The effects of the antioxidant dihydroquercetin (DHQ) were studied in a model of pulmonary fibrosis. DHQ penetration into the lesion was facilitated by encapsulation into liposomes. Pulmonary fibrosis was modeled in rats by intratracheal injection of bleomycin. For the first 7 days, the rats in the treatment group received a liposomal emulsion with DHQ, while in the comparator group rats received saline. In the control group, intact rats did not receive any exposure. Thirty days after the initiation, lung function and the pathological lesion volume were assessed by 7T 1H MRI and the lungs were taken for histologic examination. The proportion of fibrous tissue was counted by Masson's trichrome staining. Both experimental groups were characterized by a significant functional pulmonary deficiency, with low mortality and a small lesion area. In the rats treated with DHQ, the distribution of fibrous tissue was significantly altered. Significantly more fibrous tissue was found in the center of the lesion, while significantly less was in the interstitial space of alveoli. Lung density at the same time was lower in the treated lungs. Dihydroquercetin encapsulated in liposomes affects the mechanisms of bleomycin-induced pulmonary fibrosis progression in rats. While accelerated fibrosis of the lesion can restrict inflammatory processes, delayed fibrosis of the interstitium can further improve the functional state of the lungs.

We compared 2 models of metabolic syndrome in rats: high-fat diet (58% calories) with single streptozotocin injection at a dose of 25 mg/kg and replacement of water with 20% fructose solution. The model with fructose solution did not cause the main signs of metabolic syndrome over 24 weeks: concentrations of glucose, triglycerides, cholesterol, weight, and BP did not significantly differ from the control group (standard diet). At the same time, single streptozotocin administration was followed by the development of persistent hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and signs of visceral obesity. High-fat diet combined with injection of streptozotocin in a low dose can be considered a more representative model of metabolic syndrome in humans.

Common marmoset (Callithrix jacchus, CM) is a New World primate species that is of interest for preclinical trials of immunobiological products. In this study, we describe the approaches to long-term laboratory breeding and maintenance of CMs. We also establish the reference values of the main complete blood count and serum chemistry parameters evaluated during preclinical trials of immunobiological products and describe the histological characteristics of CM lymphoid organs during the development of post-vaccination immune response. We show that CMs bred in laboratory conditions excluding background infectious pathology are a relevant model that allows for a high degree of reliability in characterizing the safety and immunogenicity profile of antiviral vaccines during preclinical trials.

The dynamics of nephropathy development in rats with type 2 diabetes mellitus, caused by a high-fat diet and the streptozotocin administration (25 mg/kg), and metabolic syndrome, caused by addition of 20% fructose solution to the diet, was evaluated during the experiment. Models with moderate severity of metabolic changes without significant changes in body weight were obtained after 24 weeks. To study neuropathy severity, the method of electroneuromyography was used; the velocities of motor and sensory excitation propagation along the caudal nerve fibers were measured. In modeled diabetes mellitus against the background of hyperglycemia, a marked decrease in motor and sensory propagation rates was observed, and an increase in the response durations was noted from week 12 to week 24, indicating pronounced neuropathy. In the fructose model, the motor response duration increased from week 12, which possibly indicates the development of peripheral neuropathy.

The HRV analysis in rats was used to evaluate the relationship between the initial level of total HRV and regulatory changes in the heart function before and on days 1, 3, and 28 after modeling irreversible ischemia (II). According to the level of total HRV, rats were divided into two groups: with initially “low” and “high” levels of HRV, the LV (SDRR = 5.0 ± 0.8 ms) and HV (SDRR = 8.2 ± 0.8 ms) groups, respectively. LV and HV rats reacted differently to the cold test before and after II. Three days after II, LV rats had a better maintenance of the autonomic regulation of the heart, and 28 days later, a smaller size of myocardial area and mortality. In HV rats, the quantity of mast cells in the ischemic area was higher, and the ratio of degranulated cells in the zone unaffected by ischemia was higher in LV rats.

Цель исследования - изучение динамики морфологических изменений роговицы и заднего отдела глаза крыс при длительной гипергликемии. Методика. Исследование выполнено на 36 самцах крыс Wistar. Сахарный диабет индуцировали внутрибрюшинной инъекцией стрептозотоцина (65 мг/кг), после чего ежедневно вводили подкожно малые дозы инсулина (2 ЕД/кг). На 50-е, 58-е и 66-е сут эксперимента производили энуклеацию глаз у глубоко наркотизированных животных. Гистологические срезы фрагментов глаз окрашивали гематоксилин-эозином, проводили морфометрию параметров роговицы и сетчатки. Результаты. Средняя концентрация глюкозы и кетоновых тел крови в группе сахарного диабета составила 29,8 ммоль/л и 0,889 ммоль/л, в контрольной группе - 6,2 ммоль/л и 0,847 ммоль/л соответственно. Анализ гистологических срезов глаз выявил признаки отека роговицы, хориоидеи и наружных слоев центральных отделов сетчатки до появления других качественных и количественных морфологических изменений. Заключение. Оценка толщины роговицы, хориоидеи и наружных слоев центральных отделов сетчатки может служить предиктором развития диабетической ретинопатии. The aim was to study morphological changes in the cornea and the posterior part of rat eye during prolonged hyperglycemia. Methods. The study was performed on 36 Wistar male rats. Diabetes mellitus was induced by an injection of streptozotocin (65 mg/kg, i.p.) followed by daily injections of low doses of insulin (2 U/kg, s.c.). Eyes were enucleated from deeply anesthetized rats on days 50, 58, and 66 of the experiment. Histologic sections were stained with hematoxylin-eosin, and morphometry of the cornea and the retina was performed. Results. Mean blood concentrations of glucose and ketone bodies were 29.8 mmol/L and 0.889 mmol/L, respectively, in the diabetic group and 6.2 mmol/L and 0.847 mmol/L, respectively, in the control group. The histological analysis revealed signs of edema in the cornea, choroid and outer layers of the central retina, which preceded other morphological changes. Conclusion. Evaluating thickness of the cornea, choroid and outer layers of the central retina may serve for prediction of diabetic retinopathy.

We have reviewed current understanding of ischemic brain damage and the main therapeutic approaches. Pathological factors affecting the survival of neurons and glial cells in the focus of ischemia are outlined: depolarization, cytotoxic and vasogenic edema, calcium overload, excitotoxicity, inflammation, free radical damage. Effective and rapid reperfusion significantly improves patient’s survival and functional outcomes, but other approaches to brain infarction treatment did not approve their effectiveness in large clinical trials. Dozens of drugs (neuroprotectors) are being studied in order to compensate isolated pathological brain ischemia pathways and to increase cellular survival, but they were ineffective in large clinical trials.The reason for the ineffectiveness of neuroprotective drugs may be a lack of understanding of the drug targets real importance. Many drugs that have shown promising results in preclinical studies have not been studied in large clinical trials until now. Additional pathogenetic mechanisms revealed in the last decade expand our knowledge about the brain infarction and may become promising directions for the development of new therapeutic approaches.

The relationship between the autonomic tone and psychological personality profile was studied in 55 girls and boys (19 years of age on average) without pathologies of the cardiovascular and respiratory systems. Psychological personality traits (factors) were evaluated using the Kettell questionnaire (form A). An ECG was recorded using a Holter monitor (Sсhiller MT-100), and heart rate variability (HRV) was characterized at rest and during the rhythmic breathing and cold tests. The parameters mNN, SDNN, RMSSD, and pNN50 were calculated from 5-min fragments of ECG recordings. Based on the SDNN level, the subjects were classified into subgroups with conditionally higher and conditionally lower HRV levels of HRV (LV and HV subgroups). LV boys and girls had significantly lower HRV parameters as compared with the HV subgroup: SDNN, 60 vs. 98 ms; RMSSD, 38 vs. 66 ms; and pNN50, 15 vs. 36%, respectively. The LV and HV subjects differently responded to a functional test with forced breathing, which involves activation of the parasympathetic division of the autonomic nervous system (ANS). SDNN, RMSSD and pNN50 increased in the LV girls, while RMSSD and pNN50 remained unchanged in the HV girls. Both LV and HV boys responded by increasing the SDNN, RMSSD, and pNN50. A cold test, which stimulates the sympathetic division of the ANS, increased the SDNN in the LV girls, decreased the RMSSD and pNN50 in the HV girls, caused no change in HRV parameters in the LV boys, and increased the RMSSD in the HV boys. Gender differences were observed in responses to the tests within the LV and HV subgroups. Psychological profiles were characterized for the LV and HV subgroups. The percentage of girls who easily perceived new information, were adapted, and were tolerant of contradictions (Q1 + factor) was 75% in the HV subgroup and significantly lower, 33%, in the LV subgroup. The correlations observed between the autonomic tone and the psychophysiological personality traits can be useful for selecting effective methods for physiological and psychological correction in stress.

Müller cells are the major type of glial cells in the retina and are actively involved in ensuring its vital functions. They are responsible for maintaining homeostasis and the synaptic activity of neurons by transporting substances to all types of cells within the retina and leading them beyond it. Müller cells guide light to photoreceptors, dividing it according to the wavelength and amplifying the incoming light signal, they protect neurons from damage and are able to regenerate into photoreceptors and other retinal cells under pathological conditions. This review summarizes the knowledge about the morphology and functions of Müller cells which has been accumulated over the years of their study.

BACKGROUND: Diabetes mellitus leads to disruption of the skin repair processes, but the leading mechanisms of this pathology have not yet been identified. In this regard, in our work, we decided to check how hyperglycaemia affects the process of keratinocyte phenotype changes during wound healing. AIMS: To study the effect of hyperglycaemia on wound healing and differentiation of keratinocytes in a rat streptozotocin-induced diabetes model. MATERIALS AND METHODS: Diabetes mellitus was induced in rats by using streptozotocin, 65 mg / kg, intraperitoneally, once. The wound was applied in the supra-scapular region on the 42nd day, after which (after 8, 16, and 24 days) the repair process was evaluated using histological methods. Immunohistochemistry was used to evaluate the expression of cytokeratin-10 and cytokeratin-17. RESULTS: In rats with diabetes mellitus, wound healing slowed down in the later stages, compared with the control group. In general, wound healing was accompanied by an increase in the expression of cytokeratin-10 in its region compared with intact skin, and contractile keratinocytes activation was disrupted in diabetic rat wounds. CONCLUSIONS: Hyperglycaemia slightly slows wound healing in rats and impairs contractile keratinocytes activation.

Background : Diabetes mellitus (DM) has a negative impact on all organs. This is due to insufficiency of blood supply and the disruption of the trophic function of the nervous system. One of the most serious complication of DM is diabetic foot caused be vascular and neurological reasons. Correction of vascular disorders is effectively treated by modern therapeutic approaches, but the damage of nervous system has been studied insufficiently. Aims : To investigate the dynamics of damage to the vegetative nervous system on the laboratory model of DM. Materials and methods : DM in rats was induced by injection of streptozotocin at a dose of 65 mg/kg in citrate buffer (DM group). The control group of rats received a citrate buffer equivalent (CB group). Rats with DM were given a maintenance therapy with insulin in a dose of 2 units/kg/day. On 42 days of experience, a round wound with a diameter of 2 cm on the back of the animals was observed. Before the DM simulation, then on the 42, 50, 58 and 66 days of its development, an electrocardiogram (ECG) was recorded in the rats at a frequency of 2 kHz digitising in a state of calm wakefulness and after cold exposure. For 5 minutes ECG fragments, heart rate and heart rate variability (HRV) in the temporal domain were calculated, characterising: 1) the total heart rate variability (tHRV) according to SDRR, SDHR, KVRR and KVHR; 2) the effect of the parasympathetic department of the autonomic nervous system (aANS) for RMSSD and pNN3; 3) the contribution of the sympathetic department of the ANS (sANS) by SDAvgRR, SDAvgHR. The spectral parameters were estimated in the frequency domain: the total power of the spectrum is TR (range: 0–2.5 Hz), the powers in the low and high frequency ranges are LF (range: 0.2–0.8 Hz) and HF (range: 0.8–2.5 Hz) LF/HF. Weekly, the tail withdrawal time was measured in a temperature pain test (55°C). Results : During the development of diabetes, the level of glucose in the blood increased 4–7 times compared with the normal level. The reaction time of the pain test in rats with DM increased by 20%–30% at the end of the experiment. At 42 days, the development of bradycardia (267 beats/min) was observed in rats with DM. The indicators of tHRV decreased by a factor of 2 due to a decrease in the contribution of sANS. The reaction to CP in the SD group differs from the norm by the severity of the individual components of the HRV structure, which indicates functional denervation of the heart and the development of diabetic neuropathy. Conclusions : As the diabetes progressed, signs of neuropathy were observed. The overall HRV parameters decreased, the ratio of the contributions of sANS and pANS to the regulation of heart rate changed, and the temperature sensitivity decreased.

Expression of inducible NO-synthase mRNA and myocardial infiltration with neutrophils were studied in rats with modeled permanent ischemia and ischemia/reperfusion models. Expression of inducible NO synthase mRNA in the ischemic region increased significantly in 3, 3.5, and 4 h in modeled ischemia/reperfusion and in 3.5 and 4 h in permanent ischemia. Myocardial infiltration with neutrophils was significantly higher than in intact controls throughout the experiment without significant intergroup differences. In non-ischemic myocardium, enhanced expression of inducible NO synthase mRNA and moderate neutrophilic-lymphocytic myocardial infiltration were also observed in 3.5, and 4 h after ischemia.

Objective. The role of ATP-dependent potassium (K+ ATP) channels in the neuroprotective effect of ischemic (IPre) and pharmacological (PPre) preconditioning and changes in blood levels of nitric oxide (NO) metabolites were studied in conditions of cerebral ischemia. Materials and methods. Ischemic stroke (IS) was modeled in male rats (n = 86) by electrocoagulation of a branch of the middle cerebral artery (MCA). The nonselective K+ ATP channel blocker glibenclamide and the K+ ATP channel activator diazoxide were used. IPre and PPre were performed one day before MCA occlusion. Blood concentrations of NO, nitrates (NO3 –) and nitrites (NO2 –) were determined in experimental animals at 5, 24, and 72 h after MCA occlusion. Results. IPre decreased the lesion zone by 37% (p < 0.05), while prior administration of glibenclamide countered the action of IPre. The protective effect of PPre was analogous to that of IPre. Decreases in blood levels of oxygenated R-conformers of hemoglobin-bound NO (Hb-NO) were seen 5 h after MCA occlusion, with an inversely proportional increase in the concentration of nonoxygenated T-conformers; there were also increases in NO3 – and NO2 – concentrations. NO3 – and NO2 – levels showed normalization by one day after MCA occlusion, along with changes in the concentrations of Hb-NO complexes – R-conformers dominated, while the blood level of T-conformers reached a minimum. Furthermore, by 24 h there was a correlation between blockade of K+ ATP channels and decreases in serum NO3 – and NO2 – levels (p < 0.03). Conclusions. The neuroprotective effect of preconditioning was due to activation of K+ ATP channels. Analysis of blood levels of NO metabolites in rats with IS showed that Hb-NO complexes in the R-conformation stored and carried NO to the tissues, releasing NO on occurrence of the R → T transition in ischemic conditions.

It has previously been shown that many of the peptides that contain proline and glycine amino acids have a pronounced physiological activity, however, the amino acid sequence, which to the greatest extent determines their properties, remains unknown. In this paper, we studied the effect of modified forms of the Prolyl-Glycyl-Proline (PGP) peptide on the secretion of histamine from isolated mast cells and the permeability of vessels in the skin of rats after intradermal administering of Synacthen, lipopolysaccharide LPS and compound 48/80. We have shown that peptides Semax, Selank, PGPL FPG, GPG, PG and GP reduced the secretion of histamine from mast cells and increased the vascular permeability after the administration of Synacthen and LPS, but not compound 48/80. At the same time peptides PLP, PGA and RGP had no effect on these parameters. Thus, the structural modification of PGP affects its properties only if a glycine or proline is replaced by another amino acid.

Objectives : Diabetic retinopathy remains the major cause of blindness among the working-age population of developed countries. Considering this, experimental models of diabetes involving laboratory animals are important for assessing clinically significant methods to determine early pathologic alterations of the retina. The early detection of diabetic retinopathy in combination with a search for new pathogenetic targets will enable focusing on new strategies to limit the development of critical changes in the retina and to prolong retinal functioning during the development of diabetes mellitus. Aim : This study aimed to define parameters of electroretinography test that identifies changes due to retinal impairment in diabetes. Methods : Experimental diabetes was induced in Wistar rats by intraperitoneally injecting streptozocin (65 mg/kg; group ‘DM’). The control group (‘CB’) received intraperitoneal injections of the vehicle, i.e. citric buffer. On each consecutive day of the experiment, all rats received insulin detemir (2 u/kg). Ophthalmoscopy and electroretinography were conducted before initiating the experiment and after 50, 58 and 66 days of injectin sptreptozocin. Results : Amid 2u\kg insulin injection the glucose level in venous blood in «DM» group amounted to 30-40 mM. The ophthalmoscopy showed that the optic nerve disk paled by the 50th day, with its line erasing. During electroretinography, wave amplitude in oscillatory potential test tended to decrease. β-wave latency of photopic system increased with α-wave latency of photopic system and α- and β-waves latency of scotopic system not altering. In addition, the amplitude of rhythmic stimulation of 8 and 12 Hz decreased. Conclusion : The most apparent parameters of electroretinography for modelling streptozocin-induced diabetes are wave amplitude during the oscillatory potential test, photopic B-wave latency and the amplitude of rhythmic stimulation. These results suggest that in diabetes, ischaemic injury is an important cause of early dysfunction of inner retinal layers.

The study describes the synthesis and hypotensive effects of stable platelet activation factor (PAF) precursor 1-hexadecyl-2-m ethylcarbamoyl-phosphatidic acid (HMCP) оn outbred Wistar rats with 1-kidney 1-clip (1K1C) renovascular hypertension. Intravenous injection of 0.1, 0.5, 1 and 5 mg/kg HMCP resulted in a sharp decline of up to 50% of MAP with subsequent restoration to initial level. In some hypertensive 1K1C rats HMCP has a prolonged effect with blood pressure stabilized at 75% of initial level after 30 min post injection. HMCP was toxic at higher doses with a LD50 around 3 mg/kg.

Preconditioning of ischemic and hypoxic type was investigated as a method of protecting brain against acute ischemic injury. The preconditioning methods were applied to experimental rats 24 h before the time when local brain infarct was done by middle cerebral artery occlusion (MCAO). It was found that the ischemic and hypoxic preconditioning resulted in three general morphological changes: 1) the size of infarct zone was reduced by 2.2–3.8 times compared with rats that had not been treated with the preconditioning before MCAO; 2) the preconditioning treatment retained the number of living neurons in penumbra at the level of control rats, while without the preconditioning neuronal count in the penumbra after MCAO was 29% lower; 3) the number of glial cells in penumbra was increased after MCAO by 38% compared with the control level, and continued to increase under the preconditioning treatment up to 60%, that suggests an important role of neuroglia in neuroprotection. Selective blockers of ATP2dependant K+2channels (52hydroxydecanoate and glibenclamide) completely abolished the neuroprotective effects of the preconditioning.

The effect of peptide Semax on remodeling of cardiac sympathetic innervation was examined in rats with experimental myocardial infarction. In 28 days after ischemia/reperfusion injury, Semax diminished the growth of sympathetic innervation of ventricular septum, although it produced no effect on the density of β1 and β2 adrenoceptors.