Correction of Negative Effect of Antenatal Hypoxia on Liver Tissue Homeostasis in Newborn Albino Rats with Opioid Peptides.

We studied the possibility of correction of the negative effects of antenatal hypoxia on the liver tissue homeostasis in 7-day-old albino rats by administration of opioid peptides in a dose of 100 µg/kg on postnatal days 2-6. Administration of mixed µ/δ-opioid receptor agonist Dalargin neutralized deviations of gravimetric indicators, parameters of proliferative activity, and activity of the nucleolar apparatus of hepatocytes. Administration of the non-opiate Leu-enkephalin analogue did not normalize gravimetric parameters and nucleolar apparatus parameters, however, it significantly increased the pool of proliferating hepatocytes. Both peptides significantly reduced the intensity of free radical oxidation, improved antioxidant antiradical defense and resistance to peroxidation in the liver tissue of animals subjected to antenatal hypoxia.

Cytoprotective Effect of Peptide Sedatin, an Agonist of µ/δ-Opioid Receptors, on Primary Culture of Pulmonary Fibroblasts of Albino Rats under Conditions of Oxidative Stress.

We studied the effects of a synthetic analogue of dermorphin peptide sedatin on DNA synthesis, nucleolar apparatus, and parameters of free radical oxidation in the primary culture of pulmonary fibroblasts under conditions of oxidative stress. Oxidative stress significantly enhanced production of superoxide anion radical in the culture, sufficiently inhibited DNA synthesis in fibroblasts, and reduced the size of cell nuclei and parameters of the nucleolar apparatus. Sedatin prevented accumulation of free radical oxidation products and changes in karyometry parameters induced by oxidative stress. The peptide completely eliminated changes in the parameters of fibroblast nucleolar apparatus and abolished the inhibitory effect of oxidative stress on the number of DNA-synthesizing cells. Pretreatment with non-selective opioid receptor antagonist naloxone hydrochloride partially abolished the effects of sedatin in the primary culture of pulmonary fibroblasts.

Effect of Proline-Containing Oligopeptides PGP and RGP on Proliferative and Protein-Synthesizing Activity of Cultured Pulmonary Fibroblasts under Conditions of Oxidative Stress.

We studied the effect of glyprolines Pro-Gly-Pro (PGP) and Arg-Gly-Pro (RGP) on the primary culture of pulmonary fibroblasts from newborn albino rats under normal conditions and during oxidative stress. Under physiological conditions, the peptides had no effect on parameters of cell division. Hydrogen peroxide induced intensive oxidative stress accompanied by suppression of protein-synthesizing function. When hydrogen peroxide was added to the culture containing the test peptides, correction of the oxidative status was observed accompanied by activation of DNA-synthesizing activity and inhibition of lucigenin-dependent chemiluminescence.

PREVENTION OF HEART FAILURE PATIENTS WITH DECREASED EJECTION FRACTION IN NON-CARDIAC SURGERY: LEVOSIMENDAN OR ANESTHETIC CARDIOPROTECTION?.

BACKGROUND: Chronic heart failure (CHF) significantly worsens the prognosis of surgical treatment in noncardiac surgery, doubling mortality in compared with patients with coronary artery disease. Modern anesthesiology has at least two methods that potentially can improve the results in noncardiac surgery: anesthetic cardioprotection and the prevention of CHF decompensation with levosimendan. THE AIM: to study the efficacy of anesthetic cardioprotection andpreoperative preparation with levosimendan for the prevention of CHF decompensation in patients with reduced left ventricular ejectionfraction in noncardiac surgery. ENDPOINTS: the primary endpoint of the trial is the need and the maximum dose of inotropic drugs in the perioperative period; secondary point: the length of stay in the ICU, composite outcome, the dynamics of SI, FI, the content ofNT-proBNP and TnT Materials and methods: A randomized study was performed in three groups of patients during reconstructive operations on infrarenal part of aorta: control (traditional methodfor prevention of decompensation of CHF were used) - 31 patients; the group with the anesthetic cardioprotectivei - 31 patients; the group with a preoperative preparing with levosimendan - 30 patients. RESULTS: The incidence of heart failure (estimated by need to use inotropic drugs - IS) was 83% of control group patients and 75% of the patients of the group "VIMA" (p = 0,65). The number ofpatients needing the use of dobutamine in LS-group was significantly below, 50% (p = 0,02 relative to control group and p = 0,08 compared to the group VIMA). IS in the control group was 8 [6, 9] µg xkg⁻¹ - xmin⁻¹ ; group VIMA 8 [3; 9] mg xkg ⁻¹ xmin⁻¹ , whereas in the LS group only 2 [0; 7] mg ⁻¹ xkg⁻¹ xmin⁻¹ . Differences between groups credible, given the Bonferroni correction (p = 0,0015). In our study, was not identified significant differences in 30-day mortality: in the control group it was 3,4%; in the group VIMA of 3,1%; in the group of LS - 0% (p > 0,017); however, a composite outcome (number of adverse events (heart attack+stroke+mortality) were slightly better in the LS group - 17%, against 34% in the control group (p = 0,043). CONCLUSION: Preoperative preparation with levosimendan in patients with reduced fraction left ventricle ejection when performing reconstructive operations on the descending aorta reduces the incidence of episodes of decompensation of heart failure compared with the control group to 39,8% (p < 0,05). The use of this technique improves the composite outcome of operations on the infrarenal aorta. The study has not shown the influence of anesthetic cardioprotection in terms of hospitalization and composite outcome of surgical treatment.

Effects of Glyprolines on DNA Synthesis and Free Radical Oxidation in Mouse Gastric Mucosa Under Physiological Conditions and During Therapy with Oral Non-Steroid Anti-Inflammatory Drugs.

Studies by (3)H-thymidin autoradiography showed that injections of Pro-Gly-Pro and Arg-Gly-Pro peptides caused no changes in the DNA synthesis processes in the gastric mucosa. Both peptides induced a reduction of free radical oxidation activity, which was shown by chemiluminescence. Indomethacin induced lesions in the gastric mucosa, triggered oxidative stress, and reduced proliferative activity. Injection of Pro-Gly-Pro peptide before indomethacin corrected disorders in oxidative status and normalized DNA synthesis. Preinjection of Arg-Gly-Pro led to enlargement (by 4.6 times) of the focus of lesions in animals treated by indomethacin and augmented oxidative stress.

[EFFICACY AND SAFETY OF ROCURONIUM BROMIDE PRODUCED IN THE RUSSIAN FEDERATION: A SINGLE-BLIND RANDOMIZED CLINICAL TRIAL].

DESIGN: A single-blind comparative prospective randomised clinical trial. OBJECTIVE: To evaluate the efficacy and safety of Russian muscular relaxant (Kruarone) in comparison with Esmerone in multicomponent balanced anesthesia during laparoscopic cholecystectomy. 80 patients (23-68 years old) were examined. The patients were randomized into two equal groups. The results showed that Kruarone was effective relaxant with rapid onset of action, providing optimal conditions for muscle relaxation for laryngoscopy and tracheal intubation. Kruarone did not require frequent administration supports, providing high quality and stable neuromuscular blockade during surgery. There was no any one case of adverse events for the entire period of 24-hour surveillance, the drug has no cumulative effect. Kruarone did not cause allergic reactions and had no significant effect on hemodynamics. Thus Kruarone 0.6 mg/kg with an average total flow rate of the drug within 55 mg (39.6-75.43 mg) has the same effectiveness and safety with Esmerone in similar dosages.

Effects of antenatal hypoxia on the parameters of tissue homeostasis in the liver of albino rats.

We studied age-dependent dynamics of some liver parameters in albino rats after antenatal hypoxia. A decrease in body weight, absolute liver weight in newborn and mature rats, and a reduction of relative weight of the liver in mature animals were observed under these conditions. It was found that antenatal hypoxia promotes a decrease in DNA-synthetic activity of hepatocytes, intensifies free radical processes in the liver of newborn rats, and reduces the number of nucleoli in hepatocytes. In mature animals, antenatal hypoxia was followed by a decrease in hepatocyte sizes and area of nucleoli, an increase in the number of binuclear cells relative to mononuclear cells, and a decrease in the number of nucleoli in hepatocyte nuclei. These data can reflect impairment of tissue homeostasis in the liver of mammals exposed to antenatal hypoxia.

Proliferation and local manifestations of oxidative stress in mucous membrane of the ileum in patients at early stages of hemorrhagic fever with renal syndrome.

Activation of proliferative processes (Ki-67 proliferation index) and local oxidative stress was found in biopsy material from the mucosa of the large intestine of patients at the early stages of hemorrhagic fever with renal syndrome on days 5-10 after disease onset. Analysis of data of rectosigmoidoscopy and clinical examination refl ected the presence of colitis. It can be suggested that activation of proliferation is typically associated with local oxidative stress during various pathological processes.

Effect of HMG-CoA-reductase inhibitor on DNA synthesis and free radical oxidation in the gastric mucosa under normal conditions and during indometacin-induced ulcerative process in the stomach of albino mice.

We studied the effect of simvastatin (24 mg/kg per os for 30 days) on DNA synthesis ((3)H-thymidine autoradiography) and free radical oxidation (chemiluminescent method) in the gastric mucosa of albino mice under normal conditions and in ulcerative process induced by single indometacin administration. Simvastatin treatment activated free radical oxidation, which was seen from enhanced chemiluminescence in the mucosa homogenate (by 1.7-4.6 times). Administration of indometacin against the background of simvastatin treatment potentiated local oxidative stress and inhibited DNA synthesis. Under these conditions, the area of ulcerative lesion in the gastric mucosa increased by 3.0 times.

Effects of analogues of hydra peptide morphogen on DNA synthesis in the myocardium of newborn albino rats.

DNA-synthetic activity of myocardial cells was studied by (3)H-thymidine autoradiography in newborn albino rats after intraperitoneal injection of hydra peptide morphogen and its analogues. Administration of hydra peptide morphogen stimulated proliferative activity in the myocardium. Short analogues of hydra peptide morphogen, 6C and 3C peptides, produced a similar effect. Administration of arginine-containing analogue of hydra peptide morphogen significantly reduced the number of DNA-synthesizing nuclei in the ventricular myocardium of newborn albino rats. The role of the structure of the peptide molecule in the realization of the morphogenetic effects of hydra peptide morphogen is discussed.

Intensity of proliferative processes and degree of oxidative stress in the mucosa of the ileum in Crohn's disease.

The intensity of proliferative processes (estimated from Ki-67 expression) and degree oxidative stress (chemiluminescence assay) in biopsy specimens from the terminal portion of the ileal mucosa were studied in patients with Crohn's disease. Crohn's disease is characterized by hyper-regenerative processes in the ileal mucosa. The labeling index (Ki-67 expression) in biopsy specimens from the intact ileal mucosa in patients with the irritable bowel syndrome (reference group) was 10.64±0.62%. The corresponding values in patients receiving monotherapy with mesalazine (group 1) and combination therapy with mesalazine and dalargin (group 2) were 24.05±1.17 and 22.90±0.92%, respectively. Analysis of free radical oxidation showed that this state is accompanied oxidative stress. Spontaneous and H(2)O(2)-induced luminol-dependent chemiluminescence in biopsy specimens from the ileal mucosa was 1.8-2.3-fold higher compared to the reference group. After therapy, the labeling index in groups 1 and 2 decreased to 18.60±1.18 and 14.38±0.81%, respectively. Histologically, normalization of the disease symptoms was more pronounced after combination therapy. The decrease in free radical oxidation in this group of patients was more pronounced than after mesalazine monotherapy. Our results suggest that oxidative stress plays a role in the hyper-regenerative reaction.

Pathomorphological and immunohistochemical analysis of proliferative activity of the buccal mucosal epithelium in lichen planus.

Structural reorganization of the buccal mucosa and changes in proliferative activity of epitheliocytes in typical and erosive ulcerative lichen planus were studied. The most manifest diagnostically significant pathomorphological signs of lichen planus of the buccal mucosa are described: acanthosis, granulosis, parakeratosis, lymphocytic infiltration of the lamina propria, and edema. The most pronounced morphological changes and higher index of epitheliocyte proliferative activity (by expression of Ki-67) are characteristic of the erosive ulcerative form of the disease.

Status of free-radical oxidation and proliferation processes in patients with atopic dermatitis and lichen planus.

We studied the status of proliferation processes (by Ki-67 expression) and biogenesis of free radicals (by chemiluminescence method) in skin biopsy specimens from patients with atopic dermatitis and lichen planus. The index of Ki-67-positive nuclei significantly (p<0.05) increased to 28.40±2.00% in patients with dermatitis and to 32.6±1.9% in patients with lichen planus vs. 8.65±1.31% in the reference sample. Decompensated accumulation of free-radical oxidation products and inhibition of detoxification systems in skin biopsy specimens indicate the development of local oxidative stress. After therapy consisting of two 10-day courses of thymodepressin injections (0.1%, 1.0 ml) over 30 days, normalization of epidermis proliferation was observed. Labeling index in atopic dermatitis and lichen planus significantly decreased (p<0.05) to 17.00±1.87 and 10.9±1.1%, respectively. The role of free radicals in the development of hyperregeneratory processes during dermatoses is discussed.

Protective effect of dermorphin analogue sedatin on indomethacin-induced injury to the gastric mucosa.

Administration of indomethacin (250 mg/kg) to mice was followed by the formation of severe ulcerative and erosive injury to the gastric mucosa, inhibition of DNA synthesis, and development of oxidative stress. Fivefold pretreatment with sedatin (100 microg/kg) decreased the area of indomethacin-induced ulcers and erosions, stimulated DNA synthesis, and reduced the severity of oxidative stress. Non-arginine dermorphin analogue did not stimulate DNA synthesis and had no effect on the degree of oxidative stress. After pretreatment with L-NAME, sedatin did not modulate the synthesis of DNA under conditions of indomethacin-induced injury to the gastric mucosa.

Gastroprotective effect of dalargin in gastropathy due to treatment with nonsteroid antiinflammatory drugs.

We studied the effect of dalargin and its analogue [Dala]2-leu-enkephalin on the gastric mucosa in indomethacin-receiving animals. Indomethacin treatment was followed by severe injury to the gastric mucosa, decrease in proliferative activity of the epithelium, and stimulation of free-radical processes in gastric tissues. Dalargin significantly decreased the area of erosive and ulcerative lesions, had a normalizing effect on proliferation of epithelial cells, and reduced the degree of oxidative stress. Administration of [Dala]2-leu-enkephalin did not improve the state of the gastric mucosa.

Effect of beta-casomorphin-7 on DNA synthesis in cell populations of newborn albino rats.

We studied the effect of beta-casomorphin-7 on DNA synthesis in cell populations of newborn albino rats. Intraperitoneal administration of a beta-casein fragment heptapeptide beta-casomorphin-7 (1 mg/kg, 1 or 5 injections) activated proliferative processes in the myocardium and ectodermal and endodermal epithelium of newborn rats.

[Proliferative zones in the brain of the Amur sturgeon fry. Interactions with neuromeres and migration of secondary matrix zones].

Neurogenesis in the forebrain region was studied in the Amur sturgeon Acipenser schrenki fry using immunocytochemical marking of the proliferative nuclear antigen. The brain zones with high proliferative activities were located at the brain ventricle surface facing the periventricular cavity. In addition to the periventricular zone of primary proliferation, several secondary proliferative zones were found in the forebrain region of the Amur sturgeon.

Mechanisms for the effect of arginine-containing dermorphin analogue on proliferative processes in the gastric mucosa of albino rats.

Treatment with synthetic arginine-containing dermorphin analogue sedatin (100 mg/kg, 5 intraperitoneal injections) stimulated DNA synthesis in the gastric mucosa and decreased spontaneous and induced chemiluminescence in homogenates of the stomach from albino rats. Non-arginine sedatin analogue in the same dose had little effect on DNA synthesis and free radical oxidation. Fivefold treatment with NO synthase inhibitor L-NAME (9.3 x 10(-5) mol/kg) suppressed DNA synthesis in the gastric mucosa. Sedatin did not modulate DNA synthesis against the background of L-NAME administration.

Effect of dalargin on DNA synthesis in the gastric mucosa of albino rats.

3H-thymidine autoradiography and chemiluminescence study demonstrated pronounced effect of dalargin on the state of the gastric mucosa in albino rats. Dalargin stimulated DNA synthesis in the epithelium of the gastric mucosa and increased buffer capacity of its antiradical and antioxidant systems. Dalargin analogue not containing arginine ([D-Ala2]-leu-enkephalin) had little effect on these parameters. NO synthase inhibitor L-NAME abolished the effects of dalargin on DNA synthesis in the gastric mucosa. Our results suggest that the NO system plays an important role in the effect of dalargin on the gastric mucosa.

Epidermocyte nuclear-nucleolar system in atopic dermatitis and lichen planus.

Study of the epidermocyte nuclear-nucleolar system in atopic dermatitis and lichen planus by computer morphometry of preparations stained with 50% AgNO3 showed an increase in their morphometric parameters, reflecting hyperregeneratory processes.