The purpose of the paper was to establish pathomorphological changes in human brain structures in chronic alcohol and combined (alcohol consumed with surrogates, psychoactive, and medicinal substances) intoxication and the possibility of their differential diagnosis. Materials and methods. The following were studied in detail: sensorimotor cortex, medulla oblongata, cerebellum, thalamus, substantia nigra, as well as pericellular and perivascular oedemata in persons who had died from chronic alcohol or combined intoxication, according to 140 forensic medical examination reports and medical history with histological and pathomorphological data. In the cortex, medulla oblongata, and cerebellum, severe pathological forms of neurons (anucleated cells, shadow cells, and dark cells) were selectively studied and counted. Homeostasis parameters in the microcirculatory bed were examined. As controls, we used data of people who had died as a result of various injuries that caused shock or blood loss. Staining was performed with haematoxylin and eosin, according to Nissl and according to Spielmeyer. The results of the research showed that in combined intoxication, the lungs are involved in the pathological process. The number of affected neurons in the brainstem, cerebral cortex, and cerebellum in combined intoxication was statistically significantly higher than that in the control samples. This pathology was also observed in chronic alcohol intoxication; however, the difference from the control samples was insignificant. In chronic alcohol intoxication, the cardiac type of thanatogenesis in the form of alcoholic cardiomyopathy prevails, while in combined intoxication, the pulmonary-cerebral and cerebral types of thanatogenesis are more common. Changes in the brain in combined intoxication are mainly the result of impaired haemodynamics of the microcirculatory bed in the alveoli, as well as of a direct neurotoxic effect of ethanol on the brain; thanatogenesis in this case is pulmonary-cerebral.
Introduction. Z-drugs are a group of “non-benzodiazepine” drugs with the main mode of action regulating sleep behavior in humans through exposure to GABA receptors. There are reports indicating the toxic effects of overdose and abuse of zaleplon. However, information on the effect of Z-drugs on neurotransmitter levels is scarce.
The aim of this study was to study the effect of zaleplon exposure on neurotransmitter levels in the larvae of Danio fish using targeted metabolomics.
Material and methods. 4-hour exposure to zaleplon in concentrations of 0.1, 1.0, 10, 100 and 1000 μg/l was carried out on the larvae of Danio fish. Intervention groups were compared with control groups. Each group consisted of 20 larvae of Danio fish. Neurotransmitters and their metabolites were measured using high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS).
Results. Twenty-two metabolites associated with neurotransmission were quantified. Significantly increased metabolites were tryptophan, serotonin, 5-hydroxyindolacetic acid, acetylserotonin, epinephrine and choline. Significantly reduced metabolites were 5-hydroxytryptophan, 5-methoxytryptamine, dopamine, normetanephrine, metanephrine, kynurenine, 3-hydroxykinurenine, anthranilic acid and gamma-aminobutyric acid.
Limitation. When studying metabolic changes in neurotransmitters and toxic effects in Danio fish, the results of a group of 20 larvae were analyzed, which is a sufficient sample to state the results obtained.
Conclusion. Exposure to zaleplon caused metabolic changes in the concentrations of neurotransmitters associated with most major neurotransmitter systems.
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