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Background The use of opioids among people of the young and working age has sharply increased in recent years simultaneously with the outbreak observed in the general population. Objective To determine the trigger mechanism of the destructive effect of narcotic analgesics on the ultrastructural level of the vascular tunic of the eyeball. Methods: This experimental study was performed on 26 male rats aged 3.0 months and body weight 160–180 g with daily intramuscular injection of Nalbuphine hydrochloride during 4 weeks. The material for the study was represented by ultramicroscopic sections of the vascular tunic of the eyeball. Results In comparison with the control group there was observed swelling of the cytoplasm and the nuclei of endotheliocytes, considerably narrowed lumens of the capillaries. Plasmolemma of endotheliocytes forms protrusions into the lumen of endotheliocytes forming microvilli. Changes of destructive nature took place in the elements of the smooth endoplasmic reticulum and mitochondrial complex. Signs that are characteristic of sclerosis were found in the surrounding connective tissue complex. In particular, lesions of endothelium and basement membrane of the elements of hemomicrocirculatory bloodstream, epithelium of the ciliary processes, cellular and non-cellular elements of the iris and the uvea proper have studied. Conclusion The databased on the experimental model allow extrapolation the results obtained to humans. It is confirmed that the development of angiopathy is the trigger mechanism of the destructive effect of narcotic analgesics.

Introduction: Many anti-tumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micro milieu of dead and dying cells. Methods: Cultures of viable melanoma B16F10 cells, mouse fibroblasts and primary human fibroblast-like synoviocytes(FLS) in the presence of dead and dying cells,its supernatants or purified agonists and antagonists were used to evaluate the stimulation of proliferation. Viable cell quantification was performed by either flow cytometry of harvested cells or by crystal violet staining of adherent cells. High-performance liquid chromatography (HPLC) and liquid chromatography coupled with mass spectrometry (LC-MS) of cell supernatants were deployed to identify the nature of growth promoting factors.Co-implantation of living cells in the presence of supernatants collected from dead and dying cells and specific agonists was used to evaluate tumor growth in vivo. Results: The stimulation of proliferation of few surviving cells by bystander dead cells was confirmed for melanomacells,mouse fibroblasts and primary FLS. We found that small soluble molecules present in the protein free fraction of supernatants of dead and dying cells were responsible for the promotion of proliferation. The nucleoside inosine released by dead and dying cells acting via adenosine receptors was identified as putative inducer of proliferation of surviving tumor cells after irradiation and heat treatment. Conclusion: Inosine released by dead and dying cells mediates tumor cell proliferation via purinergic receptors. Therapeutic strategies surmountingthis pathwaymay help to reduce the rate of recurrence after radio- and chemotherapy.

Introduction Many antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells. Methods Cultures of viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast-like synoviocytes (FLS) in the presence of dead and dying cells, their supernatants (SNs), or purified agonists and antagonists were used to evaluate the stimulation of proliferation. Viable cell quantification was performed by either flow cytometry of harvested cells or by crystal violet staining of adherent cells. High-performance liquid chromatography and liquid chromatography coupled with mass spectrometry of cell SNs were deployed to identify the nature of growth-promoting factors. Coimplantation of living cells in the presence of SNs collected from dead and dying cells and specific agonists was used to evaluate tumor growth in vivo. Results The stimulation of proliferation of few surviving cells by bystander dead cells was confirmed for melanoma cells, mouse fibroblasts, and primary FLS. We found that small soluble molecules present in the protein-free fraction of SNs of dead and dying cells were responsible for the promotion of proliferation. The nucleoside inosine released by dead and dying cells acting via adenosine receptors was identified as putative inducer of proliferation of surviving tumor cells after irradiation and heat treatment. Conclusion Inosine released by dead and dying cells mediates tumor cell proliferation via purinergic receptors. Therapeutic strategies surmounting this pathway may help to reduce the rate of recurrence after radio- and chemotherapy.

This article deals with determination of changes in the structural organization of vascular tunic of the eyeball under the effect of opioid.The study was carried out on 24 mature white male rats aged 3.0-4.5 months and 170-280 g weight. The research material included histological specimen and semi-thin sections of white rats' eyeball vascular tunic. For the histological study, microscopic sections of the eyeball were stained with Hematoxylin and Eosin, Heidenhain's Azan trichrome. Specimens were studied and photographed with microscope magnification: ×600, ×1000.The first signs of microstructure disorder in all parts of vascular tunic of the eyeball are noticeable after two weeks of nalbuphine injection to the white rats. During the next four weeks of the experiment, the pathological changes increase and are manifested by the swelling and polymorphonuclear infiltration of the iris, ciliary body, choroid and by deep destructive changes of eyeball hemomicrocirculatory bloodstream. Histological and ultramicroscopic studies of the white rats' eyeball vascular tunic after six weeks of nalbuphine injections showed deep destructive changes in the structure of all parts of vascular tunic.Our study demonstrated a negative effect of the prolonged injection of opioid in the experiment on the state of microstructural organization of the eyeball vascular tunic. Development of angiopathy is the triggering for occurrence of destructive changes in the eyeball under the effect of opioid.