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Biomedical subjects

F Roy

Publications and source records attributed to F Roy.

33 records · Page 2Linked to original sources
PubMed1986

Aromatase, 17 beta-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women.

In a study of the origin of estrogens in patients with breast cancer, the concentrations of estrogens and their androgen precursors, and aromatase and 17 beta-hydroxysteroid dehydrogenase (E2DH) activities were determined in normal glandular and cancerous breast tissue. The correlation between tissue estrogens, precursor concentrations, enzyme activities and plasma levels and/or receptor status were calculated. In both normal glandular and carcinomatous breast tissue, the concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), 5 androstene-3 beta, 17 beta-diol (5-Adiol), estrone (E1), estradiol (E2) and progesterone (P) were significantly higher than plasma concentrations. While testosterone (T) concentrations were similar, dehydroepiandrosterone (DHCA) and estrone sulphate (E1S) concentrations were lower in tissue than in plasma. In carcinomatous tissue androgen concentrations were lower, but estrogen concentrations were higher than in glandular breast tissue. Estradiol (E2) concentration was positively correlated with the receptor concentration with the mean E2 concentration corresponding to an estimated receptor occupancy of about 25%, probably sufficient for a submaximal biological response. Aromatase and E2DH (E2----E1) activities were observed in all breast cancer and glandular breast tissues, activities being higher in carcinoma than in glandular breast tissues; nevertheless, aromatase activity accounts probably only for a small fraction of tissue estrogen concentration. E2DH, but not aromatase activity, was significantly higher in estrogen receptor positive than in estrogen receptor negative tissues and was negatively correlated with tissue dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) concentration; the latter two steroids are non competitive inhibitors of E2DH which inactivates E2 to E1. This effect of DHEA(S) may constitute a mechanism by which these androgens stimulate cancer growth and a rationale (besides suppression of estrogen precursors) for medical or surgical adrenalectomy in hormone sensitive metastatic mammary cancer. E2DH activity might constitute an additional marker of hormone dependency of mammary cancer.

17-Hydroxysteroid Dehydrogenases↗
PubMed1986

Comparison of the effects of nifedipine, diltiazem and verapamil on the mechanical activity of rabbit papillary muscles induced by barium chloride.

Isolated rabbit papillary muscles that do not present pacemaker activity under physiological conditions develop a spontaneous activity in the presence of 2 mmol/l BaCl2. Ba-induced contractions were unaffected by high concentrations of the Na antagonist procainamide (10(-5) mol/l). Tetrodotoxin (10(-5) mol/l), a specific blocker of the fast Na current, only slightly increased the amplitude of contractions. In contrast, the calcium entry blockers nifedipine, diltiazem, and verapamil strongly depressed the mechanical activity in a time- and dose-dependent manner. The concentrations that decreased the amplitude and frequency of contractions by 50% were determined. The order of potency was nifedipine much greater than diltiazem greater than or equal to verapamil. Ba-induced automaticity is a particularly useful model on which the potency of calcium entry blockers could be assessed.

Animals↗
PubMed1986

Modification of the basic side chain in tamoxifen: effects on microsomal metabolism and in vitro biological activity.

The effect of reducing the basicity of the side chain in tamoxifen (1) on in vitro microsomal metabolism and biological potency has been investigated. The N-methyl-N-(2,2,2-trifluoroethyl) analogue 10 and its 4-hydroxy derivative 18 have been synthesised. The side chain of 10 was not metabolised detectably by rat liver microsomes but a small amount of 18 was formed; there was no evidence of metabolic switching. The lack of metabolism of 10 is unlikely to reflect steric effects since the N,N-diethyl analogue 9 had a metabolism profile similar to that of tamoxifen, but could reflect the reduction in the basicity of the side chain. Compounds 10 and 18 had relative binding affinities (RBA) to oestrogen receptors in rat uterine cytosol and MCF-7 whole cells approximately 5 times lower than the values for tamoxifen (1) and 4-hydroxytamoxifen (3), respectively. Also 10 was similarly less potent than 1 as an inhibitor of the growth of MCF-7 cells in culture although antioestrogenicity was maintained. There was no evidence for improved cell penetration by 10 relative to 1. Of the N-acyl analogues (15-17) of tamoxifen synthesised, the N-trifluoroacetyl analogue 15 had a very low RBA. The N-acetyl (16) and N-formyl (17) analogues had RBA values comparable to that of 1 in cell cytosol or whole cell systems, but did not inhibit growth of MCF-7 cells. Thus, although metabolism of the side-chain in tamoxifen can be inhibited, reduction of biological potency results.

Animals↗
PubMed1985

Influence of calcium addition on growth of highly purified syntrophic cultures degrading long-chain Fatty acids.

Two highly purified syntrophic associations resulting in acetogenesis from stearate (SM) and oleate (OM) were obtained from the sludges of a sewage digestor. In both cases, Methanospirillum hungatei together with short, motile, gram-negative, nonfluorescent rods morphologically similar to Syntrophomonas wolfei were identified by microscopic examination. Besides growing on volatile fatty acids (butyrate through caproate), both cultures grew on oleate (C(18:1)) and numerous even-numbered, saturated long-chain fatty acids (LCFA [decanoate through stearate]). In addition, during growth on LCFA, supplementation of the culture media with calcium chloride was an absolute requirement. The sole difference between the associations was observed when SM and OM cultures were transferred from a stearate to an oleate medium. The SM culture needed 10 days before starting to degrade oleate, whereas the OM culture grew immediately, but the OM culture also grew immediately when transferred to stearate medium. Saturated LCFA degradation occurred in the presence of equinormal amounts of calcium (fatty acid/Ca ratio, 2). On the other hand, OM degradation only took place in the presence of an equimolar amount of calcium (fatty acid/Ca ratio, 1). These observations are discussed by considering the solubility constants of LCFA as calcium salts and the toxicity of the free acids against microorganisms.

Journal Article↗
PubMed1984

Trifluoperazine antagonizes postsynaptic alpha 1-but not alpha 2-adrenoceptor-mediated pressor responses in the rat.

The specificity of the alpha-adrenergic blockade by trifluoperazine was tested in pithed rats. Trifluoperazine reduced the pressor effects of (-)-noradrenaline. The log dose-response curve to methoxamine, an alpha 1-agonist, was shifted to the right whereas the vasopressor responses to BHT-920, an alpha 2-agonist, were unaffected by trifluoperazine. It was concluded that trifluoperazine acts as a peripheral vascular alpha 1-antagonist in the rat.

Adrenergic alpha-Antagonists↗
PubMed1979

A new method for the preparation of beta-amylase from sweet potato.

A simple method for the preparation of sweet potato beta-amylase by thymol amylose adsorption is described. The method is far more efficient and gives higher recovery of the enzyme. The crystalline enzyme thus obtained is found to be homogeneous by gel chromatography, polyacrylamide gel electrophoresis.

Adsorption↗
PubMedDate not supplied

A new method for evaluating the inhibitory potency of antiestrogens on breast cancer cell lines.

Breast cancer cell lines in monolayer culture are helpful in evaluating the potential antitumor activity of antiestrogens. A new method has been developed to rapidly measure the inhibitory potency of a given compound without any cell harvest and counting. Cells are incubated in 96-multiwell culture dishes in the absence or presence of an antiestrogen at 3 concentrations. At the end of incubation, cells are fixed with ethanol and colored with hematoxylin. The intensity of the coloration, which is measured with a multiscan spectrophotometer, gives an accurate evaluation of the cell number and, thereby, an estimate of the inhibitory potency of the antiestrogen. Addition of estradiol to the culture allows to evaluate the antagonistic effect of this hormone towards the inhibition of the antiestrogen. Because of its rapidity and low cost, our method should offer a new dimension in the in vitro screening of antiestrogens and probably most other antineoplastic drugs.

Breast Neoplasms↗
PubMedDate not supplied

[Vasodilator effects of LF 2.0254, a new 1,4-dihydropyridine. Comparison with nifedipine].

LF 2.0254 is a new 1.4 dihydropyridine that relaxes vascular smooth muscles by blockade of calcium entry mediated by depolarisation. In rabbit aortas contracted by KCl (15 to 55 mM) or CaCl2 (2 mM), LF 2.0254 differs markedly from nifedipine and nicardipine because of its slow onset of action, the inhibitory effect increasing with the duration of tissular contact. LF 2.0254 has only slight negative chronotropic and inotropic effects on isolated guinea-pig atria as well as in anesthetized dogs after intravenous administration. Furthermore, in open-chest anesthetized dogs, LF 2.0254 decreases mean arterial blood pressure and since cardiac output is maintained total peripheral resistance is decreased. LF 2.0254 administered orally to perinephritic hypertensive dogs (0.1 and 0.3 mg/kg) and to spontaneously hypertensive rats (0.3 to 10 mg/kg) induces a more pronounced and long-lasting hypotensive action than nifedipine. In conclusion, these results suggest that LF 2.0254 could be useful in the treatment of hypertension associated or not with cardiac insufficiency.

Animals↗