Track topics on Twitter Track topics that are important to you
Oxime-based acetylcholinesterase reactivators (briefly oximes) regenerate organophosphate-inactivated acetylcholinesterase and restore its function. Poor blood-brain-barrier passage and fast elimination from blood limit their actual use in treatment of patients exposed to organophosphates. Previous in vitro results implicated further testing of cucurbituril as a delivery vehicle for bisquaternary oximes. The present paper focuses on cell toxicity, in vivo safety and influence of cucurbituril on oxime pharmacokinetics and pharmacodynamics. Neither the K027 nor the complex caused any cell toxicity, changes in blood biochemistry or hepato- or nephrotoxicity in tested concentrations. The encapsulation of K027 increased and accelerated the blood-brain-barrier penetration. The peripheral oxime exposure also increased, supporting the suggestion that cucurbituril protects the circulating oxime from rapid renal clearance. Contrary to the comparable in vitro reactivation power of K027 and the encapsulated K027, we failed to confirm this in vivo. In theory, this might result from the non-specific binding of molecules to the cucurbituril or the interaction of K027 with cucurbituril being too strong for acetylcholinesterase reactivation. Precise explanation requires additional in silico, in vitro and also in vivo experiments.
This article was published in the following journal.
Name: Toxicology letters
The major function of compounds with an oxime moiety attached to a quarternary nitrogen pyridinium ring is to reactivate acetylcholinesterase inhibited by organophosphorus agent (OP). However, other o...
A series of benzothiazinones (BTZs) containing an oxime moiety, based on the structure of ZR-10 discovered in our lab, were designed and synthesized. Most of the compounds with alkoxyimino groups atta...
Despite the growing importance of probiotics vivid health benefits, an impediment to the use of new probiotic cultures is their safety. Hence, there is a need to strictly examine the biosafety as well...
Little used for the in vivo assessment of tissue scaffolds are quantitative methods for the evaluation of biocompatibility. To complement current histological techniques, we introduce a histomorphomet...
Nanoparticulate delivery systems have been noticed for chemotherapeutical delivery due to their ability in controlling the drug release and reducing the side effect. These systems could also be used t...
We aim to compare the morphological and chromosomal features of human embryos cultured In Vitro versus those developed in a new In Vivo culture system with encapsulation in utero as well a...
From previous studies it appeared that menaquinone-7 (MK-7) is the most effective form of vitamin K. The Japanese soya product natto is one of the richest food sources of MK-7. However, th...
A multi-center study designed to assess the accuracy of VIVO™ in determining the location of a PVC/VT foci in comparison to an electroanatomical mapping system.
The purpose of this study is to investigate the safety and efficacy of human conjunctival epithelial autologous cultivated ex vivo for reconstruction of the ocular surface in patients with...
Continuous albuterol has become the standard of care for patients in status asthmaticus. We have previously performed an in-vitro study comparing 4 different brands of continuous nebulizer...
Freedom from exposure to danger and protection from the occurrence or risk of injury or loss. It suggests optimal precautions in the workplace, on the street, in the home, etc., and includes personal safety as well as the safety of property.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series.
Activities involved in ensuring the safety of FOOD including avoidance of bacterial and other contamination.
Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.
A self-evaluation of health status.