The review of the currently existing projects focused on calculating the reference intervals of blood parameters in large samples of children of different gender and age discusses the urgent issues of calculating pediatric reference intervals of biochemical markers, the paper provides comparison of the reference intervals established within the framework of different projects. The limitations, future prospects and harmonization of pediatric reference intervals, including for juvenile athletes, are provided.
There is an inextricable link between exploration and development of the Arctic territories and emergence of associated problems of medical and biological nature. It is necessary to design and develop emergency care and prevention drugs and medical devices for use in the Arctic. This review presents an analysis of additional requirements for drugs intended for the Far North and compares methods of modeling extreme conditions in animals. We outline medical and biological problems of the region highlight key areas of Arctic pharmacology: choice of pharmaceutical form, use of cryoprotectants and design of adaptogens. The study mainly revolves around the search for information on modeling extreme environmental factors in animal experiments, as this is a key stage in preclinical studies of drugs for the Arctic medicine. We present the relevant directions of further work promoting the subject: development of the hypoxia and hypothermia assessment criteria, development of modeling methods employing large laboratory animals, improvement of the equipment used.
As markers of intoxication, adducts of blood proteins with organophosphorus compounds (OPs) allow establishing the fact of poisoning and, furthermore, enable identification of the OPs by the attached residue. This study aimed to develop a method of specific and selective extraction of blood protein adducts carrying OPs on the surface of a matrix-assisted laser desorption/ionization (MALDI) target functionalized with multimolecular structures based on lanthanum stearate using metal affinity chromatography. We have shown the ability of adsorbent to retain both full-size and dealkylated adducts of blood proteins with OPs. The developed method allowed extraction and identification of peptides of human serum albumin and human butyrylcholinesterase modified with various OPs (after incubation of human blood plasma with OPs in concentrations from 1 to 100 ng/mL), which makes this approach applicable for the purposes of OPs identification in the context of investigation of real cases of intoxication.
Reproductive organ transplantation was considered as a potential method for treatment of the ovarian factor, tubal factor, and uterine factor infertility before the advent of advanced assisted reproductive technologies. Uterus transplantation can be considered as the method for treatment of absolute uterine factor infertility similar to transplantation of non-vital organs. However, the clinical use of uterus transplantation in humans causes a lot of problems. The study was aimed to develop a program for assessment of various surgical tissue revascularization techniques for restoration of reproductive function in experimental animals with uterine factor infertility. Chinchilla rabbits (n = 20) were selected for experiments because of the fact that all mammals have similar structure of the organs. The innovative technique involving the use of ovarian arteries instead of uterine arteries (as in the standard protocol) was used in laboratory animals to develop the surgical protocol for transplantation of reproductive tissues. The animal study results show that hemodynamic characteristics of blood supply to the transplanted uterus remain unchanged. This makes it possible to use the surgical method in the experiments on the uterus transplant from a deceased donor. The proposed uterus transplantation protocol ensures high transplant survival rate and normal blood supply to the transplant, along with the reduced risk of injury to the donor and reduced complexity of the surgical procedure.
Mathematical modeling is a promising method enabling in silico calculations with subsequent suggestion of cell membrane protective agents used to reduce the consequences of exposure to hydrogen sulfide-containing gas in emergency situations. This study aimed to investigate the nature of interaction of hydrogen sulfide (H2S) and N-Acetyl-L-Cycteine (NAC) with the components of cell membranes. We built a mathematical model of interatomic interactions of cell membrane components with H2S and NAC (two separate models), then made the quantum-chemical calculations using our proprietary technique and set up GAMESS Z-matrices reflecting type and position of atoms in the molecules. The structure of the molecules was optimized with the help of MOPAC package built into ChemOffice. Lecithin-based liposomes in a sulfide solution (with Na2S being the donor of H and HS ions) were used as an experimental model of the biological membrane. Redox potential in mV was the comparison parameter in assessment of interaction of the H2S system components and NAC with phospholipid. The results include patterns showing the phospholipid reactive centers blocked by NAC under toxic exposure to H2S. Liposomal models of cell membranes were formed and redox parameters measured. Biological experiment confirmed the acceptable accuracy of the designed method of calculation of intermolecular interactions when used as a basis for further selection of agents capable of adjusting toxic doses of hydrogen sulfide. Membrane models of H2S interaction with protein and lecithin were visualized in silico and in vitro. The possibility of using NAC as an H2S inhibitor has been confirmed.
Assessment of individual responses of cells, tissues and the whole body to radiation exposure is an important challenge for radiobiology and radiation safety. The study was aimed to develop the method for estimation of the human hematopietic stem cell (HSC) individual response in the humanized mouse model. The cord blood or peripheral blood HSCs were administered to the NOD SCID immunodeficient mice. The number of maturing HSCs (CD34+ cells) and mature CD45+ leukocytes was assesed after the acute gamma exposure to the doses of 0.5 Gy, 1 Gy, and 1.5 Gy, along with the HSC share among all CD45low/+ cells within three days (period of maximum mortality) and 14 days (period of active restoration) after exposure. The relationship between the indicato values and the exposure dose was calculated by regression analysis. There was exponential relationship between the human HSC survival rate in humanized mice and the dose on day three after exposure (R2 = 0.93; F = 211; p < 0.01), while the relationship between the number of HSCs and the dose on day 14 after exposure was linear (R2 = 0.65; F = 12.9; p = 0.01). The C14/3 coefficient calculated as a ratio of the HSC share among all human CD45low/+ cells on day 14 after exposure to the same parameter on day three after exposure was proposed as an indicator of HSC mortality and HSC number restoration. C14/3 negatively correlated with the exposure dose (R2 = 0.57; F = 13.3; p = 0.004), it was higher in radioresistant mice and the model of cysteamine-induced radioresistance in humanized mice. The model mice humanized using the peripheral blood HSCs can be used to assess individual HSC response to acute external gamma exposure based on C14/3 and the data on the HSC survival and restoration.
Organization of training in the context of COVID-19 pandemic demanded the development and implementation of active epidemiological surveillance for acute respiratory infections in students and teaching staff of the Medical University. The study was aimed to identify the features of the COVID-19 epidemic process among students and teaching staff in 2020–2022. The analysis of COVID-19 incidence among students and teaching staff in the academic years 2020–2021 and 2021–2022 was carried out. The study was conducted on 6293 students enrolled in the academic year 2020–2021, 6148 students enrolled in the academic year 2021–2022, and 772 teaching staff members. In the academic year 2020–2021, COVID-19 was detected in 681 students, among whom the cumulative incidence (CI) was 10.83 (95% CI: 10.08-11.61) per 100 students, and 79 teaching staff members, among whom the CI was 10.23 (95% CI: 8.09–12.37); in the academic year 2021–2022 infection was detected in 690 students, the CI was 11.44 (95% CI: 10.64–12.24) per 100 students, and 75 teaching staff members, the CI was 9.71 (95% CI: 7.62%–11.80%). In 26.3% affected individuals, COVID-19 was detected when contacting the University outpatient clinic. The incidence among students living in the dormitories did not exceed that among students living in private apartments (p = 0.36), and no outbreaks were reported. There was a strong positive correlation between the incidence among residents of St. Petersburg and the incidence among students (r = 0.77). Over the entire period, probable setting of transmission was determined in 39.9% of infected individuals, contact most often (15.2%) occurred when working in the health care facilities. The incidence of novel coronavirus infection (COVID-19) among students and teaching staff members in the academic years 2020–2021 and 2021–2022 is directly related to their involvement in the COVID-19 epidemic process in St. Petersburg.
Chronic hepatitis B (CHB) is a common infectious disease that represents one of the main causes of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). CHB is still difficult to treat due to the lack of drugs that completely eliminate hepatitis B virus (HBV) from hepatocytes. The study was aimed to describe the CHB clinical and laboratory features, assess the efficiency of antiviral therapy and identify the factors associated with the response to antiviral therapy. The results of clinical and laboratory assessment, instrumental examination, serological and molecular testing of the patients (n = 201) followed up between 2007–2021 in the Viral Hepatitis Diagnosis and Treatment Center at the Clinical Hospital No. 85 of FMBA of Russia were assessed based on primary sources. Most of the patients in the group were males (56.7%); the HBeAg-negative patients predominated (93%). LC was diagnosed in nine patients (4.5%), among them one patient had HCC. The HBV D genotype was determined in 95.4% of cases, А genotype in 3.1% of cases, and С genotype in 1.5% of cases. After a year of treatment with the nucleos(t)ide analogues (entecavir or tenofovir) 88% of patients showed no viremia and their biochemical parameters were back to normal (88%). The overall seroconversion rate was 41.7% for HBeAg and 3% for HBsAg. Thus, high rates of virological response and enzyme activity normalization were obtained. Low baseline viremia level is an independent prognostic factor of achieving a virological response. The HBsAg level in the end of therapy makes it possible to predict relapse after the treatment cessation.
ISSN 2713-2765 (Online)