Retrospective Analysis of Lipid-Lowering and Antiplatelet Therapy Regimen by Clinical Decision Support Service Based on Real-World Data from Electronic Medical Records "Intellect 3 Study".

Aim      To evaluate prescription of lipid-lowering and antithrombotic therapy in clinical practice and to compare differences in recommendations using the clinical decision support service (CDSS).Material and methods  Electronic medical records (EMR) of 300 patients from the Chazov National Medical Research Center of Cardiology, as well as from medical organizations controlled by the Department of Health of the Lipetsk Region and the Ministry of Health of the Voronezh Region, were analyzed for the period of August - December 2022, during the pilot implementation of CDSS. Retrospective information about the prescription of lipid-lowering and antithrombotic therapy from the EMR was compared with the CDSS guidelines under the expert supervision based on digitized clinical and laboratory profiles of patients. The study primary endpoint was a change in the initially prescribed lipid-lowering and / or antithrombotic therapy as per CDSS guidelines.Results Overall 292 patients were included in the final analysis; 46 (15.7 %) were from the primary prevention group and 246 (84.3 %) from the secondary prevention group. In group 1, the lipid-lowering therapy recommended by the CDSS differed by 50 % (p<0.001) from the baseline therapy recorded in the EMR. In the secondary prevention group, 78.9 % (p<0.001) differences were found in the lipid-lowering therapy recommended in the CDSS guidelines compared to the prescriptions in the EMR. In 76.8 % (p<0.001) of patients, antithrombotic therapy was significantly different from the baseline therapy in the EMR.Conclusion      The use of CDSS may improve the practice of choosing lipid-lowering and antithrombotic therapy for prevention of cardiovascular complications.

Clinical Characteristics and Factors Associated with Poor Outcomes in Hospitalized Patients with Novel Coronavirus Infection COVID-19.

Aim      To evaluate the clinical picture and factors associated with unfavorable outcomes in admitted patients with COVID-19.Material and methods This study included all patients admitted to the COVID Center of the National Research Center of Cardiology of the Russian Ministry of Health Care from May 1 through May 31, 2020. Clinical demographic, laboratory, and instrumental indexes and associated factors were studied with one-way and multivariate logistic regression analysis.Results This study included 402 patients aged 18 to 95 years (mean age, 62.9±14.6 years); 43.0 % of them were older than 65 years. COVID-19 was frequently associated with chronic comorbidities, including arterial hypertension (74.4 %), obesity (41.6 %), history of ischemic heart disease (12.9 %), atrial fibrillation (18.9 %), type 2 diabetes mellitus (DM) (13.0 %), and oncological diseases (9.2 %). 13.0 % of patients were smokers; less than 10% had chronic lung diseases. 3.9% of patients had a combination of COVID-19 and acute coronary pathology, including acute myocardial infarction (MI) in 3.2 % (13) and unstable angina in 0.7 % (3). The most frequent clinical manifestation of COVID-19 were four symptoms: cough (81.1 %), weakness (80.3 %), shortness of breath (71.6 %), and fever (62.7 %). 46.5% of patients had shortage of breath and chest pain/compression, 40.3% had headache, 31.1% had myalgia, 28.8% had anosmia, and 25.5% had ageusia. Arterial oxygen saturation was <93.0 % in 55.7 % of cases. According to laboratory blood tests the patients had anemia (58.2 %), lymphopenia (34.8 %), neutropenia (19.2 %), thrombocytopenia (11.9 %), and increased levels of high-sensitivity C-reactive protein (hsCRP, 87.3 %), interleukin-6 (89.3 %), ferritin (62.1 %), and D-dimer (49.2 %). 56.2% of patients required various regimens of oxygen support. 83 (20.6%) patients were admitted to intensive care and resuscitation units; invasive artificial ventilation was performed only for 34 (8.5 %) patients. In-hospital mortality was 7.7 % (31 / 402). One-way regression analysis identified major factors associated with death during the stay in the hospital: age >55 years, NEWS scale score >4.0, oxygen saturation <92.0 %, blood glucose >5.4 mmol/l, hs-CRP >25.7 mg/l, and creatinine clearance <72.0 ml/min. Furthermore, the risk increased with increasing degree of changes in each factor. According to results of the multivariate regression analysis, three most significant predictors of the hard endpoint, all-cause death during the stay in the hospital, were more than 5-fold increases in aspartate aminotransferase and/or alanine aminotransferase compared to normal levels (relative risk (RR) 16.8 at 95 % confidence interval (CI) 5.0-56.3, р<0.001), pronounced changes in the lungs consistent with a CT-4 picture as shown by computed tomography (CT) (RR 13.4; 95 % CI 3.9-45.5, р<0.001), and MI/unstable angina during the stay in the hospital (RR 11.3; 95 % CI 1.4-90.6, р=0.023). The probability of death was also considerably increased by chronic obstructive pulmonary disease, impaired kidney function (creatinine clearance estimated by Cockcroft-Gault <60.0 ml/min), type 2 DM, oncological diseases, and dementia.Conclusion      This study established factors associated with unfavorable outcomes in admitted patients with COVID-19. This will allow identifying in advance patients with a high risk of complications that require increased attention to take more active diagnostic and therapeutic measures at prehospital and hospital stages.

[The Diagnostic Accuracy of Exercise Treadmill Testing and Stress Echocardiography for the Detection of Obstructive Coronary Artery Disease in Patients Aged ≥ 70 Years].

AIM: to compare diagnostic accuracy of exercise treadmill testing and stress echocardiography in the diagnosis of stable coronary artery disease (CAD) in patients aged >70 years. MATERIALS AND METHODS: The study included 390 patients aged >70 years with suspected stable ischemic heart disease, who underwent elective coronary artery angiography (CAG). Exercise treadmill testing (ETT) according to the modified Bruce protocol was carried out in 189 patients (48 %), bicycle stress echocardiography - in 179 patients (46 %). Initially we determined the prevalence of angiographically significant CAD according to the gender and chest pain character, and identified persons in whom stress testing was appropriate. After that diagnostic accuracy of both tests was evaluated in patients with atypical angina and non-anginal chest pain. RESULTS: Among 72 patients with atypical angina and non-anginal pain who underwent ETT and had unequivocal results, 38 (53 %) had obstructive CAD. ETT for detection of obstructive CAD had sensitivity 79 %, specificity 82 %, positive likelihood ratio (LR+) 4.4, and negative likelihood ratio (LR-) 0.3. Positive result increased probability of obstructive CAD from 53 % to 83 %, negative result reduced probability of obstructive CAD to 25 %. Among 111 patients with atypical angina and non-anginal pain who underwent stress echocardiography and had unequivocal results, 69 (62 %) had obstructive CAD. Sensitivity, specificity, LR+, and LR- of stress echocardiography were equal to 89 %, 95 %, 17.8, and 0.1, respectively. Positive result increased probability of obstructive CAD from 62 % to 95 %, negative result reduced probability of obstructive CAD to 16 %. CONCLUSION: bicycle stress echocardiography was found to be more accurate than ETT to rule in or rule out obstructive CAD in patients aged ≥ 70 years with atypical angina and non-anginal pain.

[Effect of minor bioactive food substances ­ rutin and hesperidin in their separate and combined alimentary arrives on the immune system of rats and the activity of nuclear factor NF-kB liver cells].

The effect of rutin and hesperidin in their separate and combined admission to the immune system and the activity of nuclear factor NF-kB of rat liver cells has been investigated. Wistar male rats with an initial body weight of 224­225 g were divided into 4 groups of 6 rats in each. The rats of the 1st group (control) received a complete semi-synthetic diet, rats in group 2 ­ the same diet supplemented with rutine (400 mg/kg b.w.); the rats of group 3 ­ with the addition of hesperidin (400 mg/kg bw); group 4 ­ with the addition of rutin and hesperidin (400 mg/kg b.w. each) for 14 days. Animals received feed in free access mode in an amount of 25­30 g per rat per day, that corresponded to 15 g of dry formula. Animals received water also in free access. It has been found that rutin and hesperidin, included in the diet of rats both alone (groups 2 and 3) and together (group 4), have immunomodulatory impact which is a reduce of lymphocyte relative content [1st gr. ­ 70.55±1.58%, 2nd gr. ­ 63.62±2.85%, 3rd gr. ­ 62.03±3.16% (p1­3<0.05), 4th gr. ­ 65.75±1.08% (p1­4<0.05)] and an increase of percentage of neutrophil leukocytes [1st gr ­ 19.98±0.97%, 2nd gr. ­ 25.35±3.14%, 3rd gr. ­ 28.27±3.30% (p1­3<0.05), 4th gr. ­ 24.15±1.52% (p1­4<0.05)] and NK-cells in the peripheral blood [1st gr. ­ 3.29±0.45%, 2nd gr. ­ 6.91±0.70% (p1­2<0.05), 3rd gr. ­ 5.88±0.79% (p1­3<0.05), 4th gr. ­ 4.64±0.32% (p1­4<0.05)], that can be considered as a shift in the direction of innate immunity factors. In addition, the combined effect of high doses of rutin and hesperidin led to a change in erythrocyte parameters: an increase in the average volume of red blood cells [1st gr. ­ 56.00±1.06 fl, 2nd gr. ­ 56.67±0.42 fl, 3rd gr. ­ 58.50± 0.99 fl, 4th gr. ­ 59.50±0.99 fl (p1­4<0.05)], and the average content of hemoglobin [1st gr. ­ 18.97±0.45 pg, 2nd gr. ­ 19.10±0.19 pg, 3rd gr. ­ 19.73± 0.32 pg, 4th gr. ­ 20.08±0.33 pg (p1­4=0.07)], as well as increase in the level of TGF-ß1 in peripheral blood [1st gr. ­ 15.55±2.13 ng/ml, 2nd gr. ­ 14.81± 2.36 ng/ml, 3rd gr. ­ 17.02±2.53 ng/ml, 4th gr. ­ 22.14±2.29 ng/ml (p1­4<0.05)] and the expression of nuclear factor NF-kB in the liver cells [1st gr. ­ 16.10± 0.60 ng/ml; 2nd gr. ­ 15.14±2.28 ng/ml; 3rd gr. ­ 15.85±2.09 ng/ml; 4th gr. ­ 20.49±1.68 ng/ml (p1­4<0.05)].

Broadly Reactive Nanobody Targeting the H3 Hemagglutinin of the Influenza A Virus.

Monoclonal antibodies and recombinant antibody fragments are a very promising therapeutic tool to combat infectious diseases. Due to their unique paratope structure, nanobodies (VHHs) hold several advantages over conventional monoclonal antibodies, especially in relation to viral infections. Influenza A viruses (IAVs) remain a major threat to public health. The hemagglutinin (HA) protein is the main protective and immunodominant antigen of IAVs. In this study, three broadly reactive nanobodies (D9.2, E12.2, and D4.2) to H3N2 influenza strains were isolated and Fc-fusion proteins (VHH-Fcs) were obtained and characterized in vitro. This modification improved the nanobodies' binding activity and allowed for their interaction with a wider range of strains. The D9.2-Fc antibody showed a 100% protection rate against mortality in vivo in a mouse lethal model. Furthermore, we demonstrated that the observed protection has to do with Fc-FcγR interactions. These results indicate that D9.2-Fc can serve as an effective antiviral agent against the H3N2 influenza infection.

[Assessment of consistency of technological process using control cards on the example of analysis of information on immunogenic activity of pertussis component of DTP vaccine].

AIM: To assess the consistency of technological process of manufacture of DTP vaccine's pertussis component on the basis of its immunogenicity using Shewhart's cards. MATERIALS AND METHODS: Published data of domestic plants belonging to public corporation Mechnikov "Biomed" and Ufa branch of scientific-production organization "Immunopreparat" ingressed in "Microgen" enterprise were used. Immunogenicity of DTP vaccine pertussis componentwas studied. RESULTS: It was revealed that technological process of manufacturing of DTP vaccine's pertussis component on production plants was not always in statistically controlled state. CONCLUSION: Obtained data showed that it is reasonable for quality control departments of manufacturing plants to use Shewhart's cards and methods of statistical management of technological processes for assessment of state of the latter.

[Prophylaxis of pertussis: development and use of acellular pertussis vaccine].

Modern data substantiating the expediency of the use of acellular pertussis vaccine were analyzed. Serious postvaccinal complications caused by the action of the corpuscular pertussis component of adsorbed DPT vaccine served as the basis for the development of acellular pertussis vaccine (APV). During the period of 1990-1996 as many as 8 international field trials of the effectiveness of APV were carried out. The results of these trials and studies were evaluated in accordance with the unified programs and criteria. The vaccines under test differed by the composition of Bordetella pertussis purified antigens they contained, the methods of their purification and the detoxification of pertussis toxin. All tested APV, with the exception SKB-2, possessed pronounced prophylactic activity.

[To 20-years anniversary of Chernobyl catastrophe: an attempt to study the vitamin, calcium, iron and selenium status of children and adult population in Slavutich and to correct elicited deficiencies].

The article concisely illustrates the vitamin and mineral state of population of town of Slavutich, including personal of Chernobyl Nuclear Power Station, children of pre-school age and pregnancy women, studied in 1992. Vitamins and minerals deficiency in the main of C and B vitamins and selenium was revealed in all the studied groups. Appropriate measures were developed and introduced to eliminate the detected dusturbances; but however some unsolved problems remained. Taking into account the forthcoming 20th anniversary of Chernobyl disarter, the authors of the come back to considering the obtained data in hope to atlract attention of medical scientific and public to the remained unsolved problems of micronutrient deficiency.

[Evaluation of the stability of pertussis vaccine OCO-3 standard]. / Otsenka stabil'nosti standarta kokliushnoi vaktsiny OCO-3.

The evaluation of the immunogenic activity and residual toxicity of the National Standard of pertussis vaccine (OCO-3) was carried out. As shown by observations lasting for a period of 25 years, the preparation possesses stable immunogenicity and its toxicity remained unchanged, which makes it possible to use OCO-3 for the routine control of the pertussis component of commercial lots of adsorbed DPT vaccine.

[Dynamics of the level of antibodies to protein antigens of the Meningococcus serogroup A in the serum of patients with meningococcal infection]. / Dinamika urovnia antitel k belkovym antigenam meningokokka serogruppy A v syvorotke bol'nykh meningokokkovoi infektsiei.

Two characteristics were determined in the sera of patients by means of radioimmunoassay (RIA) techniques: the RIA titer and the characteristic indicating the presence of highly avid antibodies in the serum. This investigation revealed that in the sera of patients with meningococcal infection of moderate severity the values of the RIA titer of IgM, IgG and IgA, as well as the values indicating the levels of highly avid IgM, IgG and IgA, increased as the infection progressed. In patients with the severe form of meningococcal infection the values of the RIA titer of IgA and IgA increased, while the RIA titer of IgG remained practically unchanged. No dynamic changes in the characteristics indicating the presence of highly avid antibodies in the serum were observed.

[A radioimmunological method for determining IgA-class antimeningococcal secretory antibodies in human saliva]. / Radioimmunologicheskii metod opredeleniia antimeningokokkovykh sekretornykh antitel IgA-klassa v sliune cheloveka.

The data on the content of secretory IgA antibodies to group A Neisseria meningitidis protein antigen in the saliva of persons, both having had contact with N. meningitidis culture and having had no such contact, are presented. The results were obtained by the method of radioimmunoassay, developed specially for the determination of N. meningitidis protein antigen.

[Local immunity in acute dysentery. II. The content of antibody-forming cells in the large intestine mucosa in acute Flexner dysentery in the dynamics of the disease]. / O mestnom immunitete pri ostroi dizenterii. Soobshchenie II. Soderzhanie antiteloobrazuiushchikh kletok v slizistoi tolstoi kishki u bol'nykh ostroi dizenteriei Fleksnera v dinamike zabolevaniia.

Antibody-forming cells were detected in the large intestine of patients with acute Flexner's dysentery by means of the modified Jerne - Nordin method of hemolysis in agar. This method allowed one to determine the classes of immunoglobulins produced by the cells contained in tissue microspecimens obtained by the biopsy of the intestinal mucosa. The maximum amount of antibody-containing cells could be detected on days 7-12 of the disease. The content of antibody-forming cells was shown to depend on the severity of dysentery, the duration of the disease and the therapeutic methods used in the process of treatment. IgA was found to be the most frequent antigen type.

[Evaluation of the reactogenicity and immunogenic potency of combined vaccine "Bubo-Kok" in the immunization of children against diphtheria, tetanus, pertussis and viral hepatitis B]. / Otsenka reaktogennosti i immunogennosti kombinirovannoi vaktsiny "Bubo-Kok" pri immunizatsii detei protiv difterii, stolbniaka, kokliusha i virusnogo gepatita B.

Combined vaccine "Bubo-Kok" is characterized by safety and high immunological activity. The number of postvaccinal reactions in children aged 1 and 2 years, immunized with vaccine "Bubo-Kok", was not statistically different from those in groups of children immunized with adsorbed DPT vaccine, as well with such vaccine in combination with vaccine against hepatitis B. After the completion of the primary course of immunization 100% of children had protective antibody titers against diphtheria, tetanus and hepatitis B. Antibody titers against pertussis, equal to or exceeding protective titers, were found in more than 70% of immunized children. The immunogenic potency of vaccine "Bubo-Kok" with respect to all its components was not inferior to that of adsorbed DPT vaccine and vaccine against hepatitis B, when introduced simultaneously in different areas of the body. Vaccine "Bubo-Kok" successfully passed state trials and was recommended for registration.

[Riboflavin metabolism in diabetes mellitus]. / Osobennosti obmena riboflavina pri sakharnom diabete.

Riboflavin excretion with urine in children suffering from diabetes mellitus is found to be significantly higher in comparison with healthy adults, the riboflavin content in the serum being normal. The total riboflavin concentration in erythrocytes is substantially lower and administration of daily-required riboflavin doses does not increase this parameter. FAD-dependent glutathione reductase in erythrocyte hemolysates is approximately 1.5 times higher than that of healthy children and does not depend on the additional intake of polyvitamins. The seeming affinity of the enzyme with exogenous FAD in sick children is almost 40 times lower in comparison with this value in healthy children, that is why the FAD-effect value in diabetes mellitus children does not exceed 1.2. Peculiarities of the riboflavin metabolism at diabetes mellitus and possibility to use the investigated parameters as criteria of vitamin B2 supply are discussed.

[Experimental vitamin D deficiency with different dietary calcium-phosphorus ratios]. / Eksperimental'naia nedostatochnost' vitamina D pri razlichnom sootnoshenii kal'tsiia i fosfora v ratsione.

Excess of phosphorus (the ratio Ca : P = 1 : 2) in a diet of growing rats strengthened such manifestations of vitamin D insufficiency as hypercalcemia and inhibition of animal growth. The data obtained suggest that excess of phosphorus is apparently important for pathogenesis of rachitis and the optimal ratio Ca : P should not be ignored in child diet.

[Effect of 1 alpha-hydroxycholecalciferol and of a varying phosphorus requirement on mineral metabolism in chronic renal insufficiency]. / Vliianie 1 al'fa-oksikholekal'tsiferola i razlichnogo potrebleniia fosfora na mineral'nyi obmen pri khronichskoi pochechnoi nedostatochnosti.

Experimental chronic kidney insufficiency caused in rats the impairments of phosphoerus-calcium turnover (hyperphosphatemia and hypocalcemia), osteoporotic alterations in bones (decreas in specific gravity, in content of Ca, P and hydroxyproline) as well as calcinosis of internal tissues, particularly in the impaired kidney tissue. Decrease in phosphorus content of food down to 0.3% inhibited distinctly the development of these impairments and modulated their severity, lowering mortality of the animals with chronic kidney insufficienty. Administration of physiologic doses (0.025 mg) of 1 alpha-hydroxy vitamin D3/(1 alpha OHD3) which is a synthetic analogue of 1,25-dihydroxycholecalciferol (hormonal form of vitamin D synthesized in kidney) into rats with chronic kidney insufficiency (with limited content of phosphorus in the food) did not exhibit any additional curative effect on the patterns of bone metabolism studied; in this case calcinosis was slightly increased and mortality of the animals also increased. After administration of 1 alpha OHD3 into rats with chronic kidney insufficiency, maintained on food containing 1.2% of phosphorus, impairments in phosphorus-calcium turnover were distinctly increased. Osteoporosis and calcinosis were elevated in the impared kidney; this led to death of all the animals within first 2 months of the experiments.

[Metabolism of 25-hydroxyvitamin D3 in the kidney and nuclear receptors of 1,25-dihydroxyvitamin D3 in small intestine mucosa of rats with vitamin B2 deficiency]. / Obmen 25-oksivitamina D3 v pochkakh i iadernye retseptory 1,25-dioksivitamina D3 v slizistoo obolochke tonkoi kishki u krys pri nedostatochnosti vitamina B2.

Effect of vitamin B2 deficiency on metabolism, reception and biochemical functions of vitamin D was studied in young rats. Deficiency in vitamin B2 was shown to cause a moderate hypocalcemia as well as a decrease in the active transport of calcium in small intestine and in concentration of 25-OH D in blood serum, lowered formation of 24,25 (OH)2D3 in kidney slices and decreasing content of nuclear receptors for 1,25 (OH)2D3 (fre and bound in vivo) in small intestine mucose. After administration of cholecalciferol into the animals deficient in vitamins D and B2 within 24 hrs or 6 days before death restoration of the calcium metabolism parameters was retarded as a result of less distinct stimulation of I-hydroxylase and of low activity of 24-hydroxylase 25-OH D3 in kidney as well as due to a moderate increase in content of bound receptors of 1,25 (OH)2D3 in small intestine mucose and, apparently, because of reduced production of the proteins dependent on vitamin D in the tissue (Ca2+-ATPase and alkaline phosphatase). The data obtained suggest the possible importance in rickets of vitamin B2 deficiency mediated via its influence on metabolism and reception of vitamin D.

[Comparison of biochemical criteria for supplying the human body with riboflavin]. / Sravnenie biokhimicheskikh kriteriev obespechennosti organizma cheloveka riboflavinom.

Various biochemical procedures were used in evaluation of vitamin B2 occurrence in 38 women. Highly specific procedures for evaluation of riboflavin in blood and urine (high performance liquid chromatography, titration with riboflavin-binding apoprotein, lumiflavin procedure) enabled to detect correlation between values of FAD-effect and excretion of riboflavin with urine as well as of total riboflavin content in erythrocytes, between concentration of free riboflavin in blood plasma and its excretion with urine. All the procedures studied were equally suitable for evaluation of vitamin B2 deficiency as shown by the data obtained as well as by similarity in values of low concentrations which corresponded to normal availability of the vitamin.

[Metabolism of riboflavin and B group vitamins functionally bound to it in insulin-dependent diabetes mellitus]. / Obmen riboflavina i funktsional'no sviazannykh s nim vitaminov gruppy Bpri insulinzavisimom sakharnom diabete.

In 35 children of 9-13 years old with insulin-dependent diabetes mellitus distinct alterations in metabolism of vitamin B2 were detected, which were manifested as elevated rate of riboflavin excretion with urine and a decrease in the vitamin content in erythrocytes, as 1.5-fold increase in activity of erythrocyte glutathione reductase and augmented affinity of erythrocyte glutathione reductase to exogenous FAD. Alterations in metabolism of riboflavin did not involve the vitamin deficiency as shown by analysis of vitamins B6 and PP (4-pyridoxic acid and I-methyl nicotinamide, respectively) excretion with urine as well as by study of the coenzymes content in blood of healthy and sick children with various rates of riboflavin consumption. Rates of 4-pyridoxic acid and I-methyl nicotinamide excretion with urine were similar both in healthy children of 9-13 years and in children of this age with diabetes mellitus. The data obtained suggest that rates of riboflavin consumption in patients with diabetes mellitus differed from those of healthy persons; these reasons should be taken into consideration in evaluation of vitamins B2 consumption in patients with diabetes mellitus.

[Comparative evaluation of biological activity of 1 alpha,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol in rats]. / Sravnitel'noe izuchenie biologicheskoi aktivnosti 1 alpha,25-dioksikholekal'tsiferola i 24,25-dioksikholekal'tsiferola u krys.

Deficiency of vitamin D in rats led to impairment of Ca2+ absorption in intestine, hypocalcemia, decrease in specific weight of femur diaphyses, decrease in content of Ca2+ and in the ratio Ca2+/hydroxyproline in diaphyses and epiphyses. These patterns were normalized after daily administration of cholecalciferol (vitamin D3) at a dose of 500 ng (20 IU) into rats within 5 days. I alpha, 25-dihydroxycalciferol at a daily dose of 30 ng stimulated absorption of Ca2+ in intestine, increased the specific weight of diaphyses and content of Ca2+ in diaphysis, but content of Ca2+ in blood and epiphyses was not normalized. Increase in 1,25 (OH)2D3 dose up to 300 ng caused a decrease in the rate of mineralization of diaphyses and epiphyses with simultaneous elevation of the Ca2+ content in blood. 24, 25-dihydroxycalciferol at a dose of 250 ng stimulated effectively both diaphyses and epiphyses mineralization, at the same time the effect was also maintained after 10-fold increase of the dose.