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Biomedical subjects

F Neumann

Publications and source records attributed to F Neumann.

At least 55 records · Page 3Linked to original sources

Biochemical and histological studies on prostates in castrated dogs after treatment with androstanediol, oestradiol and cyproterone acetate.

The effect of cyproterone acetate (CA) on experimentally induced benign prostatic hyperplasia (BPH) in the castrated dog was investigated. BPH was induced by 6 months' treatment with 3 alpha-androstanediol (3 alpha-diol) alone and in combination with 17 beta-oestradiol (Oe2). RNA, DNA and zinc content of the glands were determined in addition to histological examination and measurement of the prostates. Two different types of prostatic enlargement were observed. First, 3 alpha-diol induced typical diffuse canine hyperplasia with replacement of functional activity. DNA, RNA and the zinc content of total glands were increased compared with intact controls. Second, 3 alpha-diol plus Oe2 produced on the one hand a more striking increase of prostatic weights, but on the other a loss of typical morphological structure and function. Histologically, transformation of simple glandular epithelium into stratified squamous metaplasia occurred in addition to stimulation of fibromuscular tissue. Biochemically, a relative decrease of DNA per mg tissue was measured with a fall in the RNA to DNA ratio and zinc to the values of castrates. Administration of CA resulted in an abolition of the 3 alpha-diol effect. Biochemical determinations and histological examinations revealed an effect similar to castration after treatment with 3 alpha-diol plus CA. After treatment with 3 alpha-diol plus Oe2 plus CA fibromuscular stimulation as an oestrogen effect predominated in addition to glandular atrophy and metaplastic changes, especially in prostatic ducts. Epithelial hyperplasia is an effect of 3 alpha-diol, whereas metaplastic proliferation only occurs in oestrogenized and androgenized dogs. In both types of prostatic enlargement CA prevents development of hyperplastic prostate.

Androstane-3,17-diol

A study of the capacity for regeneration of rat and human Leydig cells.

The capacity of Leydig cells for regeneration was investigated in 12 patients with prostatic carcinoma, who underwent subcapsular orchidectomy, and in rats after testicular necrosis produced by cadmium chloride. In rats, reappearance of Leydig cells originating from the tunica albuginea could be demonstrated by histology. Testosterone concentrations increased parallel to regeneration of Leydig cells, while LH concentrations declined. In contrast to these findings, no rise of testosterone concentrations could be observed in patients up to 8 months after subcapsular orchidectomy. Human Leydig cells seem to have no capacity for regeneration, or endocrine function, despite the fact that some of these cells, which are present morphologically in the tunica albuginea or spermatic cord, remained.

Animals

Response of basal and pentagastrin-stimulated gastric secretion and of serum gastrin to short- and long-term intravenous infusion of salmon calcitonin in hyperchlorhydric subjects.

In 23 volunteers with gastric hyperchlorhydria the effect of intravenous administration of salmon calcitonin (SMC) on basal (n = 11) and pentagastrin-stimulated gastric secretion (n = 12) and on immunoreactive serum gastrin (n = 11) was studied under various experimental conditions. SMC (0.075 microgram . kg(-1) . 2h(-1) and 0.3 microgram . kg(-1) . h(-1)) caused a statistically significant reduction of HCl output of 75% and 80% and of pepsin of 55% and 90%. Serum gastrin concentration showed a dose-dependent decrease of 17% and 31% respectively. Pentagastrin-stimulated acid secretion was moderately inhibited by short-term administration of SMC (0.15 and 0.30 microgram . kg(-1) . 30 min(-1)), the effect being confined to the period of application of the hormone. Long-term infusion of the smaller dose for 2 1/2 h induced a sustained decrease of HCl output by 55%. It is assumed that SMC inhibits gastric secretion mainly by interfering with the production or liberation, or both, of gastrin. Whether long-term administration of SMC has advantages over substances currently used as therapeutic inhibitors of gastric secretion, e.g. in gastroduodenal bleeding, has yet to be investigated.

Adult

The physiological action of progesterone and the pharmacological effects of progestogens--a short review.

Substances described as progestogens differ greatly in their additional properties, which determine the limitations of their clinical use. The extrapolation of animal assays to human use requires caution, since synergism with oestrogens, which is usually necessary, shows widely-differing species-specific ratios. In other ratios, progestogens are often antagonistic to oestrogens.

Animals

[Testosterone serum concentrations after subcapsular orchiectomy (author's transl)].

Twelve patients with prostatic carcinoma in stage C or D underwent subcapsular orchiectomy. Testosterone serum concentrations were measured by radioimmunoassay before and up to eight months following orchiectomy. After an initial decrease, testosterone concentrations remained between 0.42 ng and 0.67 ng/ml serum throughout the observation period. Stimulation with 5000 IU hCG/day for three days did not cause an increase in testosterone concentrations.

Aged

Enzootic calcinosis in sheep and C-cells hyperplasia of the thyroid.

In nine sheep belonging to the same flock, C-cells hyperplasia of the thyroid, associated with calcinosis of the soft tissues is reported. The C-cells hyperplasia was probably due to excessive feeding with poultry waste, rich in calcium. The soft tissue mineralisation was a result of hypersecretion of calcitonin, a blood calcium-lowering hormone of the C-cells.

Animals

[Molecular structure and drug activity. Example: sex hormones].

In sexual-hormone activity differences arise when only a minimum change in the structure of a known molecule is made. Even the physiological hormones have similar structures but extremely different properties. Small variations of the steroid molecule lead to orally active progestogens and estrogens. The discovery of orally active androgens and the development of anabolic agents and antiandrogens proceeds also by very small changes of known structures. Out of a million possible variations of the steroid molecule, the synthesis of approximately 80 000 structures has been realized.

Amino Acid Sequence

8 alpha-Estra-1,3,5(10)-triene-1,3, 17 beta-triol as a special type of estrogen having a high vaginotrophic activity and a low uterotrophic activity in castrated mice.

The vaginotrophic and uterotrophic activities of 1-OH-8-alpha-E2 and its acetate in comparison with E2 and E3 were assessed on the basis of the effect on weights, water/fat-and RNA/DNA-contents of mouse vagina and uterus. The multiple doses of 8 alpha-steroids or E3 sufficient to achieve a maximal effect on the vagina were not enough to stimulate the uterus fully. At various periods of time after multiple injections, 1-OH-8 alpha-E2 acetate was found to have a higher vaginotrophic potency than the uterotrophic potency, when compared with E2 as a standard. The study on the time course of organ response to 8 alpha-steroids, E2 and E3 after a single injection of daily dose, being equipotent when injected one daily for 3 days, demonstrated that 1-OH-8-alpha-E2 and E3 were less vaginotrophic and uterotrophic than E2 and had a short duration of action. 1-OH-8 alpha-E2 acetate in comparison with E2 produced a long-lasting vaginotrophic effect and an early regressing uterotrophic effect. It can be confirmed that 8 alpha-steroids, like E3, are a special type of estrogen having a high vaginotrophic activity and a low uterotrophic activity.

Animals

[Problems of dose finding: sexual hormones (author's transl)].

1. Reproduction processes are differently regulated in different species. The gestagen/estrogen ratio is of paramount importance for the evaluation of gestagens. Steroids possessing inherent estrogenicity might act as estrogens in, e.g., rodents like rats and mice, but might be active as gestagens in women (e.g. norethinodrel). 2. There is a good and partly significant correlation between the activity of various gestagens in a number of experimental test models and clinical trials. The same is true for the antiovulatory activity of various gestagens in rats and women. Oral rat tests, however, are not relevant. Receptor tests are not at all suitable for dose finding. 3. Erroneously dissociated peripheral and central (inhibition of ovulation) activity of gestagens are found only if different animal species are used (e.g., test on gonadotropin inhibition in rats, gestagen test in rabbits). This is not the case if both kinds of tests are done in one species (e.g., ovulation inhibition test in rats and test on the peripheral progestational activity in rats). 4. As far as the combined oral contraceptives containing estrogens and gestagens are concerned, it seems that both components are involved in the inhibition of ovulation in rats and women. There is additive synergism. 5. Conclusions concerning the activity and duration of effect in the clinic can be drawn from the intensity and duration of the progestational effect in rabbits. 6. The oral and subcutaneous activity of estrogens in different tests in rats and mice is in parts very well correlated. This is also true for the antiovulatory activity. 7. Comparison of the estrogenic activity of ethinyl estradiol and mestranol in rats, mice and women still leaves the question unanswered whether ethinyl estradiol is more potent than mestranol. 8. Certain conclusions regarding the depot effect in the clinic can be drawn from the duration of the estrogenic activity in the Allen-Doisy test. This test is at least suitable for the selection of the optimal depot estrogen. 9. As concerns androgens, clinical dose finding is so difficult because there are no or only poor clinical parameters for androgenicity. The oral evaluation of androgens in rats and mice provides no evidence for whether or not an androgen is orally active in men. Frequently, one can only resort to conclusions form analogy. 10. The duration of androgenic activity in rats allows certain conclusions to be drawn regarding the duration of activity in men. Dose finding, however, is difficult. 11. Steroids in which the anabolic and androgenic activity in the levator ani muscle/accessory sexual gland test are dissociated (anabolics) do also show dissociation of these two partial activities in the clinic. 12. The levator ani muscle/accessory sexual gland test in rats allows also conclusions to be drawn as to the depot activity in the clinic. 13...

Anabolic Agents

Comparison of the biological effectiveness of injected testosterone propionate and testosterone released from silastic capsules.

The in vitro release and biological effectiveness of silicone rubber implants containing testosterone in orchidectomized male rats was investigated over a period of 20 weeks. A marked reduction in release in 0.9% saline solution could be observed in vitro relative to the incubation time in the medium. The reduction in release was greatest during the first few weeks of the experiment. Rat seminal vesicles and prostates, which were greatly stimulated at the start of the experiment, lost weight corresponding to the release rate in vitro. The implants containing testosterone used here were 4 to 26 times more effective than testosterone propionate injected s.c.

Animals

[The effect of glucocorticosteroids on sex differentiation in rats].

The influence of two glucocorticoids (hydrocortisone and dexamethasone) on the somatic sex differentiation of female rats was investigated. During the time of sexual differentiation of their foetuses, pregnant rats were given dexamethasone (0.1-0.3 mg/day) or hydrocortisone (20-200 mg). Both compounds interfere with foetal development by virtue of their strong growth-inhibitory activity which manifests itself in reduction of the body weight, the crown-rump length, the length of the genital folds and the genital cord. The inhibition of growth seems to be reversible. Only hydrocortisone acts teratogenically as it causes a shift of the differentiation of the female genital tract into male direction. This virilisation consists of partial stabilisation of the Wolffian ducts, the suppression of mammary nipple development and a male-type differentiation of the urogenital sinus. The relevance of these findings for human beings is briefly discussed.

Animals