Biomedical subjects

Vilim Zlender

Publications and source records attributed to Vilim Zlender.

3 recordsLinked to original sources

PubMed2006

Antidotal efficacy of pyridinium chloride derivatives against soman poisoning.

Acetylcholinesterase (AChE; EC 3.1.1.7.) is an extremely active enzyme necessary for terminating the action of acetylcholine in cholinergic synapses. The aim of this study was to evaluate the efficacy of four mono-pyridinium compounds 1-phenacylpyridinium chloride (I), 1-phenacyl-2-methylpyiridinium chloride (II), 1-benzoylethylpyridinium chloride (III), and 1-benzoylethylpyridinium-4-aldoxime chloride (IV) in the therapy of soman poisoning. Their effect was compared with HI-6 and TMB-4 oximes. The inhibitory potency (IC50) of compounds as well as reactivating (%R) and protective potency (P50) with respect to soman-inhibited AChE were determined for each of the compounds. Their acute intraperitoneal toxicity (LD50 with 95% confidence limits) was tested in mice and observed for 24 hr. The therapeutic effect was expressed as the protective index and as the therapeutic dose. The tested compounds were found to be reversible inhibitors of AChE. In vivo results show that the tested compounds are relatively toxic (their LD50 was from 74.9 to 210.0 mg/kg body weight). The best antidotal efficacy was obtained with compound II, which had the highest affinity for AChE (IC50 was 1.9 x 10(-5) mol l(-1)) and seems to be an adequate antidote in soman poisoning (its protective index and therapeutic dose were 2.8 and 2, respectively). Our results indicate that its antidotal effect is related to the reactivation or protection of AChE. The type of the substituent in the pyridinium ring generally has a significant influence on toxicity in vitro and in vivo, and on the antidotal efficacy of all new tested compounds.

Acetylcholine↗

PubMed2006

[Detection of apoptosis].

Apoptosis or programmed cell death is the most important process in a huge number of biological processes. Its detection is very important for different fields of modern biology including embryonic development, tumour biology and numerous degenerative and immunodeficiency syndromes associated with apoptotic disorders. The mechanism of apoptosis activation is very complex and accompanied by specific morphological and biochemical cell changes that differ depending on the cell type and conditions in which the cell grows. For this reason it is essential to use several methods to detect different steps of apoptosis and thus avoid false positive or false negative results. All known and used methods have some advantages and disadvantages, but none completely meets the desired conditions. This short review presents the methods most frequently used to detect apoptosis and the biological and biochemical processes which provide the bases for these methods.

Apoptosis↗

PubMed2003

[Apoptosis--programmed cell death].

During the evolution, multi-cellular organisms have developed various protective mechanisms against environmental insults. Apoptosis is one of physiological mechanisms where in fact a cell itself actively induces its own death. In contrast to necrosis where the cell death occurs usually as a result of severe physical or chemical extra cellular factors accompanied by inflammatory reactions of tissue, the apoptotic process starts without signs and symptoms of inflammation, and generally starts from the inside of the cell, involving the use of energy and active synthesis of specific proteins. Apoptosis is important for the right balance between the loss of old, non-functional cells and the formation of new ones in certain organs and tissues. In addition, it is a specific answer of an organism to a number of pathological conditions. Thus apoptosis plays a very important role both in physiologic and pathologic processes in the body throughout the life of an organism. A normal development of embryo and foetus is impossible without a very intensive apoptotic process. The dysfunction of the apoptotic mechanism is associated with a number of diseases in humans and animals. The apoptosis starts by triggering different intra- and intercellular signals and stimulations, which involve a number of extrinsic or intrinsic apoptotic pathways resulting in caspase cascade activation. Caspases belongs to the family of cisteine proteases, and have a central role in facilitating a number of morphological and biochemical changes during the programmed cell death. The understanding of these complex pathways offers new approaches to clinical treatment of fatal human diseases. The promising possibilities of application of the knowledge about the mechanism of apoptosis in the treatment of human diseases make the research in this field challenging and exciting.

Apoptosis↗