PROTAC: targeted drug strategy. Principles and limitations.

The PROTAC (PROteolysis TArgeting Chimera) technology is a method of targeting intracellular proteins previously considered undruggable. This technology utilizes the ubiquitin-proteasome system in cells to specifically degrade target proteins, thereby offering significant advantages over conventional small-molecule inhibitors of the enzymatic function. Preclinical and preliminary clinical trials of PROTAC-based compounds (degraders) are presented. The review considers the general principles of the design of degraders. Advances and challenges of the PROTAC technology are discussed.

[Cytologic study of buccal epithelium in various lengths of service in chrysotile-asbestos production].

Buccal epithelium cytograms were analyzed in workers of chrysotile-asbestos production "Kostanaiskiye mineraly" JSC. Findings are that 10-20 years of service are associated with increased number of 4th differentiation grade cells and correspondingly decreased number of 5th differentiation grade cells. Later, with 20 years of service, numbers of 4th and 5th grade epitheliocytes reach initial values. With 10-20 years of service, integral parameters of differentiation index, cornification index and intracellular relations decrease. Findings are that 10-20 years of service are connected with domination of proliferation over differentiation processes. Length of service over 20 years is with adaptive processess in the workers. These data are important in evaluation of mucosal system in variable length of occupational service.

[Buccal epithelium reactivity in children].

The purpose of this study was the analysis of the buccal smears from 200 healthy children and children with chronic tonsillitis and chicken pox. The smears were stained using Pappenheim's method. The peculiarity of buccal mucosa cytograms of children of different ages was the significant increase in mature forms of the cells (presence of differentiation stage 5 and 6 cells) in adolescents. They also had a lower area of epitheliocytes at all the stages of differentiation and of their nuclei. In chronic tonsillitis and chicken pox, the complex of cytological changes was detected, that included the increase of the leukocyte number, changes in the proportions of epitheliocytes in cell population, augmentation of inflammation-destruction and destruction indexes.

[The functional morphology of the regional inguinal lymph nodes during the endolymphatic antibiotic therapy of patients with vascular diseases of the lower extremities]. / Funktsional'naia morfologiia regionarnykh pakhovykh limfaticheskikh uzlov pri éndolimfaticheskoi antibiotikoterapii u bol'nykh s zabolevaniiami sosudov nizhnikh konechnostei.

The general structure and cell composition of the inguinal lymph nodes has been analysed at a direct endolymphatic antibiotic therapy, performed with the aim of prophylaxis of suppurative complications, when surgical interventions are performed in the vessels of the lower extremities. Morphokinetics of the lymph nodes depends on duration of the endolymphatic therapy. During early terms it reflects an increase in transport function of the regional inguinal lymph nodes, during late terms it reflects an increase in their immune role. In the lymph nodes, situating on the contralateral side, an analogous reaction is revealed; this appears to demonstrate presence of well developed collaterals between lymph vessels of the lower extremities.

[Nephropathy of pregnancy as a risk factor of congenital glomerulopathy]. / Nefropatiia beremennykh kak faktor riska vrozhdennykh glomerulopatii.

The study is concerned with morphological alterations in fetal and neonatal renal glomeruli in late gestosis. Nephropathy of pregnancy is established to be a factor of risk of renal dysembryogenesis, presenting with renal immaturity and focal dysplasias in mature fetuses and newborns as well as fraught with congenital glomerulopathies. The employment of immunofluorescence techniques permitted clarification of immune complex pathogenetic role in development of fetal and neonatal glomerulopathies in late gestosis. The results of the study support the necessity for antenatal protection of the fetus aimed at pathogenetic prophylaxis of congenital nephropathies.

[Changes in the peripheral blood picture in acute appendicitis in relation to accelerated development]. / Izmeneniia kartiny perifericheskoi krovi pri ostrom appenditsite v sviazi s akseleratsiei.

The authors have noted changes in the peripheral blood picture in patients with acute phlegmonous and catarrhal appendicitis for the last 20 years. General leukocytosis was found to be higher with a simultaneous elevation of a relative amount of lymphocytes, monocytes and eosinophils; the relative neutrophilia decreased with no changes in the absolute amount of neutrophils. The causes of these changes are supposed to be the same as those of acceleration.

[So-called pseudolymphomatosis of the stomach]. / O tak nazyvaemom psevdolimfomatoze zheludka

An observation of a polymorphnocellular variant of pseudolymphomatosis of the stomach diagnosed retrospectively is described. Initially, the case was treated as lymphogranulomatosis of the stomach, and in connection with the latter the patient was given long-term immunodepressive therapy. At autopsy (6 years later) atrophy of the lymphoreticular tissue and mucinous carcinoma of the stomach were revealed. The authors hold that the second tumour developed against the background of the immuno-depressive therapy, whereas at the beginning the condition was pseudolymphomatosis.