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Vol 20, No 2 (2020)

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Original research

Stress-induced increased expression of TLR2, TLR3, and TLR4 genes in hypothalamic tissue

Yankelevich I.A., Shustov M.V., Martyshkina Y.S., Filatenkova T.A.

Abstract

The aim of this work was to study the expression of Toll-like receptors (TLRs) genes in the hypothalamic structures of the brain, after the application of acute stressful effects. A hypothesis has been put forward about Toll-like receptors as a key link in the mechanisms of the implementation of a stress reaction, including at the level of the central nervous system (CNS). The important role of TLR in the pathogenesis of stress-mediated diseases of the central nervous system is assumed. The expression of TLR2, TLR3, and TLR4 genes in rat hypothalamus was studied for after 3 hours after the application of acute emotional-physical stress. A reliable increase in the level of gene expression of all three receptors at the mRNA level in stressed animals was established compared with the control. The obtained experimental data indicate the activation of the system of Toll-like receptors at the level of the central nervous system under stress. The activation of several receptors of the TLR family with different specificities in the absence of an increase in microbial load, including at the level of pathogen-associated molecular factors (PAMP), may also indicate the likely significant role of endogenous TLR ligands in the described processes.

Medical academic journal. 2020;20(2):11-16
pages 11-16 views

Relationship between cytokeratins CK8/18&19 and KIM-1 level in urine with apoptosis and necrosis of nephrotheliocytes in rats with toxic nephropathy

Sivak K.V., Guseynov R.G.

Abstract

The aim of the article. The aim of this work was to elucidate the role of apoptosis and necrosis in kidney tissue in the development of acute renal damage in poisoning rats with uranyl acetate. The research objectives included modeling acute poisoning in rats, collecting urine and kidney tissue with identifying markers of programmed cell death, tissue polypeptide antigen (TPA, fragments of cytokeratin CK8/18 & 19), and KIM-1 level in urine. An analysis of the relationship between an early increase in urinary excretion of the TPA and apoptosis level, a kidney injury molecule KIM-1, and necrosis of the tubular epithelial cells during rat poisoning with nephrotoxin uranyl acetate dihydrate.

Materials and methods. Uranyl acetate dihydrate (CAS # 6159-44-0) was administered to 18-week old female Sprague-Dawley rats weighing 175–199 g by intragastrically at a dose of 30 mg / 100 g body weight once through an atraumatic probe. Rats were divided into 2 groups: group 1 — intact animals (12 individuals), group 2 — animals with induced AKI (36 individuals). Daily urine was collected before, on the 1st, 3rd, and 7th day after poisoning in metabolic cages. The concentration of creatinine, KIM-1, tissue polypeptide antigen was measured in urine. In the kidney tissue samples, the fraction of dead cells and nephrothelial cells with apoptotic signs of nuclear changes by fluorescence microscopy with AMD — Hoechst 33342 staining was determined. Data processing was performed using GraphPad Prism 6.0.

Results. Acute kidney injury in rats with uranyl acetate dihydrate leads to a rapid increase in urinary excretion of cytokeratin fragments CK8/18 & 19 due to subtotal damage to nephrothelial cells due to activation of apoptosis, and then an increase in KIM-1 as a marker of necrotic cell death. Fluorescence microscopy of nuclear chromatin stained renal tubule cells showed a significant increase in the proportion of cells with apoptotic bodies, chromatin condensation, and a change in the shape of the nuclei.

Conclusion. Examination of the curves of risk function showed that only creatinine in blood (p = 0.0002) and urine KIM-1 (p = 0.0005) had a significant level of association with rat mortality and necrosis of the nephrothelial cells. A comparative analysis of the relationship between apoptosis biomarker levels — TPA (cytokeratin fragments CK8/18 & 19) and urinary nephrotoxicity marker KIM-1 with the proportion of kidney cells dying by the mechanism of necrosis and apoptosis revealed positive correlations of Spearman in pairs of “cytokeratin CK8/18 & 19 — apoptosis” (r = 0.73, 95% CI 0.45–0.88, p < 0.0001), “KIM-1 — necrosis” (r = 0.98, 95% CI 0.96–0.99, p < 0.0001). The revealed relationship indicated the possibility of determining urinary tissue polypeptide antigen TPA as a marker of the early stage of acute kidney damage as a surrogate marker of tubular cell apoptosis, and KIM-1 as a marker for necrosis of nephrothelial cells.

Medical academic journal. 2020;20(2):17-26
pages 17-26 views

Influence of some cinnamic acid derivatives on changes of the tricarboxylic acid cycle enzymes activity in rats under brain ischemia conditions

Voronkov A.V., Pozdnyakov D.I., Adjiahmetova S.L., Chervonnaya N.M., Rukovitsina V.M., Oganesyan E.".

Abstract

The aim of the study was to assess the effect of certain derivatives of cinnamic acids on changes of the tricarboxylic acid cycle enzymes activity under experimental cerebral ischemia.

Materials and methods. Brain ischemia was modeled by irreversible right-sided coagulation of the middle cerebral artery. Test compounds: 4-hydroxy-3,5-ditretbutyl cinnamic acid, coumaric, coffee, synapic, cinnamic, 4-hydroxycinnamic and ferulic acids, as well as a reference drug — succinic acid was administered at a dose of 100 mg / kg per os for 3 days after the reproduction of ischemia. Then, changes in the activity of aconitase, citrate synthase, and α-ketoglutarate dehydrogenase were evaluated in the supernatant of the brain.

Results. The use of all the studied compounds and the reference drug helped to restore the activity of enzymes of the tricarboxylic acid cycle. The most pronounced results were obtained when animals were treated by 4-hydroxy-3,5-ditretbutyl cinnamic acid, against the background of which the activity of citrate synthase was higher than in animals treated by succinic, coumaric, coffee, synapic and ferulic acids by 1.53 (p < 0.05), 1.41 (p < 0.05), 1.4 (p < 0.05), 1.46 (p < 0.05) and 1.41 (p < 0.05) times, respectively. Also, with the administration of 4-hydroxy-3,5-ditretbutyl cinnamic acid, the activity of aconitase was higher compared to rats that were administered with succinic, coumaric, coffee, synapic and ferulic acids by 2.47 (p < 0.05), 2.49 (p < 0.05), 3.44 (p < 0.05), 2.59 (p < 0.05) and 1.9 (p < 0.05) times, respectively.

Conclusion. The administration of the studied in this work cinnamic acid derivatives helps to restore the activity of citrate synthase, aconitase, and α-ketoglutarate dehydrogenase in rats under conditions of cerebral ischemia. The most pronounced changes in the activity of enzymes were obtained with the iadministration of 4-hydroxy-3,5-ditretbutyl cinnamic acid.

Medical academic journal. 2020;20(2):27-32
pages 27-32 views

The effect of aminoguanidine on acute lung injury induced by influenza A/H1N1/PDM09

Aleksandrov A.G., Savateeva-Lyubimova T.N., Stosman K.I., Muzhikyan A.A., Sivak K.V.

Abstract

Background. Acute lung injury is one of severe course of influenza infection with mortality up to 40% of patients, despite on etiological and pathogenetic therapy.

The aim of the article to study of the effects of aminoguanidine on correcting on acute lung injury induced by influenza virus A/California/7/09MA (mouse-adapted) (H1N1)pdm09, collection Smorodintsev Research Institute of Influenza.

Materials and methods. The study was performed on 95 outbred female mice. The mouse-adapted pandemic influenza virus A/California/7/09MA (H1N1)pdm09 was used for modeling viral infection at a dose of 1 LD50. The mortality was analysed. Levels of advanced glycation end-products (AGEs), proinflammatory cytokines in lung; saturation index and leukocytes marker parameters in blood; pathological and histological studies of lung were performed on 4 and 7 days post infection.

Results. Aminoguanidine led to 2-fold decrease in mortality in mice with virus-induced acute lung injury; significantly suppressed the growth of AGEs and proinflammatory cytokine levels in lung; reduced decrease of saturation index and hematological inflammatory markers; decreased level of inflammatory injury in lung tissue.

Conclusion. Aminoguanidine relieved virus-induced acute lung injury in mice. These AGEs inhibitor reduced the proinflammatory response and structural changes in respiratory tract epithelial cells induced by reactive carbonyl compounds on cell membrane.

Medical academic journal. 2020;20(2):33-44
pages 33-44 views

Food safety of bivalves from the South Vietnam: organochlorine compounds and heavy metals as risk factors for human health

Donets M.M., Tsygankov V.Y., Kulshova V.I., Elkhoury J., Boyarova M.D., Gumovsky A.N., Gumovskaya Y.P., Bogatov V.V., Prozorova L.A., Chernova E.N., Lysenko E.V., Ngo Х.

Abstract

The aim of the work is to study the accumulation of organochlorine pesticides, polychlorinated biphenyls and heavy metals in the soft tissues of commercial bivalves from continental reservoirs of the south Vietnam and to assess health risks for population.

Materials and methods. Four genera of bivalves from the Mekong Delta — Corbicula sp., Geloina sp., Ensidens sp., Scabies sp. — were studied. Organic pollutants were determined by gas chromatography-mass spectrometry, heavy metals – by atomic absorption in flame and flameless atomizers. Health risks were assessed by determining the hazard quotient (HQ) and the incremental lifetime cancer risk (ILCR).

Results. To minimize the risk of poisoning when consuming Corbicula sp., Geloina sp., Ensidens sp. and Scabies sp. maximum consumption levels should be 83, 15, 1 and 6 pcs/day, respectively. The risk of developing cancer can be increased with the consumption of Corbicula sp. Ensidens sp. and Geloina sp. in an amount of 2–12 pcs/day.

Conclusion. The maximum consumption levels of four bivalves genera were determined, at which there is no health risks for the population of South Vietnam. All risks are associated with α-HCH, PCBs, Mn and Fe. Safety assessment of local food (in particular, not traditional for tourists) is an urgent task to ensure the safety of life and health of Russian citizens abroad.

Medical academic journal. 2020;20(2):45-48
pages 45-48 views

Experimental evaluation of the effect of beta-D-glucan on the survival of irradiated mice

Murzina E.V., Sofronov G.A., Simbirtsev A.S., Aksenova N.V., Veselova O.M., Zavirskiy A.V., Krylova T.G., Shamtsyan M.M.

Abstract

The relevance is determined by the need to develop new means of antiradiation protection, which could be used for irradiating people in case of emergency situations or for medical use of ionizing radiation for diagnostic or therapeutic purposes.

Aim: to evaluate the prospects of beta-D-glucan as a candidate drug for the development of a pharmacological means to reduce the toxic effects of radiation exposure.

Materials and methods. In experiments on male mice the protective effect of beta-D-glucan derived from Pleurotus ostreatus mushroom on the parameters of 30-day survival of irradiated rodents exposed to lethal doses of X-ray radiation was studied. Beta-D-glucan was administered intragastrically in different doses in preventive or therapeutic regimens.

Results. It was shown that intragastric administration of beta-D-glucan at a dose of 500 mg/kg 1 h after 7.5 Gy X-Ray irradiation protected from the death of irradiated mice. There was a 27% increase in the 30-day survival rate of mice compared to the control group (47% and 20%, respectively). This dose of the drug also increased the 30-day survival rate of mice by 26% when administered 0.5 h before or 2 hours after 8 Gy irradiation. The good tolerance of intragastric administration of beta-D-glucan in mice at a dose of 500 mg/kg was shown. There were no negative effects of the drug during 3 weeks of follow-up.

Conclusion. The results can indicate that beta-D-glucan derived from Pleurotus ostreatus has an antiradiation potential in the oral route of administration, having a protective effect on the survival of lethally irradiated animals, and shows the properties of a radiomitigator and radioprotector, but the identified effect requires further study.

Medical academic journal. 2020;20(2):59-68
pages 59-68 views

Distribution of introduced human mitochondrial DNA in early stage mouse embryos

Kustova M.E., Sokolova V.A., Kidgotko O.V., Bass M.G., Zakharova F.M., Vasilyev V.B.

Abstract

Objective. The aim of study was the analysis of human mitochondrial DNA (mtDNA) distribution among murine blastomeres in the embryos developing after an injection of human mitochondria suspension at the stage of one or two cells is presented.

Material and methods. Mice CBA/C57Black from Rappolovo aged three weeks were used. Zygotes were obtained upon hormonal stimulation of animals and mated with males. 3–10 pL of mitochondrial suspension from HepG2 cells was injected into a zygote or one blastomere of a two-cell embryo. Zygotes or two-cell embryos cultured in M3 medium drops covered with mineral oil in Petri dishes. Upon reaching the two-, four- or eight-cell stage the cultured embryos were separated into blastomeres. The latter were lysed and the total DNA was isolated. Human mtDNA was detected by PCR using species-specific primers.

Results. The development of 2848 mouse embryos was monitored. In 520 embryos that achieved the stage of 2, 4, 8 in proper time the presence of human mtDNA was assayed in each blastomere. Along with murine mtDNA all embryos contained human mitochondrial genome, which is an evidence of artificially modelled heteroplasmy. Not every blastomere of transmitochondrial embryos contained foreign (human) mtDNA. Mathematical elaboration evidenced an uneven distribution of human mtDNA in cytoplasm within the time elapsed between the injection of human mitochondria and the subsequent splitting of the embryo.

Conclusion. The results obtained confirm our previous notion of the presence of 10–11 segregation units of human mtDNA in the total amount of mitochondria (about 5 ∙ 102) injected into an embryo.

Medical academic journal. 2020;20(2):69-78
pages 69-78 views

Lecture

Evaluating of prognostic value of biomarker and upper reference limit calculating

Bunenkov N.S., Bunenkova G.F., Komok V.V., Grinenko O.A., Nemkov A.S.

Abstract

Objective: to develop algorithm of assessment of prognostic value of biomarker (troponin I) for predicting death after coronary artery bypass grafting.

Materials and methods. Data collection was performed according to prospective non-randomized clinical trial AMIRI — CABG in Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia between 2016–2019 years with 336 patients. There is database with clinical, laboratory and instrumental data. Statistics were calculated with SAS Enterprise Guide 6.1 software. Prognostic capability of biomarker for death were evaluated with logistic regression. Spline of relation between death and biomarker level were plotted using coefficient of logistic regression and intercept. Upper reference limit was calculated with Youden index.

Results. There was developed algorithm to assess prognostic value of biomarker and its usefulness for clinical application and to define upper reference limit of biomarker. This algorithm could be useful for physicians and researchers for data analysis.

Conclusion. Presented algorithm of data analysis allows to assess prognostic value of novel biomarker and its clinical usefulness.

Medical academic journal. 2020;20(2):79-86
pages 79-86 views

Clinical research

Clinical and neurophysiological peculiarities of tumor-related epilepsy

Tolstykh N.V., Gurchin A.F., Koroleva N.Y., Stolyarov I.D.

Abstract

Detection and correction of structural tumor-associated epilepsy remain relevant at the present time. Seizures occur in 75–90% of cases in patients with gliomas of malignancy’s various degrees.

The aim of this work was to clarify the links of pathogenesis and clinical and neurophysiological features of structural epilepsy in intracerebral tumors.

Materials and methods. We examined 23 patients with intracerebral tumors and symptomatic epilepsy.

Results. Epileptiform activity was registered in 2 or more regions in more than half of the patients — 12 people (52.18%), and 7 of them (58.3%) it spread to neighboring leads. No association was found between the size of the tumor and the number of attacks.

Conclusions. Grade I–II tumors predominate among patients with tumor-related epilepsy. In this population with a high frequency after surgery, both tumor control and freedom from seizures can be achieved. It is necessary to manage this group of patients after surgery with regular neurophysiological monitoring (MRI, positron-emission tomography and video-EEG monitoring) to correct antiepileptic therapy and maintain a high level of quality of life.

Medical academic journal. 2020;20(2):87-96
pages 87-96 views

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