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Biomedical subjects

R H Asch

Publications and source records attributed to R H Asch.

At least 181 records · Page 10Linked to original sources

Surgical induction of endometriosis in the rabbit: effects on fertility and concentrations of peritoneal fluid prostaglandins.

The association of endometriosis and infertility is well know. However, the exact mechanisms involved remain unclear. To study the effect of endometriosis on fertility, an experimental model was developed using New Zealand White rabbits. Endometrium obtained from one uterine horn was surgically implanted into the peritoneum, and the viability of the implants was demonstrated histologically. Adipose tissue was implanted in another group of animals which served as a control. The induction of endometriosis significantly impaired fertility rates (25%) as compared with the control group (75%). The decrease in fertility was independent of adhesion formation and primarily due to a defect in ovulation; however, a postovulatory effect cannot be excluded. Peritoneal fluid prostaglandin (PG) F concentrations increased significantly after the induction of endometriosis, whereas PGE concentrations and the PGF:PGE ratio showed no change. There was no change in PGF or PGE levels in the control group. The increased PGF in peritoneal fluid may alter follicular rupture, ovum transport, corpus luteum function, or implantation, thus representing a mechanism by which endometriosis may cause infertility.

Adipose Tissue↗

Presence of a human chorionic gonadotropin--like substance in human sperm.

An hCG-like material has been extracted from human sperm. These experiments were designed to characterize this material. Sperms of 10 volunteers were separated from seminal fluid, washed in PBS three times, and resuspended in 0.5 ml of the same buffer. Samples were pooled; cells were disrupted by sonication and extracted in alkaline buffer by constant agitation at 4 degrees C. The extract was ultracentrifuged at 4 degrees C. Supernate was lyophilized and reconstituted in 2 cc of distilled water. This material presented a dose-response curve parallel to those of IS2-hCG and CR119 in beta hCG RIA. When chromatographed in a Sephadex G-150 column the extract eluted within the hCG range and immunoreacted in the specific beta hCG RIA. When absorbed onto a concanavalin A--Sepharose column, all recovered immunoreactive material eluted after exposure to alpha-D-methylglucoside, indicating that it is a glycoprotein. The extract stimulated progesterone and testosterone secretion in porcine granulosa cells and decapsulated rat testis, respectively, indicating its biologic potency.

Adenylyl Cyclases↗

Acute decreases in serum prolactin concentrations caused by delta 9-tetrahydrocannabinol in nonhuman primates.

The acute effects of single injections of delta 9-tetrahydrocannabinol (THC) on serum prolactin (PRL) concentrations were studied in oophorectomized female and intact adult male rhesus monkeys. Some animals were challenged with thyrotropin-releasing hormone (TRH) to determine whether THC influences pituitary responsiveness to releasing hormone. THC markedly suppresses serum PRL concentrations in animals of both sexes. TRH injections resulted in normal PRL release when administered simultaneously with or 30 minutes after THC administration. These results suggest that the serum prolactin-lowering effect of THC occurs principally at a suprapituitary level.

Animals↗

Effects of delta 9-tetraphydrocannabinol administration on gonadal steroidogenic activity in vivo.

The effects of delta 9-tetrahydrocannabinol (THC) administration on gonadal steroidogenic activity in vivo were studied in two animal models: (1) luteal function of the rhesus monkey and (2) periovulatory steroid concentrations of rabbits treated with human chorionic gonadotropin (hCG). THC-treated monkeys demonstrated progesterone concentrations and luteal phase lengths which were not different from those in untreated controls. THC did not impair the normal pattern of response of the corpus luteum to increasing doses of hCG as measured by serum progesterone concentrations and luteal phase lengths. Rabbits treated with THC manifested normal periovulatory steroidal patterns (progesterone, testosterone, and dihydrotestosterone). These data suggest that THC does not significantly inhibit steroidogenesis by a direct action on the ovary. Its effect may be mediated by a central mechanism of action.

Animals↗

Evidence for a human chorionic gonadotropin-like material in the rabbit blastocyst.

Extracts from (1) 300 day 6 rabbit blastocysts, (2) 300 day 2 unfertilized ova, and (3) uteri from the nonpregnant does were analyzed in the following assays in order to determine the presence of a chorionic gonadotropin: (1) in vitro bioassay for testosterone production by decapsulated rat testes, (2) in vitro bioassay for progesterone production by porcine granulosa cells, (3) in vitro determination of adenylyl cyclase-stimulating activity in rabbit Graafian follicles, (4) gel filtration in a Sephadex G-150 column and assay of the elutions in a radioimmunoassay (RIA) specific for the beta-subunit of human chorionic gonadotropin (hCG), (5) parallelism with hCG standard preparations in beta-hCG RIA, and (6) concanavalin A-column chromatography. The rabbit blastocyst extracts showed an hCG-like material in all of the systems tested. None of the other two extracts presented hCG-like activity in any of the assay. The immunoreactive material in the beta-hCG RIA of the blastocyst extracts after gel filtration presented a profile different from that of pure hCG; this may represent heterogeneity due to a species difference or a slightly different molecular weight. These results confirmed previous findings of several investigators and those from our laboratory in that the preimplanted rabbit embryo contains a gonadotropin with characteristics similar to hCG.

Adenylyl Cyclases↗

Dynamic hormonal tests in a case of premature ovarian failure.

The case of a patient with premature ovarian failure and a history of polycystic ovarian disease was described. Dynamic gonadal and pituitary tests were done. Ovarian, adrenal, and peripheral veins were catheterized to determine the steroid secretion under HCG stimulation. In vitro studies of the capacity of ovarian steroidogenesis confirmed the refractory nature of the gonad. Lack of gonadal response, both in vivo and in vitro, to stimulation suggests a possible alteration in ovarian sensitivity to gonadotropins as a possible cause of premature menopause.

Adult↗

Effects of danazol on gonadotropin levels in castrated rhesus monkeys.

Danazol is widely used in the management of endometriosis and mammary dysplasia. However, its mechanism of action is still obscure because of the few studies done and the controversial results obtained. Antigonadotropic activity has been postulated by some investigators, whereas others have observed no effect on the gonads. In the present study, three castrated female rhesus monkeys received 400 mg of danazol daily, by gavage for 19 days, while 2 controls received 400 mg of lactose daily. Blood samples were drawn every other day from 2 weeks prior to 3 weeks after the administration of the drug. Plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased rapidly and then were maintained until danazol was discontinued. Prompt return to pretreatment levels occurred 1-2 days after the discontinuation of therapy. Prolactin levels were normal during therapy. Luteinizing hormone releasing factor (LH-RF), 100 microgram, administered intravenously during danazol therapy, caused a normal, prompt release of gonadotropins, demonstrating an intact pituitary response. The authors conclude that 1) danazol is a potent antigonadotropic agent, 2) its effect is abolished promptly after discontinuation, and 3) its probable biological action is at the hypothalamic level.

Animals↗

Precoital single doses of delta9-tetrahydrocannabinol block ovulation in the rabbit.

delta9-Tetrahydrocannabinol (delta9-THC) inhibits pituitary gonadotropin secretion in castrated rhesus monkeys. Also, delta9-THC blocks the ovulatory reflux in rabbits. We report now the dose-response relationship of precoital single doses of delta9-THC on luteinizing hormone (LH) release and ovulation in the rabbit. Forty-five female rabbits in estrous were divided into nine groups of five animals. Groups 1 to 5 received a single intramuscular dose of delta9-THC (5,2.5, 1.25, 0.612, and 0.306 mg/kg, respectively) 2 hours before mating; animals of group 6 received vehicle only. In animals of groups 7 and 8 ovulation was induced with 100 IU of human chorionic gonadotropic (hCG), given intravenously 2 hours after the administration of delta9-THC (5 mg/kg) or vehicle. Rabbit luteinizing hormone (rLH) was measured in plasma 90 to 120 minutes after coitus or hCG administration. After the injection of 5 mg of delta9-THC, luteinizing hormone-releasing factor (LH-RF) (20 microgram intravenously) was administered to the animals of group 9. All animals of groups 6, 7, and 8 ovulated. A dose-response curve was observed in the animals treated with delta9-THC and natural mating. Whereas none of the animals treated with 5 or 2.5 mg/kg ovulated, one of the group treated with 1.25 mg/kg, two of the group treated with 0.612 mg/kg, and all treated with 0.312 mg/kg ovulated. Ovulations correlated with postcoital levels of rLH. All animals of group 9 ovulated, indicating that the site of action of delta9-THC is suprapituitary, probably hypothalamic.

Animals↗

Demonstration of a chorionic gonadotropin-like substance in rabbit morulae.

Rabbit morulae were treated with specific indirect immunofluorescence and immunoperoxidase histochemical techniques. The first antibody in both systems was rabbit anti-human chorionic gonadotropin (hCG) beta-subunit. Negative controls revealed a complete absence of reaction. All morulae incubated with the double-antibody system showed a positive reaction. Rabbit morulae thus present a substance with antigenic determinants similar to the beta-subunit of hCG. The physiologic role of this substance is unknown.

Animals↗

Primary and membranous dysmenorrhea.

Organic, physiologic, and psychologic causes of dysmenorrhea are presented. Signs and symptoms include pelvic fullness, nausea, vomiting, diarrhea, urinary frequency, nervousness, and headaches. Primary dysmenorrhea has been treated with analgesics, diuretics, and antispasmodics. Androgen therapy was also found to be effective, but it cannot be used for women who have acne or hirsutism. Surgery is rarely indicated for primary dysmenorrhea.

Dysmenorrhea↗

Pure crystalline estradiol pellet implantation for contraception.

The subcutaneous implantation of estradiol pellets was found to be a simple and effective contraceptive method with good patient acceptance and minimal untoward effects. The pellets (25 mg each) were implanted through a Kearn's trocar into the abdominal wall, 2.5 to 5 cm above and parallel to Poupart's ligament. The regimen began with four pellets, and the dose was maintained or decreased by one pellet every 6 months (four, three, two, one). A potent progestogen was utilized monthly for induction of withdrawal bleeding. Altogether, 236 patients were followed for a total of 1,060 courses in 6,360 cycles (489,02 woman-years). Two pregnancies occurred during therapy. Pearl's index was 0.37. No significant alterations occurred in body weight and blood pressure. Glucose tolerance test, standard blood profiles, and Papanicolaou smears were normal during therapy. No cases of thrombophlebitis, blurred vision, headaches, gastric symptoms, or amenorrhea-galactorrhea were observed. The suppression of ovulation was confirmed by endometrial biopsies, basal body temperature, and serum follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in a selected group of patients.

Abdominal Muscles↗

Intrasellar subarachnoid herniation or empty sella associated with galactorrhea.

Eight of 115 patients with empty sella had concurrent galactorrhea. All 8 patients had abnormal sellae, and the diagnosis of empty sella was made by polytome pneumoencephalography. There were no obvious endocrine dysfunctions, but 2 patients had elevated prolactin levels. One mechanism for production of galactorrhea may involve compression of the hypothalamus and/or pituitary stalk; this was suggested by most of our observations. There may be a coincidental association of empty sella with galactorrhea, and this association is probably more common than previously noted. Evaluation of patients with galactorrhea and abnormal sellae by polytome pneumoencephalography is emphasized.

Adolescent↗

Implantation of pure crystalline pellets of estradiol for conception control.

Estradiol pellet implantation for contraception offers another alternative in conception control. The occurrence of only two pregnancies in 1,668 cycles (Pearl index: 1,42) reflects its efficacy. The advantages over oral contraceptives are: (1) absence of gastrointestinal symptoms, (2) minimal untoward effects, (3) no patient failure, and (4) convenience. Progressive stepdown in dose reduces the total amount of steroid used in long-term contraception. Contraceptive effect may not occur during the first month of implantation; adequate precaution should be taken. Because of the efficacy, minimal untoward side effects, and excellent patient acceptability, this regimen may be considered for contraception in developing countries and when other modalities are contraindicated.

Adolescent↗

The use of an impeded androgen--danazol--in the management of benign breast disorders.

Danazol, an impeded androgen with moderate antigonadotropin properties, was administered to 58 patients with a variety of benign breast disorders. The disturbances were present from 3 months to 20 years; the ages ranged from 21 to 50 years. The dose varied from 100 to 400 mg. per day for 74 to 310 days, depending upon the severity of the disorder. Most of the patients had favorable responses: 44 (75.8 per cent) experienced complete relief of subjective discomfort with disappearance of clinical signs; 17 (65.3 per cent) of the 26 patients followed from 11 to 32 months after discontinued therapy, remained symptom-free, while the others experienced moderate to complete recurrence. Fifty per cent of the women did not menstrate while on medication. Side effects were few and transient.

Adult↗

Failure of seminal plasma to enter the uterus and oviducts of the rabbit following artificial insemination.

Twelve adult does in estrus were artificially inseminated with 1 ml of semen from bucks that had received injections of 3H-thymidine 22 to 32 days previously. The ejaculates contained radioactive seminal plasma and unlabeled sperm. The reproductive tracts of the does were removed at selected intervals after insemination, divided into segments of no more than 300 mg, and processed for scintillation counting. Significant levels of radioactivity were never detected in any uterine or oviductal segment. The technique was capable of detecting as little as 1.5 X 10(-4) ml of semen in a segment. These results demonstrate that seminal plasma is not transported from the vagina into the uterus or oviducts in the rabbit, emphasizing the importance of the motility of spermatozoa in their passage to the site of fertilization.

Animals↗