IntroductionMany 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.MethodsCultures 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.ResultsThe 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.ConclusionInosine 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.
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.
The aim: Research of blood lipid spectrum, level of anti-inflammatory cytokines and C-reactive protein of coronary heart disease patients. Materials and methods: There was examined 61 patients with unstable angina, who had been on hospital care in the cardiology department of the Lviv National Emergency Hospital. Their average age was 68.3 ± 1.9 years. The control group included 20 generally healthy persons. There was estimated blood lipid spectrum, C-reactive protein, fibrinogen and proinflammatory cytokine of patients. Results: There was determined considerable increase total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides and coefficient of atherogenicity. High level of C-reactive protein and pro-inflammatory cytokines were detected in patients with unstable angina. Conclusions: In patients with unstable angina was revealed a significant increase of proinflammatory cytokines levels in the blood serum: interleukin-1β, interleukin-6, interleukin-17, TNF-α and C-reactive protein, fibrinogen, which indicates activation of the inflammatory process. In patients with unstable angina was detected a significant disorder of blood lipid spectrum. For its correction should be recommended diet and hypolipidemic agents.
The medical community is gaining increased attention to streamlining a clear mechanism for reporting critical test results in the clinic. DSTU ISO 15189: 2015 requires laboratories to report critical test results to clinitians within a specified period of time. Moreover, they should have a clearly established procedure in place. In order to standardize processes and avoid misunderstandings between stakeholders, international organizations (RCPA, AACB, CLSI) have developed terminology, communication algorithm and requirements for data documentation. In order to harmonize this part, a lot of surveys have been conducted as to which analytes should be included in the notification sheet and, in particular, the limits of their values for hematological, hemostasiological and biochemical studies. According to ICSH recommendations, critical risk results include hemoglobin, leukocytes, neutrophils, platelets, activated partial thromboplastin time (aPTT), prothrombin time (PT) / international normalization ratio (INR) and fibrinogen. The laboratories include different biochemical tests in the alert list. The most common analytes are glucose, potassium, sodium and calcium. It should be noted that this alert list is only recommended for clinical laboratories, such as the number of indicators and alert threshold of analytes should be agreed with the clinicians of a particular medical institution, taking into account their experience and local patient population. The developed recommendations will allow to react as quickly as possible to situations that may threaten patient’s life, provide qualified medical care in a timely manner and adjust work processes in accordance with the requirements of international standards.
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