AIMS: K117 and K127 are bis-pyridinium aldoximes but K117 is a bis-pyridinium bis-aldoxime while K127 has only one single aldoxime in addition to its amide substituent. Is there any difference in pharmacokinetics in these compounds that otherwise have the same chemical structure? Both K117 and K127 are developed as antidotes in acetylcholinesterase and butyrylcholinesterase poisoning in terrorist attacks or intoxication with other organophosphorous compounds. Their distributions have been scouted in the bodies of rats. MAIN METHODS: White male Wistar rats were intramuscularly injected. The animals were sacrificed, tissue samples were homogenized, and either K117 or K127 concentrations were determined using reversed-phase high-performance liquid chromatography. KEY FINDINGS: Both K117 and K127 were present in all tissues that were analyzed including blood (serum), the brains, cerebrospinal fluid, the eyes, livers, kidneys, lungs and testes. Their pharmacokinetics and body distributions are similar. SIGNIFICANCE: Either K117 or K127 meets the essential requirements for antidotes. Dose dependence and kinetics of their distribution were compared to that of other pyridinium aldoximes.
- MeSH
- acetylcholinesterasa chemie MeSH
- antidota farmakokinetika MeSH
- butyrylcholinesterasa chemie MeSH
- chemické bojové látky farmakokinetika MeSH
- cholinesterasové inhibitory farmakokinetika MeSH
- krysa rodu rattus MeSH
- organofosfáty antagonisté a inhibitory MeSH
- oximy analýza farmakokinetika MeSH
- potkani Wistar MeSH
- pyridinové sloučeniny analýza farmakokinetika MeSH
- reaktivátory cholinesterasy farmakokinetika MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Precise and efficient endocytosis is critical for sustained neurotransmission during continuous neuronal activity. Endocytosis is a prerequisite for maintaining the auditory function. However, the differences between the patterns of endocytosis in cochlear inner hair cells (IHCs) and outer hair cells (OHCs) remain unclear. Both IHCs and OHCs were obtained from adult C57 mice. Patterns of endocytosis in cells were estimated by analyzing the uptake of FM1-43, a fluorescent. The observations were made using live confocal imaging, fluorescence intensities were calculated statistically. Results revealed the details about following phenomenon, i) sites of entry: the FM1-43 dye was found to enter IHC at the apical area initially, the additional sites of entry were then found at basolateral membrane of the cells, The entry of the dye into OHCs initially appeared to be occurring around whole apical membranes area, which then diffused towards the other membrane surface of the cells, ii) capacity of endocytosis: fluorescence intensity in IHCs showed significantly higher than that of OHCs (P<0.01). We have found different patterns of endocytosis between IHCs and OHCs, this indicated functional distinctions between them. Moreover, FM1-43 dye can be potentially used as an indicator of the functional loss or repair of cochlear hair cells.
- MeSH
- biologický transport fyziologie MeSH
- endocytóza fyziologie MeSH
- fluorescenční barviva analýza metabolismus MeSH
- kvartérní amoniové sloučeniny analýza metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- orgánové kultury - kultivační techniky MeSH
- pyridinové sloučeniny analýza metabolismus MeSH
- sluchové evokované potenciály fyziologie MeSH
- vnější vláskové buňky chemie metabolismus MeSH
- vnitřní vláskové buňky chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
