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Biomedical subjects

M Rajalakshmi

Publications and source records attributed to M Rajalakshmi.

At least 37 records · Page 2Linked to original sources
PubMed1993

Environmental release of chemicals and reproductive ecology.

Reproductive ecology is defined as "the study of causes and mechanisms of the effects of environmental risk factors on reproductive health and the methods of their prevention and management." Major areas of concern, within the purview of this paper, relate to adverse pregnancy outcomes, effects on target tissues in the male and the female, and alterations in the control and regulatory mechanisms of reproductive processes. Teratogenic potential of chemicals, released as a result of accidents and catastrophes, is of critical significance. Congenital Minamata disease is due to transplacental fetal toxicity caused by accidental ingestion of methyl mercury. Generalized disorders of ectodermal tissue following prenatal exposure to polychlorinated biphenyls have been reported in Taiwan and Japan. The Bhopal gas disaster, a catastrophic industrial accident, was due to a leak of toxic gas, methyl isocyanate (MIC), in the pesticide manufacturing process. The outcome of pregnancy was studied in female survivors of MIC exposure. The spontaneous abortion rate was nearly four times more common in the affected areas as compared to the control area (24.2% versus 5.6%; p < 0.0001). Furthermore, while stillbirth rate was found to be similar in the affected and control areas, the perinatal and neonatal mortality rates were observed to be higher in the affected area. The rate of congenital malformations in the affected and control areas did not show any significant difference. Chromosomal aberrations and sister chromatid exchange (SCE) frequencies were investigated in human survivors of exposure. The observed SCE frequencies in control and exposed groups indicated that mutagenesis has been induced. Strategies for the management, prediction, and preventability of such disasters are outlined.

Abortion, Spontaneous↗
PubMed1992

Effect of cyproterone acetate on structure and function of rhesus monkey reproductive organs.

A low dose of Cyproterone acetate (CPA; 1 mg/kg body weight/day for 70 days) was administered to adult male rhesus monkeys to assess its effects on testicular and epididymal structure and function in a nonhuman primate species. CPA caused extensive degenerative changes in morphology of seminiferous, efferent duct, and epididymal epithelia, including decrease in diameter of seminiferous and epididymal tubules and their lumen, height of epididymal epithelium, and an increase in intertubular connective tissue. The protein profile of spermatozoa showed alterations during their epididymal transit in control and CPA-treated monkeys. In CPA-treated animals, 19 polypeptides were acquired and nine were eliminated during epididymal transit in contrast to acquisition of 12 and loss of 14 polypeptides in control animals. Treatment with CPA also resulted in the appearance of 14 new polypeptides in epididymal cytosol and luminal fluid, probably of lysosomal origin. The protein pattern of caput and cauda epididymal tubule cytosol, maintained in organ culture and exposed to 100 microM CPA for 3 days, showed absence of eight polypeptides. These results indicate that even at the low dose used in this study, CPA has caused spermatogenic arrest, degenerative changes in the epididymal structure, and alterations in epididymal and sperm protein profile. Suppression of serum testosterone levels indicates the need for androgen supplementation if CPA is to be used for male contraception.

Androgen Antagonists↗
PubMed1992

Serum and semen levels of immunoreactive prolactin, LH and FSH in normospermic, oligospermic and azoospermic men with obstructive infertility prior to and after vasoepididymostomy.

Attempts were made to validate RIA for prolactin (PRL), LH and FSH in semen from normospermic, oligospermic and azoospermic subjects. The RIA used to measure PRL and LH in semen fulfilled the criteria of reliability, whereas low levels of FSH in semen precluded the validation of FSH assay in semen. Semen levels of PRL and LH were significantly (P < 0.05) higher than serum levels in all groups of subjects investigated. Semen levels of FSH in azoospermic men after vasoepididymostomy (VEA), were significantly (P < 0.05) higher compared to azoospermic men prior to surgery. Serum levels of PRL were significantly higher (P < 0.05) in normospermic men compared to oligospermic and azoospermic men prior to and after surgery. Semen levels of PRL in normospermic men were comparable with oligospermic and azoospermic subjects prior to and after surgery. Serum levels of LH in oligospermic and azoospermic men who did not undergo surgery and in men reporting oligospermia after VEA were comparable to normospermic subjects but in men showing azoospermia post surgically, serum LH levels were significantly (P < 0.005) elevated. Semen levels of LH in men reporting azoospermia before surgery and in subjects showing oligospermia or azoospermia post surgically were significantly lower (P < 0.05) compared to men with normal sperm count. Serum levels of FSH were significantly elevated (P < 0.05) compared to semen levels in oligospermic men prior to surgery but this increase was not seen in post VEA subjects. These results were discussed.

Epididymis↗
PubMed1991

Evaluation of the ability of a new long-acting androgen ester to maintain accessory gland function in castrated rhesus monkey.

The ability of 40 mg of milled suspension of a new long-acting androgen ester (20 Aet-1) to restore and maintain accessory gland function was compared with that of testosterone enanthate (TE) in castrated adult rhesus monkeys. Castration did not abolish the ejaculatory response since only two animals did not void semen in the postcastration period. A single intramuscular injection of 40 mg of these compounds stimulated accessory gland function at levels lower than in the pretreatment period. 20 Aet-1-induced stimulation of prostatic acid phosphatase activity never exceeded control levels unlike that induced by testosterone enanthate which caused hyperstimulation on day 21 of drug treatment. In terms of support of accessory gland function, 20 Aet-1 would appear to offer hope of being a successful androgen for supplementation therapy in male animals.

Acid Phosphatase↗
PubMed1991

In vitro organ culture of rhesus monkey epididymal tubules.

The caput and cauda epididymal tubules of rhesus monkey were cultured for 5 days using a simple organ culture system. The viability of the tubules in culture was established by assessing: (a) the histology of the epididymis; (b) motility and viability of spermatozoa; and (c) scanning electron microscopic morphology of spermatozoa before and at the end of culture. The efficacy of the culture was evaluated by introducing the antiandrogen, cyproterone acetate, into the culture medium. Cyproterone acetate caused degenerative changes in the histology of the epididymis and coiling of the epididymal spermatozoa which may be due to alterations in epididymal milieu.

Androgen Antagonists↗
PubMed1991

Steroid metabolism by germ cells and spermatozoa in men after vasoepididymostomy.

The ability of germ cells (spermatocytes and spermatids) and spermatozoa present in human ejaculate to metabolize steroids was studied in men with obstructive infertility who had undergone vasoepididymostomy as corrective surgery. Steroid metabolism by spermatozoa in men who had undergone vasovasostomy was also investigated. Germ cells converted testosterone mainly to androstenedione. In addition to androstenedione, dihydrotestosterone and androstanediols were also formed in incubations using spermatids. Both types of germ cells converted estradiol to estrone. Spermatozoa from subjects who had undergone vasoepididymostomy or vasovasostomy converted testosterone to androstenedione as in normal men, while spermatozoa from infertile subjects converted testosterone mainly to dihydrotestosterone. Seminal fluid, free of germ cells, did not show steroid-metabolizing capability.

Adult↗
PubMed1990

Inhibition of spermatozoa maturation in rhesus monkey by cyproterone acetate.

The morphology of spermatozoa from the initial segment, caput, corpus and cauda epididymides of normal and cyproterone acetate-treated animals was studied using light and scanning electron microscopy to understand the changes taking place during spermatozoa maturation. A progressive and significant decrease in the percentage of spermatozoa that retained the cytoplasmic droplet and a shift in its position from proximal end of the midpiece to its distal end were seen during epididymal transit; these events were inhibited in cyproterone acetate-treated animals. A large percentage of spermatozoa from the initial segment and the caput epididymides showed coiling of the spermatozoa tail which involved the midpiece, principal piece and the endpiece. The percentage of spermatozoa that showed the coiled tail decreased; a gradual straightening of the spermatozoa tail with less complex types of coiling was also seen during epididymal transit. Cyproterone acetate reversed these changes occurring during maturation. These results indicate that spermatozoa maturation in the rhesus monkey, occurring between the corpus and cauda epididymides, is an androgen-dependent event.

Androgens↗
PubMed1990

Effect of two new androgen esters on serum levels of testosterone in castrated rhesus monkey.

The pharmacokinetics of two new androgen esters were tested in castrated male rhesus monkeys. A single injection of 40 mg of 20 Aet-2 (testosterone-trans-4-n-pentyl cyclohexyl carboxylate) increased serum testosterone to three times the castrate levels and was maintained nearly at this level until day 182. When given as four separate injections of 20 mg each, 20 Aet-2 increased serum testosterone within 24 hours and the peak levels were attained on day 2 (34.6 +/- 6.20 nmol/L) which was more than five times the levels obtained by 40 mg 20 Aet-2 given as a single injection. This was followed by a decrease in serum testosterone until day 98 when the levels were similar to that in animals given a single injection of 20 Aet-2. Administration of 40 mg of 3 Ad (testosterone-cis-3-(n-hexyl) cyclobutane carboxylate) given as a single injection increased serum testosterone levels to reach a peak level (47.4 +/- 4.64 nmol/L) on day 5 followed by a gradual decrease to castrate levels by day 70. The profile of serum testosterone in animals injected with 80 mg of 3 Ad as four separate injections was similar to that in animals given a single dose of 40 mg of 3 Ad. The data suggest a correlation between the bioavailability of the drug and the formulation of the vehicle. The possible effect of hydrolysis rate on pharmacokinetics of the drugs is discussed.

Animals↗
PubMed1990

Effect of non-aromatizable androgens on testicular and accessory gland functions in rhesus monkeys (Macaca mulatta).

Adult male rhesus monkeys were injected intramuscularly 100 micrograms, 1000 micrograms 5 alpha-androstane-3 alpha, 17 beta-diol or 100 micrograms dihydrotestosterone (DHT) per day for 70 days. A decrease in seminiferous tubular diameter was seen in treated animals. Androstanediol treatment disrupted spermatogenesis in most tubules. Sperm motility decreased within 40 days and by Day 70 non-motile spermatozoa were seen in 2 animals of each group treated with androstanediol. DHT treatment also decreased sperm motility progressively from Day 40. Both androgens caused retention of the cytoplasmic droplet and an increase in coiling of the tail of spermatozoa. Seminal fructose was decreased by Day 40 (1000 micrograms androstanediol) or Day 70 (100 micrograms androstanediol and 100 micrograms DHT). Seminal glycerophosphocholine (GPC) and acid phosphatase levels decreased by Day 70 in all treatment groups. Both steroids decreased circulating concentrations of testosterone without altering FSH or oestradiol values.

Androgens↗
PubMed1989

Effect of dihydrotestosterone on testicular and accessory gland function in male rhesus monkeys.

Pituitary, testicular and accessory gland functions were assessed at intervals of 10-20 days in adult male rhesus monkeys given 10, 100 or 1000 micrograms dihydrotestosterone (DHT). Circulating levels of LH and testosterone were suppressed. Ejaculated spermatozoa showed morphological abnormalities and decrease in motility but sperm counts were unaffected. Seminal fructose was decreased in animals receiving DHT. Sexual behaviour was maintained in these animals.

Acid Phosphatase↗
PubMed1989

Pharmacokinetics and pharmacodynamics of a new long-acting androgen ester: maintenance of physiological androgen levels for 4 months after a single injection.

The pharmacokinetics and pharmacodynamics of testosterone trans-4-n-butylcyclohexyl carboxylate (Code name: 20 Aet-1), a new long-acting androgen ester, were evaluated in castrated adult rhesus monkeys and compared with those of testosterone enanthate (TE). A single intramuscular injection of 40 mg of 20 Aet-1 returned serum testosterone (T) to within or close to the diurnal physiological range for 80-136 days. In contrast, a similar dose of TE increased serum T to supraphysiological levels and the response evoked was of short duration. The ratio of T to dihydrotestosterone (T/DHT) ratio in monkeys treated with 20 Aet-1 was comparable to that found in control animals while in TE-treated animals, it was highly elevated. Serum estradiol (E2) elevation by 20 Aet-1 was also of smaller magnitude compared to TE. 20-Aet-1 suppressed LH levels from day 5 until day 115. The levels of LH on day 115 were 45.8% lower compared to the levels on day 13 post-castration. TE suppressed LH levels from day 1-7 post-injection. The values on day 7 were 76.6% lower compared to values on day 13 post-castration. Thus, TE-induced suppression of LH was of shorter duration, but of greater magnitude compared to the effect caused by 20 Aet-1. Similarly, FSH was suppressed for a longer duration (days 21-74) by 20 Aet-1 than by TE. The results indicate that the new testosterone ester has highly favourable pharmacokinetic properties and may prove to be the androgen of choice for supplementation therapy in contraceptive regimens.

Androgens↗
PubMed1989

Seminal fructose in normal and infertile men.

Fructose levels and fructolysis index in human semen were analysed to assess a correlation, if any, between the levels of this glycolysable sugar and sperm concentration. Semen was collected from normospermic men and men with azoospermia or oligospermia. Seminal fructose levels were elevated in men with obstructive azoospermia and in men who remained azoospermic following vasoepididy mostomy done to correct epididymal blockage. Men with sperm concentration of less than 20 million/ml pre-operatively or following vasoepididy mostomy, showed significantly high levels of fructose and lower fructolysis index. Fructose levels in normospermic infertile men, as well as in men with normal sperm counts (more than 20 million/ml), were similar to that in men of proven fertility.

Adult↗
PubMed1985

Appearance of specific proteins in rat epididymis during postnatal development.

In the immature 30-day-old caput and cauda epididymides of the rat, only a single prealbumin protein was visible. Additional epididymis-specific proteins appeared in the caput on day 45, coinciding with the entry of testicular fluid containing first wave of spermatozoa. In the cauda epididymides, additional proteins appeared only on day 50. These results indicate that the functional differentiation of caput precedes that of the cauda epididymidis.

Age Factors↗
PubMed1985

Hormonal regulation of specific proteins in the rat epididymis.

In the adult caput epididymidis, three specific prealbumin proteins (B2, B3, and B4) could be visualized by polyacrylamide gel electrophoresis. Castration caused the disappearance of B2 and B4, and B3 became faint. Androgen administration to castrated rat restored the protein pattern to normal. In the cauda epididymidis of the control rat, four prealbumin proteins (B1-B4) were seen of which only B3 was evident after castration. The dose of androgen administered was insufficient to restore the protein pattern of the cauda epididymidis. The caput epididymidis thus appears to have a lower androgen requirement than the cauda in regard to its protein pattern.

Animals↗
PubMed1983

Steroid metabolism by monkey and human spermatozoa.

Freshly ejaculated spermatozoa from monkey and human were washed and incubated with tritium labelled androgens or estradiol to study the pattern of spermatozoa steroid metabolism. When equal concentrations of steroid substrates were used for incubation, monkey and human spermatozoa showed very similar pattern of steroid conversion. Spermatozoa from both species converted testosterone mainly to androstenedione, but reverse conversion of androstenedione to testosterone was negligible. Estradiol-17 beta was converted mainly to estrone. The close similarity between the spermatozoa of monkey and men in their steroid metabolic pattern indicates that the rhesus monkey could be an useful animal model to study the effect of drugs on the metabolic pattern of human spermatozoa.

Androstenedione↗
PubMed1981

Hormonal effects of different doses of estramustine phosphate (Estracyt) in patients with prostatic carcinoma.

Ten patients with previously untreated prostatic carcinoma were studied to evaluate the hormonal effects of different doses of estramustine phosphate (Estracyt). The drug was given by mouth in increasing doses; during the first month 70 mg daily, during the second 140 mg, during the third 280 mg and during the fourth and following months 560 mg. The following hormonal parameters were studied before the treatment and then once weekly during a period of four months: testosterone, dihydrotestosterone, androstenedione, cortisol, FSH and LH. The levels of the steroids were also re-assessed one to two years later. The patients were also followed clinically at regular intervals. Initial testosterone levels of approximately 20 nmol/l plasma were reduced to approximately 0.6 nmol/l already by the lowest Estracyt dose of 70 mg/day. No further decrease was obtained by a stepwise increase of doses up to 560 mg/day. The plasma levels of dihydrotestosterone, androstenedione, FSH and LH were also reduced significantly following the administration of the lowest daily Estracyt dose and then remained at that low level. Cortisol levels increased steadily during the four months of the study. After longterm treatment the hormonal indices were by and large the same as during the last initial treatment period. Initially, the clinical effect of the treatment was excellent. In 4 patients, however, the therapy had to be discontinued after some time, because of complicating oedema (2 patients) or refractoriness to therapy (2 patients). Three years after initiating the therapy 6 patients still were on Estracyt treatment. All of them were doing well subjectively. In 5 patients the prostatic cancer was in remission or at least stable. In one patient, however, skeletal metastases were progressing. In conclusion, Estracyt was found to possess a maximal hormonal (oestrogenic) effect already in doses far below those usually recommended.

Administration, Oral↗
PubMed1979

Biologically active luteinizing hormone (LH) in plasma. III. Validation of the in vitro bioassay when applied to male plasma and the possible role of steroidal precursors.

An in vitro bioassay method for measuring LH activity was applied to male plasma. This method is based on the specific testosterone response to LH activity by interstitial cells from mouse testes. In contrast to assays conducted on female plasma, non-parallel response lines were obtained between serial dilutions of untreated male plasma and the International Reference Preparation for Human Pituitary Gonadotrophins FSH and LH/ICSH) for bioassay (code no. 69/104). In an attempt to eliminate this source of error, which would invalidate the assays, plasma was subjected to either ether extraction or charcoal adsorption prior to assay. While ether extraction was ineffective, charcoal treatment eliminated the source of non-parallelism. Evidence is presented indicating that the inclusion of a charcoal pre-treatment step provides an assay method for LH which fulfils the recognized criteria of reliability when applied to male plasma. An investigation of the likely causes of non-parallelism was undertaken by incubating mouse interstitial cells with various steroids and steroid sulphates at concentrations likely to be present in plasma. While most of the presumed precursors of testosterone were converted to testosterone, steroid sulphates (dehydroepiandrosterone sulphate and pregnenolone sulphate) at high concentrations as present in male plasma were the most active compounds in forming testosterone. However, the amount of testosterone produced from these precursors under controlled conditions was insufficient to account entirely for the deviation from parallelism observed with male plasma. Hence, the non-parallelism observed with untreated plasma samples cannot be entirely explained by the presence of steroidal testosterone precursors in male plasma.

Adsorption↗