Evaluation of Peripheral Neuropathy in Rat Models of Metabolic Syndrome and Diabetes Mellitus.

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.

Comparison of Metabolic Changes after 6 Months of High-Carbohydrate Diet or High-Fat Diet with Low Dose Streptozotocin Injection in Rats.

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.

Inducible NO Synthase mRNA Expression and Infiltration of Rats Myocardium with Inflammatory Cells in 2-4 Hours after Modeled Permanent Ischemia or Ischemia/Reperfusion.

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.

Oxidative Status in Different Areas of the Cerebral Cortex of Wistar Rats during Focal Ischemia and Its Modulation with Carnosine.

Oxidative status was assessed in different areas of the cerebral cortex of male Wistar rats under normal condition and during permanent 24-h focal ischemia. In intact animals, the level of lipid hydroperoxides in the frontal lobes of both hemispheres was by 36% higher than in other cortical areas, while total antioxidant activity was by 25% higher than in other areas. During ischemia, changes in oxidative status were localized only in the ischemic focus and penumbra zone and did not involve other cortical areas. We demonstrated for the first time a neuroprotective effect of therapeutic administration of carnosine in low doses (50 mg/kg) on parameters of the oxidative status under conditions of focal ischemia comparable to its effect of high doses (500 mg/kg) as well as its local effect in the penumbra zone. A dose-dependent effect of carnosine on antioxidant activity in the penumbra zone during ischemia was also demonstrated. These findings confirm effectiveness of not only preventive carnosine administration, but also its application in the postischemic period of the stroke.

Changes in Sympathetic Innervation of the Heart in Rats with Experimental Myocardial Infarction. Effect of Semax.

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 ß1 and ß2 adrenoceptors.

Changes in Sympathetic Innervation of Rat Caudal Artery in Experimental Myocardial Infarction. Effect of Semax Peptide.

Activation of the sympathetic nervous system aggravates the course of myocardial infarction. Semax peptide moderated the degree of this activation and prevented the increase in the density of sympathetic endings in rat caudal artery in 28 days after ischemia or ischemia/reperfusion. The peptide reduced the density of α-adrenoreceptors in the caudal artery of rats with myocardial infarction. Semax produced no effect on ß-adrenoreceptors in both experimental models. The experiments on isolated segments of the caudal artery revealed reduced vascular responsiveness to electrical stimulation and norepinephrine infusion in rats treated with Semax after ischemia/reperfusion injury.

[THE ROLE OF INFLAMMATION IN THE DEVELOPMENT OF PROLIFERATIVE VITREORETINOPATHY].

This paper focuses on the risk factors of primay and secondary proliferative vitreoretinopathy, modern views of pathophysiology of this disease, and the role of inflammation in its development. Special attention is given to the involvement of pigment epithelial cells, macrophages, hyalocytes, gliocytes, supporting fibers (Muller's cells), mediators of inflammation, such as cytokines, chemokines, and growth factors, with reference to their interaction in the processes of proliferation and development of retinal membranes.

Effects of activated protein C on the size of modeled ischemic focus and morphometric parameters of neurons and neuroglia in its perifocal zone.

The effects of activated protein C (APC) on the quantitative parameters of neurons and neuroglia in the perifocal zone of infarction induced in the left hemispheric cortex were studied in two groups of rats. Group 1 animals served as control (control infarction). Group 2 rats were injected with APC (50 µg/kg) in the right lateral cerebral ventricle 3 h after infarction was induced, and after 72 h the infarction size was evaluated and the neurons and neuroglia in the perifocal zone were counted. APC reduced the infarction size 2.5 times in comparison with the control and reduced by 16% the neuronal death in the perifocal zone layer V, causing no appreciable changes in layer III, and did not change the size of neuronal bodies but increased (by 11%) the size of neuronal nuclei in layer III. The protein maintained the sharply increased count of gliocytes in the perifocal zone of infarction and promoted their growth. Hence, APC protected the neurons from death in the ischemic focus by increasing the gliocyte count and stimulating the compensatory reparative processes.

Dihydroquercetin-Loaded Liposomes Change Fibrous Tissue Distribution in the Bleomycin-Induced Fibrosis Model.

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.

[Lornoxicam for prevention of myocardial injury during acute ST-elevation myocardial infarction].

10% of patients with acute ST-elevation myocardial infarction (STEMI) treated with reperfusion therapy fail to develop an enzyme rise, but do exhibit transient ECG changes, which are consistent with an aborted myocardial infarction. Following reperfusion by primary PCI in STEMI, oxidative stress and an inflammatory response are induced immediately. Inflammation is a critical component of STEMI. Both COX isoforms are involved in reperfusion and ischemic myocardial injury. To evaluate the effectiveness of lornoxicam - nonselective NSAID, in decrease of myocardial injury during acute ST-elevation myocardial infarction. We analyzed 22 patients with STEMI, 14 of them received 16 mg and 8 mg lornoxicam after 20 min and 8 hours, respectively, after arrival to hospital. 12 f them received alteplase, 10 patients with cardiac pain up to 24 hours from the beginning, did not receive reperfusion therapy. All patients received anticoagulants, antiplatlet therapy, -blockers. The primary end point was all-cause mortality by the day 30 and hospitalization due to congestive heart failure by the 1st year. There was no difference in mortality and heart failure by the 30 day and 1st year respectively, between the patients with STEMI treated with lornoxicam or placebo. Randomized controlled trials are needed to explore potential cardioprotective effects of lornoxicam in patients with acute STEMI.

[Dynamics of autoimmune myocarditis development in rats].

The development of autoimmune myocarditis in rats after a single hypodermic injection of rat myosin mixed with a complete Freund's adjuvant (CFA) (400 microg/kg in 200 microl) was studied. The rats from the control group were injected with only CFA. The titer of antibodies to myosin, infiltration of lymphocytes into the myocardium, ultrastructural damage of myofibrils, mitochondria, and nuclei of cardiomyocytes were maximally pronounced on days 14-21 after the immunization with myosin, which indicates a peak of the inflammatory reaction. The content of nitrites and nitrates in the blood serum and myocardium of immunized rats were also studied. A certain contribution to the development of the inflammation is made by CFA: in rats injected with only CFA, morphological signs of myocarditis were found, but to a much lesser degree than in the group immunized with myosin.

[Protective effect of lornoxicam on development of myocardial infarction in rats under conditions of ischemia and ischemia-reperfusion].

Activation of inflammation and enzyme cyclooxygenase with formation of proinflammatory prostaglandins is a key element of development of myocardial infarction in patients with acute coronary syndrome. Basing on literature data and own experience we suggested that single intravenous injection of 230 mg/kg of nonselective inhibitor of type 1 and 2 cyclooxygenase lornaxicam in the phase of initialization of inflammation 20 min after onset of ischemia would lead to reduction of myocardial infarction volume in rats in irreversible ischemia and ischemia with subsequent reperfusion. The conducted study allowed to reveal that administration of lornoxicam in recommended for human use dose lowered mortality of animals and increased number of capillaries per one cardiomyocyte in case of irreversible coronary artery occlusion. In ischemia-reperfusion as in irreversible myocardial ischemia lornoxicam reduced volume of necrosis and degree of thinning of left ventricular wall in the region of infarction, and lowered volume of connective tissue in periinfarction zone of the myocardium in remote period.

[Clinicomorphological rationale for mediastinal lymphadenectomy in the surgical treatment of disseminated destructive pulmonary tuberculosis].

The paper analyzes morphological changes and results of surgical treatment in 515 patients with destructive pulmonary tuberculosis. Two hundred and seventy-four patients underwent mediastinal lymphadenectomy and in 241 patients lung resections or pneumonectomies were not followed by lymphadenectomy or solitary caseous molten lymph nodes were removed during an operation. In disseminated destructive pulmonary tuberculosis, active tuberculosis of intrathoracic lymph nodes (ILN) was found in 97%. The latter's significant signs are an enlarged lymph node of more than 2.0 cm, consolidation, periadenitis, and fluctuation. The incidence, extent, and pattern of ILN lesion varied in a lung tuberculous process depending on its site, form, and inflammation phase.

[Neuroprotective activity of the proline-containing dipeptide noopept on the model of brain ischemia induced by the middle cerebral artery occlusion].

The influence of noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) on the extent of ischemic cortical stroke was investigated in experiments on white mongrel male rats with ischemia induced by a combination of the middle cerebral artery occlusion with ipsilateral common carotid artery ligation. Animals were treated with noopept (0.5 mg/kg, i.p.) according to the following schedule: 15 min and 2, 24, and 48 h after the occlusion. Test rats were decapitated 72 h after occlusion, brains were extracted and frozen, and thin brain slices were stained with 2,3,5-triphenyltetrazolium chloride. The slices were scanned and processed using Auc 1 computer program, which estimates the percentage of damaged area relative to that of the whole ipsilateral hemisphere. The conditions of coagulation the distal segment of middle cerebral artery were selected, which caused necrosis localized in the fronto-parietal and dorso-lateral regions of the brain cortex without any damage of subcortical structures. The extent of the brain damage in control group (treated by saline) was 18.6%, while that in the group treated with noopept was 12.2%, thus demonstrating a decrease in the infarction area by 34.5% (p < 05). The data on noopept efficacy on the model of the extensive ischemic injury of brain cortex show that this drug has good prospects for use in the neuroprotective treatment of stroke.

[EFFECT OF THE PROLYL-GLYCIL-PROLINE (PGP) AND ITS ACETYLATED FORM (N-AcPGP) ON PERMEABILITY OF SKIN VESSELS IN RATS].

This study is dedicated to the research of the regulatory peptide PGP and its acetylated form (N-AcPGP) effect on the paw edema formation and vascular permeability in rat skin. Edema was induced by subcutaneous administration of histamine. Vascular permeability was determined by intradermal injection of mast cells activators corticotropin-releasing hormone (CRH), lipopoly-saccharide (LPS), Synacthen (corticotropin analogue), histamine and compound 48/80. We established that PGP reduced the size of the paw edema, but N-AcPGP had an opposite effect increasing paw edema. Skin vascular permeability didn't increase in rats under the administration of PGP or N-AcPGP with additional injections of CRH, LPS and Synacthen, but with additional injections of histamine and substance 48/80. We demonstrated in vitro that pretreatment with both PGP and N-AcPGP reduced histamine secretion by rat's peritoneal mast cells under activation by Synacthen. These results provide evidence that the effect of the peptides on vascular permeability is mainly mediated by the influence on the secretory activity of mast cells.

[The role of ATP-dependent potassium channels and nitric oxide system in the neuroprotective effect of preconditioning]. / Rol' ATF-chuvstvitel'nykh kalievykh kanalov i oksida azota v zashchitnom effekte prekonditsionirovaniya mozga.

AIM: To study a role of ATP-dependent potassium channels (K+ATP) in the neuroprotective effect of ischemic (IP) and pharmacological (PP) preconditioning and evaluate the dynamics of blood nitric oxide (NO) metabolites in cerebral ischemia. MATERIAL AND METHODS: A model of ischemic stroke induced by the electrocoagulation of a middle cerebral artery (MCA) branch was used in male rats (n=86). Glibenclamide, a selective inhibitor of ATP-sensitive K+ channels, and diazoxide, a potassium channel activator, were used. IP and PP were performed 24 h before MCA occlusion. Blood concentrations of NO, NO3- and NO2-were measured 5, 24 and 72 h after occlusion. RESULTS: IP decreased a lesion area by 37% (p<0/05) and the preliminary introduction ofglibenclamide levelled the effect of IP. A protective effect of PP was similar to that of IP. A decrease in oxygenated R-conformers of Hb-NO and a reverse increase in non-oxygenated T-conformers as well as NO3- и NO2-were noted 5h after MCA occlusion. In the first 24 h after MCA occlusion, contents of NO3- and NO2- returned to normal values. There were changes in the concentrations of Hb-NO complexes as well, with the predominance of R-conformers and minimal contents of T-conformers. Moreover, the correlations between K+ATP channel blockade and the decrease in serum NO3- and NO2 were found (p<0/03). CONCLUSION: The neuroprotective effect of preconditioning is caused by the activation of K+ATP channels. An analysis of NO metabolite concentrations in the blood of rats with IP suggests that Hb-NO complexes belonging to R-conformers deposit and carry NO in tissues releasing NO accumulated via R→T transfer in conditions of ischemia.

[Some aspects of heart rate variability estimation in rats].

This study focuses on researching of heart rate variability (HRV) in rats with autoimmune myocarditis. Intact rats were investigated additionally. It was registered 2-, 5- and 20-min duration ECG from awake animals at rest-conditions and after cooling probe (CP), and then time domain and spectral parameters of HRV were calculated. We shown that 1) after CP decreasing of parasympathetic influence and augmentation of sympathetic influence on heart rate regulation in rats with autoimmune myocarditis was more manifested than in intact rats, 2) in CP with the 5-min ECG interval's duration was more informative for HRV estimation, 3) intracardiac inflammation leads to modification of correlation interconnection between some HRV-parameters, and that may talk about features of heart's chronotropic regulation in rats with autoimmune myocarditis.

[THE CHARACTERISTICS OF RETINA AT THE DEVELOPMENT OF PROLIFERATIVE VITREORETINOPATHY IN RATS AFTER INTRAOCULAR INJECTION OF CONCANAVALIN A AND DISPASE].

In this article we review and discuss the advantages of two proliferative vitreoretinopathy models in rats: intravitreal injection of proteolytic enzyme dispase and proinflammatory lectin concanavalin A. For the first time we selected clear morphological criteria for the retina evaluation during the inflammatory response. We also compared the effects of the injection of dispase and concanavalin on the 7th day after the drugs administration. We conclude that different doses of dispase can be used to get a stable model of PVR on different periods after the injection procedure.

[INFLUENCE OF 29-40 AND 65-76 MCP-1 FRAGMENTS ON MYOCARDIUM MORPHOLOGY IN RATS AFTER T9CTHFMIA-R'FPFRFTTON].

Monocyte chemotactic protein-1 (MCP-1) is a chemokine that stimulates monocytes and macrophage migration into the sites of acute of chronic inflammation. Our study shows morphological changes in ischemic myocardium followed by the administration of two synthetic structural fragments of MCP-1 that are monocyte/macrophage migration inductor peptide IX and peptide X an inhibitor. Results show that peptides can change time points of the inflammatory response in myocardium. Peptide IX administration leads to increased and accelerated inflammatory response, i. e. attracts an additional number of monocytes and macrophages into the inflammatory focus. The introduction of the peptide X observed prolonged inflammatory process with the overall gain signs of myocardial damage.

[Potential for the cytochemical study of CSF smears in the determination of neuroleukemia variants]. / O vozmozhnosti tsitokhimicheskogo issledovaniia likvornykh mazkov dlia opredeleniia variantov neiroleikemii.

The cytochemical test for PAS-positive material in CSF smears can be used for identification of leukemic cells of the lymphoid line. Qualitative smears were obtained from the CSF by the sedimentation method. Five patients were examined. A very suggestive case is described. The cytochemical studies of CSF smears help diagnose neuroleukemia and evaluate the treatment efficacy.