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Biomedical subjects

J P Raynaud

Publications and source records attributed to J P Raynaud.

At least 163 records · Page 9Linked to original sources
PubMed1976

Action of midcycle contraceptive (R 2323) on the human endometrium.

Over 2,148 cycles of midcycle oral administration of R 2323 (50 mg. per day on Days 15,16, and 17), the authors recorded a drug-failure pregnancy rate of 5 per cent and an unusually regular cycle length of 28 +/- 2 days. During this trial, endometrial biopsies obtained in the luteal phase were examined by light and electron microscopy and compared to pretreatment biopsies. Light microscopy indicated a weakly secretory endometrium suggestive of some, albeit low, progesterone impregnation. Ultrastructural examination revealed deleterious changes in the development of the nucleolar channel system and giant mitochondria and a delay in the migration of glycogen granules. This low progesterone impregnation could be explained either by a direct effect of R 2323 on cell ultrastructure or by interference with progesterone availability. It would appear that R 2323 acts as a temporary substitute for progesterone at the receptor level but that it does not induce all the biological manifestations of this hormone, in particular, the endometrial changes required for implantation.

Biopsy↗
PubMed1976

Potent inhibitory activity of a new antiestrogen, RU 16 117, on the development and growth of DMBA-induced rat mammary adenocarcinoma.

When initiated the same day as dimethylbenzanthracene (DMBA) administration, daily treatment with 8 or 24 mug of the new antiestrogen RU 16117 (11alpha-methoxy ethinyl estradiol) completely prevented the appearance of mammary tumors in all animals up to the last time interval studied (130 days after DMBA administration). At daily doses of 0.5 and 2.0 mug of RU 16117, the tumor incidence was reduced to 78.6% and 40.0%, respectively. The levels of receptors for estradiol, progesterone, and prolactin in tumor tissue were reduced after treatment with 2.0 mug RU 16117 while the binding of growth hormone and insulin was not affected. While plasma LH levels were decreased after treatment with 8 or 24 mug RU 16117, plasma prolactin levels were slightly increased in animals receiving the highest dose of the antiestrogen. When RU 16117 was given at the daily dose of 24 mug for a period of 4 weeks, RU 16117 led to 65% reduction of the number of already established DMBA-induced mammary tumors. Not only the tumor number but also the tumor size was reduced by RU 16117 in a manner similar to that following ovariectomy. That the inhibitory effect of RU 16117 was not due to its low estrogenic activity is indicated by the absence of inhibitory effect of similar treatment with a range of doses (0.1-12.5 mug per day) of estradiol-17beta which cover the low estrogenic activity of the doses of RU 16117 used. Decreased levels of receptors for estradiol-17beta, progesterone, and prolactin were found in the tumors remaining after ovariectomy while treatment with the dose (24 mug) of RU 16117, efficient to inhibit tumor growth, has a similar inhibitory effect on the levels of estradiol-17beta and prolactin receptors. The present data indicate that the potent inhibitory effect of RU 16117 on the development and growth of DMBA-induced mammary tumors results from actions at both the hypothalamic-pituitary and tumor levels. The action at the peripheral level would be possibly secondary to a reduced sensitivity of the tissue to circulating hormones through lowering of hormone receptor concentrations.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Comparative action of fenfluramine on the uptake and release of serotonin and dopamine.

The anorectic agent, fenfluramine, proves to be a good inhibitor of serotonin uptake in vitro, in synaptosomes from rat whole brain (IC50 = 8.5 +/- 0.6 X 10(-7) M). After administration in vivo, its inhibitory activity in vitro equals that of chlorimipramine and in contrast to the latter, its effect is of long duration. Fenfluramine is also effective in promoting the release of serotonin from pre-loaded synaptosomes. In comparison, the structurally related compound, amphetamine, has little activity with respect to these serotonin mechanisms. It is, however, active both in inhibiting the uptake of dopamine and in promoting its release, whereas fenfluramine is inactive. The implication of these mechanisms in the serotonin-depleting capacity as well as in the anorectic activity of fenfluramine is discussed.

Animals↗
PubMed1976

Binding of [3H] methyltrienolone (R 1881) in rat prostate and human benign prostatic hypertrophy (BPH).

Methyltrienolone (R 1881 - 17beta-hydroxy-17alpha-methyl-estra-4, 9, 11-trien-3-one) binding to rat ventral prostate cytosol has a specificity typical of an androgen receptor. In human benign prostatic hypertrophy (BPH) tissue, the specificity of [3H] R 1881 binding is different from that measured in rat prostate: progesterone and R 5020 (17, 21-dimethyl-19-nor-4, 9-pregnadiene-3, 20-dione) being more potent while 19-nortestosterone is less potent competitor. Moreover, the synthetic progestin [3H] R 5020 binds to BPH tissue with a similar specificity. These data suggest the presence of progestin binding components or of an atypical androgen receptor in human BPH cytosol.

Animals↗
PubMed1976

Specific progesterone receptors in dimethylbenzanthracene (DMBA)-induced mammary tumors.

Properties of a progesterone receptor present in the cytosol (105,000 xg supernatant) of dimethylbenzanthracene (DMBA)-induced mammary tumors were studied using the highly potent progestin [3H]R 5020 (17, 21-dimethyl-19-nor-pregna-4, 9-diene-3,20-dione). As shown by sucrose gradient analysis, specific binding of [3H] R 5020 is associated with components migrating at 7-8S and 4S. Low affinity binding of the synthetic progestin is eliminated by treatment with dextran-coated charcoal. [3H] R 5020 binding is highly progestin-specific since it is easily displaced by unlabelled norgestrel, R 5020 and progesterone while estradiol-17beta, dihydrotestosterone, testosterone, testosterone and diethylstilbestrol have much lower activity. Dexamethasone and cortisol have little, if any, effect on [3H] R 5020 binding.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Assay of androgen binding sites by exchange with methyltrienolone (R 1881).

Methyltrienolone (R 1881 - 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one) binds specifically to androgen receptor in rat prostate cytosol where, unlike androstanolone, it is not metabolized. By exchanging bound endogenous hormone in rat prostate cytosol with labelled R 1881, it is possible to measure total (free anc occupied) binding sites. This assay method has also been applied to the measurement of androgen receptor sites in human benign prostatic hypertrophy where R 1881 has the added advantage of not being bound by any contaminating plasma protein (sex hormone binding protein).

Animals↗
PubMed1976

Comparative binding specificity of methyltrienolone in human and rat prostate.

The binding of methyltrienolone (R 1881) in crude human hyperplastic prostate cytosol was determined by a charcoal assay. Maximum binding was observed after 2-3 h of incubation at 0 degrees C. This binding decreased steadily thereafter and reached 41% of the 2-hour values after 96 h of incubation. In human hyperplastic prostate, the binding of 3H-R 1881 was competed by low concentrations of R 1881, R 5020 and progesterone and by high concentrations of dihydrotestosterone (DHT) and 17 alpha-methyl-DHT. In the rat prostate, on the other hand, this binding was competed by low concentrations of DHT and 17 alpha-methyl-DHT and only by high concentrations of progesterone and R 5020. The apparent association constant (Ka) of R 1881 was determined in three human prostates and found to be 0.2-0.4 X 10(9) liters/mol; the number of binding sites ranged from 101 to 158 fmol per mg of protein. These findings constitute further evidence for the existence of relatively large amounts of a progesterone-binding component in human hyperplastic prostate.

Animals↗
PubMed1976

Bovine ostertagiosis, a review. Analysis of types and syndromes found in France by post mortem examinations and total worm counts.

We have completed an analysis of the total worm counts (including digests) performed on 74 weaned cattle of various ages and sacrified in our laboratory. We identified 21 cases of animals suffering from Ostertagiosis (harbouring over 40,000 adults + immatures in the lumen and the mucosa) or moribund animals showing symptoms and lesions of Ostertagiosis. The results are presented with the Parasite profiles (percentage of G.I. genera) and Parasite levels ("Very low, Low and Average" for carrier animals and "High" and "Very High" for animals suffering from parasitism). We have observed typical cases of Type I on weaned calves but not on calves grazing when suckling their own dams (Charollais, Limousin type), Pretype II and typical Type II on 2 year old or older animals. Variants of Type II were found : Fasciologis/Ostertagiosis complex and Parturient Ostertagiosis which seems to be well-known by practitioners. Complexes of a clinical Type II + stage of Pretype II with 1 to 2 million hypobiotic L4 larvae could explain the difficulty to control very severe diseases. Oedematous ostertagiosis is also described as an original type or syndrome in 2 to 3 year old cattle : the typical lesion is a dramatic oedema of the abomasum which is found enlarged up to X 2 or X 3 times its normal size/weight. The abomasal folds and the edges are filled with a watery oedema and have an appearance of "foetal membranes". As only few parasites are present the disease is considered to be an allergic over reaction in adult animals. It is recommended that the peptic digestion of the abomasal mucosa and differential counts of the various developmental stages of the parasites be added to the routine technique used in diagnosis laboratories.

Abomasum↗
PubMed1975

[Toxicity by relay. II. A method for the asessment of safety to human consumers of carbadox, a growth-promoting additive to the feed of slaughter pigs].

A toxicity by relay. II. A method for the assessment of safety to human consumers of carbadox, a growth-promoting additive to the feed of slaughter pigs. A new methodology called "toxicity by relay" has been used to assess the potential hazard to humans of incorporating an additive into animal feeds. This methodology considers a farm-reared animal as a "relay" between the food additive and the human consumer, and employs laboratory animals as "pseudo-consumers". These laboratory animals are fed throughout their entire lives with the meat or organs of the "relay" animals which have been reared on feeds supplemented with various levels of the additive. In the present study, the toxicity of carbadox was assessed in this way. In pigs, where it is used as a growth promoter, carbadox is metabolised into serveal different products, and so an assessment of its safety using traditional methods of studying the toxicity of a substance and tis known metabolites, would perhaps be subject to error. A safety factor for man, in relation to the safety factors for rats and dogs, was calculated using (a) the comparative consumption of the laboratory animals and man; (b) an assessment of the highest dosage likely to be consumed in normal circumstances compared to the laboratory dosage, and (c) the consideration that in the laboratory there is no period of withdrawal from feeding before sacrifice as is the case with animals for slaughter. Pigs were used as "relays" in the present study by supplementing their feed with carbadox. The meat and/or livers of these animals were then fed daily to (a) rats for a period of 3 generations; (b) rats for 24-25 months, and (c) dogs for 60 months. No abnormalities were observed at the termination of the experiments. We may therefore conclude that there is no hazard for the human consumer from the use of carbadox as a pig-feed additive.

Animal Feed↗
PubMed1975

Effect of estrogen plasma binding on sexual differentiation of the rat fetus.

alpha-Fetoprotein, the estradiol-binding plasma protein (EBP), binds estradiol but not R 2858 (11beta-methoxy-17-ethynyl-estradiol) specifically. R 2858 interferes more markedly than estradiol with the sexual differentiation of the male rat fetus following treatment of the mother during the final stages of gestation. Moreover, its tissular uptake is higher. These facts suggest that alpha-fetoprotein protects the fetus from the high circulating hormone concentrations present in the pregnant mother. The hormone, once transferred to the fetus, is retained in its vascular bed by EBP.

Animals↗
PubMed1975

Methyltrienolone, a specific ligand for cellular androgen receptors.

Methyltrienolone (R 1881), 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one, a very active androgen, binds specifically to rat prostate cytosol with a higher affinity than androstanolone. Unlike the physiological hormone, however, it is not bound by human sex steroid plasma binding protein, SBP. This specific ligand is thus a useful tool for the detection of elusive androgen receptors and for their study, for instance, in human tumors where interference from plasma contamination has to be circumvented.

Animals↗
PubMed1975

[Radioimmunoassay of synthetic steroids].

The sensitivity of a radioimmunoassay depends on the intrinsic association constant of the interaction between ligand and antibody. Its specificity depends on the position of the chain which forms the link with the antigen. Thus, an antibody specific of estradiol has been obtained by coupling estradiol to albumin via a chain at position 7. For synthetic steroids the structure of which is sufficiency different from that of natural hormones, the requirements for a sensitive assay method not involving chromatography are simply maximum affinity and positioning of the couple at a site which does not undergo metabolic attack. These criteria were used to develop assays for R 2858 and R 2453 which obviate the need to administer radioactive product in clinical pharmacology. Cross-reaction with structural analogs may be used to assay competitors. Thus, R 2323 antibody, highly specific for endogenous steroids, may be used to assay other trienes such as R 1697 (trenbolone) and R 2010 (norgestrienone).

Antibody Specificity↗