[The effect of noradrenaline and dopamine agonists and antagonists on oxygen consumption in some insect and crustacean species]. / Einfluss von Noradrenalin- und Dopamin- Agonisten und -Antagonisten auf den Sauerstoffverbrauch einiger Insekten- und Crustaceen-Arten.

The effect of drugs on oxygen consumption in some invertebrate species (insect larvae and crustacea) was investigated. Insect larvae showed an increase in oxygen consumption under the influence of sympathomimetic drugs such as isoprenaline or orciprenaline which could be prevented by beta-receptor antagonists like propranolol or butoxamine. The drugs had no effect in crustacea. On the other hand, in these animals dopamine agonists of different chemical structure (amphetamine, apomorphine, lisuride) caused an increase in oxygen consumption whereas the dopamine antagonist metoclopramide had an opposite effect.

Estradiol in saliva for monitoring follicular stimulation in an in vitro fertilization program.

A rapid and sensitive radioimmunoassay (RIA) was developed to compare serum and saliva estradiol (E2) levels in patients undergoing ovulation induction in an in vitro fertilization and embryo transfer (IVF-ET) program. Serum and saliva E2 were compared in 23 patients. The sensitivity of the saliva RIA standard curve was 11 fmol/tube (equal to 3.2 pg/tube). There was a highly significant correlation between serum and saliva E2 throughout the stimulated cycles (r = 0.769; P less than 0.001). The ratio of serum to saliva E2 was constant throughout the stimulated cycles (1.7% +/- 0.3%, mean +/- standard deviation [SD]). The E2 concentration per follicle was 1548 pmol/l in serum and 23 pmol/l in saliva. Mean E2 levels in saliva (+/- SD) were 74 +/- 21 pmol/l at midcycle and 46 +/- 12 pmol/l at midluteal phase. The findings indicate that measurement of saliva E2 provides a reliable, noninvasive method and may replace serum measurements for monitoring stimulated cycles in an IVF-ET program.

Prognostic value of the heterologous ovum penetration test for human in vitro fertilization.

In order to evaluate the prognostic value of the heterologous ovum penetration test (HOP-test) the results of this test were compared with the fertilization rate of human ova in a programme for in vitro fertilization and embryo transfer (IVF/ET). Sperm from 29 husbands (23 normozoospermic and 6 with an abnormal semen profile) were exposed on one occasion to approximately 30 hamster ova in the HOP-test and on 1 to 3 occasions to 1 to 4 preovulatory oocytes obtained from the respective wives. The mean penetration rate (+/- SEM) of the hamster ova was 43 +/- 4% (range: 0-62%) for the normozoospermic men, and 23 +/- 6% (range: 0-47%) for the men with abnormal semen profiles. In 20 out of 23 couples in which the husbands were normozoospermic, sperm penetrated the hamster ova as well as they fertilized human ova; however, in one couple, a false-positive result was obtained (penetration of the hamster ova and no fertilization of the human oocytes) and in one couple a false-negative result occurred. One negative IVF result was correctly predicted by the HOP-test. In the 6 patients with disturbed sperm motility no correct positive or negative results were obtained, whilst 4 false-positive and 2 false-negative results occurred using the HOP-test. Although the number of patients with disturbed sperm motility was small, the data suggest that the HOP-test is of limited value in predicting fertility in an IVF program for couples with reduced fertility.

Pharmacokinetics of 19-nortestosterone esters in normal men.

A reliable method for the isolation of 19-nortestosterone (NT), testosterone (T) and dihydrotestosterone (DHT) by high-performance liquid chromatography (HPLC) and quantitation of the individual steroids by radioimmunoassays is described. The method was used to measure serum concentrations of NT, T and DHT in a pharmacokinetic study and in a clinical trial for male fertility control. Following intramuscular injection of either 50 mg 19-nortestosterone-3-(p-hexoxyphenyl)-propionate (NP) or 50 mg 19-nortestosterone-decanoate (ND) serum NT increased rapidly to maximal concentrations of 4.6 +/- 3.2 and 2.0 +/- 1.3 nmol/l (+/-SD), respectively, in the 6 volunteers. The half-life time was 8 days for ND and 21 days for NP. Based on these findings a clinical trial with NP was performed. NP was given to 5 healthy men in doses of 100 mg/week for the first 3 weeks followed by 200 mg/week for 10 further weeks. Serum NT levels increased gradually and maximal concentrations were reached in the 13th treatment week (20.2 +/- 3.4 nmol/l). Measurable amounts of NT were detectable for 19 weeks after the last injection. The study shows that NT accumulates under this treatment regime and wider spacing of the injection intervals may be possible in future trials.

Effect of flutamide or cyproterone acetate on pituitary and testicular hormones in normal men.

To test the effects of antiandrogen treatment on the endocrine system 20 normal young men were treated with 750 mg/day flutamide [4-nitro 3'-trifluoromethylisobutyranilide (FLU)] or 100 mg/day cyproterone acetate (CPA) for 14 days followed or preceded by a placebo treatment of the same duration 4 weeks apart. Allocation of both drugs and sequence of active and placebo substance was by random number in a double blind design. On days 1 and 14 two basal blood samples were obtained 15 min apart followed by an iv injection of 25 micrograms GnRH and 10 mg metoclopramide (MTCL). Subsequently blood samples were taken after 25, 45, 60, and 90 min. On day 8 the GnRH/MTCL test was performed after 13 basal blood samples were obtained to establish a baseline for PRL concentrations unbiased by short term stress. After 14 days of FLU treatment, serum testosterone (T) increased significantly [17.4 +/- 1.4 (SE) vs. 26.9 +/- 1.5 nmol/liter, as well as estradiol (E2) concentrations (144 +/- 12 vs. 177 +/- 20 pmol/liter). Dihydrotestosterone increased slightly after 14 days of FLU administration (1.59 +/- 0.14 vs. 1.98 +/- 0.30 nmol/liter). At the same time basal LH concentrations were significantly elevated (5.9 +/- 0.5 vs. 8.6 +/- 0.6 ng/ml), whereas FSH levels were not affected (2.8 +/- 0.6 vs. 2.8 +/- 0.6 ng/ml). No changes in PRL values were detected throughout treatment with FLU. The effect of CPA was quite different. At the end of the treatment phase, serum T levels were reduced considerably (14.6 +/- 1.8 vs. 3.3 +/- 0.4 nmol/liter). Serum E2 decreased similarly (95 +/- 13 vs. 35 +/- 6 pmol/liter). Conversion of T to dihydrotestosterone was also diminished significantly (1.72 +/- 0.33 vs. 1.14 +/- 0.33 nmol/liter). Both gonadotropins were significantly depressed after 14 days of CPA administration (LH, 5.6 +/- 0.7 vs. 2.8 +/- 0.4 ng/ml; FSH, 2.4 +/- 0.3 vs. 1.4 +/- 0.2 ng/ml). Basal PRL levels were not affected, although the response of MTCL was reduced at the end of the treatment phase. Both drugs reduced the response of LH and FSH to GnRH administration.