We propose a new model of blood loss in awake rats with volume loss up to 40% of total blood volume in the phase of hemorrhagic shock and partial blood replacement up to final blood loss up to 30% of total blood volume. During blood withdrawal, the rats showed manifestation of baroreflex, increased blood levels of glucose and lactate, and decreased concentration of oxyhemoglobin. Partial blood volume compensation was followed by recovery of hemodynamics the levels of glucose and oxyhemoglobin. Thus, taking into account the awake status of rats and compensatory mechanisms, our model of blood loss with a fixed volume of blood drawing and its partial compensation is a relevant model for studying the efficacy of blood substitutes.

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.

The non-exchangeable sorption of tryptophan by the AV-17-2P anion exchanger from solutions of different compositions was studied. The sorption of the amino acid was shown to be independent of the nature of the accompanying component. This was explained by quantum-chemical modeling, which gave variants of attachment and energy characteristics of the bonds formed in the sorbent phase during non-exchangeable sorption of tryptophan by a highly basic anion exchanger in the salt form. The polar interactions play the major role, and π–π interactions produce an additional effect during the non-exchangeable sorption of amino acids on highly basic aromatic anion exchangers.

A short synthetic peptide from the C-terminal part of the caveolin-3 structure was tested for experimental autoimmune encephalomyelitis (EAE) treatment in rats. The structure–function similarity established between the novel synthetic peptide of pCav3 and the well-known immunomodulator immunocortin determined pCav3’s ability to reduce EAE symptoms in Dark Agouti (DA) rats injected with pCav3 (500 µg/kg). pCav3 was found to interfere with the proliferation of lymphocytes extracted from the LNs of DA rats primed with homogenate injection, with IC50 = 0.42 μM (2.35 mcg/mL). pCav3 affected EAE in a very similar manner as immunocortin. The high degree of homology between the amino acid sequences of pCav3 and immunocortin corresponded well with the therapeutic activities of both peptides, as demonstrated on EAE. The latter peptide, possessing a homologous structure to pCav3, was also tested on EAE to explore whether there were structural restrictions between these peptides implied by the MHC-involved cell machinery. Consequently, immunocortin was further examined with a different autoimmune disease model, collagen-induced arthritis (CIA), established in Sprague–Dawley rats. CIA was established using an intentionally different genetic platform than EAE. Based on the results, it was concluded that the effectiveness of pCav3 and immunocortin peptides in EAE rat model was almost identical, but differed in the rat model of rheumatoid arthritis; thus, efficacy may be sensitive to the MHC type of animals used to establish the autoimmune disease model.

Selecting standard and reference states for a thermodynamic description of the non-exchange sorption of substances by ion exchangers is considered a stoichiometric process. It is shown that it is best to choose different reference states for free and sorption centers associated with the absorbed substance, since this allows calculations of the thermodynamic constants and energy characteristics of sorption. Results from calculating thermodynamic characteristics of sorption are presented and discussed for systems with the participation of amino acids (glycine and phenylalanine).

A model of a chronic lung inflammation in SPF Sprague-Dawley rats was developed by repeated intratracheal administration of LPS in a dose of 0.4 mg/kg. On day 22 of the study, male rats treated with LPS have relative monocytopenia and reduced mean concentration of hemoglobin in the erythrocyte and the mean platelet volume in comparison with the control animals (saline). Intratracheal administration of LPS induced an inflammatory process in the lungs characterized by focal atelectasis, compensatory emphysematous expansion of subpleural pulmonary acini, focal mononuclear and neutrophilic perivascular and peribronchial infiltration, and minor focal mononuclear and neutrophilic infiltration of the alveolar walls. Against the background of LPS administration, germinal centers appeared in the lymphoid follicles of the white pulp of the spleen, and focal mononuclear infiltration of the tracheal mucosa and/or submucosa was observed in some animals.

CO2 inhalation is currently the most common method of euthanasia for laboratory rats and mice, and it is often used for further terminal blood sampling for clinical biochemical assays. Lately, this method has been criticized due to animal welfare issues associated with some processes that develop after CO2 inhalation. The stress reaction and the value of the clinical laboratory parameters significantly depend on the used anesthetics, method, and the site of blood sampling. Especially in small rodents, an acute terminal state followed by a cascade of metabolic reactions that can affect the studied biochemical profile may develop and cause unnecessary suffering of animals. The aim of this study was to compare the stability of biochemical parameters of outbred Sprague Dawley rats and CD-1 mice serum collected after CO2 inhalation or the intramuscular injection of tiletamine–zolazepam–xylazine (TZX). The serum content of total protein and albumin, cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotr ansferase (ALT), alkaline phosphatase (ALP), total bilirubin, and creatinine was decreased by the injection of TZX in comparison with CO2 inhalation. In addition, the levels of calcium, phosphates, chlorides and potassium were lowered by TZX vs. CO2 administration, while the level of sodium increased. Finally, the level of the majority of serum clinical biochemical parameters in rats and mice tend to be overestimated after CO2 inhalation, which may lead to masking the possible effect of anti-inflammatory drugs in animal tests. Injection anesthesia for small rodents with TZX is a more feasible method for terminal blood sampling, which also reduces the suffering of animals.

В статье описаны физико-химические свойства и механизмы действия диоксида кремния. Вследствие широкого спектра терапевтического действия диоксида кремния (снижение эндогенной интоксикации, нормализация кишечного микробиоценоза, уменьшение системной воспалительной реакции, активация детоксикационной функции) использование аэросила как матрицы при производстве лекарственных средств для лечения и профилактики хирургической инфекции является интересным направлением для научных исследований. Использование сорбционных матриц при моделировании новых препаратов средств для комплексного лечения гнойно-воспалительных процессов мягких тканей, по нашему мнению, является эволюционно обоснованным подходом, что требует дальнейшего изучения с целью определения показаний к широкому применению в хирургической практике.

A structural analogue of the DSIP, peptide KND, previously showed higher detoxification efficacy upon administration of the cytotoxic drug cisplatin, compared to DSIP. DSIP and KND were investigated using the model of acute myocardial infarction in male SD rats and the model of acute focal stroke in C57Bl/6 mice. A significant decrease in the myocardial infarction area was registered in KND-treated animals relative to saline-treated control animals (19.1 ± 7.3% versus 42.1 ± 9.2%). The brain infarction volume was significantly lower in animals intranasally treated with KND compared to the control saline-treated animals (7.4 ± 3.5% versus 12.2 ± 5.6%). Injection of KND in the first minute of reperfusion in the models of myocardial infarction and cerebral stroke reduced infarction of these organs, indicating a pronounced cardioprotective and neuroprotective effect of KND and potentiality for the treatment of ischemia-reperfusion injuries after transient ischemic attacks on the heart and brain, when administered during the reperfusion period. A preliminary pilot study using the model of myocardial infarction with the administration of DSIP during occlusion, and the model of cerebral stroke with the administration of KND during occlusion, resulted in 100% mortality in animals. Thus, in the case of ischemia-reperfusion injuries of the myocardium and the brain, use of these peptides is only possible during reperfusion.

The energy of interaction between various amino acids (glycine, alanine, and phenylalanine) and an AV-17 strongly basic anion exchanger in chloride and nitrate ionic forms under nonexchange absorption conditions is assessed by quantum chemistry calculations. We found that the amount of water in the starting fragments of sorption participants, the counterion of the anion exchanger, and the amino acid radical play an important role in energy and in the ratio of different intermolecular interactions (Coulomb, hydrophobic, and hydrogen bonds) to form ion-molecular structures in the ion-exchanger phase.

For evaluation of the effect of high-fat diet on the development of diabetic complications, the rats were maintained on standard or high-fat diet. In 3 weeks, diabetes mellitus was modeled by single intraperitoneal injection of streptozotocin. Changes in hematological parameters, physical and biochemical parameters of the urine, and in the development of thermal allodynia were different after 15-week standard and high-fat diets.

Background and Objectives: Mutual effect of the preliminary and therapeutic intranasal treatment of SD rats with DSIP (8 days) on the outcome of focal stroke, induced with intraluminal middle cerebral occlusion (MCAO), was investigated. Materials and Methods: The groups were the following: MCAO + vehicle, MCAO + DSIP, and SHAM-operated. DSIP or vehicle was applied nasally 60 (±15) minutes prior to the occlusion and for 7 days after reperfusion at dose 120 µg/kg. The battery of behavioral tests was performed on 1, 3, 7, 14, and 21 days after MCAO. Motor coordination and balance and bilateral asymmetry were tested. At the end of the study, animals were euthanized, and their brains were perfused, serial cryoslices were made, and infarction volume in them was calculated. Results: Although brain infarction in DSIP-treated animals was smaller than in vehicle-treated animals, the difference was not significant. However, motor performance in the rotarod test significantly recovered in DSIP-treated animals. Conclusions: Intranasal administration of DSIP in the course of 8 days leads to accelerated recovery of motor functions.

Introduction: The article presents the results of the functional tests to improve the assessment of MIA-induced osteoarthritis development and the effectiveness of NSAID therapy. Materials and methods: In the study, 26 male SD rats were used. MIA-induced osteoarthritis was simulated in the right knee joint. After an intra-articular injection of MIA, the animals were treated with ibuprofen and meloxicam. Pain assessment was studied in the following functional tests: incapacitance (hind limb weight bearing) test, von Frey test (mechanical allodynia), grip strength test, and knee diameter measurement. At the end of the study, a histological analysis of the knee joint was performed. Results and discussion: An intra-articular MIA injection reduced 1.5 times the paw withdrawal threshold. In the rats that suffered MIA-induced osteoarthritis, the difference between the diameters of the intact and injected joints was 1.05 mm, compared to 0.03 mm difference in the control group. Hind limb weight bearing asymmetry was 89.5% when simulating MIA-induced osteoarthritis. The muscular hind limb grip strength in rats with MIA-induced osteoarthritis was significantly reduced on 3rd and 7th days after simulating osteoarthritis. Ibuprofen and meloxicam showed significant efficacy in all the above tests, although ibuprofen effectiveness was more pronounced than that of meloxicam. Conclusion: The following functional tests were identified as the most significant and sufficient to assess the development of MIA-induced osteoarthritis and analgesic efficacy of NSAIDs: incapacitance test, allodynia test (von Frey filaments), measurement of hind limb grip strength and measurement of the diameter of the inflamed knee joint. The histological analysis made it possible to confirm the correspondence of the physiological response and pathological changes in the knee joint.

The results from an experimental study are presented along with a thermodynamic description of three-component sorption systems of the AV-17-2P-Сl-OH-amino acid type. It is shown that the exchange of mineral ions for zwitterlyte ions corresponds to the His < Phe < Trp order of sorption in binary systems, and to the order His < Trp < Phe for superequivalent absorption. Сl–OH exchange is suppressed by the competing exchange of mineral ions for ions of amino acid.

Исследованы межчастичные взаимодействия в фазе анионообменника АВ-17в Сl-форме при необменном поглощении биполярных ионов глицина, фенилаланина и триптофана. Квантово-химическое моделирование образующихся структур проводили с помощью программы Gaussian 03 методом гибридного функционала плотности B3LYP в базисе 6-31G++(d,p). Показано, что усложнение строения радикала аминокислоты приводит к уменьшению выигрыша энергии сорбции

The influence of new promising peptide (APCH3 and PT1) and nonpeptide analgesics (sevanol) on the behavior of male ICR mice was studied. All studied compounds at doses producing significant analgesic effects did not influence the behavior of mice in open-field tests. However, APCH at doses 10,000 times greater than the pharmacologically active dose produced sedative effects. Also, sevanol at a dose of 35 mg/kg caused statistically significant behavioral changes relative to the pharmacologically active dose (1 mg/kg) but not to the controls.

The authors have analyzed international experience in creating legal documents regulating the use of animals for scientific purposes. Topical issues related to the use of laboratory animals for scientific purposes in the Russian Federation, including for the purpose of preclinical studies on the efficacy and safety of new medicines, are discussed. The negative effects of the lack a clear and consistent legal framework for the organization and limits of the use of laboratory animals for research purposes in the Russian Federation are identified. Particular attention is paid to the issue of bioethics, the principles of ethical expertise of research activities involving laboratory animals and the issues of bioethical committees activities. The basic directions of perfection of normative-legal acts and methodological documents in the field of organization and limits of the use of laboratory animals for research purposes are proposed.