Tick-borne encephalitis (TBE) is a vector-borne infection associated with a variety of potentially serious complications and sequelae. Vaccination against TBE is strongly recommended for people living in endemic areas. There are two TBE vaccination schemes - standard and rapid - which differ in the onset of protection. With vaccination in a rapid schedule, protection starts as early as 4 weeks after the first dose and is therefore especially recommended for non-immune individuals travelling to endemic areas. Both schemes work reliably in immunocompetent individuals, but only little is known about how TBE vaccination works in people with HIV infection. Our aim was to assess the immunogenicity and safety of the rapid scheme of TBE vaccination in HIV-1 infected individuals. Concentrations of TBE-specific IgG > 126 VIEU/ml were considered protective. The seroprotection rate was 35.7% on day 28 and 39.3% on day 60. There were no differences between responders and non-responders in baseline and nadir CD4 + T lymphocytes. No serious adverse events were observed after vaccination. The immunogenicity of the TBE vaccination was unsatisfactory in our study and early protection was only achieved in a small proportion of vaccinees. Therefore, TBE vaccination with the rapid scheme cannot be recommended for HIV-1 infected individuals.
- MeSH
- dospělí MeSH
- HIV infekce komplikace MeSH
- HIV-1 * MeSH
- imunogenicita vakcíny * MeSH
- klíšťová encefalitida prevence a kontrola MeSH
- lidé MeSH
- očkovací schéma MeSH
- vakcinace * MeSH
- virové vakcíny aplikace a dávkování imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Etoposide is a well-known and widely used anticancer drug that displays several side effects. In addition, tumors often acquire resistance to this drug. Our aim is to develop a combination therapy that would augment toxicity of etoposide in malignant cells. Based on literature and our experiments, we selected mifepristone (RU486) as a potential supporting molecule that is able to enhance etoposide toxicity against cancer cells. All experiments were performed with Hep G2 cells, a well-known and described human hepatocellular carcinoma cell line. By using xCELLigence system, we demonstrated that mifepristone enhances toxicity of etoposide in a dose dependent manner with concomitant caspase-3 activity. We evaluated upregulation of Bax because mifepristone was demonstrated to modulate proapoptotic Bax protein expression. Our data show only weak and not statistically significant increase of Bax expression. On the other hand, we show that mifepristone increases etoposide toxicity via inhibition of ABC transporters, coupled with significant increase of intracellular etoposide concentration. In conclusion, we demonstrate that mifepristone has a synergistic effect with etoposide treatment in the Hep G2 cells and that the effect is related to ABC transporters inhibition.
- MeSH
- ABC transportér z rodiny G, člen 2 antagonisté a inhibitory MeSH
- antitumorózní látky fytogenní farmakologie MeSH
- biologický transport účinky léků MeSH
- buňky Hep G2 MeSH
- buňky K562 MeSH
- etoposid farmakologie MeSH
- kaspasa 3 metabolismus MeSH
- lidé MeSH
- mifepriston farmakologie MeSH
- nádorové proteiny antagonisté a inhibitory MeSH
- P-glykoproteiny antagonisté a inhibitory MeSH
- protein X asociovaný s bcl-2 metabolismus MeSH
- synergismus léků MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
- MeSH
- aromatické hydroxylasy metabolismus MeSH
- cytochrom P-450 CYP1A2 metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- glykosidy farmakologie chemie MeSH
- hepatocyty enzymologie účinky léků MeSH
- lidé MeSH
- N-demethylasy metabolismus MeSH
- regulace genové exprese enzymů účinky léků MeSH
- silymarin farmakologie chemie MeSH
- Check Tag
- lidé MeSH
- MeSH
- komunitní zdravotní střediska organizace a řízení zásobování a distribuce MeSH
- oblast s nedostatečnou zdravotní péčí MeSH
- pomocní ošetřovatelé zásobování a distribuce MeSH
- pomocný zdravotnický personál zásobování a distribuce MeSH
- porodní asistentky zásobování a distribuce MeSH
- venkovské obyvatelstvo MeSH
- zdraví venkovských oblastí MeSH
- zdravotnické služby pro venkov organizace a řízení pracovní síly MeSH
- zubní technici zásobování a distribuce MeSH