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排序方式: 共有8416条查询结果,搜索用时 15 毫秒
81.
Gibbons DL 《Medical world news》1984,25(5):84-6, 91-2, 99-102
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84.
Preben Jakobsen Bente Søresen Lars Bastholt Mansoor Raza Mirza Susanne B. Gjedde Henning T. Mouridsen Carsten Rose 《Cancer chemotherapy and pharmacology》1994,35(1):45-52
A high-pressure liquid chromatographic method for determination of the bisdioxopiperazine derivative ADR-529 (ICRF-187), a compound proven effective in protection against anthracycline-induced cardiotoxicity, has been developed. The limit of quantitation was 5 ng/ml using a narrow-bore 5-m silica column and UV detection. The method was used for determination of pharmacokinetic profiles of ADR-529 after a 3-weekly i.v. administration of different doses of ADR-529 (600–1000 mg/m2) together with different doses of epirubicin (E, 60–100 mg/m2), fixed-dose cyclophosphamide (C, 600 mg/m2), fixed-dose 5-fluorouracil (F, 600 mg/m2), and daily administration of tamoxifen (T, 30 mg; CEF-T) in the treatment of patients with metastatic breast cancer. Pharmacokinetic parameters for epirubicin were also determined. The aim of the study was to determine (1) whether the pharmacokinetics of ADR-529 as part of a combination with CEF-T changes with increasing doses of ADR-529 and increasing doses of epirubicin and (2) whether the pharmacokinetics of epirubicin in the same combinations is altered with the administration of increasing doses of ADR-529. A total of 82 patients were included. A crossover study including 16 of the patients showed no significant difference in epirubicin pharmacokinetic parameters when epirubicin was given with or without concomitant administration of ADR-529. Apart from minor changes in the distributional half-lives, the pharmacokinetic parameters of epirubicin were not altered with increasing doses of ADR-529, nor were the pharmacokinetic parameters of ADR-529 itself. Escalating doses of epirubicin did not significantly alter the pharmacokinetic parameters of ADR-529 with the exception of a 30% increase in the terminal half-life and a decrease in total body clearance when the epirubicin dose was raised from 60 to 100 mg/m2. We conclude that concomitant administration of ADR-529 does not alter the distribution and elimination of epirubicin in doses suitable for preventing the anthracycline-induced cardiotoxicity. 相似文献
85.
Altered matrix degradation may be playing a role in the development of initial mesangial expansion and subsequent glomerulosclerosis in persons with heroin abuse. We studied whether morphine, a metabolite of heroin, had any effect on lysosomal content of cathepsin B and L in mesangial cells. Morphine (10–6 M) increased (P<0.01) mesangial cathepsin B and L activity (control, 22.1+2.2 vs. morphine, 31.4+1.4 mol NMec/g protein,N=5). Morphine (10–6 M) also increased (P<0.01) glomerular cathepsin B and L activity (control, 0.1+0.01 vs. morphine, 2.2±0.2 pmol NMec/g protein,N=3). This effect of morphine occurred in a dose-dependent manner. These results suggest that morphine enhances cathepsin B and L activity in mesangial cells and isolated glomeruli. This effect of morphine may enhance capacity of mesangial cells to degrade increased amount of mesangial macromolecules. 相似文献
86.
Clemens Allgaier Henning Wellmann Angelika Schobert Gerhart Kurz Ivar von Kügelgen 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(1):25-30
The ATP-induced increase in tritium outflow from cultured chick sympathetic neurons prelabelled with [3H]-noradrenaline was investigated.Seven days-old dissociated cell cultures of embryonic paravertebral ganglia, loaded with [3H]-noradrenaline (0.05 M), were superfused in the presence of (+)-oxaprotiline and exposed to ATP, ATP-analogues, or 1,1-dimethyl-4-piperazinium (DMPP) for 2 min. ATP (3 LM-3 mM), 2-methylthio-ATP (3–100 M), as well as DMPP (10 and 100 M) induced a significant overflow of tritium. The EC50-value of ATP was 20 M. Both the ATP-induced and the DMPP-induced tritium overflow was Ca2+-dependent and sensitive to tetrodotoxin (0.3 M) and -conotoxin (0.1 M); in addition, it was inhibited by the 2-adrenoceptor agonist 5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline (UK-14,304; 1 M). The effects of ATP and DMPP were not additive. The ATP-induced as well as the DMPP-induced overflow of tritium was diminished by the P2-purinoceptor antagonists suramin (300 M) and reactive blue 2 (3 M); in all 4 cases, the inhibition amouted to approximately 40%. The tritium overflow induced by ATP or DMPP was almost abolished by the nicotinic receptor antagonist mecamylamine (10 M) and markedly inhibited by hexamethonium (100 M). Neither ATP nor electrical stimulation caused an overflow of tritium from cultures loaded with [3H]-choline.The results suggest that ATP at molar concentrations induces noradrenaline release from cultured chick sympathetic neurons via an action on a subclass of the nicotinic cholinoceptor. 相似文献
87.
Kenyon SH Waterfield CJ Asker DS Kudo M Moss DW Bates TE Nicolaou A Gibbons WA Timbrell JA 《Biochemical pharmacology》1999,57(11):1311-1319
The effect of the industrial chemical, hydrazine (4-12 mM), on methionine synthase (EC 2.1.1.13) activity and levels of the sulphur amino acids homocysteine, cysteine, and taurine as well as GSH were investigated in vitro in isolated rat hepatocyte suspensions and monolayers in order to explain some of the adverse in vivo effects of hydrazine. None of the concentrations of hydrazine were overtly cytotoxic in hepatocyte suspensions (measured as lactate dehydrogenase [LDH] leakage) after 3 hr. However, after 24 hr in culture cells treated with 12 mM, hydrazine showed a significant increase in LDH leakage. Methionine synthase activity was reduced by hydrazine (8 and 12 mM) in suspensions (by 45 and 55%, after 3 hr) and monolayers (12 mM; 65-80% after 24 hr). This was not due to nitric oxide production and the inhibitor of nitric oxide synthase, Nomega-nitro-L-arginine, failed to protect against the hydrazine-induced loss of ATP and GSH and the reduction in urea synthesis at 24 hr. Homocysteine export was increased by 6 mM hydrazine, and total taurine content of treated cells was increased by 12 mM hydrazine. Thus, hydrazine was found to have several important and possibly deleterious effects on some parts of the sulphur amino acid pathway. 相似文献
88.
R. Bültmann Marie Trendelenburg Florin Tuluc Henning Wittenburg Klaus Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1999,359(4):339-344
In order to assess the consequences of a concomitant blockade of P2X-receptors and ecto-nucleotidases, effects of 13 P2-receptor
antagonists were investigated on contractions of the rat vas deferens elicited by α,β-methylene ATP (α,β-MeATP) and ATP and
on the removal of ATP from the incubation medium by vas deferens tissue.
Increasing concentrations of all antagonists reduced and finally abolished contractions elicited by α,β-MeATP (3 μM), with
IC50-values ranging from 1.1 to 100 μM. Pyridoxalphosphate-6-azophenyl-2’,4’-disulphonate (PPADS), 6-azophenyl-4-amino-5-hydroxy-naphthalene-1,3-disulphonate
(NH02), 4,4’-diisothiocyanatostilbene-2,2’-disulphonate (DIDS) and uniblue A also progressively reduced and finally abolished
contractions elicited by ATP (1 mM). 8,8’-[Carbonylbis(imino-3,1-phenylenecarbonyl-imino)]-bis-(1,3,5-naphthalenetrisulphonate)
(NF023), sura- min, pyridoxalphosphate-6-azophenyl-2’,5’-disulphonate (iso-PPADS), trypan blue and reactive blue 19, in contrast,
caused only partial blockade, by 34–43% maximally; reactive blue 2 and reactive red 2 had no effect; and 6,6’-(1,1’-biphenyl-4,4’-diylbisazo)-bis-4-amino-5-hydroxy-naphtha-lene-1,3-disulphonate
(NH01) and Evans blue even enhan- ced the response to ATP. For antagonists causing full or partial inhibition, the IC50-values against ATP were close to those against α,β-MeATP. All antagonists attenuated the removal of ATP, with IC25%-values ranging from 0.8 μM to >320 μM.
The results confirm the frequent combination, in one antagonist molecule, of P2-receptor blockade and blockade of ecto-nucleotidases.
This dual action underlies the effect of such compounds on contractions of the vas deferens elicited by ATP which, for certain
substances (e.g., suramin, reactive blue 2), can be explained by a simple model in which the antagonist simultaneously blocks
the degradation of ATP and a single contraction-mediating receptor (P2X1). Several observations, however, do not conform with this model, and the existence of multiple contraction-mediating receptors
for ATP or multiple, pharmacologically distinct ecto-nucleotidases has to be considered.
Received: 23 October 1998 / Accepted: 11 January 1999 相似文献
89.
Henning Honecker Hans Rommelspacher 《Naunyn-Schmiedeberg's archives of pharmacology》1978,305(2):135-141
Summary In the present paper a sensitive method is described to measure tetrahydronorharmane (THN) in the urine of man and rats as well as in the forebrain of rats. The compound is extracted into diethyl ether, separated by thin layer chromatography (TLC), acetylated with radiolabelled acetic anhydride and further isolated by two-dimensional TLC development. The existence of THN in urine of man was proven by using chromatography with different solvent systems, cocristallisation, isotope dilution technique as well as mass-spectrometry. The amount of THN in the urine varied over a wide range.With the same method it was demonstrated that THN occurs also in the forebrain of rats. The concentration increases after loading with tryptamine.The findings are discussed in view of the hypothesis that THN acts as a compound modulating neuronal mechanism. 相似文献
90.
The spatial contrast at which Observers are able to discriminate between horizontal and vertical gratings in a 2AFC task shows the same dependence on spatial and temporal frequency as does 2AFC detection. We conclude that mechanisms carrying information about spatial contrast have their sensitivity to low spatial frequency sinusoidal gratings improved by flicker and that such mechanisms are likely to mediate the detection of low spatial-frequency gratings both at low and at high temporal frequencies. 相似文献