Aim.Clinical guidelines for the management of adult patients suffering from drug-induced liver injuries (DILI) are intended for all medical specialists, who treat such patients in their clinical practice.Key findings.The presented recommendations contain information about the epidemiological data, terminology, diagnostic principles, classification, prognosis and management of patients with DILI. The recommendations list pharmacological agents that most commonly cause DILI, including its fatal cases. Dose-dependent and predictable (hepatotoxic), as well as dose-independent and unpredictable (idiosyncratic) DILI forms are described in detail, which information has a particular practical significance. The criteria and types of DILI are described in detail, with the most reliable diagnostic and prognostic scales and indices being provided. The pathogenesis and risk factors for the development of DILI are considered. The clinical and morphological forms (phenotypes) of DILI are described. The diseases that are included into the differential diagnosis of DILI, as well as the principles of its implementation, are given. The role and significance of various diagnostic methods for examining a patient with suspected DILI is described, with the liver biopsy role being discussed. Clinical situations, in which DILI can acquire a chronic course, are described. A section on the assessment of causal relationships in the diagnosis of DILI is presented; the practical value of using the CIOMS-RUCAM scale is shown. All possible therapeutic measures and pharmacological approaches to the treatment of patients with various DILI phenotypes are investigated in detail. A particular attention is paid to the use of glucocorticosteroids in the treatment of DILI.Conclusion.The presented clinical recommendations are important for improving the quality of medical care in the field of hepatology.

Cell migration is one of the most important processes in which the cytoskeleton plays a main role. The cytoskeleton network is formed by tubulin microtubules, actin filaments, and intermediate filaments (IFs). While the structure and functions of the two aforementioned proteins have been extensively investigated during the last decades, vimentin IFs structure and their role in cell migration and adhesion remain unclear. Here, we investigated polarity determination in rat fibroblasts with either a knocked out vim gene or with a mutation that blocks filament formation on the stage of unit‐length filaments (ULFs). Structured illumination microscopy has demonstrated the difference in the morphology of IFs in wild‐type fibroblasts and of ULFs in mutant fibroblasts. We have developed an approach to measure cell stiffness separately on the trailing and leading edges using atomic force microscopy. Young's modulus values on the leading and trailing edge of migrating rat fibroblasts differ approximately by two times, being larger on the leading edge. The knockout of the vim gene leads to having comparable values of Young's moduli on both edges. Vimentin‐null cells change the direction of migration more frequently than those expressing wild‐type or mutated vimentin. Our results have shown the principle role of vimentin, not only in the form of IFs, but also as ULFs, in the determination of the polarity and the directionality of fibroblast migration.

No abstract

No abstract

No abstract