Effect of N,N' -bis(dichloroacetyl)-1,8-octamethylenediamine on the chemical composition of the rat seminiferous tubules

The effect of N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine on the chemical composition of the rat seminiferous tubules was investigated. Daily oral administration of 62.5 mg/kg for 21 days significantly reduced testis weight (p less than .01), protein nitrogen and enzyme activity of the tubules (p less than .01), increased tubal concentration of ribonucleic acid by 33%, glycogen by 56%, lactic acid by 1406%, and ascorbic acid by 34% and reduced oxygen consumption rate by 32% and bicarbonate by 21%. A total inhibition of hyaluronidase activity occurred. It is concluded that this compound causes metabolic disturbance in the rat seminiferous tubules of an amplitude adequate to stop spermatogenesis.     

Spironolactone in the treatment of hirsutism

Spironolactone was used in 90 hirsute women because of its antiandrogenic effect. The drug was administered twice daily from the 4th to the 22nd day of six cycles (total dosage was 200 mg per day). The results suggest that spironolactone is suitable for the treatment of hirsutism.     

Formulation of a potential antipregnancy vaccine based on the beta-subunit of human chorionic gonadotropin (beta-hCG). III. Evaluation of various vehicles and adjuvants

Rabbits were used to test the efficacy of several materials as supplementary adjuvants when administered as part of a vaccine formulation consisting of the beta-subunit of human chorionic gonadotropin linked to tetanus toxoid (beta-hCG-TT) and adsorbed on Al(OH)3. In the amounts used, Corynebacterium parvum, levamisole, thymic factor, and N,N-dioctadecyl-N',N'-bis(2-hydroxyethyl)propanediamine exhibited little adjuvant activity although the latter material elicited marginal increments when incorporated in liposomes. A Salmonella lipopolysaccharide preparation (SPLPS) and a streptococcal preparation (OK-432) each gave approximately 7-fold increments in titer. The SPLPS preparation was pyrogenic at the doses used. OK-432 was nonpyrogenic and did not cause other evident undesirable effects. It may therefore prove to be a useful adjuvant. It gave a nearly flat dose response curve over the range of 0.5 to 4.0 mg per rabbit. Incorporation of beta-hCG-TT on Al(OH)3 in a water-in-oil emulsion caused a moderate increase in titers. Incorporation into liposomes or an oil-in-water emulsion was not effective.     

Effect of a lower-dose cetrorelix acetate protocol on in-vitro fertilization outcome

OBJECTIVE: To determine whether a low initial dosage of cetrorelix acetate could prevent a premature luteinizing hormone (LH) surge in women undergoing controlled ovarian stimulation. METHOD: Treatment with a recombinant follicle stimulating hormone was started on Day 3 of the menstrual cycle, and 0.125 mg of cetrorelix was injected daily from Day 5 of the ovarian stimulation until the diameter of the dominant follicle reached at least 16 mm. The dosage was then doubled and maintained at 0.250 mg/day until the day before the injection of human chorionic gonadotropin. RESULT: There was a significant decrease in serum LH concentration 1 day after doubling the cetrorelix dosage, and the LH concentration remained low during the follicular phase. Clinical pregnancy occurred in 18 women (42.8%), with 2 intrauterine fetal deaths before the 12th week. CONCLUSION: Increasing the cetrorelix dosage from 0.125 to 0.250 mg/day when the follicular size is appropriate can prevent a premature LH surge.     

The effect of prostaglandins and prostaglandin inhibitors on spermatogenesis.

The effect of the prostaglandin inhibitors, aspirin and indomethacin and of prostaglandins PGE1 and PGE2 on spermatogenesis in the mature male mouse has been studied. Aspirin at 100 mg/kg and at 200 mg/kg, and indomethacin at 1.0 mg/kg given orally twice a day for fifteen days produced a marked increase in spermatogenesis. The number of step 7 spermatids increased significantly over controls at about the same rate in all three groups. No significant changes in seminal vesicle weight or testicular weight was noted, although testicular weight did show an increase. Administration of prostaglandins E1 and E2 subcutaneously in doses of either 2 mg/kg or 3 mg/kg once a day for fifteen days produced a marked decrease in spermatogenesis. Step 7 spermatids decreased significantly at both dosage levels of PGE2 and at the higher dosage level of PGE1. Spermatocyte showed a significant decrease at the higher dose of PGE2. Testicular weight showed a significant decrease at the higher dose of PGE2. Seminal vesicle weight showed a significant decrease at the lower dose of PGE1 and at the higher dose of PGE2. Epididymal weight decreased at the higher dose of PGE2. Increased numbers of exfoliated immature germ cells and mature spermatozoa were observed in the epididymus of both the PGE1 and PGE2 treated animals.     

The effects of norgestrel, ethinyl estradiol, and their combination, Ovral, on lactation and the offspring of rats treated during lactation

This report considers the effects of Ovral and its estrogenic and pr ogestational components on lactation and the offspring of rats treated during lactation. Ovral contains .5 mg of norgestrel and .05 mg of ethinyl estradiol and in rats represents 10 mcg per kg of the progestogen and 1 mcg per kg of the estrogen. In this study these doses and 5 and 25 multiples were employed singly and in combinations maintaining a 10 to 1 ratio. Lactation females were treated by gavage with the drugs dissolved in corn oil. There were suitable controls. 60 lactating rats were treated, beginning on day of delivery and continuing for 21 days, with one of 9 different dosage schedules. Each litter was reduced to 6, 3 males and 3 females. The mothers were sacrificed on Day 22. The young were sacrificed at the age of 6 weeks. The highest mortality of the young was due to cannibalism but the incidence of this was apparently not due to the drug treatment. Drug treatment had no eff ect on survival of the young or on their growth weights. Growth weights of various organs were not affected. Data suggest that no biologically important amounts of these drugs are secreted in the milk when they are administered to lactating mothers at 1, 5, or 25-fold multiples of the clinical dose. No significant effects were seen on the bodies or on any of the organ weights of the mothers sacrificed at the time of weaning the young.     

A quantitative study of the effects of acetylsalicylic acid on spermatogenesis and organs of the rat.

Although the occurrence of prostaglandins in the male reproductive organs is consistent, their physiological role in fertility and reproduction is not known. The influence of acetylsalicylic acid, an inhibitor of prostaglandin synthesis, on the male reproductive tract was investigated in Sprague-Dawley rats of proven fertility. Acetylsalicylic acid dissolved in phosphate buffer was administered once a day at two dosages (300 mg/kg body weight and 150 mg/kg body weight) over a period of 12 days and a period of 6 days. The animals were killed 24 hours after the final treatment and the testes, epididymides, ductus deferens, seminal vesicles, kidneys, and adrenal glands were removed and placed in Bouin's solution. Subsequently, the tissues were cleaned and weighed and the testes were prepared for quantitative study under the light microscope. Organ weights were not significantly altered in the animals that were treated with acetylsalicylic acid. Cell counts indicated that there was a significant increase in the mean number of preleptotene spermatocytes and spermatids in those animals treated with the drug for 6 days at a dose of 150 mg/kg body weight. Treatment at the same dosage for a period of 12 days produced a significant decrease in the mean numbers of preleptotene and pachytene spermatocytes and spermatids. The mean diameter of the seminiferous tubules was also significantly decreased in the latter group of animals. In the group of animals treated with ASA for 12 days at a dose of 300 mg/kg body weight the mean diameter of the seminiferous tubules was significantly increased. No clear conclusion as to the effect of the drug on spermatogenesis or the various organs could be drawn.     

Induction of ovulation by intermittent intravenous purified follicle-stimulating hormone in polycystic ovarian disease

IIV FSH was administered to eight women with PCOD to induce ovulation. These patients had been previously treated unsuccessfully with CC or IM gonadotropins. The drug was administered by a pump at 120-minute intervals. Dosage was 1 ampule Metrodin (75 IU of FSH less than 0.11 IU of LH)/day. Eight cycles of treatment were effected. With the IIV regimen, ovulation rate was 75% (six cycles). Two multiple pregnancies and one abortion (mola vescicularis) were observed. Preovulatory E2 plasma levels and the number of follicles recruited per cycle varied from 530 to 3800 pg/ml and from 4 to 15, respectively. Maximal follicular diameter was between 16 and 28 mm. LH levels significantly decreased, while FSH levels were unchanged, resulting in a decrease of LH/FSH ratio. It is concluded that the IIV FSH regimen offers an additional modality for the induction of ovulation in PCOD patients. Further clinical trials with alternative regimens are needed, however, to identify the optimal dosage and frequency of administration of the drug.     

Relationship between maternal methadone dosage and neonatal withdrawal

OBJECTIVE: To determine whether maternal methadone dosage affects duration and degree of neonatal narcotic withdrawal. METHODS: This was a retrospective cohort study of pregnant women with opioid addiction who delivered live-born singletons between April 1990 and April 2001. Inpatient detoxification or outpatient methadone maintenance therapy was offered. Women who had a positive drug screen or whose neonate tested positive for opioids were considered to be supplementing. We evaluated indices of neonatal withdrawal according to the maximum daily methadone dosage in the last week of pregnancy. RESULTS: Seventy women with opioid addiction were followed. Median methadone dosage was 20 mg (range 0-150 mg), and 32 infants (46%) were treated for narcotic withdrawal. Among women who received less than 20 mg per day, 20-39 mg per day, and at least 40 mg per day of methadone, treatment for withdrawal occurred in 12%, 44%, and 90% of infants, respectively (P < 0.02). Methadone dosage was also correlated with both duration of neonatal hospitalization and neonatal abstinence score (r(s) =.70 and.73 respectively, both P <.001). Neonates were more likely to experience withdrawal if their mothers were supplementing with heroin, 68% versus 35% (P =.01). Regardless of supplementation, there was a significant relationship between methadone dosage and neonatal withdrawal (P <.05). CONCLUSION: Maternal methadone dosage was associated with duration of neonatal hospitalization, neonatal abstinence score, and treatment for withdrawal. Heroin supplementation did not alter this dose-response relationship. In selected pregnancies, lowering the maternal methadone dosage was associated with both decreased incidence and severity of neonatal withdrawal.     

Treatment of hyperprolactinemic amenorrhea with Metergoline

The ergoline derivative, Metergoline, in a dosage of 4 to 24 mg/day, was administered for one to eight months to 42 patients with hyperprolactinemic amenorrhea. Mean serum prolactin (PRL) concentrations before treatment were 91.2 ng/mL in the patients with functional hyperprolactinemia (N = 29) and 256.9 ng/mL in the patients with pituitary tumor (N = 13). Within four weeks, Metergoline treatment reduced these PRL concentrations to 39.5 ng/mL and 82.9 ng/mL, respectively. In this study Metergoline treatment resulted in restoration of menstruation in a total of 37 patients; 28 patients ovulated, and eight became pregnant. It is considerably more effective in functional hyperprolactinemia than in hyperprolactinemia caused by adenoma.     

醋炔诺酮肟的抗着床作用原理的研究

醋炔诺酮肟(2.5～5.0毫克/公斤/日)于妊娠第2天单次或第2、3天连续二次灌胃,可使小鼠卵子在输卵管(42.6～67.8%)运行提前一天进入子宫;但在妊娠第1天给予2.5毫克/公斤,则有76.6%卵子滞留于输卵管内,其中17.2%孕卵出现滞育现象(2细胞期)或异常。卵子移植实验表明,该药主要是抑制内膜分化,直接损伤胚泡作用较小。以醋炔诺酮肟1毫克/公斤/日给予妊娠第2和3天大鼠,第4天血清雌二醇峰、孕酮和子宫胞浆雌二醇受体水平均显著地受到抑制。提示醋炔诺酮肟可能通过加速小鼠卵子转运、干扰大鼠着床的激素平衡和抑制内膜分化,导致孕卵与内膜发育不同步,从而达到抗着床作用。     

Conjugated estrogens and the overnight dexamethasone suppression test.

Basal (8:00 AM) serum cortisol levels in peri- or postmenopausal women treated with 0.625 mg daily of conjugated equine estrogens were only slightly higher than pretreatment levels. A 1.25 mg/day dosage resulted in a significant increase in basal serum cortisol levels. In women treated with either dosage, 8:00 AM serum cortisol levels 8 to 10 hours after 1 mg of oral dexamethasone were suppressed to below 5 microgram/100 ml, although there was a significant rise in post-dexamethasone serum cortisol levels in those treated with the higher dosage. It is concluded that while replacement dosages of estrogens increase circulating total serum cortisol levels, they do not interfere with the interpretation of the overnight dexamethasone suppression test.     

Effect of gossypol on domestic fowl, Gallus domesticus

Domestic fowls (Gallus domesticus) were administered gossypol (10 mg/kg body weight/day) by oral intubation for 15 weeks. Drug treatment did not have any effect on body growth rate. The drug treatment, however, caused a marked decrease in the weights of testis and epididymis. Predominant changes in the histoarchitecture of testis (desquamation of germinal epithelium and inhibition of spermatogenesis) were observed following gossypol treatment. Epididymal tubules in gossypol treated animals were devoid of spermatozoa. Gossypol treatment had no effect on hematological parameters (total erythrocyte count, total leucocyte count, hematocrit and hemoglobin) studied in the present investigations.     

On resorption and the effects of vaginally administered terbutaline in women with premature labor

In a randomized, single-blind study, of a pilot nature, the administration of terbutaline sulphate was found to cause significant inhibition of contractions in premature labor. This effect became evident within 30 min when the dosage was 0.1 mg in 1 ml cellulose gel, applied vaginally, and within 2 h when released from a 5-g medicated vaginal polymer ring containing 10% terbutaline sulphate. No generalized effects of the terbutaline were noted (such as increased blood pressure or tachycardia) and the level of terbutaline in peripheral venous blood remained low. Vaginally administered terbutaline can obviously be quickly resorbed, giving a localized effect. Thus applied, terbutaline would appear to offer a number of advantages as regards treatment procedure.     

A corticotropin releasing hormone receptor antagonist does not delay parturition in rats

OBJECTIVE: To determine the effects of CP-154, 526, a corticotropin releasing hormone (CRH) receptor antagonist, on the length of normal rat gestation. STUDY DESIGN: Twenty-four timed-pregnant Sprague-Dawley rats were purchased for this study. The drug and placebo were administered to the animals using an osmotic pump surgically inserted in the dorsal subcutaneous space. Six animals received 6 mg/kg/day of the drug, six animals received 12 mg/kg/day of the drug and twelve animals received the placebo. The gestational period, weight of each pup and number of pups in each litter were recorded and compared in the drug group versus placebo group. RESULTS: No difference was noted in the gestational period of the drug and placebo rats. The mean weight of pups in both the drug and placebo groups was 6.18 g. The number of pups per litter were similar in the drug and placebo groups. CONCLUSION: Antagonism of CRH receptors in rats has no effect on the length of gestational period, pup weight or number of pups per litter. Further studies are needed to define the role of CRH and its antagonism in primate pregnancy, as has been done in sheep.     

Fetal exposure to pimozide: a case report

BACKGROUND: Pimozide is an antidopaminergic, antipsychotic drug. Exposure during human pregnancy has not been reported previously, and recommendations on its use are based on extrapolation from other antipsychotics with antidopaminergic activity. CASE: A 26-year-old woman had Gilles de la Tourette syndrome and obsessive-compulsive disorder. It was not possible to discontinue pimozide during pregnancy, although the dosage was reduced to 1 mg daily. In addition, she was treated with 20 mg fluoxetine until gestational week 27. By request of the patient, elective cesarean section was scheduled for week 38. As a precaution, pimozide was withdrawn 2 weeks prior to the section. During this period the patient's symptoms severely intensified, and an emergency cesarean section had to be performed at 36 weeks. A healthy male infant weighing 2,448 g was delivered. Pediatric examination of the infant and electroencephalogram demonstrated no neurologic abnormalities. On day 4 both mother and infant were discharged. CONCLUSION: This is the first published report on fetal exposure to pimozide.     

Progestational activity of a new diacetate progesterone derivative

The synthetic progestogen AY-11440 (pregna-4,6-dien-20-one-6-chloro-3, 17-dihydroxydiacetate) was tested at several doses for 3 cycles in 14 postmenopausal women and 7 ovulating women. Data collected included cervical mucus, vaginal smear stained by Papanicolaou's method, and endometrial biopsy stained by several standard methods, all taken on the day after the last pill. Patients and doses were the following: 14 postmenopausal women with vasomotor syndrome who were given 1.25 mg Premarin for 21 days and .1 mg, 1 mg, or 3 mg AY-11440, for the last 10 days of a cycle; and 7 cycling women seeking contraception, given .1, .5, or 1 mg AY-11440 daily from Day 5-25. Cervical musuc was usually negative for ferning. In postmenopausal women, vaginal smears were estrogenic and comparable to normal Cycle Day 12 in those given .1 mg; progestational like Day 20-22 in those given 1 mg; and early progestational like Day 18 in those given 3 mg. Endometria appeared early proliferative at the .1 and 1 mg doses and progestational (Day 22-23) at 3 mg. Among the fertile women vaginal smears ranged from progestational (Day 18 to late progestational (Day 25) and endometria resembled Day 22-24. Although the effects were variable among individuals, generally the effects were dissociated, in the sense that cervical mucus was most sensitive and endometrium was least changed by the drug.     

复方甲孕环酯的临床研究

本文总结了复方甲孕环酯(首称复方孕素1号)十年来的临床研究。结果表明,于月经周期的第十天(大约排卵前3—5天)服药二片、第十六天再服一片(内含甲地孕醇-3-环戊烷丙酸酯50毫克、炔雌醚0.25毫克),经试用1213例、共9651月经周期,妇女年避孕有效率达99.1%。对830例服药者的副反应调查中,173例(占20.8%)有不同程度的副反应,一般持续一天.绝大多数人的经期、经量正常。药物安全性随访观察,未见不良反应。停药后观察的七例,均能生育。临床使用中存在的主要问题是部分妇女的月经周期缩短,其中以年轻的妇女发生率较高.     

Cisplatin, methotrexate, and 5-fluorouracil combination chemotherapy for advanced ovarian cancer

A combination chemotherapy including cisplatin, 25 mg/m2 on Days 1,8; methotrexate, 30 mg/m2 on Day 1; and 5-fluorouracil, 600 mg/m2 on Day 1 has been evaluated in 28 previously untreated and 10 pretreated patients with advanced ovarian cancer after debulking surgery when feasible. The pathological response rates (complete + partial responses) were 69.2 and 50% in untreated and pretreated patients, respectively. Overall 24-month survival and progression-free survival (PFS) are 19.2 and 10.9%, respectively. A significant difference in survival and PFS is evident between patients with less and more than 2 cm residual disease and between responders (CR + PR) versus nonresponders. No renal toxicity was induced and no cycles had to be delayed because of hemathologic toxicity.     

敌枯双和环磷酰胺对SD大鼠胚胎致畸作用比较

目的:寻找作为SD大鼠胚胎-胎仔发育毒性试验(Ⅱ段生殖毒性)较理想的阳性对照药物。方法:在大鼠胚胎-胎仔发育毒性试验中,分别在妊娠第10日给予不同剂量敌枯双和环磷酰胺,于妊娠第20日解剖观察胎仔畸形,从致畸种类、致畸率等指标分析比较致畸作用。结果:敌枯双11.0mg/kg组和13.8mg/kg组外观畸形率分别为84.62%和86.84%(P<0.01),而且种类较多,如:脊柱裂、心脏外露、尾畸形、肛门闭锁、骨骼畸形等;环磷酰胺组发生的畸形较少,以骨骼发育迟缓为主。结论:敌枯双对大鼠的致畸率高、致畸种类多,是较好的阳性对照药物。