Illinois) on days 1 and 30. In addition, the subjects received either 4 or 8 mg/day testosterone replacement by means of a testosterone microcapsule injected intramuscularly on day 1. Serum luteinizing hormone (LH) and FSH levels were measured by sensitive and specific two-site directed fluorometric assays on multiple occasions during the 3-week control period and the 9-week treatment period. Serum LH levels declined to a nadir between 2 and 4 weeks and stayed suppressed throughout the remainder of the treatment period in both the 4- and 8-mg testosterone groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparative effects of two different delivery systems on gonadotropin-releasing hormone (GnRH) antagonist-induced suppression of gonadotropins and testosterone in man.

The Nal-Glu gonadotropin-releasing hormone (GnRH) antagonist, when given in daily subcutaneous (SC) doses of 5 mg or higher, maximally suppresses serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels to near undetectable levels and induces azoospermia in normal men; lower doses (1.5 and 3.0 mg) are less effective. Cost and convenience are important considerations in contraceptive development. Studies with GnRH agonists suggest that constant delivery is more effective in suppressing gonadal function than equal doses by single daily injection. In this study, we examined whether the constant infusion (CI) of a submaximal suppressive dose (1.5 mg) of Nal-Glu would be more effective in suppressing the pituitary-gonadal axis than its repeated single daily injections (SDI). This (1.5 mg) dose was selected because the 5 mg dose given once daily SC for 21 days led to maximal suppression of LH, FSH, and testosterone (T) levels, whereas 1.5 mg once daily for 21 days gave only partial suppression. It was felt that if continuous infusion was considerably more effective than intermittent administration of this submaximal dose, then the development of long-acting sustained release delivery systems for contraceptives based on GnRH antagonist analogs would allow both reduced cost and enhanced convenience. One and a half mg of Nal-Glu was administered SC either as a SDI or CI over 24 hours for 21 days to two groups of five normal men. Three measurements of serum LH, FSH, and T were performed before antagonist injection and 1, 2, 4, 8, 12, 16, and 24 hours after Nal-Glu injection on days 0, 1, 7, 21.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pharmacokinetics and pharmacodynamics of a parenteral testosterone microsphere formulation in the male rat. Demonstration of dose dependence and controlled release.

This study examined the pharmacokinetics (the time course and pattern of testosterone release) and pharmacodynamics (effects on accessory sex organ weights, and serum LH and FSH levels) of a biodegradable testosterone microsphere formulation in the male rat. Two hundred seventy-five 55-day-old, sexually mature male rats underwent surgical orchiectomy or sham surgery and were divided into five groups as follows, to receive placebo or testosterone microsphere systems designed to release 25, 75, or 225 micrograms/day testosterone: group I: intact age-matched controls, sham operated, placebo microspheres; group II: surgically orchiectomized, placebo microspheres; group III: surgically orchiectomized, 25 micrograms/day testosterone microspheres; group IV: surgically orchiectomized, 75 micrograms/day testosterone microspheres; and group V: surgically orchiectomized, 225 micrograms/day testosterone microspheres. Serum testosterone levels were fairly uniform from day 2 to 85 without any significant trend. After day 100, serum testosterone levels gradually fell into the castrate range by day 196. There was a dose-dependent increase in serum testosterone levels in groups III, IV, and V over those seen in group II (castrated rats, placebo treated). Prostate and seminal vesicle weights were significantly lower in castrated animals treated with placebo or the 25-micrograms/day testosterone microsphere system (group III). Mean prostate and seminal vesicle weights in groups IV and V were not significantly different from those in intact controls (group I) in the first 85 days. After day 85-100, seminal vesicle and prostate weights declined gradually in groups III, IV, and V, approaching castrate range by day 196.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗