Chiral ITP of the weak base methadone using inverse cationic configurations with H+ as leading component and multiple isomer sulfated β-CD (S-β-CD) as leading electrolyte (LE) additive, has been studied utilizing dynamic computer simulation, a calculation model based on steady-state values of the ITP zones, and capillary ITP. By varying the amount of acidic S-β-CD in the LE composed of 3-morpholino-2-hydroxypropanesulfonic acid and the chiral selector, and employing glycylglycine as terminating electrolyte (TE), inverse cationic ITP provides systems in which either both enantiomers, only the enantiomer with weaker complexation, or none of the two enantiomers form cationic ITP zones. For the configuration studied, the data reveal that only S-methadone migrates isotachophoretically when the S-β-CD concentration in the LE is between about 0.484 and 1.113 mM. Under these conditions, R-methadone migrates zone electrophoretically in the TE. An S-β-CD concentration between about 0.070 and 0.484 mM results in both S- and R-methadone forming ITP zones. With >1.113 mM and < about 0.050 mM of S-β-CD in the LE both enantiomers are migrating within the TE and LE, respectively. Chiral inverse cationic ITP with acidic S-β-CD in the LE is demonstrated to permit selective ITP trapping and concentration of the less interacting enantiomer of a weak base.
Head-column field-amplified sample stacking of cations from a low conductivity sample followed by enantiomeric separation using negatively charged chiral selectors was studied experimentally and with computer simulation. Aspects investigated include the direct electrokinetic injection of the analytes into the background electrolyte, the use of a selector free buffer plug, the contribution of complexation within the buffer plug and the application of an additional water plug between sample and buffer plug. Attention was paid for changes of ionic strength which is known to have a significant impact on complexation and thus effective mobility. Racemic methadone was selected as a model compound, randomly substituted sulfated β-cyclodextrin as chiral selector and phosphate buffers (pH 6.3) for the background electrolyte and the buffer plug. Results confirm that the buffer plug is providing a spacer between cationic analytes and the negatively charged selector during electrokinetic injection. Simulation predicts the required length and composition of the plug for a given injection time to avoid an interference with the selector. A short water plug added between the low conductivity sample and a high conductivity buffer plug is demonstrated to provide best conditions to achieve high sensitivity in enantioselective drug assays with sulfated cyclodextrins as selectors.
The fundamentals of electrokinetic injection of the weak base methadone across a short water plug into a phosphate buffer at low pH were studied experimentally and with computer simulation. The current during electrokinetic injection, the formation of the analyte zone, changes occurring within and around the water plug and mass transport of all compounds in the electric field were investigated. The impact of water plug length, plug injection velocity, and composition of sample, plug and background electrolyte are discussed. Experimental data revealed that properties of sample, water plug and stacking boundary are significantly and rapidly altered during electrokinetic injection. Simulation provided insight into these changes, including the nature of the migrating boundaries and the stacking of methadone at the interface to a newly formed phosphoric acid zone. The data confirm the role of the water plug to prevent contamination of the sample by components of the background electrolyte and suggest that mixing caused by electrohydrodynamic instabilities increases the water plug conductivity. The sample conductivity must be controlled by addition of an acid to prevent generation of reversed flow which removes the water plug and to create a buffering environment. Results revealed that a large increase in background electrolyte concentration is not accompanied with a significant increase in stacking.
Opiáty jsou v současné době využívány k potlačení neuropatické bolesti nebo bolesti u pacientů s nádorovým onemocněním, ale také zneužívány narkomany k vyvolání pocitů euforie. Podávání opiátů ovlivňuje v organizmu nejen nervový systém, ale také celou řadu dalších fyziologických funkcí včetně funkcí imunitních. Jelikož opioidní receptory, přes něž opiáty působí, byly prokázány i na buňkách imunitního systému, je nutné uvažovat jak přímé, tak přes nervový systém zprostředkované působení opiátů na buňky imunitního systému. Imunomodulační vlastnosti opiátů byly prokázány v celé řadě modelů. Zvláště zvýšená citlivost k virovým a bakteriálním infekcím u drogově závislých bývá vysvětlována negativními účinky opiátů na imunitní systém. Experimenty na zvířecích modelech však ukazují, že působení opiátů jemnohemsložitější amůže se projevovat jak v supresi, tak ve stimulaci jednotlivých imunologických parametrů. Zatímco proliferace lymfocytů testována in vitro je po podání opiátů zpravidla snížena, produkce prozánětlivých cytokinů a funkce makrofágů mohou být zesíleny. Poukazuje to na komplexnější působení opiátů na imunitní systém, které závisí na experimentálnímmodelu, dávce drogy, způsobu její aplikace, době testování a na testovaném parametru. Tento článek shrnuje současné poznatky o vlivu opiátů především na buňky imunitního systému s poukázáním na celosvětový problém zneužívání nelegálních opiátů a o významu metadonu v substituční léčbě.
Opiates have been recently used for suppression of the neuropathic pain or to relieve pain in patients with cancer diseases. However, opiates are also used by drug abusers to achieve feeling of euphoria. These drugs influence not only the nervous systembut they can alsomodulatemany other physiological functions including those of the immune system. Since opioid receptors have been found on the surface of cells of the immune system, two possiblemechanisms of opiate actions have to be considered. The first one represents a direct action of the opiates through the opioid receptors on immune cells; the second mechanism is mediated by the nervous system. The immunomodulatory properties of the opiates have been demonstrated in numerous models. Especially the enhanced sensitivity to viral and bacterial infections, observed in drug abusers, is accounted to the side effects of opiates. Experimental animal models have shown even more complex actions of opiates, which can lead to suppression as well as to stimulation of individual immunological parameters. Although proliferation of lymphocytes tested in vitro after application of opiates in vivo is generally reduced, production of the pro-inflammatory cytokines and some functions ofmacrophages can be enhanced. Effects of opiate action depend on the experimental model used, the drug dose, way of drug application, time of testing and on the tested immunological parameter. This article summarizes recent knowledge of effects of opiates on the functions of cells of the immune system. It also refers global problems of exploitation of illegal drugs and the importance of methadone in the substitution treatment.
- MeSH
- finanční podpora výzkumu jako téma MeSH
- heroin chemie imunologie metabolismus MeSH
- imunitní systém fyziologie účinky léků MeSH
- lidé MeSH
- methadon chemie imunologie metabolismus MeSH
- morfin chemická syntéza chemie krev MeSH
- narkotika chemie imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
