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17 záznamů v Medvik Filtry

Článek

Transport mechanisms of a novel antileukemic and antiviral compound 9-norbornyl-6-chloropurine

Journal of enzyme inhibition and medicinal chemistry. 2015 ; 30 (1) : 57-62. [pub] 20140331

J Enzyme Inhib Med Chem
ISSN 1475-6374
Medvik
Zdroj

6-Chloropurines substituted at the position 9 with variously modified bicyclic skeletons represent promising antiviral and anticancer agents. This work aimed to investigate the transport mechanisms of 9-[(1R*,2R*,4S*)-bicyclo[2.2.1]hept-2-yl]-6-chloro-9H-purine (9-norbornyl-6-chloropurine, NCP) and their relationship to the metabolism and biological activity of the compound. Transport experiments were conducted in CCRF-CEM cells using radiolabeled compound ([(3)H]NCP). The pattern of the intracellular uptake of [(3)H]NCP in CCRF-CEM cells pointed to a combination of passive and facilitated diffusion as prevailing transport mechanisms. NCP intracellular metabolism was found to enhance its uptake by modifying NCP concentration gradient. The transport kinetics reached steady state under the conditions of MRP and MDR proteins blockade, indicating that NCP is a substrate for these efflux pumps. Their inhibition also increased the cytotoxicity of NCP. Our findings suggest that the novel nucleoside analog NCP has potential to become a new orally available antileukemic agent due to its rapid membrane permeation.

Abstrakt

Vliv kyseliny ethakrynové na intracelulární transport viru vakcínie

Váchová, Barbora
Autor Váchová, Barbora

Studentská vědecká konference 1. lékařské fakulty. 2012 ; () : 76, 16.

ISBN 978-80-7262-943-5
Medvik
Zdroj

Článek

Ethacrynic and alpha-lipoic acids inhibit vaccinia virus late gene expression

Antiviral research. 2009 ; 81 (2) : 156-165.

Antiviral Res
Medvik
Zdroj

Smallpox was declared eradicated in 1980. However recently, the need of agents effective against poxvirus infection has emerged again. In this paper, we report an original finding that two redox-modulating agents, the ethacrynic and alpha-lipoic acids (EA, LA), inhibit growth of vaccinia virus (VACV) in vitro. The effect of EA and LA was compared with those of beta-mercaptoethanol, DTT and ascorbic acid, but these agents increased VACV growth in HeLa G cells. The inhibitory effects of EA and LA on the growth of VACV were further confirmed in several cell lines of different embryonic origin, in epithelial cells, fibroblasts, macrophages and T-lymphocytes. Finally, we have analyzed the mechanism of action of the two agents. They both decreased expression of VACV late genes, as demonstrated by western blot analysis and activity of luciferase expressed under control of different VACV promoters. In contrast, they did not inhibit virus entry into the cell, expression of VACV early genes or VACV DNA synthesis. The results suggest new directions in development of drugs effective against poxvirus infection.

MeSH
antivirové látky farmakologie MeSH
exprese genu účinky léků MeSH
financování organizované MeSH
HeLa buňky MeSH
kultivované buňky MeSH
kyselina ethakrynová farmakologie MeSH
kyselina lipoová farmakologie MeSH
lidé MeSH
luciferasy metabolismus MeSH
plakové testy MeSH
replikace viru účinky léků MeSH
reportérové geny MeSH
virus vakcinie růst a vývoj účinky léků MeSH
western blotting MeSH
Check Tag
lidé MeSH
Publikační typ
srovnávací studie MeSH

Článek

Reversal of carboplatin resistance in human laryngeal carcinoma cells

Neoplasma. 1999 ; Roč. 46 (č. 6) : s. 335-341.

ISSN 0028-2685
Medvik
Zdroj

Článek

Kličková diuretika

Diagnóza (Praha). 1999 ; Roč. 2 (č. 26) : s. 10,11.

ISSN 1212-3595
Medvik
Zdroj

Klíčová slova
ETOZALIN,
MeSH
diuretika MeSH
furosemid farmakokinetika farmakologie MeSH
kyselina ethakrynová farmakokinetika farmakologie MeSH
torasemid MeSH

Článek

Bioelectrical cochlear noise and its contralateral suppression: relation to background activity of the eighth nerve and effects of sedation and anesthesia

Experimental Brain Research. 1997 ; 116 (2) : 259-269.

Exp Brain Res
ISSN 0014-4819
Medvik
Zdroj

The bioelectrical activity of the cochlea, without any ipsilateral acoustic stimulation, was recorded in awake guinea pigs (GPs) between electrodes chronically implanted at the round window (RW) and the skull. Measuring its power in the band centered around 1.0 kHz (0.5-2.5 kHz) provided an indirect measure of the ensemble background (EBA) activity of the eighth nerve. Contralateral white-noise (CLWN) stimulation reduced this EBA, presumably by activation of medial olivocochlear fibers. The aim of the investigation was to validate measurements of EBA and of its contralateral suppression in order to study the medial efferent function. The first goal was to find the best conditions for recording the EBA in the absence of ipsilateral stimulation and for studying its suppression by contralateral acoustic stimulation, which implies that no noise was generated by the experimental animal. Thus recordings were compared in normal, awake GPs and in GPs under sedation with xylazine, anesthetized with a combination of xylazine and ketamine, and with and without temperature regulation. In order to monitor the effects of sedation and anesthesia, the recordings were analyzed not only in the 0.5- to 2.5-kHz frequency band but also in the other frequency bands, 5-50 Hz, 50-150 Hz, and 150-500 Hz, which presumably include general central and neuromuscular contributions. The results show that sedation with xylazine accompanied by regulation of body temperature does not affect the EBA value nor its contralateral suppression. Nevertheless, anesthesia should be avoided, even with control of body temperature. The second goal of this study was to identify the specific cochlear contribution to the raw RW signal. Thus recordings were performed in normal and deafened animals and analyzed in the frequency band 0.5-2.5 kHz and also in the other frequency bands of 5-50 Hz, 50-150 Hz, and 150-500 Hz. The results indicate that most of the cochlear activity lies in the frequency band 0.5-2.5 kHz, with also some minor contribution coming from the 150- to 500-Hz band. Analysis and comparison of power values in the different conditions indicate that specific cochlear EBA power was about 60 microV2. From a commonly accepted mean background discharge rate of 50 spikes/s (sp/s), the EBA power without CLWN should have been around 4.4 microV2 if the fibers' activity was random. This difference suggests that there is probably some degree of synchrony between individual fibers. There was a reduction of approximately 45% during CLWN stimulation. This suppression might correspond to a reduction in both discharge rate and synchrony of the fibers.