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Various nucleoside antiviral agents and their metabolites were examined for their ability to be cleaved across the glycosidic bond by Escherichia coli thymidine phosphorylase. The increasing order of susceptibility to cleavage was U greater than T much greater than C derivatives. Nucleosides that were unsaturated in the sugar moiety were more susceptible than saturated ones. 3'-Deoxy-2',3'-didehydrothymidine was a substrate, whereas 3'-azido-, 3'-fluoro-, 3'-oxo- and 3'-thiapyrimidine nucleosides were resistant to this enzyme. 相似文献
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Perfluorochemicals as US contrast agents for tumor imaging and hepatosplenography: preliminary clinical results 总被引:3,自引:0,他引:3
Mattrey RF; Strich G; Shelton RE; Gosink BB; Leopold GR; Lee T; Forsythe J 《Radiology》1987,163(2):339-343
In animals, perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents that produce hepatic, splenic, and tumor enhancement. The use of Fluosol-DA 20%, an emulsion of perfluorodecalin and perfluorotripropylamine, was studied in nine non-critically ill patients with cancer who had liver lesions. US studies without Fluosol were compared with studies obtained 24, 48, and 72 hours after Fluosol infusion. Vital signs and extensive laboratory analyses are performed before and after Fluosol infusion. Liver metastases from colonic, pancreatic, and gastric carcinoma exhibited rim or diffuse enhancement after a Fluosol dose of 1.6 g/kg or greater. Fluosol produced echogenic enhancement of the liver and spleen relative to kidney at a dose of 2.4 g/kg, allowing the detection of nonenhancing lesions. In addition, Fluosol at a dose of 1.6 g/kg or greater allowed detection of lesions not seen before contrast medium was administered in three of the seven patients studied. There was a mild increase in the level of serum glutamic oxaloacetic transaminase in two patients, one given 2.4 and the other 3.2 g/kg of Fluosol. Mild and transient allergic reactions without change in vital signs were experienced by two patients. 相似文献
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I B Taraporewala J W Cessac T C Chanh A V Delgado R F Schinazi 《Journal of medicinal chemistry》1992,35(15):2744-2752
The antiviral/antitumor marine alkaloid dercitin was used as a lead compound to design analogues with anti-HIV and tumor inhibitory activities. Deletion of structural features contributing to cytotoxicity led to analogues with lowered T-lymphocyte toxicity profiles. One compound, 5, induced complete protection against HIV-1 infectivity in vitro at 12.5 micrograms/mL (38 microM) without T-cell toxicity up to 400 micrograms/mL. Compound 4 and 5 also inhibited the binding of HIV-1 to H-9 lymphocytes. These compounds may exert antiviral activity by a unique dual extracellular and intracellular mode of action--both preventing viral attachment to lymphocytes as well as intercalating with viral nucleic acid. Analogues with higher cytotoxicity such as 2 which retain the thiazole ring of the natural product proved effective in completely inhibiting the cell proliferation of breast, colon, and lung tumor cell lines at 1.5 microM concentration compared to a 70 microM dose level of 5-fluorouracil. A means of molecular separation of antiviral activity from cytotoxicity was thus achieved, and putative pharmacophores for antiviral and antitumor actions of the prototype molecule dercitin have been deduced. The 2-thio-9-acridinone derivatives 4 and 5 represent a new structural type exhibiting activity against HIV in vitro, serving as chemical leads in the design of anti-AIDS agents, while thiazolo[5,4-b]acridines such as 2 provide leads in the drug design of new antitumor agents. 相似文献
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Dohle GR; Ramos L; Pieters MH; Braat DD; Weber RF 《Human reproduction (Oxford, England)》1998,13(3):620-623
Male genital tract obstructions may result from infections, previous
inguinal and scrotal surgery (vasectomy) and congenital bilateral absence
of the vas deferens (CBAVD). Microsurgery can sometimes be successful in
treating the obstruction. In other cases and in cases of failed surgical
intervention, the patient can be treated by microsurgical or percutaneous
epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction
(TESE) and intracytoplasmic sperm injection (ICSI). We present the results
of 39 ICSI procedures for obstructive azoospermia in 24 couples. The
aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD
in nine and genital infections in four. Sperm retrieval was accomplished
via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was
only applied when PESA failed to produce enough spermatozoa for
simultaneous ICSI. In six patients, the ICSI procedure was performed with
cryopreserved spermatozoa after an initial PESA procedure. Fertilization
occurred in 47% of the metaphase II oocytes; embryo transfer was performed
in 92% of procedures and resulted in a clinical pregnancy in 13/39
procedures. Ongoing pregnancy was achieved in 10/39 procedures. One
pregnancy was terminated early after prenatal investigation showed a
cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine
pregnancies resulted in the live birth of 10 children, without any
congenital abnormalities. Epididymal and testicular retrieved spermatozoa
were successfully used for ICSI to treat obstructive azoospermia, and
resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI
procedures, a success rate of 25.6% per treatment cycle and of 27.7% per
embryo transfer.
相似文献
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