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J. Kralovanszky N. Prajda S. Kerpel-Fronius T. Bagrij E. Kiss G. J. Peters 《Cancer chemotherapy and pharmacology》1993,32(3):243-248
Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow. We studied the biochemical consequences of the gastrointestinal toxicity caused by 5-fluorouracil and the potential of high-dose uridine treatment to influence these adverse effects. 5-Fluorouracil caused dose-related decreases in the biochemical parameters (thymidine kinase, sucrase, maltase, alkaline phosphatase) selected as early markers of the impaired metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluorouracil treatment, and complete regeneration of the mucosa took 6–7 days. Delayed high-dose uridine administration failed to mitigate the severity of the gastrointestinal damage that ensued after 5-fluorouracil treatment, but caused significantly earlier regeneration of the mucosa. 相似文献
104.
Diarrhetic shellfish poisoning (DSP) is a serious and globally widespread phytoplankton-related seafood illness. Although DSP is rarely life-threatening, it causes incapacitating diarrhea and vomiting with no known medical treatments. In addition, phytoplankton producing DSP toxins have been identified in temperate coastal waters worldwide, and their numbers may be increasing as a result of coastal eutrophication. The toxic effects of the major DSP toxins, okadaic acid and dinophysistoxin-1 (35-methylokadaic acid), appear to originate from their inhibitory activity against a family of structurally related serine/threonine protein phosphatases (PSPases). In particular, the inhibition of essential PSPases (e.g. PP1 and PP2A) has catastrophic consequences in most eukaryotic cells. Exploiting the potent inhibitory property of the DSP toxins, we have developed an enzyme-based assay (PP2A assay) capable of detecting both okadaic acid and dinophysis- toxin-1 in nanogram amounts. The assay employs purified PP2A, which has an extremely high affinity for both DSP toxins. This provides the PP2A assay with a level of sensitivity comparable to, or surpassing, that of most monoclonal antibody probes. To evaluate the PP2A assay as a means of detecting contaminated shellfish, a series of spike recovery experiments was conducted. The findings from these studies suggest that the PP2A assay has the potential for development into a rapid and relatively simple method for detecting PSPase inhibitors in crude extracts produced from shellfish. 相似文献
105.
A case is presented which demonstrates the potential utility of the extracranial-intracranial bypass procedure for the treatment of vasospasm after subarachnoid hemorrhage. Extracranial-intracranial bypass surgery offers another alternative to the treatment of patients with vasospasm who have failed aggressive medical management. 相似文献
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The composition of the clientele from an ophthalmological practitioner's office is described with special reference to the occurrence of glaucoma and disc haemorrhages (h in singular; hh in plural). This study could not be planned as an epidemiological survey and gives no clue to sensitivity or specificity of hh in glaucoma. During a period of about 10 years ending with 1986 there were 731 patients with h and/or glaucoma. When detected, 185 patients had h but no glaucoma, 33 had both h and glaucoma and 513 had glaucoma but no h. During the follow-up period hh were detected in 83 cases of glaucoma, and glaucoma developed in 27 cases with hh. The detection rate of hh among glaucoma was low but steady, indicating that hh may occur at any stage of the glaucoma process. This study shows no predilection for hh in cases with general hypertension or diabetes, nor is the frequency of hh among pseudoexfoliation cases significantly lower than among cases without this stigma. 相似文献
108.
Isotretinoin (Accutane Capsules) is a synthetic vitamin A compound used for treatment of recalcitrant cystic acne. It has numerous ocular toxic side effects which include anterior segment inflammation, dry eye syndrome, contact lens intolerance, altered refraction, photosensitivity, and reduced night vision. Eye care practitioners should be aware of these potential side effects and be prepared to communicate with the prescribing physician if side effects present. 相似文献
109.
P. A. Milligan P. E. McGill C. W. Howden A. W. Kelman B. Whiting 《European journal of clinical pharmacology》1993,45(6):507-512
Summary A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine.Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g·L–1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-24(5-OHP)], the ratio of these i.e. AUC0-24(5-OHP):AUC0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period).A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation.No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations. 相似文献
110.