Effect of a helium and oxygen mixture on physiological parameters of rats with cerebral arterial air embolism.

Introduction: Cerebral arterial air embolism (CAE) is a serious and potentially dangerous condition that can interrupt the blood supply to the brain and cause stroke. One of the promising gas mixtures for emergency treatment of air embolism is an oxygen-helium mixture. Methods: We modeled CAE in awake rats by injecting air into the common carotid artery. Immediately after CAE, animals were either untreated or underwent hyperbaria, oxygen inhalation, heated air inhalation, or helium-oxygen mixture inhalation. Body temperature, locomotor activity, respiratory and cardiovascular parameters were monitored in the animals before CAE modeling, and 3 and 24 h after CAE modeling. Results: After 3 hours of CAE modeling in awake rats, depression of the nervous, cardiovascular and respiratory systems, as well as decreased body temperature were observed. 24 h after CAE modeling multifocal cerebral ischemia was observed. Normobaric helium-oxygen mixture inhalation, on par with hyperbaric treatment, restored body temperature, locomotor activity, respiratory volume, respiratory rate, and blood pressure 3 hours after CAE, and prevented the formation of ischemic brain damage lesions 24 h after CAE. Discussion: Thus, inhalation of a heated oxygen-helium gas mixture (O2 30% and He 70%) immediately after CAE improves the physiological condition of the animals and prevents the foci of ischemic brain damage formation.

Selective targeting of α7 nicotinic acetylcholine receptor by synthetic peptide mimicking loop I of human SLURP-1 provides efficient and prolonged therapy of epidermoid carcinoma in vivo.

α7-Type nicotinic acetylcholine receptor (α7-nAChR) promotes the growth and metastasis of solid tumors. Secreted Ly6/uPAR-Related Protein 1 (SLURP-1) is a specific negative modulator of α7-nAChR produced by epithelial cells. Here, we investigated mechanisms of antiproliferative activity of recombinant SLURP-1 in epidermoid carcinoma A431 cells and activity of SLURP-1 and synthetic 21 a.a. peptide mimicking its loop I (Oncotag) in a xenograft mice model of epidermoid carcinoma. SLURP-1 inhibited the mitogenic pathways and transcription factors in A431 cells, and its antiproliferative activity depended on α7-nAChR. Intravenous treatment of mice with SLURP-1 or Oncotag for 10 days suppressed the tumor growth and metastasis and induced sustained changes in gene and microRNA expression in the tumors. Both SLURP-1 and Oncotag demonstrated no acute toxicity. Surprisingly, Oncotag led to a longer suppression of pro-oncogenic signaling and downregulated expression of pro-oncogenic miR-221 and upregulated expression of KLF4 protein responsible for control of cell differentiation. Affinity purification revealed SLURP-1 interactions with both α7-nAChR and EGFR and selective Oncotag interaction with α7-nAChR. Thus, the selective inhibition of α7-nAChRs by drugs based on Oncotag may be a promising strategy for cancer therapy.

Synthetic Peptide Fragments of the Wtx Toxin Reduce Blood Pressure in Rats under General Anesthesia.

Previously, it was shown that the non-conventional toxin WTX from the venom of the cobra Naja kaouthia, when administered intravenously, caused a decrease in blood pressure (BP) and an increase in heart rate (HR) in rats [13]. To identify the site of the toxin molecule responsible for these effects, we studied the influence of synthetic peptide fragments of the WTX on BP and HR in normotensive male Sprague-Dawley rats under general anesthesia induced by Telazol and Xylazine. It was found that peptides corresponding to the WTX central polypeptide loop, stabilized by a disulfide bond, at intravenous injection at concentrations from 0.1 to 1.0 mg/mL caused a dose-dependent decrease in BP, with the HR increasing only in the first 5-10 min after administration. Thus, WTX fragments corresponding to the central polypeptide loop reproduce the decrease in blood pressure caused by the toxin.

Effect of zeolite-chlorella top dressing on scar metabolism and conversion of dairy cows' feed.

In scientific and economic experience, the effect of zeolite-chlorella top dressing (CCP) from 28-29% zeolite, 1.5-2% Chlorella vulgaris powder and 75-76% cake on the productive effect of feed and digestion metabolism of dairy cows has been studied. Tetra-edric frame-hollow zeolite crystals have selectively adsorbing and ion-filtering properties, and chlorella enriches with amino acids and vitamins. The introduction of CCP into the diet of cows of the experimental group increased the mineral-vitamin balance and positively affected the metabolism of cicatricial digestion. The pH shift from 6.14 to 6.17 activated the ecosystem of the rumen microflora, increased the synthesis of LVH 0.79 mmol/100ml, due to an increase in the volume of acetates from 54.1±3.0 to 57.2±2.2 mmol/100ml, increased the number of infusoria by 41.1 thousand/ml more than the control group. An increase in the amylolytic activity of the rumen chyme by 2.8 mg/starch, and cellulolytic activity by 2.8% increased scar digestion. This increased the consumption of the dry matter of the diet by cows of the experimental group by 0.48 ± 0.06 kg/head. /day. and daily milk yields by 1.06 ± 0.03 kg against the control. An increase in protein and fat in milk with a decrease in somatic cells, and in the blood of erythrocytes and hemoglobin increased biosynthesis, which increased the conversion rate of feed from 0.68 to 0.72, and protein from 17.0% to 18.9%.

Taxifolin Reduces Blood Pressure in Elderly Hypertensive Male Wistar Rats.

Male Wistar rats aged 10 months were assigned to groups according to the initial level of systolic BP: hypertensive (systolic BP >115 mm Hg) and normotensive (systolic BP <115 mm Hg). The animals were injected intraperitoneally with 100 µg/kg taxifolin daily for 7 days. Systolic BP and HR were measured on the next day after single taxifolin administration and on the next day after 7-day injection course. In the group of hypertensive animals, systolic BP markedly decreased on the next day after the first injection; this decrease became even more pronounced (to the level of normotensive animals) at the end of the taxifolin course. In the group of normotensive animals, systolic BP remained unchanged. Hence, we demonstrate the possibility of course administration of taxifolin for BP normalization in hypertensive patients.

Interim Results of the BYHEART Observational Study: Exogenous Phosphocreatine Effect on the Quality of life of Patients with Chronic Heart Failure.

Aim      Improvement of quality of life is one of the most important goals for the treatment of patients with chronic heart failure (CHF). This study searched for ways to increase the efficiency of CHF treatment based on parameters of quality of life in CHF patients during and after the treatment with exogenous phosphocreatine (EP).Material and methods  The effect of a single course of EP treatment on quality of life of patients with functional class (FC) II-IV CHF with reduced or mid-range left ventricular ejection fraction was studied as a part of the all-Russia prospective observational study BYHEART. The presence of FC II-IV CHF and a left ventricular ejection fraction <50 % were confirmed by results of 6-min walk test (6MWT) and findings of echocardiography after stabilization of the background therapy.Results An interim data analysis showed that the course of EP treatment was associated with a significant improvement of quality-of-life indexes as determined by the Minnesota Living with Heart Failure Questionnaire (LHFQ) total score. These indexes significantly increased and remained at a satisfactory level for 6 mos. following completion of the treatment course. Also, the treatment significantly beneficially influenced the clinical condition of patients (heart failure severity scale), results of 6MWT, and the increase in left ventricular ejection fraction.Conclusion      The conclusions based on results of the interim analysis should be confirmed by results of the completed study. Complete results are planned to be published in 2022.

Implementation of evidence-based recommendations to reduce elective surgical case cancellations.

BACKGROUND: Cancellation of elective surgical cases leads to a waste of resources, financial burden, patient dissatisfaction, extended hospital stay, and unnecessary repetition of preoperative preparations. AIM: The objective of this study was to identify, analyze and manage the causes of cancellation of elective surgical cases in our institution. METHODS: This quality improvement study compared preoperative cardiovascular event and case cancellation rates before and after implementing the practice of perioperative cardiovascular risk management. The study included the following phases: (1) Screening and identification of the most important reason for case cancellation; (2) Developing the strategy and internal protocol based on the international recommendations to minimize perioperative cardiovascular risk; (3) Implementing the internal protocol and monitoring preoperative cardiovascular events and case cancellation rate. RESULTS: We achieved a reduction in surgical case cancellation rate: 83 (3.7%) out of 2242 in 2018 and 28 (1.1%) out of 2538 cases in 2019 were cancelled after the patient had been delivered to the operating room area. CONCLUSION: Screening and identification of gaps in perioperative care as well as implementation of evidence-based recommendations can significantly improve the quality of patient care. In our case, implementing the internal protocol of cardiovascular risk management in perioperative period resulted in a reduction of preoperative hypertensive crisis, myocardial ischemia, heart rhythm disorder rates and in subsequently reduction in case cancellation rate.

[The optimization of technique of detection of cryoglobulins in conditions of clinical diagnostic laboratory].

The technique is proposed to evaluate cryoclobulins associated with IgM and IgG on the basis of detection of immune complexes circulating in healthy individuals and patients with liver cirrhosis. It is demonstrated that in patients with liver cirrhosis content of cryoclobulins associated with IgM increases almost twice and those associated with IgG more than two and a half times as compared with healthy individuals. It is established that in healthy individuals cryoclobulins are also present in blood in small amount. The proposed approach to detection of cryoclobulins permits to minimize time of implementation of study and also discharge of reagents.

[EXPERIMENTAL MODELS OF STRESS URINARY INCONTINENCE].

Despite numerous medical and surgical treatment strategies available, the problem of stress urinary incontinence (SUI) in women is still not completely resolved. Continuing research is underway to modify the sling operations and develop new bulk-enhancing agents, including the use of tissue engineering and cell technologies. To evaluate the safety and effectiveness of new methods at the preclinical stage, adequate and reproducible experimental models of SUI in laboratory animals should be used. This article presents analysis of all SUI models described in the scientific literature and the results of an experimental study comparing two primary ways of modeling, based on bilateral pudendal nerve damage in female rats. The experiment results showed that only bilateral electrocoagulation of proximal part of pudendal nerves by the posterior approach ensured a stable and long-term SUI symptoms in animals in the form of leak point pressure reduction in the urodynamic study and increase of the of the urethral lumen according to histomorphometric analysis. The results suggest that an adequate experimental SUI model is urethral rabdomiosphincter denervation by pudendal nerve electrocoagulation by the posterior surgical approach, when the nerve is damaged in the area of its separation from sciatic nerve. In this case stable and reproducible results are obtainable.

[Molecular genetic characterization of the HIV-1 variants abundant in Kirgiziia].

The results of the molecular epidemiological analysis of HIV-1 circulating in Kirghizia were presented. In the area of Kirghizia this type of the work was performed for the first time. Two main genetic variants were discovered: variant IDU-A dominating in the area of the former Soviet Union, as well as recombinant form CRF02_AG. The possibility of further recombination process between these two variants of HIV-1 was suggested.

[Characteristics of psychologic features of tantalum production workers].

The article covers results of psychologic examination of apparently healthy workers of contemporary tantalum production. The authors describe changes in psychoemotional state of workers engaged into major tantalum production workshops, in accordance with occupational length of service.

Peculiarities of circulatory system response on influence of modern tantalum manufacture factors in workers.

Objective of this study was to examine functional condition of cardiovascular system among workers at "Ulba Metallurgical Plant" JSC (located in Ust-Kamenogorsk, Eastern Kazakhstan)--one of the world largest enterprises with the full production cycle from processing of tantalum containing raw materials to finished products. All workers that participated in the examination were divided into three groups: (I)--up to 5 years of occupation; (II)--from 5 to 9.9 years of occupation; and (III)--more than 10 years of occupation experience in the tantalum industry. The cardiovascular system, health concern and their contributing factors were assessed. In group I the factor of profitability of blood circulation was up to 3000 conventional units, which corresponds to the optimal fatigue; In group II the factor of profitability of blood circulation was increased up to 3525±327,3 conv. units--critical values zone. In group III the factor of profitability of blood circulation was up to 3000 conv. units. A relative improvement in the central hemodynamic indices compared with those in group II may be due to the development of adaptation. The assessments of functional condition of cardiovascular system among the workers specialize in different stages of tantalum production revealed the necessity of paying special attention at the cycle of tantalum processing and the years of work experience in an occupation.

[Regulation of erythropoiesis in patients with suppressed hematopoiesis during mountain climatic treatment].

AIM: to estimate the regulation of erythropoiesis and the coagulation system in patients with suppressed hematopoiesis in a mountain hospital (3200 m above sea level). SUBJECTS AND METHODS: The investigation included 12 patients with aplastic anemia (AA) and 10 with idiopathic thrombocytopenic purpura (ITP). Blood was received at a Bishkek hospital, then on days 20 and 40 of stay in the mountains. The authors studied erythropoietin (EPO) by enzyme immunoassay (Protein Contour kit, Russia), serum ferritin (SF) by immunoradioassay (Immunotech kit, Czech Republic), hypoxia-inducible factor-1alpha (HIF-1alpha), homocysteine (HC), hepcidin, endothelin (ET), and thrombomodulin (TM) by sandwich enzyme immunoassay, by applying monospecific antisera and monoclonal antibodies against relevant antigens (IDG Int Inc, USA). RESULTS: On staying in the mountains, there was a gradual increase in the content of hemoglobin in patients with AA and ITP. On day 40, in keeping with higher hemoglobin (Hb) levels, both groups showed a decrease in HIF-1alpha concentrations to the normal values (from 8.2 to 4.5 pg/ml). Due to the anemic syndrome, baseline EPO was increased by 5-7 times in the patients from both groups. On days 20-40, the content of EPO showed a 1.3-2.5-fold increase. In AA, HC was almost 3 times greater than the normal values; in ITP, it was 1.5-fold increased. On day 20 and during the patients'stay in the mountains, the level of HC remained in the normal range in both groups. CONCLUSION: Hypoxic hypoxia positively affects a number of hematological parameters, by normalizing erythropoiesis (Hb, EPO, and HIF-1alpha), iron metabolism (SF), and the coagulation system (HC, ET, and TM).

Effects of preliminary administration of haloperidol in low doses on the effects of haloperidol on behavioral reactions and command neuron membrane potential in edible snail.

We studied the effects of preliminary administration of haloperidol in low doses on changes in motor activity of edible snail and in electrical properties of defensive behavior command neurons induced by chronic administration of haloperidol. The rate of locomotion decreased after injections of haloperidol preparations (C6, C12, C30, C200 and a mixture C12+C30+C200) for 3 days. Similar changes were observed after 3 days of haloperidol administration. Haloperidol preparations in low doses produced a modulating effect on the decrease in locomotion rate and hyperpolarization of command neurons in edible snails caused by chronic exposure to haloperidol: the decrease in locomotion rate caused by chronic haloperidol treatment was prevented by preliminary injection of haloperidol in low doses C6, C12 and C30; the depolarizing shift of command neuron membrane potential was also abolished after consecutive injection of the same haloperidol preparations C6, C12 and C30.

[Physiologic shiftwise evaluation of respiratory system changes in miners engaged into underground coal mining].

Functional shiftwise evaluation of physiologic respiratory parameters was conducted in 166 miners. The conclusion was that each separate occupation has specific requirements.

[Hygienic evaluation of work activities in employees engaged into open-cast mining and chromium-ore concentration].

Despite contemporary equipment usage on mining enterprises, work conditions are influenced by some hazards.

[Hygienic evaluation of work conditions in shift open-cast mining work in North Kazakhstan].

Shift open-cast development and mining take place in Shubarkul coal deposit situated in semidesert with sharply continental climate. Health state and work capacity of the miners are influenced by climate, occupational and social environmental hazards.

[Automated database in analysis of pneumoconiosis prevalence in coal miners].

Using simulator of forecasting dust occupational diseases with automated information system, the authors analysed risk of pneumoconioses development in coal miners.

[Evaluating general and occupational morbidity on mining enterprises of Kazakhstan].

Evaluating risks of occupational and occupationally mediated diseases is a main parameter in further social and hygienic monitoring of work conditions and health state among mining industry workers.