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Biomedical subjects

J P Raynaud

Publications and source records attributed to J P Raynaud.

At least 109 records · Page 6Linked to original sources

Effects of RU16117, an orally active weak oestrogenic compound, in postmenopausal women.

Daily oral administration of 1, 3 or 10 mg of RU16117 (11 alpha-methoxy ethinyl oestradiol) to normal postmenopausal women led to a progressive decrease of basal serum LH levels to 60.4 +/- 17.0, 35.1 +/- 9.1 and 20.1 +/- 2.8% of control (pretreatment values, P less than 0.01), respectively, after 4 wk of drug administration. Although the pattern was similar, the inhibitory effect of RU16117 was even more pronounced on FSH than LH levels: a 50% decrease of basal LH and FSH levels was obtained at the daily 1.8 and 1.2 mg doses of RU16117, respectively. No significant change of basal serum gonadotrophin levels was observed with the daily 0.3 mg dose. Administration of 1 mg of RU16117 every second day or 10 mg once a week led to a relatively small but significant (P less than 0.05) 20--25% decrease of basal serum LH levels after 4 wk of treatment in four out of five women. While daily 0.3 and 1.0 mg doses of RU16117 had no significant effect on the LH response to 100 microgram LHRH, the 3.0 mg dose delayed the response up to 90 min. The 10 mg dose, on the other hand, led to a markedly delayed and reduced response. Treatment for the same period (4 wk) with 1 mg RU16117 every second day or 10 mg once a week led to a small (20--25%, P less than 0.05) inhibition of the LH response to LHRH. At the dose of 10 mg once a week, RU16117 had no or minimal effect on endometrial histology. Since RU16117, an orally active weak oestrogenic compound, has been shown to have anticarcinogenic activity in the rat, the present findings suggest that this new steroid could be useful for the treatment of climacteric symptoms.

Aged↗

Inhibition of progesterone secretion during the luteal phase by two luteinizing hormone-releasing hormone agonists in Macaca fascicularis.

The administration of 200 microgram of the potent luteinizing hormone-releasing hormone (LHRH) agonist [D-Leu6,des-Gly-NH2(10)]LHRH ethylamide on day 6 following the plasma estradiol peak to 11 female monkeys (Macaca fascicularis) during two consecutive menstrual cycles decreased plasma progesterone levels by 40.0% +/- 3.9% as compared with previous control cycles. The plasma estradiol profile and the cycle length were not affected significantly by the treatment. Similar results were obtained with 25 microgram of [D-Ser(TBU)6,des-Gly-NH2(10)]LHRH ethylamide administered to one monkey at the same period of the cycle, such treatment leading to a 41% inhibition of circulating progesterone levels. Although plasma progesterone levels were still reduced in the two post-treatment cycles in monkeys treated with the high dose (200 microgram) of [D-Leu6,des-Gly-NH2(10)]LHRH ethylamide, the recovery cycle was normal after the administration of a lower dose (25 microgram) of [D-Ser(TBU)6, des-Gly-NH2(10)] LHRH ethylamide. The M. fascicularis monkey thus appears as a valid model with which to study the inhibitory effects of LHRH agonists on luteal function.

Animals↗

Synthesis and biochemical screening of phenylselenium-substituted steroid hormones.

The syntheses of phenylselenium-substituted progesterone [21- (1) and 17 alpha-(phenylseleno)progesterone (2)] and testosterone [16 beta- (3) and 16 alpha-(phenylseleno)testosterone (4)] derivatives are described, along with data which help to establish the stereochemistry of the substituents in the testosterone molecules. Except for 21-(phenylseleno)-progesterone, the molecules exhibit greatly reduced receptor-binding capabilities.

Animals↗

Adrenocorticotropin analogs and glucocorticoids in the hypophysectomized rat. I. Effects on liver polyribosomes and rough endoplasmic reticulum.

Hypophysectomy decreased polyribosome aggregation and activity in rat liver. Polyribosome aggregation was measured by sucrose density gradient analysis and polyribosome activity was determined by the incorporation of labeled amino acids into protein in a cell-free system using pH 5 enzymes from sham-operated rats. Hypophysectomy also totally disorganized the rough endoplasmic reticulum of hepatocytes, as shown by electron micrographs. The sc administration of the ACTH fragments, Hoe 433 (corticotropic) and Org 2766 (noncorticotropic), and of glucocorticoids (dexamethasone or corticosterone) to hypophysectomized rats restored these parameters to the levels recorded in sham-operated rats in a dose-dependent fashion 5 h after injection; the effects were maintained until at least 24 h. The sc administration of the noncorticotropic but metabolically less stable fragment, ACTH-(1-10), had only a partial effect. The potency of a noncorticotropic ACTH fragment (Org 2766) in hypophysectomized rats suggests that ACTH may act on liver protein synthesis without the intervention of glucocorticoids or pituitary hormones.

Adrenocorticotropic Hormone↗

Adrenocorticotropin analogs and glucocorticoids in the hypophysectomized rat. II. Effects on cerebral cortex polyribosomes.

The capacity of free polyribosomes from rat cerebral cortex to incorporate labeled amino acids into protein (polyribosome activity) was compared in normal, hypophysectomized, and treated hypophysectomized rats. Polyribosome activity was measured in a cell-free system using a pH 5 supernatant from sham-operated rats. The polyribosome activity of hypophysectomized rats was 10-20% less than that of sham-operated rats. Subcutaneous treatment of hypophysectomized rats daily for 10 days with ACTH, corticotropic ACTH fragments [10-2- microgram of ACTH-(1-24), ACTH-(1-23), or Hoe 433 (ACTH-(1-17))], or glucocorticoids (1 mg corticosterone or 10 microgram dexamethasone) stimulated activity to a level 25-50% higher than that in sham-operated rats. Polyribosome aggregation, as measured by sucrose density gradient analysis, was also greater in treated hypophysectomized rats than in sham-operated rats. On the other hand, a daily sc dose of 100 microgram of the noncorticotropic fragment, ACTH-(1-10), did not stimulate brain polyribosome activity in hypophysectomized rats but merely restored it to the level observed in sham-operated rats. The present study suggests that stimulation of cerebral protein synthesis by ACTH and corticotropic ACTH analogs may be partly due to their ability to promote adrenal steroid secretion. Their stimulatory effect and that of glucocorticoids might explain their physiological roles during stress and learning.

Adrenocorticotropic Hormone↗

Long-term effects of prenatal oestrogen treatment on genital morphology and reproductive function in the rat.

Prenatal exposure to RU 2858 (11 beta-methoxy-19-nor-17 alpha-pregna-1,3,5(10)-trien-20-yne-3,17-diol) alters the genital tract of rat offspring more markedly than does oestradiol which is bound to a specific plasma protein. The morphological changes observed in the male fetus are partly restored during infancy and maturity. The main effect of the treatment is seen in the female offspring and consists of alterations of the genital tract and of reproductive function.

Animals↗

Evaluation of the efficacy of salinomycin in the control of coccidiosis in chicks.

Salinomycin (Coxistac) was tested for efficacy in broilers reared in floor pens at 60 and 80 ppm fed continuously from 1 to 56 days of age. One trial was conducted. Comparisons were made with unmedicated, infected and medicated, noninfected treatments (controls) in addition to infected treatments given either monensin at 100 ppm or halofuginone at 3 ppm continuously (days 1 to 56) in the feed. Coccidia exposure was obtained by infection via the feed. Salinomycin was highly efficacious at 60 ppm based upon improved performance, lesion score, hematocrit, and serum optical density compared with the unmedicated, infected group. Statistical analysis of main effects on weight gain, feed conversion ratio, hematocrit value, and serum optical density showed no significant differences between salinomycin, monensin, or halofuginone. The weight gain of birds given salinomycin at 80 ppm was depressed significantly (P less than .01) at 56 days as a result of decreased feed consumption.

Animals↗

Luteolytic activity of LHRH and [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide: a new and physiological approach to contraception in women.

The administration of five subcutaneous 250-microgram doses of luteinizing hormone-releasing hormone (LHRH) at 4-hour intervals on 1 or 2 consecutive days between days 1 and 9 following the spontaneous LH surge in normal women shortened the luteal phase from 1 to 4 days in 16 out of 17 treatment cycles. Treatment appeared to be more efficient when LHRH was administered on days 6 to 9 after the LH surge as compared with days 1 to 5. In fact, the luteal phase was shortened from 3.3 +/- 0.2 versus 1.4 +/- 0.2 days (P < 0.01) and the serum progesterone level was decreased to 44 +/- 5 versus 71 +/- 6% of control levels (P < 0.01) when the neurohormone was injected late as compared with early in the luteal phase. A similar luteolytic effect has been obtained after intranasal administration of 500 microgram of [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide at 0800 and 1700 h on one day between days 4 and 9 following the LH peak. In six women treated with the LHRH analogue during two consecutive cycles, the luteal phase was shortened by 2.6 +/- 0.4 days (range 0.5-4.5 days) and plasma progesterone levels were reduced to 61.3 +/- 9.2% of control. As determined by daily blood sampling for LH, FSH, estradiol, and progesterone, normal cycles occurred immediately after treatment. The present data indicate the luteolytic effect of treatment with LHRH or a LHRH agonistic analogue in normal women and support the interest of such a new and physiological approach for the control of corpus luteum function and menstrual cycle in women.

Administration, Intranasal↗

Efficacy of a long-acting oxytetracycline against chlamydial ovine abortion.

The treatment of ovine abortifacient chlamydias with Terramycin/LA 200 was examined in three successive experiments in which ewes were inoculated intradermally with 6 x 10(5) PFU chlamydia at 80 days of pregnancy. The efficacy of the treatment was estimated by comparing a control group with a treated group for number of live lambs, number of abnormal lambings, length of pregnancy, average weight of lambs at birth and genital excretion of chlamydia at lambing. Sixty to eighty per cent of the ewes in the control group aborted. Under these conditions a single treatment of 20 mg/kg of Terramycin/LA at day 105 of pregnancy, i.e. four weeks after the inoculation, is not effective. On the other hand, a combination of injections, one three weeks and one five weeks after the inoculation, result in longer pregnancies on average, fewer abortions and more liveborn lambs. However, the treatment does not modify either the weight of liveborn lambs or the vaginal excretion of chlamydia at lambing. The adaptation of this treatment to practical conditions and its interest are discussed.

Abortion, Veterinary↗

Swine dysentery. Comparison of experimental diseases produced by infection with colonic mucosa or with Treponema hyodysenteriae, French strains, and of "natural" disease.

Oral inoculation of colonic mucosa scrapings and intestinal contents of animals affected with swine dysentery, or of pathogenic strains of Treponemia hyodysenteriae, as well as spontaneous contamination in infected pens caused in average swine dysentery to appear in 359 out of 409 SPF piglets. The morbidity is high irrespective of the method of contamination: after pen contamination, 75 out of 83 piglets were dysenteric; after only one ingestion of contaminated matter, 265 out of 280 animals were ill; and after inoculation of T. hyodysenteriae, 25 out of 35. Mortality in dysentery was always higher than 80%, respectively 48 out of 60 animals, 132 out of 154, and 13 out of 14. Very few animals were self-cured. The average incubation period varied according to the mode of contamination between 9 and 13 days. Animals having contracted an acute form of the disease died 16 to 23 days after contamination, and those with a chronic from 19 days, also after contamination. The increase in the number of Treponema, of Campylobacter and of Balantidium observed after the onset of the disease was approximately equivalent for all three modes of contamination. This disease was characterized by an alternance of dysentery stricto sensu and of mucoid diarrhea, the latter occurring more frequently in cases of self-cure and in chronic forms.

Animals↗

Method of evaluating the efficiency of anticoccidial drugs in floor-pen trials with multiple in-feed infection versus "seeding" model.

The evaluation of the efficacy of anticoccidials requires floor pen experiments. With the method of infection suggested, i.e., the ingestion of an infecting feed during 5 consecutive days, it is easier to check animal contamination than with the "seeder birds" method, and the anticoccidial has a dual action, it protects the animals and at the same time diminishes they environmental contamination. The presence of a non experimentally infected group, treated by an anticoccidial drug makes it possible to judge normal performances of the animals. In addition to lesion scorings, serum coloration and hematocrits are excellent criteria to evaluate the incidence of parasitism. An experimental work plan is suggested.

Animal Feed↗

Estrogen-sensitive progestin-binding sites in the female rat brain and pituitary.

The following properties of the cytoplasmic progestin receptor were studied in the hypothalamus, cortex, pituitary and uterus of the estrogen-primed castrated adult female rat using the highly potent progestin R 5020 (promegestone). (a) Sedimentation pattern. In sucrose density gradients, the R 5020-progestin receptor complex sedimented with a coefficient of about 6 to 7S. (b) Binding parameters. R 5020 bound to the progestin receptor with an intrinsic dissociation constant of about 10(-9) M as measured by a Dextran-coated charcoal (DCC) technique. The number of binding sites, however, differed widely. (c) Specificity. Only progestins competed for [3H]R 5020 binding. (d) Estrogen-dependency. In both immature and castrated adult rats, estrogen administration increased the number of R 5020-specific binding sites, assayed in vitro by a DCC technique, in the uterus, pituitary and hypothalamus, but not in the amygdala, hippocampus nor in the cortex. The increase was maximum between 40 and 48 h after priming with the potent estrogen, moxestrol, and could not be induced by androgens nor by progestins.

Adrenalectomy↗

Biotransformations of glafenine in the rat and in man.

The biotransformations of a therapeutic dose of the non-narcotic analgesic, glafenine, have been studied in the rat and in man. In the rat, the ester bond is extensively hydrolysed to give glafenic acid which is the major metabolite excreted in bile and in urine. Two minor pathways have been identified one leading by hydroxylation of the benzene ring of glafenine or glafenic acid in para of the amino-substituent to the corresponding phenols, the other, by oxidation of the quinoline nitrogen of glafenic acid, to its N-oxide. In vivo this N-oxide is partly reduced into the parent compound. Hydroxyglafenic acid is the product of both direct oxidation of glafenic acid and hydrolysis of hydroxyglafenine. The glyceric esters are conjugated as glucuro-ethers and/or sulfo-esters and the carboxylic metabolites as acyl glucuronides. The conjugation rate, high for glafenine, its phenol homologue and glafenic acid, is low for hydroxyglafenic acid and the N-oxide. The analogous urinary excretion patterns in man and in the rat suggest a similarity in the biotransformation of glafenine in these two species.

Animals↗