Abstract：
:1. In many cancer patients, 5-fluorouracil (5-FUra) treatment is toxic and even causes death. Nevertheless, all patients are subjected to a standard therapy regimen because there is no reliable way to identify beforehand those patients who are predisposed to 5-FUra-induced toxicity. In this study, we identified the dihydrouracil/uracil (UH2/Ura) ratio in plasma or urine as a potential biomarker reflecting the activity of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-FUra metabolism. 2. UH2/Ura ratios were measured by high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-MS/MS) in both healthy subjects (n=55) and in patients (n=20) diagnosed with grade I/II gestational trophoblastic tumours. In addition, rats (n=18) were used as an animal model to verify a correlation between UH2/Ura ratios and DPD levels in the liver. 3. A significant circadian rhythm was observed in UH2/Ura ratios in healthy subjects, whereas a disrupted rhythm occurred in cancer patients who were continuously infused with a high dose of 5-FUra. In rats, UH2/Ura ratios, liver DPD levels and PBMC DPD levels showed a definite circadian rhythm. Significant linear correlations with liver DPD levels were demonstrated for plasma UH2/Ura ratios (r=0.883, P<0.01), urine UH2/Ura ratios (r=0.832, P<0.01) and PBMC DPD levels (r=0.859, P<0.01). 4. The UH2/Ura ratio in biological fluid was significantly correlated with liver DPD levels; hence, this ratio could be a potential biomarker to identify patients with a deficiency in DPD.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Jiang H,Lu J,Ji Jdoi
10.1038/sj.bjp.0705651subject
Has Abstractpub_date
2004-02-01 00:00:00pages
616-23issue
4eissn
0007-1188issn
1476-5381pii
sj.bjp.0705651journal_volume
141pub_type
临床试验,杂志文章abstract：:1. The 37 amino acid human calcitonin gene-related peptide (CGRP), was injected intra-arterially into the isolated, blood perfused spleen of the dog. 2. The only vascular response observed to CGRP, once threshold had been reached (10-20 fmol), was a dose-dependent splenic arterial vasodilatation. 3. The mean intra-art...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11890.x
更新日期：1989-04-01 00:00:00
abstract：:1. The vasodilator response to acetylcholine (ACh) was investigated in the aortic arches of the leopard frog (Rana pipiens). 2. With adrenaline pre-constricted preparations, both ACh and sodium nitroprusside (SNP) caused concentration-dependent relaxations. Damage to the endothelial layer abolished relaxations to ACh,...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15568.x
更新日期：1996-07-01 00:00:00
abstract：:The modulatory effects of protein kinase C (PKC) on the activation of cytosolic phospholipase A2 (cPLA2) and adenylyl cyclase (AC) have recently been described. Since the signalling cascades associated with these events play critical roles in various functions of macrophages, we set out to investigate the crosstalk be...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702219
更新日期：1998-12-01 00:00:00
abstract：:1 The cardiovascular effects of intravenous desipramine (0.03 and 0.1 mg/kg), maprotiline (0.5 mg/kg), mianserin (1.0 and 3.0 mg/kg) and phentolamine (0.25 mg/kg) were examined and compared in pithed rats. Several experimental procedures were used in order to distinguish between the effects of the compounds on cardiac...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb10421.x
更新日期：1980-02-01 00:00:00
abstract：:1. In order to investigate the vasodilator mechanisms of the K+ channel openers, cromakalim, pinacidil and nicorandil, we measured changes in cytoplasmic Ca2+ concentration [( Ca2+]i) simultaneously with force by a microfluorimetric method using fura-2, a calcium indicator, in canine coronary arterial smooth muscle ce...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12106.x
更新日期：1990-09-01 00:00:00
abstract：:1 Non-adrenergic non-cholinergic (NANC) vasodilator nerves regulate tone in certain vascular beds. We have investigated the mechanisms of the NANC dilator response in the isolated small mesenteric artery of the rabbit by use of the tension myograph. 2 Small second or third order (150-300 microm in diameter) arteries o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701610
更新日期：1998-01-01 00:00:00
abstract：UNLABELLED:Sensory neurons play important roles in many disorders, including inflammatory diseases, such as sepsis. Sepsis is a potentially lethal systemic inflammatory reaction to a local bacterial infection, affecting thousands of patients annually. Although associated with a high mortality rate, sepsis outcome depen...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12056
更新日期：2013-12-01 00:00:00
abstract：:1. The purpose of the present investigations was to determine the influence of increasing age on the pharmacokinetics and pharmacodynamics of midazolam in male BN/BiRij rats as an animal model of aging. 2. Midazolam was administered intravenously at a dose of 2.5 mg kg-1 and its pharmacokinetics were determined on the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14482.x
更新日期：1992-09-01 00:00:00
abstract：:British Journal of Pharmacology (BJP) is pleased to publish a new set of guidelines for reporting research involving animals, simultaneously with several other journals; the 'ARRIVE' guidelines (Animals in Research: Reporting In Vivo Experiments). This editorial summarizes the background to the guidelines, gives our v...
journal_title：British journal of pharmacology
pub_type： 社论
doi：10.1111/j.1476-5381.2010.00873.x
更新日期：2010-08-01 00:00:00
abstract：:Recent evidence has indicated that the mitogen platelet-derived growth factor (PDGF) can act acutely to regulate arterial tone. In this study we demonstrate that the BB isoform of PDGF (PDGF-BB) can cause endothelium-independent relaxation of rabbit isolated mesenteric arteries. In endothelium-denuded arteries, PDGF-B...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703771
更新日期：2000-12-01 00:00:00
abstract：:In the rabbit isolated pulmonary artery, neither the ETA receptor antagonist, BQ-123 (10 microM), nor the ETB receptor antagonist, BQ-788 (10 microM), inhibited the contractions induced by 1 nM endothelin-1 (ET-1). However, the combination of BQ-123 and BQ-788 completely inhibited the ET-1-induced contraction. In cont...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb16901.x
更新日期：1994-10-01 00:00:00
abstract：:1. In circular smooth muscle of the guinea-pig gastric fundus, transmural nerve stimulation evoked a cholinergic excitatory junction potential (e.j.p.), and blockade of the e.j.p. by atropine revealed a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (i.j.p.). 2. The amplitude of the e.j.p. was inc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15290.x
更新日期：1996-03-01 00:00:00
abstract：:The characteristics of the rat epidydimal adipocyte beta-adrenoceptor have been examined using lipolysis and cyclic AMP accumulation in adipocytes as well as adenylate cyclase activity in fat cell membranes. The pA2 values corrected for binding to bovine serum albumin of the selective antagonists betaxolol (beta 1-sel...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:In rat aortic rings, hydroxocobalamin (10-30 microM) produced concentration-dependent reductions of the relaxant action of nitric oxide (NO) and the endothelium-dependent, NO-mediated, relaxant action of acetylcholine. In anococcygeus muscles, hydroxocobalamin (10-30 microM) reduced but also prolonged, NO-induced rela...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13429.x
更新日期：1993-01-01 00:00:00
abstract：:The aim of this study was to evaluate the potency of YM-53601 ((E)-2-[2-fluoro-2-(quinuclidin-3-ylidene) ethoxy]-9H-carbazole monohydrochloride), a new inhibitor of squalene synthase, in reducing both plasma cholesterol and triglyceride levels, compared with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703545
更新日期：2000-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Previous findings suggest that the growth and differentiation factor midkine (Mdk) is a negative regulator of osteoblast activity and bone formation, thereby raising the possibility that a specific Mdk antagonist might improve bone formation during fracture healing. EXPERIMENTAL APPROACH:In the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13503
更新日期：2016-07-01 00:00:00
abstract：:1. An investigation has been made of the effects of cadmium and zinc ions upon the contractile response of the guinea-pig isolated ileum to methacholine, histamine, potassium ion and a.c. field stimulation. The metal ions depress the response to all of these agents.2. Radioisotope studies showed that cadmium and zinc ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb08046.x
更新日期：1971-03-01 00:00:00
abstract：:1. In the rat isolated diaphragm preparation hexamethonium and other low potency competitive antagonists of acetylcholine (ACh), including gallamine and hyoscine butylbromide, reverse block by the potent antagonists tubocurarine, pancuronium and alcuronium. 2. In the presence of tubocurarine, hexamethonium increases t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07414.x
更新日期：1975-05-01 00:00:00
abstract：:If one drug, B, antagonizes another, A, by producing the opposite physiological effect, the antagonist concentration-effect curves should be affected by the recording system, which limits the range of agonist responses. With pieces of isolated guinea-pig ileum taken from adjacent parts of the same animal, one recorded...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704169
更新日期：2001-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Drugs targeting brain kappa-opioid receptors produce profound alterations in mood. In the present study we investigated the possible anxiolytic- and antidepressant-like effects of the kappa-opioid receptor agonist salvinorin A, the main active ingredient of Salvia divinorum, in rats and mice. EX...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00230.x
更新日期：2009-07-01 00:00:00
abstract：:1. In vivo microdialysis in halothane-anaesthetized rats and synaptosomal [3H]-noradrenaline uptake studies in vitro were used to evaluate the effects of imidazole (medetomidine) and imidazoline (clonidine and UK 14,304) alpha 2-adrenoceptor agonists on extraneuronal levels of noradrenaline in the frontal cortex. 2. L...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb14962.x
更新日期：1995-04-01 00:00:00
abstract：:1. The effects of the selective alpha 2-adrenoceptor agonist, medetomidine, were assessed on plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP), haemodynamics and on urine water and solute excretion in conscious, chronically cannulated, 7 month-old spontaneously hypertensive (SHR) and age-matched Wist...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11932.x
更新日期：1989-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:While the 5-HT and Rho-kinase (ROCK) pathways have been implicated in the development of pulmonary arterial hypertension (PAH), the nature of any interactions between them remain unclear. This study investigated a role for ROCK in 5-HT-regulated proliferative responses in lung fibroblasts in vivo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.310
更新日期：2008-10-01 00:00:00
abstract：:Airway hyper-reactivity to inhaled adenosine, mediated via mast cell activation, is a cardinal feature of asthma. Animal models have been developed in several species to mimic this phenomenon, but only in the rat has a mast cell involvement been clearly defined. In this study, a model of ovalbumin-induced adenosine hy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706271
更新日期：2005-08-01 00:00:00
abstract：:1. DNP (2,4-dinitrophenol) reduced the duration of the action potential of guinea-pig ventricular muscle at a greater rate than did anoxia. The effect was dose-dependent and was modified by the concentration of glucose in the medium. DNP (0.1 mM) reduced the amplitude of the action potential of muscles incubated with ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb07309.x
更新日期：1972-04-01 00:00:00
abstract：:Adenosine enhanced histamine release and prolonged the adenosine 3':5'-cyclic monophosphate (cyclic AMP) response in purified rat peritoneal mast cells following immunological challenge. The effect on the cyclic AMP response, which was blocked by 8-phenyltheophylline, probably results from an interaction with A2-purin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb08823.x
更新日期：1985-05-01 00:00:00
abstract：:1. Despite the observation of pharmacological responses to neuropeptide Y (NPY) in mammalian kidneys, there are species differences in the ease with which specific NPY binding sites can be demonstrated; we have investigated whether this can be explained by differential metabolism of NPY by a membrane-bound peptidase. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12429.x
更新日期：1991-10-01 00:00:00
abstract：:1. We examined the gastric mucosal blood flow (GMBF) and ulcerogenic responses following barrier disruption induced by sodium taurocholate (TC) in diabetic rats and investigated the role of capsaicin-sensitive sensory neurons in these responses. 2. Animals were injected streptozotocin (STZ: 70 mg kg(-1), i.p.) and use...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701974
更新日期：1998-08-01 00:00:00
abstract：:1 gamma-Aminobutyric acid (GABA, 0.1 to 1 mM) had no significant effect on the amplitude, rise time, half decay time or frequency of miniature endplate potentials (m.e.p.ps) at the frog or mouse neuromuscular junctions in vitro. 2 Addition of GABA (1 mM) to preparations previously treated with 11 mM K+-Ringer did not ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb10937.x
更新日期：1980-01-01 00:00:00
abstract：:5-Hydroxytryptamine(1B/1D) (5-HT(1B/1D)) receptor coupling to contraction was investigated in endothelium-denuded rabbit isolated renal arteries, by simultaneously measuring tension and intracellular [Ca(2+)], and tension in permeabilized smooth muscle cells. In intact arterial segments, 1 nM - 10 microM 5-HT failed t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703387
更新日期：2000-06-01 00:00:00
