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101.
Antiretroviral activity and cytotoxicity of novel zidovudine (AZT) derivatives and the relation to their chemical structure 总被引:1,自引:0,他引:1
Turk G Moroni G Pampuro S Briñón MC Salomón H 《International journal of antimicrobial agents》2002,20(4):282-288
Zidovudine (AZT) was the first nucleoside analogue licensed for the treatment of HIV infection. Efforts have continuously been made to improve the therapeutic characteristics of this drug, most of them focussed on prodrugs design. Here we describe the anti-HIV-1 activity and cytotoxicity of six novel AZT derivatives namely 3'-azido-3'-deoxy-5'-O-oxalyl-N-valinethymidine, 3'-azido-3'-deoxy-5'-O-oxalyl-N-leucinethymidine, 3'-azido-3'-deoxy-5'-O-oxalyl-N-isoleucinethymidine, 3'-azido-3'-deoxy-5'-O-oxalyl-N-phenylalaninethymidine, 3'-azido-3'-deoxy-5'-O-oxalylthymidine acid, 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine and 5-chloro-6-hydroxy-5,6-dihydro-3'-azido-3'-deoxythymidine which were perfectly characterized. AZT-Val, AZT-Leu, AZT-iLeu, AZT-Phen, AZT-Ac and AZT-Iso have shown a similar or higher selectivity index than that of AZT itself, in one or both of the different cell cultures used (PBMC and MT2). However, AZT-ClOH showed no anti-HIV activity. These results suggest that using amino acids in the design of AZT derivatives improves AZT activity. 相似文献
102.
Erdem I Kaynar-Tascioglu J Kaya B Goktas P 《International journal of antimicrobial agents》2002,20(5):384-386
This study evaluated the in vitro effects of the combination of a carbapenem (imipenem or meropenem) with a quinolone (ciprofloxacin or levofloxacin) using a microbroth dilution chequerboard technique and multidrug-resistant Pseudomonas aeruginosa strains. The ciprofloxacin and meropenem combination was only synergistic against 2 strains (6.2%) and ciprofloxacin and imipenem against 1 strain (3.1%). Levofloxacin and imipenem or meropenem were not synergistic for against any strain. None of the combinations showed an antagonistic effect. 相似文献
103.
Cysteine proteases are widespread in nature. Their implication in numerous vital processes and pathologies make them highly attractive targets for drug design. The proper functioning and regulation of activity of cysteine proteases is a delicate balance of many factors, one of the most crucial being the protease inhibitors. In this review the basic principles of physiological protease inhibition by protein inhibitors are discussed with the focus on papain-like lysosomal cysteine proteases and the caspases, and their inhibitors. 相似文献
104.
Carbohydrates are mostly digested to glucose, fructose and galactose before absorption by the small intestine. Absorption across the brush border and basolateral membranes of enterocytes is mediated by sodium-dependent and -independent membrane proteins. Glucose and galactose transport across the brush border occurs by a Na(+)/glucose (galactose) co-transporter (SGLT1), whereas passive fructose transport is mediated by a uniporter (GLUT5). The passive exit of all three sugars out of the cell across the basolateral membrane occurs through two uniporters (GLUT2 and GLUT5). Mutations in SGLT1 cause a major defect in glucose and galactose absorption (glucose-galactose Malabsorption), but mutations in GLUT2 do not appear to disrupt glucose and galactose absorption. Studies on GLUT1 null mice and Fanconi-Bickel patients suggest that there is another exit pathway for glucose and galactose that may involve exocytosis. There are no known defects of fructose absorption. 相似文献
105.
Early multimodal therapy in adult Wilms' tumor: case report 总被引:1,自引:0,他引:1
Camci C Turk HM Erkilic S Buyukberber S Uner A Ozsarac C 《Journal of chemotherapy (Florence, Italy)》2002,14(5):530-532
Wilms' tumor occurs rarely in adults, especially after the third decade. In adults, the prognosis of Wilms' tumor is worse than in children. In this case report, we present a 48-year old patient who relapsed with advanced stage shortly after primary surgery. A definitive treatment plan has not been established because of the rarity of this tumor in adults. After surgical removal, multimodal therapy should be begun immediately for long-lasting, complete remission. 相似文献
106.
Endovascular treatment of experimental canine aneurysms: feasibility with MR imaging guidance 总被引:5,自引:0,他引:5
PURPOSE: To evaluate the feasibility of using magnetic resonance (MR) imaging to guide and monitor endovascular therapeutic procedures. MATERIALS AND METHODS: Endovascular therapeutic procedures were performed with MR imaging guidance in eight dogs by using a 1.5-T MR unit with echo-planar imaging capabilities. Carotid arterial aneurysms were surgically created in four dogs. The ability to depict, track, and position catheters, guide wires, and Guglielmi detachable coils was assessed. Catheters were first positioned with fluoroscopic guidance. Tracking and depiction were achieved with MR imaging by using commercially available catheters filled with a gadopentetate dimeglumine solution and a fast, two-dimensional, time-resolved, variable-rate k-space sampling technique. RESULTS: When either a catheter or the coaxial space between a catheter and a guide wire was filled with a solution of gadopentetate dimeglumine, catheter movement was always depicted. In the animals with aneurysms, it was possible to depict movement of a catheter into and out of the aneurysm. This was achieved by superimposing reconstructed images obtained during catheter movement onto a previously acquired MR angiogram ("road map"). Prototype Guglielmi detachable coils were successfully positioned and detached. Aneurysm obliteration was monitored with the acquisition of new road map images. CONCLUSION: The results demonstrate the feasibility of using MR imaging to guide endovascular therapeutic procedures. 相似文献
107.
The authors prospectively collected unblinded data from 27 consecutive patients following thalamic stimulation. A significant reduction of midline tremor was achieved after unilateral surgery, but a staged contralateral surgery had an additional effect. A subgroup analysis showed significant beneficial effects for head, voice, tongue, and face tremor. The most frequent reversible side effects were disequilibrium, dysarthria, and paresthesias. We observed more pulse generator adjustments for speech problems in the bilaterally implanted group. 相似文献
108.
Cristina R Ferrone Miguel-Angel Perales Stacie M Goldberg C Joy Somberg Daniel Hirschhorn-Cymerman Polly D Gregor Mary Jo Turk Teresa Ramirez-Montagut Jason S Gold Alan N Houghton Jedd D Wolchok 《Clinical cancer research》2006,12(18):5511-5519
PURPOSE: Plasmid DNAs encoding cytokines enhance immune responses to vaccination in models of infectious diseases and cancer. We compared DNA adjuvants for their ability to enhance immunity against a poorly immunogenic self-antigen expressed by cancer. EXPERIMENTAL DESIGN: DNAs encoding cytokines that affect T cells [interleukin (IL)-2, IL-12, IL-15, IL-18, IL-21, and the chemokine CCL21] and antigen-presenting cells [granulocyte macrophage colony-stimulating factor (GM-CSF)] were compared in mouse models as adjuvants to enhance CD8+ T-cell responses and tumor immunity. A DNA vaccine against a self-antigen, gp100, expressed by melanoma was used in combination with DNA encoding cytokines and cytokines fused to the Fc domain of mouse IgG1 (Ig). RESULTS: We found that (a) cytokine DNAs generally increased CD8+ T-cell responses against gp100; (b) ligation to Fc domains further enhanced T-cell responses; (c) adjuvant effects were sensitive to timing of DNA injection; (d) the most efficacious individual adjuvants for improving tumor-free survival were IL-12/Ig, IL-15/Ig, IL-21/Ig, GM-CSF/Ig, and CCL21; and (e) combinations of IL-2/Ig+IL-12/Ig, IL-2/Ig+IL-15/Ig, IL-12/Ig+IL-15/Ig, and IL-12/Ig+IL-21/Ig were most active; and (f) increased adjuvanticity of cytokine/Ig fusion DNAs was not related to higher tissue levels or greater stability. CONCLUSIONS: These observations support the potential of cytokine DNA adjuvants for immunization against self-antigens expressed by cancer, the importance of timing, and the enhancement of immune responses by Fc domains through mechanisms unrelated to increased half-life. 相似文献
109.
Macan J Turk R Plavec D Bosan-Kilibarda I 《Arhiv za higijenu rada i toksikologiju》2000,51(4):381-387
The aim of this study was to analyse the frequency of poisoning with psychoactive drugs (benzodiazepines, antidepressants and neuroleptics) over the last 15 years in Croatia. The analysis was based on poisoning incidents reported over the phone (hot line) to the Zagreb Poison Control Center and included two periods: 1985-1991 (period I) and 1992-1999 (period II). The data were analysed separately for children and adults. Each phone call was counted as one poisoning incident. Child poisoning with neuroleptics was significantly higher in period II than in period I and so was the adult poisoning with antidepressants, amytriptyline, and combined psychoactive drugs. The frequency of total psychoactive drug poisoning was significantly higher in adults than in children in both periods. From 1992, the frequency of adult poisoning with antidepressants considerably increased as one of the many consequences of war-related stress. The results indicate a need for careful psychiatric evaluation and more critical use of antidepressants in affected individuals. 相似文献
110.
The pathologic features of bronchiolitis were studied in horses and ponies from 30 minutes to 27 days after an oral dose of 3-methylindole (3MI). From 30 minutes to 3 hours, lesions were limited to nonciliated bronchiolar epithelial (Clara) cells, which lost apical caps and cytoplasmic granules and had dilated smooth endoplasmic reticulum (SER). At 12 hours, necrotic Clara cells were exfoliated; degeneration and necrosis were evident, in bronchiolar ciliated cells. Rare epithelial cells with hyperplastic SER appeared on the denuded basal lamina at 24 hours. Inflammatory cells, epithelia, fibroblastlike cells, collagen, and debris occluded many bronchiolar lumens from 3 to 6 days. Reorganization resulted in a simple columnar bronchiolar epithelium with relatively normal ciliated cells and fewer fibroblastlike cells. However, mature Clara cells were rare at 27 days, and collagenous bands still divided bronchiolar lumens. Thus, 3MI toxicosis is a persistent model of equine bronchiolitis with many morphologic features of the spontaneous disease. 相似文献