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991.
A. Corallo JP Savineau R. Tricoche and S. Foungbe 《Fundamental & clinical pharmacology》1991,5(4):319-329
The effects of the aqueous extract of leaves of Bridelia atroviridis (Bridelia), a small African tree, on the mechanical activity of rat uterus were studied. The aqueous extract of leaves of B atroviridis administered in a concentration-dependent manner (5 x 10(-6)-1.2 x 10(-3) g/ml) induced contractions that were antagonized by various calcium entry blockers (nifedipine, diltiazem, manganese chloride). In absence of external calcium ions, repeated applications of a supramaximal concentration of Bridelia (1.2 x 10(-3) g/ml) evoked sustained and repeated contractions the amplitude of which was congruent to 20% of those obtained in the physiological external calcium concentration. Bridelia-induced contractions in calcium-free medium were inhibited by isoprenaline (8 x 10(-7) M), caffeine (15 x 10(-3) M) and trifluoperazine (10(-5) M). Contractile responses induced by Bridelia in both calcium-containing and calcium-free media were antagonized by prior incubation of uterus with phorbol 12, 13-dibutyrate (6 x 10(-7) M), cholera toxin (6 x 10(-8) M) or pertussis toxin (5 x 10(-7) g/ml). These results show that Bridelia has a potent uterotonic action in the rat. The cellular basis of this action appears to be complex, and involves various mechanisms including calcium mobilization from both intra and extracellular compartments and activation of phospholipase C through a G-protein. 相似文献
992.
Y. Horsmans JP Desager S. Pauwels and C. Harvengt 《Fundamental & clinical pharmacology》1991,5(3):193-201
Nifedipine (NF), a calcium channel blocker, is often prescribed in association with other drugs. Therefore, it was interesting to know whether or not, nifedipine, which is metabolized by the cytochrome P-450NF, was able to induce or to inhibit in vivo the activity of the hepatic mixed function oxidase system. The study was conducted in ten young healthy male volunteers receiving 20 mg NF slow release bid for 15 days. Due to the small number of subjects, comparison of the NF pharmacokinetics at dose 1 and 26 failed to show a bimodality in the frequency distribution of its area under the plasma concentration-time curve (AUC 274.5 to 317.1 ng ml-1 h, NS). Hepatic microsomal autoinduction (t1/2 2.87 to 3.06 h, NS) was not found. No statistically significant effect was seen on the aminopyrine breath test and on the debrisoquine metabolic molar ratio performed before and at the end of the treatment. Unlike what has been suggested by in vitro studies, NF treatment did not modify significantly the urinary excretion of 6 beta-hydroxycortisol (318 to 265 micrograms/d, NS). After the last dose, the total oral clearance of NF was highly correlated with the metabolic clearance to 4-hydroxyantipyrine (r = 0.88; P = 0.005) but the other parameters of antipyrine biotransformation remained unchanged. We conclude that repeated nifedipine oral intake does not modify enzymatic activities of hepatic P-450 cytochromes involved in the biotransformation of antipyrine, aminopyrine, debrisoquine and cortisol. 相似文献
993.
Mortality in Systemic Sclerosis (Scleroderma) 总被引:10,自引:0,他引:10
LEE P; LANGEVITZ P; ALDERDICE CA; AUBREY M; BAER PA; BARON M; BUSKILA D; DUTZ JP; KHOSTANTEEN I; PIPER S; RAMSDEN M; ROSENBACH TO; SUKENIK S; WILKINSON S; KEYSTONE EC 《QJM : monthly journal of the Association of Physicians》1992,82(2):139-148
Two hundred and thirty-seven patients with systemic sclerosiswere followed prospectively in a scleroderma clinic. The overall3, 6, and 9-year survival rates were 86, 76 and 61 per centrespectively. Renal, cardiac and pulmonary disease, and olderage at enrolment were adverse prognostic factors associatedwith reduced survival. There were no significant differencesin survival between males and females or in patients with restrictedcompared to those with diffuse skin thickening. Death from systemicsclerosis was most frequently due to pulmonary hypertension,with fewer than expected deaths from renal or cardiac causes.Twenty-eight per cent of deaths were due to causes unrelatedto systemic sclerosis, most commonly cancer and ischaemic heartdisease, and in older patients 相似文献
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Interleukin-6 and its receptor are expressed by human megakaryocytes: in vitro effects on proliferation and endoreplication 总被引:3,自引:0,他引:3
Navarro S; Debili N; Le Couedic JP; Klein B; Breton-Gorius J; Doly J; Vainchenker W 《Blood》1991,77(3):461-471
Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in the megakaryocytic differentiation. Recently, we have observed that IL-6 is synthesized by several human cell lines with megakaryocytic features. In this study, we have investigated whether a similar phenomenon occurs during normal megakaryocytic differentiation. Human megakaryocytes (MK) were obtained by culturing normal marrow in liquid culture with aplastic plasma (AP). First, an IL-6 secretion in bone marrow culture enriched in MK as well as in purified MK populations was demonstrated by a biologic assay. Second, IL-6 mRNA was detected in a purified population of MK by the polymerase chain reaction and dot blot analysis. IL-6 mRNA and protein were undetectable in platelets. Third, in situ hybridization procedure demonstrated the presence of IL-6 mRNA in individual immature MK. Fourth, IL-6 protein was detected in MK at the unicellular level by an immunoalkaline phosphatase technique using a monoclonal antibody against IL-6. Furthermore, the presence of IL-6 receptor (IL-6-R) on MK was demonstrated by in situ hybridization using an IL-6-R probe and in situ autoradiography after binding with [125I]-labeled recombinant IL-6. The IL-6 endogenously produced in liquid cultures containing normal human plasma or AP was subsequently neutralized. This resulted in a 50% decrease of the MK growth with a minor shift in the ploidy distribution toward lower values. In semisolid cultures the addition of anti-IL-6 antibodies led to a 42% decrease in colony number in cultures stimulated by IL-3 but not in other conditions of culture. These results suggest that normal human megakaryocytopoiesis might be regulated in part by an IL-6 autocrine loop. 相似文献
997.
S Attoub L Moizo JP Laigneau B Alchepo MJM Lewin and A Bado 《Fundamental & clinical pharmacology》1998,12(3):256-262
Summary— We investigated the effects of the novel CCKB /gastrin antagonist YM022 on gastric acid secretion in vivo and in vitro, compared to CI-988 and L365.260 as reference antagonists. In the anaesthetized rat, pentagastrin-induced stimulation of gastric acid secretion was dose-dependently and up to 100% inhibited by iv administration of YM022 with an ID50 of 0.009 ± 0.0006 μmol/kg h in comparison to 0.6 ± 0.03 and 3.40 ± 0.05 μmol/kg h for CI-988 and L-365,260, respectively. In the gastric fistula cat, iv administration of YM022 produced a similar inhibitory effect with an ID50 of 0.02 μmol/kg in comparison to 1.6 and 2.5 μmol/kg for CI-988 and L-365,260, respectively. Furthermore, bolus injection of 0.6 μmol/kg YM022 produced 100% inhibition within 30 min and 85% inhibition was still observed after 3 h. In the isolated rabbit gastric glands, CCK8 -stimulated 14 C-aminopyrine uptake was inhibited according to the following rank order of potency: YM022 (IC50 = 0.0012 μM) ≫ CI-988 (IC50 = 0.2 μM) ≫ L365.260 (IC50 = 2.8 μM). Unlike with L365.260, no influence of CI-988 and YM022 on histamine-stimulated acid output was shown in this study. Thus, YM022 is a highly potent and selective gastric CCK8 /gastrin receptor antagonist and has a long-lasting inhibitory effect on gastric acid secretion. 相似文献
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