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Bill J Gurley Ashley Swain Gary W Barone D Keith Williams Philip Breen C Ryan Yates Leslie B Stuart Martha A Hubbard Yudong Tong Sreekhar Cheboyina 《Drug metabolism and disposition》2007,35(2):240-245
Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo. 相似文献
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Mequitamium iodide (LG 30435) is a novel quaternary ammonium phenothiazine with potential as an anti-asthmatic agent. In vitro binding experiments were performed in order to clarify the molecular mechanisms underlying its biological activity. Mequitamium iodide was found to bind with high affinity only to histamine H1 receptors in rat brain membranes (Ki = 9 nM) and to muscarinic acetylcholine receptors in various tissues homogenates (Ki = 12-77 nM) with no clearcut selectivity for any of the known subtypes. The interaction with muscarinic receptors in rat cerebral cortex and lung parenchyma was competitive, as showed by saturation studies. Lower affinity values (Ki = 1-10 microM) were found for serotonin 5-HT2, platelet-activating factor (PAF), verapamil and beta-adrenergic agents. These results indicate that both the potent antimuscarinic and antihistamine and the relatively weak anti-PAF pharmacological effects of mequitamium iodide may be explained by the direct interaction of the substance with the respective receptors. 相似文献
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Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk 总被引:1,自引:0,他引:1
Olmer M; Renucci JE; Planells R; Bouchouareb D; Purgus R 《Nephrology, dialysis, transplantation》1997,12(4):691-693
Conventional risk factors have very low predictive power in identifying
haemodialysis patients at high risk of vascular accidents. A role for
apolipoprotein E isotypes was looked for in a small, but rigorously
defined, cohort of longterm haemodialysis patients. In individuals with
high vascular risk, as identified by higher common carotid intima/media
thickness, we found an excess of apolipoprotein E4 alleles. This
preliminary result requires confirmation in large patient cohorts.
相似文献
6.
F Parazzi B Faravelli L Gallo M Nosenzo A Razzetti D Barone R Bandelloni E D'Amore 《Tumori》1987,73(1):33-36
The usefulness of tumor marker assay in pleural effusions for differential diagnosis is still debated. From the observation of common antigens on tissue polypeptide antigen (TPA) and keratins 8, 18 and 19 and vimentin, all substances contained in normal and neoplastic mesothelium, we felt it opportune to evaluate the use of TPA assay in 105 pleural effusions (46 benign and 59 malignant). The values were much higher than those found in blood. In hydrothorax the median value was 454 U/l (range, 59-1923), in exudative effusions 846 U/l (range, 258-4485), in metastatic pleural effusions 1277 U/l (range, 58-32352) and in mesotheliomas 7705 (range, 759-16000). The maximum value found in nonmalignant effusions was 4485 U/l; this value was taken as a cutoff level, so only 29.9% of the tumors were positive to the test. Our results showed this assay to be not very important for a differential diagnosis of malignant and nonmalignant pleural effusions. Nevertheless, the different TPA patterns in mesotheliomas (66.6% positive) and metastatic pleural effusions (15.9%) suggest that further studies are warranted. 相似文献
7.
G Tarzia E Occelli N Corsico L Gallico F Luzzani D Barone 《Il Farmaco; edizione pratica》1989,44(1):17-28
Some 2-aminoalkyl-8-chloro- and 2-aryl-1,2,4-triazolo[3,4-a]-phthalazine-3-(2H)-ones were synthesized and preliminarily tested in vitro and in vivo as potential benzodiazepine-receptor (BZRs) ligands. 2-Aryl-1,2,4-triazolo[3,4-a]-phthalazine-3(2H)-ones displaced in vitro 3H-diazepam (3H-DZ) from rat brain specific binding sites with Ki (nM) comparable to DZ and chlordiazepoxide used as reference compounds. The specific binding of the triazolones of this study was not enhanced in vitro by 4-aminobutyric acid (GABA) and in vivo they did not show any activity in counteracting the pentylenetetrazole (PTZ) induced convulsions (mice). One of these compounds (IV a) antagonized the effects of DZ in the bicuculline (BIC) induced convulsions test (mice) and the DZ induced muscle relaxant effects in the horizontal wire test. 相似文献
8.
Inhibition of neuronally induced relaxation of canine lower esophageal sphincter by opioid peptides 总被引:3,自引:0,他引:3
M S Barnette M Grous C D Manning J F Callahan F C Barone 《European journal of pharmacology》1990,182(2):363-368
Opioid peptides have profound effects on gut motility. To assess their actions on enteric neurons regulating sphincteric smooth muscle, the ability of several opioid agonists to antagonize the neuronally induced relaxation of canine lower esophageal sphincter smooth muscle was examined. Opioid peptides selective for mu (FK 33-824) or delta [( D-Pen2,D-Pen5]enkephalin) receptors produced a concentration dependent inhibition of electrical field stimulation (EFS)-induced relaxation. In contrast, neither kappa (ketocycloclazine) or sigma (SK & F 10047) opioid agonists were potent inhibitors of EFS-induced relaxation. This inhibition was relatively selective for opioid agonists since BHT 933 (alpha 2 adrenoceptor agonist) and SK & F 89124 (D2 dopamine agonist) did not inhibit EFS-induced relaxation. Furthermore, naloxone antagonized the effects of both FK 33-824 and DPDPE. These functional data suggest that opioid receptors are present on sphincteric intrinsic inhibitory neurons and that stimulation of these neuronal receptors can regulate lower esophageal sphincter relaxation. 相似文献
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Induction of procoagulant activity in human leukocytes with lipoglycans from mycoplasmas. 总被引:1,自引:0,他引:1
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G Miragliotta G Barone R A Monno D Fumarola P F Smith 《Journal of clinical microbiology》1987,25(7):1295-1297
Lipoglycans from mycoplasmas possess the ability to induce the elaboration of procoagulant activity. This represents a third endotoxic property for these polymers, in addition to the pyrogenicity and clotting of Limulus lysate reported previously. Lipoglycans from three species of Acholeplasma (A. axanthum, A. granularum, and A. oculi) stimulated the elaboration in vitro of procoagulant activity by human mononuclear cells to differing extents. Two serotypes, 3 and 4, of Ureaplasma urealyticum also exhibited this stimulatory activity. The activities of lipoglycans tested were, in decreasing order, A. oculi greater than U. urealyticum type 4 greater than A. axanthum greater than U. urealyticum type 3 greater than A. granularum. 相似文献