The role of the metabolic status of lymphocytes in the pathogenesis of rheumatoid arthritis

Objective: to study in dynamics metabolic changes in lymphocytes on the model of adjuvant-induced rheumatoid arthritis (RA) in warm-blooded animals.Material and methods. The RA model was elicited by administering Freund's complete adjuvant (AF) to male Wistar rats. Lymphocyte metabolism was corrected with a mixture of citric and succinic acids, which was injected for 4 weeks (at doses of 17 and 88 mg/kg body weight) from the first day of model formation. Animals of the control group were injected subcutaneously with isotonic sodium chloride solution. The total number of leukocytes, the size of lymphocytes and the activity of lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in these cells were determined. Changes in the musculoskeletal system were assessed radiographically and actometrically in the «open field» model.Results and discussion. In the first 2 weeks of the experiment in the model group, an increase in the level of leukocytes by 65% compared to the control (p=0.002) was noted, an increase in the activity of lymphocytes SDH by 51% and a decrease in the total («horizontal») mobility of animals by 30% were also revealed. Subsequently, the level of leukocytes decreased by 25%, the activity of LDH and SDH – by 38%, the radius of lymphocytes – by 14% (p<0.01). The action of carboxylic acids was dose-dependent: at the maximum dose, no statistically significant differences in the total number of leukocytes, LDH and SDH activity in lymphocytes, as well as their sizes were found between the group with adjuvant- induced RA and the control group.Conclusion. In animals with adjuvant-induced RA, correction of the metabolic status of lymphocytes with a mixture of citric and succinic acids, which are key substrates of the Krebs cycle, led to a decrease in structural damage of musculoskeletal system and, as a consequence, to the maintenance of normal range of motion.

PSVI-18 Efficiency of the use of ultrafine particles of silicon dioxide in the synchronization scheme of estrus of heifers

The intensification of the reproduction of a herd of cattle requires the use of highly effective synchronization schemes for estrus. All schemes available today give a low percentage of fertilization with frontal insemination. The aim of this study was to assess the effect of ultrafine particles of silicon dioxide on fertility and the level of sex hormones in heifers during synchronization of sexual heat with subsequent frontal insemination. Ultrafine particles of silicon dioxide were injected in isotonic sodium chloride solution. The synchronization scheme included two-fold application of prostaglandin preparations; blood was taken from under the tail vein to determine the hormonal status on days 1, 11, and 14 of the experiment. The results of the study showed that ultrafine particles of silicon dioxide had a positive effect on the level of sex hormones. Concerning progesterone, the difference between the values of increase in the level in the experimental and control groups was 112.1% (P ≤ 0.01) on the 11th day. On the 14th day of the experiment, the difference between the values of the decrease level was 19.6% (P ≤ 0.05). Follicle-stimulating hormone increased by 9.1% (P ≤ 0.05) by the 14th day of the experiment compared with the previous value. In the heifers of the experimental group, the excess was more significant, i.e.15.4% (P ≤ 0.05); the level of luteinizing hormone in the experimental group on the 14th day of the experiment exceeded the level of the control by 31.1% (P ≤ 0.05). According to the results of the examination for pregnancy, an increase in fertility was revealed by 20.0% in the experimental group in comparison with the control group. This study demonstrates the potential of using ultrafine silica particles in estrus synchronization schemes for heifers to increase heifer fertility. The research was carried out in accordance with the research plan for 2019–2021. FGBNU FSC BST RAS (No. 0761-2019-0006).

COMPARATIVE CHARACTERISTICS OF CHANGES IN HEMO - AND LYMPHOMICROCIRCULATORY VESSELS OF ILEUM ACCUMULATED LYMPHOID NODES OF RATS IN THE CASE OF APPLICATION OF INFUSION SOLUTIONS IN EXPERIMENTAL BURN DISEASE

Relevance. Thermal burns of the skin cause the development of burns, the main factor of which is endogenous intoxication. The infusion of detoxification solutions is a mandatory component of the treatment of burns, as it corrects its course and prevents the development of certain stages and complications. According to the stage of the burn disease and the different direction of its links in its pathogenesis, infusion therapy should not only restore water-electrolyte balance and detoxify the body, but also contribute to the normalization and stabilization of vital (including immune) body functions. Objective: study of changes in the vessels of the hemo- and lymphomicrocirculatory system of Peyer's patches in burnt rats at the stages of burn disease, under conditions of intravenous infusion of isotonic sodium chloride solution and combined colloidal-hyperosmolar solutions (lactoprotein and sorbitolum). Materials and methods. The experiment was performed on 72 white rats. Experimental animals were divided into 4 groups (18 animals in each group). I, II, III - rats with skin burn trauma, which received a separate infusion of isotonic sodium chloride (I), lactoprotein with sorbitol (II) and hecoton (III), at a dose of 10 ml / kg. IV - intact animals (control group). Simulation of burn disease was performed by inflicting burn injury by applying to the lateral surfaces of the body of animals four copper plates, which were previously kept for 6 minutes in water with a constant temperature of 100 ° C. Histological and electron microscopic examination were performed. Light microscopy was used. Results. Intravenous administration of the applied infusion solutions caused various phase changes of the hemo- and lymphomicrocirculatory tract of Peyer's patches of the ileum of burnt rats, depending on the applied solution. In the case of infusion of burnt rats with 0.9% sodium chloride solution, the negative effects of burn disease were exacerbated, which were manifested by damage to the vascular wall of the hemo- and lymphocapillary channels, resulting in plasma and lymph seepage through the affected areas into the perivascular space. This process was accompanied by a violation of the rheological properties of blood, the formation of edema. The established "membrane-plastic effect" of lactoprotein with sorbitol revealed clear organ-specific features, which had manifestations of penetration through the damaged wall of microvascular electron-dense impregnations, which contributed to a significant thickening of the basement membrane in the wall of the blood capillary formation and its gradual formation of rounded membranous structure. This structure of variable electron density not only strengthened the vascular wall, but also served as a closure, helping to close the vascular lumen at the site of largest damage. The difference between the perinodal lymphatic capillaries in burnt rats infused with lactoprotein and sorbitol is characterized by the phenomenon of "overflow" of the lymphocapillary channel with cells in different functional states. In the case of infusion of hecoton solution, the effect of "overflow" of the lymphocapillary channel was not observed, which indicates adequate implementation of the immune function of immunocompetent cells. Conclusions. Intravenous infusion of colloid-hyperosmolar solutions causes various changes in the hemo- and lymphomicrocirculatory tract of Peyer's patches. Infusion of a 0.9% sodium chloride solution leads to a deepening of the negative consequences of burn disease, which manifests itself in the form of damage to the vascular wall of the hemo- and lymphocapillary channels. Infusion of solutions of lactoprotein with sorbitol and hecoton helps to preserve the vascular wall of the nodular lymphatic capillaries. When a solution of lactoprotein with sorbitol is applied around the damaged vessels of blood capillaries and venules, annular membrane formations are formed, which promote selective recirculation of structurally intact lymphocytes.

Exogenous surfactant in the late respiratory phase of COVID-19

The article presents data on the course of inhalations with a native surfactant administered in two patients (66 and 53 years old) at the late respiratory phase of the new coronavirus infection of COVID-19 (the 22nd and the 19th days from the disease onset) who received non-invasive artificial lung ventilation.Subjects and methods. For inhalations, an AeroNeb™ micropump nebulizer was used; for one inhalation, 75 mg of surfactant-BL was dissolved in 5 ml of isotonic sodium chloride solution. The treatment course included 5 days with 2 inhalations a day.Results. In both patients, upon the end of this therapy with the native surfactant, regression of respiratory failure was noted, the level of respiratory support was reduced to insufflation with humidified oxygen, and rehabilitation measures were started with subsequent discharge from the hospital.

Effects of Granisetron on Spinal Anesthesia-induced Hypotension

Objective: It was aimed to evaluate the effect of intravenous (IV) granisetron used for nausea and vomiting prophylaxis on hypotension and bradycardia caused by spinal anesthesia. Methods: 120 ASA 1-2 patients undergoing elective surgery under spinal anesthesia were randomly divided into Group G (Ganisetron; n=60) and Group P (Placebo; n=60) groups. Five minutes before spinal anesthesia, Group G received 1 mg intravenous granisetron diluted in 10 mL of isotonic sodium chloride solution and Group P received 10 mL of isotonic sodium chloride solution. Spinal anesthesia with hyperbaric bupivacaine 0.5%, 15 mg at the level of L4-5 was applied for both groups. Hemodynamic data, sensory and motor block parameters were recorded before and after spinal anaesthesia every 5 minutes during 20 minutes of surgery. Results: There was no difference in the demographic data of both groups. Although hemodynamic data showed a decrease in both groups according to initial values, blood pressure measurements in group G were significantly higher than the first measure values. There was no significant difference in heart rate values between the groups. Conclusion: Intravenous granisetron reduces hypotension after spinal anesthesia, but it has no significant effect on heart rate.

TOXICOLOGICAL ASSESSMENT OF THE PREPARATION SUBMASTIN-KRS IN AN ACUTE EXPERIMENT ON LABORATORY ANIMALS

The article presents the results of toxicometric assessment of Submastin-KRS in an acute experiment on white laboratory rats and mice when it is intragastrically and intramuscularly administered. The preparation was administered once into the stomach using a metal atraumatic probe at a dose range from 2000,0 to 27 mg/kg. A single injection volume was 500,0 ml (mouse) and 0,5 ml (rat); intramuscularly – at doses from 5,0 to 1200,0 mg/kg in a volume of 21 ml per mouse and 250,0 ml per rat. The animals of the Placebo group, administered the preparation in the same volume and by the same method of administration, received sterile isotonic sodium chloride solution. It was found that in case of the tested methods of administration in the range of the studied doses of the preparation, there was no deaths of animals, therefore, the mean lethal dose (LD0,25) of the preparation Submastin-KRS was not determined. Consequently, the experimental data obtained make it possible to classify the dosage form of the preparation Submastin-KRS to low-hazard substances.

A Comparative Study of Ropivacaine with Dexamethasone and Ropivacaine with Dexmedetomidine in Ultrasound Guided Brachial Plexus Blockade for Adult Upper Limb Surgeries

BACKGROUND Blockade of brachial plexus at several locations from the roots to the terminal branches will allow for surgical anaesthesia of the upper extremity and shoulder. We have attempted to compare the efficacy of dexamethasone and dexmedetomidine when used as an adjunct to brachial plexus blockade when used as a sole anaesthetic for upper arm surgeries. METHODS After obtaining ethical committee clearance, a prospective observational study was conducted in patients undergoing upper arm surgeries. Patients were compared in two groups; Group 1 received 18 mL Ropivacaine (0.5 %) and Dexamethasone 8 mg (2 mL); Group 2 received Ropivacaine (0.5 %) and 75 mcg Dexmedetomidine along with 1.25 mL isotonic sodium chloride. RESULTS Mean time of onset of sensory blockade was 12.1 ± 1.1 min in Group 1 and 10.3 ± 1.2 min in Group 2. Mean Duration of Analgesia in Group 1 was 1024.5 ± 62.0 min and in Group 2 was 1394.3 ± 189.6 min. Mean Onset of Motor block in Group 1 was 18.2 ± 1.5 min and in Group 2 was 14.7 ± 1.0 min. Mean Duration of motor block in Group 1 was 697.2 ± 37.3 min and in Group 2 was 776.3 ± 48.0 min. CONCLUSIONS Our study revealed that dexmedetomidine is a better alternative for decreasing the onset of motor block along with enhanced quality and duration of supraclavicular block. KEYWORDS Interscalene, Dexamethasone, Dexmedetomidine

Thoracoscopy and chemical pleurodesis in treatment of pancreatogenic pleural effusion

Objective. To determine the opportunities of thoracoscopy and the effectiveness of induction of chemical pleurodesis by intrapleural administration of drugs for pancreatogenic pleurisy. Material and methods. We analyzed the results of surgical treatment of 17 patients with acute pancreatitis and 14 with pancreatic cysts after necrosis complicated by pancreatogenic pleural effusions, accounting for 3,7 % of all effusions. Results. Mild and moderate pleurisy was successfully suppressed in 4 cases (12.9 %) by pleural punctures. Six patients (19.4 %) with pancreatic necrosis and huge pleural effusion in case of severe conditions underwent pleural drainage. In 20 cases (64.5 %), fragmented pleurisy was treated using thoracoscopy. Pleurodesis was performed by means of insufflation of talcum powder in five cases that permitted to reduce the drainage time from 7.14 2.96 days without pleurodesis to 4.2 1.1 days (p = 0.026). Pleurodesis using application of trichloroacetic acid had no effect in three patients. Five patients received 200300 g of octreotide diluted with 40 ml of isotonic sodium chloride solution into the pleural cavity through the drainage. The drainage period reduced to 3.5 1.0 days (p = 0.018). The effect was maximally expressed in the cases with high amylase level in the pleural exudate. After that, 20 patients underwent various operations on the pancreas. Conclusions. Thoracoscopy is indicated to patients with pancreatogenic pleurisy for removal of fragments and sanation of the pleural cavity. Intraoperative pleurodesis with talcum effectively suppresses pleurisy and reduces the drainage period while application of trichloroacetic acid has no essential influence. Intrapleural administration of octreotide allows rapid reducing exudation when amylase index is high. Our study supports the effectiveness of mini-invasive procedures (videothoracoscopy combined with talcum powder pleurodesis and intrapleural administration of octreotide) to sanitize the pleural cavity, suppress pleurisy and shorten drainage periods.

PROGESTERONE AND GONADOTROPINS DYNAMICS IN THE BLOOD OF HEIFERS DURING ESTRUS SYNCHRONIZATION WITH THE USE OF SILICON DIOXIDE ULTRAFINE PARTICLES

The paper presents the results of studying the possibility of controlling the links of hormonal regulation of the reproductive cycle of cattle using silicon dioxide in an ultra-dispersed form to increase fertilization during frontal insemination. The aim of the study was to analyze the effect of silicon dioxide UDPs when used in the scheme for synchronizing the sexual cycle of heifers on the dynamics of progesterone, FSH and LH and the fertilization of animals from frontal insemination. The studies were carried out on breeding age heifers of the red steppe breed. We formed two groups by 10 heifers – the control and the experimental one. In both groups, the synchronization of estrus was carried out by double application of estrophan. In the experimental group, the animals were simultaneously injected with estrophan with a solution of silicon dioxide ultra-dispersed particles in isotonic sodium chloride solution (dose of silicon dioxide 10 μg/kg). Blood for the determination of hormones was taken from heifers on the 1st, the 11th and 14th days of the experiment. All animals were inseminated frontally with deep-frozen semen by the rectocervical method. It was found that in the experimental and control groups, the dynamics of gonadotropins during the induced sexual cycle was similar; however, the LH level before insemination in heifers of the experimental group exceeded that in the control by 0.81 ng/ml (34.4%). Fertility of heifers in the experimental group was 70.0%, in the control – 50.0%. The effect of silicon dioxide in the UDP form on the dynamics of sex hormones and the fertility of heifers from frontal insemination during estrus synchronization was studied for the first time.

SAFETY ASSESSMENT OF THE NEW DRUG "MT-6" IN AN ACUTE EXPERIMENT ON WHITE MICE

The article presents the results of assessing the safety of the new drug "MT-6" in an acute experiment on white mice. Experiments to assess acute toxicity were carried out in three series of experiments with intragastric, subcutaneous and intramuscular routes of administration in duplicate. The drug was administered intragastrically once after a 12-hour fasting diet in doses from 5500 to 10000 mg/kg in a volume of 0.5 ml per mouse; subcutaneously – in the dose range from 2000 to 6800 mg/kg in a volume of 0.5 ml per mouse; intramuscularly – in doses from 2000 to 6800 mg/kg in a volume of 0.25 ml per mouse. Control animals were injected with sterile isotonic sodium chloride solution in the same volumes and by the same methods. During the first day after the administration of the drug, the experimental animals were monitored continuously, then for 14 days – 2 times a day. On the basis of toxicometric data obtained during the experiment, the parameters of acute toxicity of the drug "MT-6" were established: with intragastric administration LD50 7828.5 mg/kg, with subcutaneous administration LD50 4994.1 mg/kg, with intramuscular LD50 3841.9 mg/kg. Based on this, it was concluded that the investigated drug belongs to GOST 12.1.007-76 to the 4th hazard class – low-toxic substances; according to Hodge and Sterner (1943) to the 5th hazard class – practically non-toxic substances; according to Sidorov K.K. (1977) – to the 6th class of hazard – relatively harmless substances.