[The functioning of call-center in conditions of COVID-19 pandemic].

In conditions of persisting high morbidity of COVID-19, issues related to prompt and timely medical care of population remains actual ones. The purpose of the study to analyze activities of the call-center of the Ministry of Health Care of the Udmurt Republic related to organization of medical care of COVID-19 patients in the Udmurt Republic. MATERIALS AND METHODS: The statistical (descriptive statistics) and descriptive methods were applied. The indicators of functioning of the call-center of the Ministry of Health Care of the Udmurt Republic in 2020-2022 were analyzed. The psychological characteristics of telephone counseling were studied. The satisfaction of medical organizations and citizens with services of call-center operators was assessed. THE RESULTS: The main principles of telephone counseling are confidentiality, maintenance of framework of working conversation, respect to personality of addressee. In 2020 the call center phone line received 34160 calls, in 2021 - 128339 calls, in 2022 - 65618 calls. In 25 months of operation the call-center operators received 228,117 calls from citizens related to issues of new coronavirus infection. The number of patient calls to the hot-line increases significantly when incidence of new coronavirus infection increases (r=0.885; p<0.05). Most frequently (25.1%) citizens contacted the call-center of the Ministry of Health Care of the Udmurt Republic due to inability to reach the polyclinic and on issues related to primary before-doctor care. The second place in terms of frequency (18.5%) took issues related to PCR-test results. The third place (14.1%) took issues related to duration of quarantine for patients and persons residing with them, possibility for children to attend preschool and educational institutions. The number of outgoing calling in 2020 was 16146, in 2021 - 89269 and in 2022 9936 calls. During 25 months of operation, call-center operators made 204,782 calls to citizens to monitor their health status and invite them to vaccinations and health screenings. More than half of outgoing calls (58.3%) were related to audio-monitoring of patients undergoing outpatient treatment with making-up of electronic protocol. CONCLUSIONS: During the period of increasing of COVID-19 morbidity, the call-center becomes an independent structural unit of organizing patient care. The medical organizations and citizens are satisfied with functioning of the call-center of the Ministry of Health Care of the Udmurt Republic organized in order of improving the organization of medical care of patients with COVID-19.

[The common morbidity of children population in conditions of propagation of new coronavirus infection COVID-19 in 2017-2019].

The health of children population is one of the indicators of the social and epidemiological well-being of society. The purpose of the study was to study main trends of propagation of various classes of diseases in children population in conditions of propagation of the new coronavirus infection. The data of Rosstat for the Udmurt Republic covering the pre-COVID period (2017-2019) and the period of COVID-19 propagation (2020-2021). The analytical method, descriptive statistics technique, the calculation of intensive and extensive indicators were applied. It is established that in 2017-2019, general morbidity of the children population aged 0-7 years decreased by 8.7%, while in conditions of higher propagation of COVID-19 (2020-2021) there was an increase by 11.0 %. In the children population aged 0-14 years, general morbidity decreased by 10%, and hereinafter it increased on 12.1%. At that, in the pre-COVID period in children population aged from 0 to 17 years, morbidity rate decreased for 14 classes of diseases, for 15 classes in children population aged from 0 to 14 years. During the period of higher propagation of COVID-19 morbidity rate for only 5 classes of diseases decreased in both age groups of children population.

[Quantitative assessment of breast cancer resistance protein during pregnancy in rabbits]. / Kolichestvennaia otsenka belka rezistentnosti raka molochnoi zhelezy pri beremennosti u krolikov.

Breast cancer resistance protein (BCRP,ABCG2) is an efflux transporter protein that transports various substrates from the cell to the extracellular space or organ cavities. The aim of this study was a complex assessment of the amount of BCRP during pregnancy in rabbits. The amount of BCRP in samples of the rabbit jejunum, liver, kidney, cerebral cortex, and placenta was determined by enzyme immunoassay, and in human hepatocellular carcinoma (HepG2) cells by the Western blot. To study the mechanisms involved in control of the dynamic BCRP levels during pregnancy, serum concentrations of sex hormones were investigated by radioimmunoassay and relative amounts of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in these organs were evaluated using the Western blot method. The putative role of CAR and PXR in regulation of the BCRP level by progesterone was evaluated in vitro experiments on HepG2 cells. It was found that amount of BCRP in the jejunum of pregnant rabbits was higher than in the placenta, liver, kidneys, and cerebral cortex. An increase in the amount of BCRP in the liver of rabbits was noted on the 21st day of pregnancy and a tendency to the increase was also detected on the 28th day; in the kidney and cerebral cortex increased BCRP levels were detected on the 28th day and 14th day of pregnancy, respectively, as compared with non-pregnant females. In vitro experiments with HepG2 cells have shown that the increase in the BCRP level is determined by the activating effect of progesterone on PXR.

Functioning of P-Glycoprotein during Pregnancy in Rabbits.

The level P-glycoprotein (Pgp) in organs of pregnant rabbits and its content and activity in the placental barrier at different stages of pregnancy were studied. An increase in Pgp content in the jejunum on days 7, 14, 21, and 28 of pregnancy in comparison with this parameter non-pregnant females was revealed by ELISA; in the liver, Pgp content was higher on day 7 and tended to increase on day 14; in the kidney and cerebral cortex, Pgp content was higher on day 28 of pregnancy in parallel with an increase in serum progesterone concentration. We also observed a decrease in Pgp content in the placenta on days 21 and 28 of pregnancy in comparison with day 14 and a decrease in Pgp activity in the placental barrier, which was confirmed by enhanced penetration of fexofenadine (Pgp substrate) through the barrier.

[Evaluation of female sex hormones influence on the protein-transporter p-glycoprotein functioning in vitro]. / Otsenka vliianiia zhenskikh polovykh gormonov na funktsionirovanie belka-transportera glikoproteina-P in vitro.

The effects of female sex hormones estradiol and progesterone on P-glycoprotein (Pgp) functioning have been investigated using Caco-2 cells. Pgp activity was analyzed in a transwell system by the transport of its substrate, fexofenadine. The amount of the transporter protein was analyzed by enzyme immunoassay. Incubation of Caco-2 cells with 10 µM estradiol and incubation for 3 days increased activity and synthesis of Pgp. Moreover, this effect was suppressed by the inhibitor of the constitutive androstane receptor (CAR) CINPA 1. Incubation of these cells with 100 µM progesterone for 3 days increased Pgp synthesis, but its activity remained unchanged due to non-genomic (direct) inhibition of Pgp molecule by gestagen. The pregnan-X receptor inhibitor (PXR), ketoconazole suppressed the inducing effect of progesterone on Pgp synthesis. The combination of 10 µM estradiol and 100 µM progesterone increased Pgp synthesis, but did not increase the transporter protein activity, due to direct inhibition of the Pgp molecule by progestogen. Thus, it was found that estradiol increased activity and synthesis of Pgp by stimulating CAR, and progesterone stimulated transporter protein synthesis by activating PXR.

[A role of P-glycoprotein in neurology]. / Rol' glikoproteina-R v nevrologii.

On the basis of the analysis of literature data, the authors show a role of P-glycoprotein in the pathogenesis, pharmacotherapy and a prophylaxis of neurologic diseases (Alzheimer's disease, Parkinson's disease, epilepsy, stroke).

[INFLUENCE OF ETHINYLESTRADIOL - GESTODENE COMBINATION ON THE FUNCTIONAL ACTIVITY AND EXPRESSION OF P-GLYCOPROTEIN.]

The influence of a combination of ethinylestradiol (6.5 mg/kg) and gestodene (16.5 mg/kg) on the functional activity of P-glycoprotein efflux transporter and its expression in the liver and small intestine was studied on 20 Chinchilla rabbits. P-glycoprotein functional activity was characterized by the pharmacokinetics of its marker substrate - fexofenadine upon single peroral administration. P-glycoprotein expression was investigated by the immunohistochemical method. It was established that 14-day administration of ethinylestradiol - gestodene combination did not influence the functional activity of P-glycoprotein. After 21-day administration of this combination, the maximum concentration of fexofenadine and its area under concentration - time curve were increased and its clearance was decreased. These data are indicative of the inhibition of P-glycoprotein functional activity in the organism. Immunohistochemical analysis showed a reduction in the total expression of P-glycoprotein in the liver and small intestine after joint administration of ethinylestradiol and gestodene for 21 days, which confirmed a decrease in P-glycoprotein synthesis. Correlations between P-glycoprotein activity, its expression in the liver, and estradiol level were revealed.

[P-glycoprotein: structure, physiological role and molecular mechanisms of modulation functional activity].

In the review of literature the structure, localization and a physiological role of efflux biobiotics and xenobiotics transporter - P-glycoprotein - is characterized, molecular mechanisms of induction and inhibition of its functional activity are systematized.

[Altered collagene characteristics and lysyl oxidase activity in lathyrism].

Experiments were carried out on rats with lathyrism, which was induced by adding semicarbazide (0.075%) into drinking water for 45 days. The data obtained show a 30% reduction in the body weight and an increase in.organ weight coefficients. Semicarbazide intake led to the pelvic limb paralysis, scoliosis, bone tissue degradation, cartilage growth, 46% decrease of the calcium level in the femur. It has been detected essential structural changes in extracellular matrix based on the collagen cross-links reduction. The activity of lysyl oxidase, a key enzyme for the collagen development, showed 5-fold decrease in the aorta tissues. The level of formaldehyde, a nonenzymic cross-links developer, has been measured in the liver tissue by the aldehyde trap (5,5-dimethyleyclohexane-1,3-dione) administration and then fluorimetric determination of formaldimedone. Under semicarbazide load, the formaldehyde level in the liver tissue was reduced by 47%. Therefore, semicarbazide influences not only the enzymic development of aldehyde groups in collagen, but the level of other aldehydes, which can cause cross-links. This experimental model of lathyrism is appropriate for investigation of the lysyl oxidase inhibitors effect on extracellular matrix.

[Modifying effect of low-molecular metabolities on the state of extracellular matrix of connective tissue of animals].

On the basis of complex approach to bone and haematopoetic tissue interaction the authors studied the influence of low weight metabolites on stromal fibroblasts and components of extacellular matrix of bone and skin (collagen and glycosaminoglycans). Specificity of different metabolites action on physico-chemical abilities of type I collagen, amino acid composition changes, surface charge, ratio of alpha- and beta-compounds, BrCN-fragments of alpha-1 component cross-links was shown. The dose dependence of formiate effect on processes of proteins glycosilation, cross-linking in bone and cartilage connective tissue and serum glycoproteins was established. The results obtained showed sensitivity of the bone tissue exstacellular matrix to influence of low-weight metabolites action at the level of post-synthetic modification of its components, their intermolecular interaction and process of osteogenesis.

[The sphincter-related biliodigestive anastomoses in anomalies of bile ducts]. / Zhomnye bilidigestivnye anastomozy pri anomaliiakh zhelchevyvodiashchikh putei.

The authors made an analysis of anomalies of the bile ducts with special reference to anatomical peculiarities and iatrogenic lesions of the bile ducts. The anomalies of bile ducts were found in 2.07% of 676 patients operated on for complicated cholelithiasis. Primary operative interventions and reoperations in the patients were completed with the formation of the constriction-biliodigestive anastomoses of different levels having antireflux functions. The authors describe the operation technique and results of the treatment of bile duct obstruction.

[State and prospects of demographic processes in the Udmurt Republic]. / Sostoianie i perspektivy demograficheskikh protsessov v Udmurtskoi Respublike.

Analyzes the time course of demographic indices in Udmurtia in recent years. Socioeconomic measures are offered, aimed at deceleration and arrest of the depopulation process.