Background. Given the metabolic dynamics of acute coronary syndrome (ACS), the study of molecular lipid metabolites is of particular importance because their composition most rapidly reflects the changes occurring at the time of the acute event. Several prospective studies have demonstrated the prognostic value of ceramides, however, the study of their dynamics and association with clinical parameters of patients with ACS is underrepresented. Objective. To investigate changes in Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) ceramide concentrations and their association with clinical and anamnestic parameters in patients with ACS. Design and methods. Lipidomic analysis by high-performance liquid chromatography tandem mass spectrometry was performed among 110 patients with ACS. Results. At admission to the hospital the ceramide level was the highest and decreased with time (for all p < 0.001). The peculiarities of ceramide concentrations depending on clinical and anamnestic parameters of patients with ACS are shown. Ceramides were found to be weakly correlated with age and high-sensitivity troponin I, and moderately correlated with lipid profile at different time periods. For the first time, information on Cer(d18:1/16:0) and Cer(d18:1/24:0) levels depending on disease debut, Cer(d18:1/16:0) concentration depending on duration of the pain attack, and Cer(d18:1/18:0) level depending on the presence of family history of cardiovascular disease is presented. Conclusion. The dynamics of ceramide concentrations over time and the peculiarities of their levels depending on the clinical and anamnestic parameters of patients with ACS expand the understanding of the importance of lipid metabolites.

Diseases associated with disorders of sexual development, the reproductive system, delayed of puberty onset are of high relevance. This negatively affect the health of young people, the demographic indicators, fertility and require a search for therapy. This review presents current data on the role of the kisspeptin ligand-receptor system KISS/KISS1R, the discovery of which was of revolutionary significance for deciphering the genesis of neuroendocrine regulation of the reproductive system.

A review and analysis of clinical and experimental research from recent decades, aimed at studying kisspeptin and its agonists as a potential therapeutic approach. Data are presented on the positive effect of kisspeptin on the pulse secretion of GnRH and gonadotropins, which can be used in the treatment of hypogonadotropic hypogonadism, ovulation disorders and other diseases of the reproductive system. Outside the human hypothalamus, kisspeptin and its receptor are expressed in the brain in key limbic and paralimbic regions, and in peripheral tissues. We summarise data on the pharmacological use of kisspeptin in reproductive disorders and fertility treatment, as well as its putative utility in hypoactive sexual desire disorder, osteoporosis and non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated fatty liver disease.

The article describes the advantages and features of experimental models of thermal burns using in vitro, ex vivo and in vivo test systems. An objective assessment of the application of each approach depending on the type of study is given. For example, cell culture models are simple but do not fully reflect the structure of human skin, which limits their translational value. Ex vivo models, such as skin explants, provide the necessary architectonics to study intercellular interactions, but they also have drawbacks, primarily related to short viability. In general, in vitro and ex vivo models have limitations in reproducing all aspects of burn wound pathogenesis and healing. In this regard, laboratory animals, primarily mice, rats, and pigs, are widely used to study burn wound pathology, its effects on the body, and the efficacy of therapy. The decision to use experimental animal models is made taking into account their translational relevance to humans. In rodents, wound healing occurs mainly by contraction, in contrast to the re-epithelialisation and granulation seen in humans, which contributes to faster wound healing in rodents. The significant similarities between certain properties of pig and human skin make the latter a relevant test system in pharmacodynamic studies of thermal burn wounds.

Background. For preclinical studies of drugs a relevant task is the selection of specific biochemical markers reflecting damage to the central nervous system, both in toxicological and pharmacological experiments. One of such markers may be protein S100b, the level of which will make it possible to assess the damage of the central nervous system of various genesis. Objective. The aim of the study was to assess changes in the level of S100b protein in the blood and in brain homogenates in brain tissue injuries of various genesis. Design and methods. The study was conducted on males of outbred rats and mice. A total of 62 animals were used: 47 rats and 15 mice. To determine the concentration of S100b protein, ELISA kits Rat S100b/S100 beta Elisa kit (Sandwich Elisa) were used) for rats and Mouse S100b/S100 beta Elisa kit (Sandwich Elisa) for mice. Statistical analysis was performed using licensed GraphPad Prism 9 software. Results: Changes of protein S100B was explored on models of alcohol neuropathy, bilateral and focal cerebral ischemia, traumatic brain injury. Forming of all pa[1]thologies led to increasing of protein S100B both in blood plasma and in brain tissues in case of traumatic brain injury. For alcohol neuropathy, focal and cerebral ischemia and traumatic brain injury changings of this marker level reached statistic meaning. Conclusion. Increased concentration of S100b is a sign of neuronal damage as a result of ischemic, traumatic and toxic factors, as well as in hypoclycemic conditions. Thus, protein S100b can be used in preclinical studies as a marker of brain damage, responding to damage of various genesis in studies of pharmacodynamics and pharmacological safety of drugs.

Relevance. The evaluation of control samples contamination is a necessary element for confirming the correctness of toxicokinetic studies (TK), concomitant with the study of toxicity of drugs and products. At the same time, insufficient elaboration of existing regulatory documents necessitates discussion of practical aspects and improvement of the regulatory framework. Purpose. The work is devoted to the consideration of experimental experience of control samples contamination in TK studies. Materials and methods. As experimental examples, two studies of TK drugs performed using rabbits with oral administration of study drugs for 28 (Study 1) or 90 (Study 2) days were considered. Results. Study 1 revealed a contamination level of 17–25 % (on the first and last days of study drug administration, respectively). Contamination of bioassays can occur in vivo (contamination of animals) and ex vivo (at the stage of bioassay sampling, at the pre-analytical stage and analytical stage). The nature of the analyte detection in the samples made it possible to exclude contamination in vivo, and the results of an internal investigation suggested that it occurred at the stage of biosample selection. In Study 2, a number of preventive measures were implemented and a slight level of contamination was obtained (0.83 %), which did not affect the completeness and correctness of results interpretation. Conclusion. Based on experimental experience, recommendations for minimizing and preventing contamination of control samples during the biological part, pre-analytical and analytical stages of studies were formulated. Presumably, in the presence of a random nature of contamination indicating its ex vivo origin, the level of contamination not exceeding 25 % can be considered insignificant, i.e. not leading to further deviation and cancellation of the results of the entire study

In IgG4-associated disease, several organs and tissues are often affected, especially kidney tissue, and is characterized by interstitial nephritis, obstructive nephropathy, and in rare cases glomerulopathy (including membra[1]nous nephropathy).

IgG4-associated disease was isolated as an independent nosological form in 2003, when patients with type 1 autoimmune pancreatitis were found signs of systemic damage (involvement of the biliary tract, salivary glands, retroperitoneal space), and in 2012 the first international nomenclature of the disease was proposed.

The clinical manifestations of IgG4-associated disease are nonspecific and diverse, which determines the difficulties of differential diagnosis, including infections and tumors, and increases the period from the onset of the disease to diagnosis to an average of 2 years. IgG4-associated disease is more likely to develop in middle age and old age. The prevalence of the disease is higher among men than among women. Thus, autoimmune pancreatitis type 1, retroperitoneal fibrosis and tubulointerstitial nephritis are more common in men, and sialoadenitis, dacryoadenitis and thyroiditis are more common in women.

In this article, we present a clinical case of IgG4-associated systemic disease with a combined lesion of the tubulo-interstitial and glomerular compartments of kidney tissue with nephrotic syndrome as the only initial manifestation. The combination of IgG4-tubulo-interstitial nephritis with membranous nephropathy is an ex[1]tremely rare pathology. Nephrobiopsy was crucial in the diagnosis of this condition, which allowed the patient to be prescribed proper and timely treatment.