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Biomedical subjects

R Stoll

Publications and source records attributed to R Stoll.

At least 109 records · Page 6Linked to original sources

Toxicological evaluation of cyclosporin A.

Toxicological studies in a variety of different animal species have shown that cyclosporin A (CS-A) is a unique immunosuppressant, since it does not cause myelotoxic, teratogenic, mutagenic, or carcinogenic effects. This is undoubtedly due to the fact CS-A produces its immunosuppressive effects by a specific action on T lymphocytes rather than by a cytotoxic mechanism. The incidence of acute inflammatory lesions was also not significantly higher in treated animals than in controls. Clear-cut organ toxicity only occurred in rats and cynomolgus monkeys, where at high doses nephro- and hepatotoxicity were observed.

Animals↗

Influence of an early grafted adenohypophysis on the thyroid of the chick embryo.

A hypophyseal pars distalis from an 11-day-old chick embryonic donor was implanted in the extraembryonic coelom of a 3-day-old recipient in order to evaluate the reactions of the thyroid of the host embryo and thus the functional capabilities of the grafted pituitary related to the thyroid. The graft did not modify the general growth of the embryo, but strongly influenced thyroidal development. The volume, colloid content, and radioiodide uptake of the thyroid gland were significantly increased, from Day 10 of incubation, compared with controls, as was the development of cytological structures, studied with the electron microscope. However, all these characteristics progressively returned to normal values between Days 14 and 17, in spite of the presence of this additional hypophysis. The grafted hypophysis thus acted autonomously during a first period resulting in increased stimulation of the thyroid. However, from Day 14, the influence of the graft decreased progressively and disappeared after Day 16. This signified the loss of its autonomy, and the mechanism of this loss, particularly the possible role of the hypothalamus, is discussed.

Animals↗

Action of testis graft from puromycin- or cAMP-pretreated donor embryos on the regression of Müllerian ducts in the female chick embryo.

Female chick embryos grafted with a piece of embryonic testis manifest in a high percentage of cases a regression of their Müllerian ducts (MD) under the influence of a anti-Müllerian hormone (AMH) secreted by the graft. Puromycine or cAMP administered to grafted females reduced significantly the percentage of those presenting a MD regression. In the present work puromycin or cAMP was administered to the male graft-donor embryos and not to the grafted females as was done previously. A testis graft from a puromycin-pretreated donor was significantly less active on the MD than that from a normal embryo. It could be then concluded that puromycin acted at the level of the testis by inhibiting the AMH production. On the other hand, the treatment of donors with cAMP did not modify their testes with regard to their action on the grafted female MD. This showed that cAMP directly protected the MD against the AMH.

Animals↗

Development of the testes in female domestic fowls submitted to an experimental sex reversal during embryonic life.

The sex differentiation of the female chick embryo can be totally inverted toward the male sex by an early extraembryonic testis grafting. This sex reversal remains permanent, as shown by three adult fowls described in this paper. They possess two testes associated with normally differentiated male excretory ducts and their Müllerian ducts have regressed. The development of male sex characteristics such as external features, behavior and complete spermatogenesis is evidence that these cocks have endocrine and exocrine capabilities similar to those of normal cocks. Although these cocks were able to mate with female fowls, they were sterile. A mechanism is discussed by which grafted testes induce such modifications in females. Hypotheses considering the heterogametic sex (female in birds) as exerting a dominant influence on the phenotypic sexual differentiation can be discarded in light of our results because a homogametic testis provokes the definitive sex inversion of a female.

Animals↗

[Development of the adrenal medulla in rats subjected to treatment inducing the Sipple syndrome].

The human Sipple syndrome associates a thyroid-C-cell tumor and a pheochromocytoma. A treatment with the antithyroid drug thiamazole allows obtaining experimentally a similar syndrome in rat. Present paper seeks to analyse changes which happened in the medullary zone of adrenal glands before and during the development of the tumors. During the treatment by thiamazole both adrenal cortex and medulla were atrophied. After the treatment was stopped, the weight of the gland increased, as compared with its previous state, and this was chiefly due to the hyperplasia of medullary cells, from which pheochromocytomas originate. The initial atrophy of adrenal gland depends on the thiamazole-induced hyperthyroidism, but the mechanism of the medullary hyperplasia subsequent to the treatment ending is unknown. It results probably from a secondary hyperthyroidism.

Adrenal Gland Neoplasms↗

Effect of diphosphonate treatment on phosphate transport by renal brush border vesicles.

Treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) given in doses of 10 mg P/kg s.c. for 7 days inhibits bone mineral retention and decreases the tubular capacity to reabsorb inorganic phosphate (Pi) in thyroparathyroidectomized (TPTX) rats. In the present work we show that pretreatment with EHDP depressed Na+-dependent Pi uptake by brush border membrane vesicles (BBMV) isolated from renal cortex of TPTX rats. The effect of EHDP was observed after feeding both high (1.2%) and low (0.2%) phosphorus diets. The EHDP-induced changes observed in vitro at the brush border level parallel the variations in the overall tubular Pi transport capacity as assessed by clearance techniques in conscious rats. Na+-dependent glucose uptake by BBMV, as well as alkaline phosphatase activity in cortical homogenates and in the BBMV were not affected by EHDP treatment. Accordingly, EHDP, given in doses that block bone mineral retention, appears to specifically affect the Na+-dependent transport of Pi across the luminal membrane of proximal tubules of renal cortex.

Animals↗

[Conditions for the appearance of parafollicular tumors in the thyroid gland of rats treated with thiamazole].

When rats are treated by an antithyroid drug as the thiamazole, an hyperplasia of the parafollicular thyroideal cells can occur during the treatment, as shown in our previous works, or not, as in the present experiment. This difference depends on the dose of drug used, but it both cases parafollicular tumours never appear during this treatment. Whatever was the initial reaction of the parafollicular cells during the treatment, an important hyperplasia of these cells always expands after its stop and is frequently followed by the development of parafollicular tumours. Then, the initial hyperplasia sometimes obtained is not prerequisite for the formation of neoplasm. The mechanism of tumoral formation must be investigated in the disorders which follow the stop of the treatment.

Animals↗

[New data about experimental Sipple syndrome in the rat].

Sipple syndrome, associating a C cells or parafollicular thyroid tumor and a pheochromocytoma of the medullary part of adrenal gland, can be experimentally induced with the use of an antithyroid drug, the thiamazole, in the rat. The treatment is applied here either between 3 and 11 months, or between 6 and 14 months of age. Tumors appear a long time after the treatment is stopped. Hypotheses are proposed to explain this phenomenon.

Adrenal Gland Neoplasms↗

Effect of dietary phosphate intake on phosphate transport by isolated rat renal brush-border vesicles.

Renal brush-border membrane vesicles isolated from rats kept for 6-8 weeks on a low-phosphate diet (0.15% of dry matter) showed a markedly faster Na(+)-dependent phosphate uptake than did membrane vesicles isolated from animals kept on a high-phosphate diet (2% of dry matter). Phosphate-uptake rate by brush-border membrane vesicles isolated from animals on a low-phosphate diet remained significantly increased after acute parathyroidectomy. Dietary adaptation was also observed in animals that had been parathyroidectomized before exposure to the different diets. In animals on the low-phosphate diet parathyrin administration inhibited phosphate uptake by brush-border vesicles only if the animals were repleted with P(i) (5ml of 20mm-NaH(2)PO(4)) 1h before being killed. After acute phosphate loading and parathyrin administration the difference in the transport rate between the two dietary groups remained statistically significant. The results suggest that the adaptation of proximal-tubule phosphate transport to dietary intake of phosphate is reflected in the Na(+)/phosphate co-transport system located in the luminal membrane of the proximal-tubule cell. Since the dietary effects on phosphate transport by brush-border membranes are only partially reversed by acute changes in parathyrin concentration and are also observed in chronically parathyroidectomized animals, the adaptation of the Na(+)/phosphate co-transport system to dietary phosphate intake seems to involve an additional mechanism independent of parathyrin.

Alkaline Phosphatase↗

Phosphate transport by rat renal brush border membrane vesicles: influence of dietary phosphate, thyroparathyroidectomy, and 1,25-dihydroxyvitamin D3.

In the present work we have investigated whether the changes in the renal handling of inorganic phosphate (Pi) induced by 1) dietary Pi, 2) removal of parathyroid glands and 3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are associated with alterations in the Na-dependent Pi uptake by brush border membrane vesicles (BBMV) isolated from renal cortex. Sham-operated (SHAM) or thyroparathyroidectomized (TPTX) rats treated or not with 26 pmol/day of 1,25(OH)2D3 i.p. were fed low (0.2%) or high (1.2%) P diet for 7 days. The results showed that in SHAM, TPTX and TPTX+1,25(OH)2D3 the Pi uptake by BBMV was greater after low than high Pi diet. It was greater in TPTX than in SHAM counterparts fed either diets. In TPTX fed low or high Pi diet 1,25(OH)2D3 decreased the Pi uptake to the level observed in SHAM. A striking parallelism was found between variations in Pi uptake by BBMV and in the tubular Pi reabsorption of the whole kidney. The Na-dependent glucose, the mannitol uptake by BBMV, and the alkaline phosphatase activity in cortical homogenates and BBMV were not affected by the various treatments. Thus, dietary Pi, chronic TPTX and 1,25(OH)2D3 appear to specifically affect the Na-dependent Pi transport system bound to the brush border membranes of renal cortical tubules. The alterations observed at this membrane level could account, at least in part, for the changes induced by these factors on the overall tubular reabsorption of Pi.

Animals↗

[C-cell hyperplasia in the thyroid of the normal rat].

During life of normal rat, it appears an hyperplasia of thyroïdeal C cells, eventually till tumors, a progressive hypertrophy of parathyroïd glands and a fall of calcemia. Chronological study of these phenomena shows that C cells hyperplasia precedes parathyroïd hypertrophy. This last so appears as a reaction against hypocalcemia provoked by hyperplasia of parafollicular cells.

Aging↗

[Frequency of anemia in Rostock students].

For the purpose of determining the frequency of anaemia a check-up was made in 735 students (498 females, 237 males) at an age of at least 19 years at the beginning of their university studies. 9.4% of them had subnormal haemoglobin values. 91.3% of them were female students. A comparison between the test persons with a decrease of haemoglobin values and those without it on the one hand and data gathered from the students' health certificate on the other hand, revealed no ensured aetiologic connection. Analyzing the state of health of that group with lowered Hb-values showed that more than half of them suffered from diseases (mostly infections) at the time, when the blood examination was made. A check-up made one year later resulted in a high percentage of normalized values. Comparisons taken from medical literature clearly indicate that the frequency of anaemia of this student population examined here is relatively low in total. From an organizational point of view, complete check-up examinations shoudl be carried out or induced for female students by the outpatient departments working at the institutions of higher learning because they provide better possibilities of covering them.

Adult↗

[Action of the testosterone treated chicken testis on the regression of the Müllerian duct].

After administration of testosterone propionate to male chick embryos and chickens, their testis have an activity, on the retrogression of mullerian ducts, much more important than that observed in testis of normal subjects of the same age, activity measured by grafting testis fragments in undifferentiated female chick embryos. The results suggest that testosterone gives such an effect by inhibiting pituitary gonadotropins, peculiarly FSH.

Animals↗

[Hormone of mullerian regression, inducing agent of the testis in chick embryo].

When embryonic testes are grafted in the coelom of female chick embryos, one observes significantly related effects on the mullerian ducts which regress more or less and on the gonads, with inhibition of the left ovary and eventual transformation of the right rudiment into a testes. The hormone responsible for mullerian regression is also a testes inductor.

Animals↗

[Development of follicular and parafollicular adenomas in the thyroid of rats treated with thiamazole (author's transl)].

Hypothyroidism is induced in rats treated with thiamazole, an antithyroid drug. If this phase lasts long enough, the follicular cells develop adenomas. Within the same period, the number of parafollicular or C cells increases threefold on an average, but without producing corresponding adenomas, the formation of which is inhibited. When treatment is stopped, a second phase appears during which thyroid function reverts to normal. The previously observed inhibition disappears, and, after a period of latency, the hyperplastic C cells develop parafollicular adenomas. The type of tumors to be found in treated rats (either of them, or both simultaneously) is determined by respective durations of the two phases. The endocrine mechanisms of these phenomena are discussed.

Adenoma↗