Adamed Sp zoo

Acetylcholine has been well known as one of the most exemplary neurotransmitters. In humans, this versatile molecule and its synthesizing enzyme, choline acetyltransferase, have been found in various non-neural tissues such as the epithelium, endothelium, mesothelium muscle, blood cells and immune cells. The non-neuronal acetylcholine is accompanied by the expression of acetylcholinesterase and nicotinic/muscarinic acetylcholine receptors. Increasing evidence of the non-neuronal acetylcholine system found throughout the last few years has indicated this neurotransmitter as one of the major cellular signaling molecules (associated e.g. with kinases and transcription factors activity). This system is responsible for maintenance and optimization of the cellular function, such as proliferation, differentiation, adhesion, migration, intercellular contact and apoptosis. Additionally, it controls proper activity of immune cells and affects differentiation, antigen presentation or cytokine production (both pro- and anti-inflammatory). The present article reviews recent findings about the non-neuronal cholinergic system in the field of immune system and intracellular signaling pathways.

The minimal inhibitory concentration (MIC) of an antimicrobial agent for a microbial population (MIC50, obs and MIC90, obs) is an interpolated value determined for antibacterial drugs by in vitro methods. Many studies have tried to determine the correlation between the MIC50, obs or MIC90, obs value and the physicochemical parameters to allow quantitaive structure activity relationship (QSAR) predictions of efficacy. A rigorous evaluation of approaches to this problem is presented here. In order to find a correlation between chemical structure and the derivatives of the MIC values for 9 indicatory bacterial strains, it is necessary to employ a number of physicochemical parameters in combination. Only an arithmetic expression composed of many features illustrating the chemical structure of the molecule can be linked to the ƒMIC50, obs value. This article demonstrated that, despite the complexity of the MIC value used as the end point, it is possible to validate the model in a limited extent.

The correlation between 52 physicochemical parameters and mean residence time (MRT) for 27 drugs used in human and dog were investigated. The physicochemical parameter values calculated provided a basis for deriving a series of arithmetic expressions, which were used to build a mathematical model describing the relationship between them and the MRT values. From the entire set of analyzed parameters, a subset of 14 was identified that contributed to the derivation of an arithmetic expression: [Formula: see text] the value of which is highly correlated with the MRT value in dogs ( P < .001) and allowed prediction of the MRT predicted (MRT(pred)). In humans, no correlation was found that allowed the calculation of MRT(pred). These results indicate that predicting the pharmacokinetics of any specific drug for humans based on pharmacokinetic data obtained in the dog should be undertaken with knowledge of the inherent limitations.