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Renal selective N-acetyl-L-gamma-glutamyl prodrugs: studies on the selectivity of some model prodrugs. 总被引:2,自引:1,他引:1 下载免费PDF全文
J. C. Drieman H. H. Thijssen H. A. Struyker-Boudier 《British journal of pharmacology》1993,108(1):204-208
1. In this study, a number of structurally different N-acetyl-L-gamma-glutamyl prodrugs were investigated with respect to selective uptake by the kidney in male Wistar rats. 2. All prodrugs were tested in vitro in rat kidney slices and kidney homogenate to study their uptake and conversion. It was found that the prodrugs of para-nitroaniline (agPNA), aminophenyl acetic acid (agAFA), sulphamethoxazole (agSM), sulphadimethoxine (agSDM), propranolol (agPP) and metoprolol (agMP) were accumulated by a probenecid-sensitive carrier. The prodrug of 4'-aminoantipyrine (agAAP) was not accumulated by a probenecid- or buthionine sulphoximine-sensitive carrier. Unlike all other prodrugs, agAAP and agMP were not, or only a very limited extent converted to the parent compound in vitro. 3. agPNA, agAFA and agPP were also investigated in vivo. The tissue distribution of the prodrugs and the parent drugs was established, as was their urinary excretion and pharmacokinetic behaviour. agPNA and agAFA showed selective uptake by the kidney, in contrast to agPP which accumulated in the liver. The distribution of the parent compounds following prodrug administration was as follows: agPNA was found in kidney and plasma: agAFA in kidney only; agPP in liver only. 4. The factors which determine the selectivity of N-acetyl-L-gamma-glutamyl prodrugs are discussed. The main factors are: the transport into the kidney, the conversion rate, the residence time of the prodrug in the kidney and the presence or absence of competition for uptake and conversation by other tissues, e.g. the liver.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
954.
W. Weber G. Kewitz K. L. Rost M. Looby M. Nitz L. Harnisch 《European journal of clinical pharmacology》1993,44(Z1):S23-S25
A population kinetic analysis was carried out on sparse plasma gentamicin (GE) concentration data from 469 neonates obtained as part of a routine therapeutic drug monitoring (TDM) programme in the hospital neonatology unit.The best predictors of the kinetic parameters of the monoexponential model, volume of distribution (Vd) and clearance (CL), were the weight (WT) and gestational age (GA). Vd of the neonates was only related to WT, whereas the half-life was only related to the GA. 相似文献
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By means of a synoptophore vergence eye movements were recorded in dyslexic and normal children while they were attempting to track small targets moving in simulated depth. Of the dyslexic children 64% were unable to make proper vergence movements when macular sized fusion targets (2 1/2 degrees) were employed, but their vergence control was better for larger (7 degrees) targets. The normal readers and the remaining dyslexics showed normal vergence responses for both large and small moving fusion stimuli. The results suggest that many dyslexics suffer a disorder of visuomotor control and perception for stimuli falling on the macula; this may explain their characteristic visual problems when reading. Hence recording vergence eye movement responses to small moving fusion stimuli may be useful in the investigation and treatment of children with reading difficulties. 相似文献
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Reactive oxidant species (superoxide, hydrogen peroxide, hydroxyl radical, hypohalous acid, and nitric oxide) are involved in many of the complex interactions between the invading microorganism and its host. Regardless of the source of these compounds or whether they are produced under normal conditions or those of oxidative stress, these oxidants exhibit a broad range of toxic effects to biomolecules that are essential for cell survival. Production of these oxidants by microorganisms enables them to have a survival advantage in their environment. Host oxidant production, especially by phagocytes, is a counteractive mechanism aimed at microbial killing. However, this mechanism may be contribute to a deleterious consequence of oxidant exposure, i.e., inflammatory tissue injury. Both the host and the microorganism have evolved complex adaptive mechanisms to deflect oxidant-mediated damage, including enzymatic and nonenzymatic oxidant-scavenging systems. This review discusses the formation of reactive oxidant species in vivo and how they mediate many of the processes involved in the complex interplay between microbial invasion and host defense. 相似文献
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The product of ORF O located within the domain of herpes simplex virus 1 genome transcribed during latent infection binds to and inhibits in vitro binding of infected cell protein 4 to its cognate DNA site 下载免费PDF全文
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A 32 year old male research physician accidentally received a minor wound from a needle which had been previously used on rabbit tissue. Within 15 minutes serious anaphylactic reactions started and he was taken to hospital where his condition stabilised within five hours. Serum immunoglobulin E antibodies to rabbit epithelium were high (16.2 U/ml), although other antibody titres were low. Allergy tests were not carried out before employment, so this alarming scenario could not have been predicted. People with confirmed laboratory animal allergy should be warned of the dangers of continued unprotected exposure and avoidance of the allergen should be encouraged by good laboratory practice and respiratory protective equipment. 相似文献