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101.
D A Campbell R D Schoenwald M W Duffel C F Barfknecht 《Investigative ophthalmology & visual science》1991,32(8):2190-2200
The activity of arylamine acetyltransferase with p-aminobenzoic acid (PABA), sulfamethazine (SMZ), and aminozolamide as substrates was studied in rabbit tissue homogenates of the corneal epithelium, stroma-endothelium, iris-ciliary process, and liver. Rabbits were classified as rapid or slow acetylators with respect to their rate of hepatic acetylation of SMZ. The ocular disposition of aminozolamide in the two phenotypes was compared using a topical ocular infusion method that permitted a constant concentration to remain in contact with the intact cornea. The effect of hepatic-acetylator phenotype on the intraocular pressure (IOP) recovery rate and drug concentrations in tissues after single-dose administration of aminozolamide also was studied. In general, the rank order of arylamine acetyltransferase activity regardless of substrate was liver greater than iris-ciliary process greater than corneal epithelium greater than stroma-endothelium. The specific activity with aminozolamide as substrate was greater than that with SMZ in each tissue homogenate and greater than with PABA as substrate in all tissues except the stroma-endothelium of slow hepatic-acetylator rabbits. Very low enzyme activity ratios for ocular acetylation between rapid and slow hepatic-acetylating rabbits indicated that acetylation in the ocular tissues did not correspond with the acetylation phenotype. At various times during and after topical infusion to the anesthetized rabbit, assay determinations of drug and metabolite in ocular tissues indicated that there were no significant differences between phenotypes in the disposition of either drug or metabolite. These results correlate with the IOP measurements after topical infusion; they also showed no difference in the effect of aminozolamide between hepatic-acetylator phenotypes. These results indicate that the ocular disposition and the decrease in IOP from topical application of aminozolamide is independent of the hepatic-acetylation phenotype in the rabbit. There are significant amounts of acetyltransferase activity in the ocular tissues of the rabbit with these three substrates, indicating that acetylation may be occurring for other arylamine drugs used in the eye. 相似文献
102.
矽宁对肺泡巨噬细胞功能的影响 总被引:1,自引:0,他引:1
矽宁、梯络龙等药物具有明显降低由Zymosan刺激的大鼠肺泡巨噬细胞的耗氧量,抑制其释放超氧离子、过氧化氢及化学发光量。矽宁具有较强的亲合肺巨噬细胞的能力,并有剂量-效应关系。 相似文献
103.
MW Blom PR Bartel DK Sommers CH Van Der Meyden PJ Becker 《Fundamental & clinical pharmacology》1992,6(1):5-9
This study compares the effects of buspirone (5 mg), chlordiazepoxide (5 mg), hydroxyzine (10 mg) and placebo on psychomotor function and EEG, when taken thrice daily for a period of two weeks, with those after a single dose administration. Nine healthy volunteers participated in the study. The battery of psychomotor tests included peak velocity of saccadic eye movements (SEM), a Sternberg memory scanning and choice reaction time test (SMS-CRT) and critical flicker fusion frequency (CFFF). The peak velocity of saccadic eye movements was significantly impaired by the single dose of hydroxyzine (P = 0.03) in comparison to the multidose results. A similar comparison regarding buspirone only approached significance (P = 0.07). The SMS-CRT and CFFF did not reveal any difference between the multi and single dose regimens. Spectral analysis of the EEG did not distinguish between the multi and single dosage schedules regarding the respective drugs in the low doses administered. 相似文献
104.
105.
P-31 MR spectroscopy of normal human brain and brain tumors 总被引:2,自引:0,他引:2
Hubesch B; Sappey-Marinier D; Roth K; Meyerhoff DJ; Matson GB; Weiner MW 《Radiology》1990,174(2):401-409
Image-guided phosphorus-31 magnetic resonance (MR)-localized image-selected in vivo spectroscopy was performed on normal human brain and brain tumors. Peak area ratios, absolute molar concentrations of metabolites, and pH were determined. T1 values in normal brain were measured. The most important finding was that the metabolite concentrations detectable with MR spectroscopy in brain tumors were reduced from 20% to 70%. Phosphomonoesters, phosphodiesters, and phosphocreatine (PCr) showed the greatest decreases, while inorganic phosphate (Pi) showed the least change. The PCr-Pi ratio was significantly reduced in tumors. The pH of brain tumors (7.12 +/- 0.03) was more alkaline than that of normal brain (6.99 +/- 0.01). The authors conclude that the metabolite concentrations and pH in human brain tumors differ significantly from those in normal brain. These differences may be ultimately useful in characterizing tumors in man. 相似文献
106.
Ultrasound examination of the hydatic liver 总被引:9,自引:0,他引:9
107.
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109.
Shibutani S Ravindernath A Terashima I Suzuki N Laxmi YR Kanno Y Suzuki M Apak TI Sheng JJ Duffel MW 《Cancer research》2001,61(10):3925-3931
An increased incidence of endometrial cancer has been reported in breast cancer patients taking tamoxifen (TAM) and in healthy women participating in the TAM chemoprevention trials. Because TAM-DNA adducts are mutagenic and detected in the endometrium of women treated with TAM, TAM adducts are suspected to initiate the development of endometrial cancer. Treatment with TAM has been known to promote hepatocarcinoma in rats, but toremifene (TOR), a chlorinated TAM analogue, did not. TAM adducts are primarily formed via sulfonation of the alpha-hydroxylated TAM metabolites. To explore the mechanism of the lower genotoxicity of TOR, the formation of DNA adducts induced by TOR metabolites was measured using (32)P-postlabeling/ high-performance liquid chromatography analysis and compared with that of TAM metabolites. When alpha-hydroxytoremifene was incubated with DNA, 3'-phosphoadenosine 5'-phosphosulfate, and either rat or human hydroxysteroid sulfotransferase, the formation of DNA adducts was two orders of magnitude lower than that of alpha-hydroxytamoxifen. alpha-hydroxytoremifene was a poor substrate for rat and human hydroxysteroid sulfotransferases. In addition, the reactivity of alpha-acetoxytoremifene, a model activated form of TOR, with DNA was much lower than that of alpha-acetoxytamoxifen. Thus, TOR is likely to have lower genotoxicity than TAM. TOR may be a safer alternative by avoiding the development of endometrial cancer. 相似文献
110.
Renate RJ de Groot-Besseling Theo JM Ruers Iris L Lamers-Elemans Cathy N Maass Robert MW de Waal Johan R Westphal 《BMC cancer》2006,6(1):149