Analgesic and Psychotropic Effects of a New Bradykinin Antagonist.

A bradykinin B1 receptors antagonist PAV-0056, an 1,4-benzodiazepin-2-one derivative, intragastrically administrated to mice at doses of 0.1 and 1 mg/kg causes analgesia in the "formalin test" not inferior to that of diclofenac sodium (10 mg/kg) and tramadol (20 mg/kg). PAV-0056 at doses of 0.1 and 10 mg/kg has no anxiolytic and central muscle relaxant effects in mice and does not damage the gastric mucosa in rats. Based on the results of the conditioned place preference test, PAV-0056 also does not induce addiction in mice.

Pharmacological Effects of a New Soluble Guanylate Cyclase Stimulator in Experimental Ischemic Stroke.

We studied the action of a new indolinone derivative GRS, acetylsalicylic acid (ASA), and their combination on platelet aggregation, vasodilatory endothelial function, neurological status, and cerebral infarction area in experimental focal cerebral ischemia/reperfusion in rats. GRS compound (10 mg/kg), ASA (10 mg/kg), and their combination in the same doses were administered orally once a day as a suspension in 1% starch solution over 5 days after pathology modeling. Sham-operated and control animals were administered 1% starch solution. On day 5 after pathology modeling, platelet aggregation and brain damage area were studied in a half of rats in each group, and the vasodilatory function of the endothelium was studied in the other half. Neurological deficit was assessed 4 h and 1, 3, and 5 days after pathology modeling. GRS compound and ASA equally effectively prevent platelet aggregation and the development of neurological deficit in rats. GRS compound restores the vasodilatory effects of the endothelium, but only ASA contributes to reduction of the cerebral infarction area. In case of combined administration, GRS and ASA do not exhibit synergy in their antiaggregant effect.

Pharmacological Effects of a New Indolinone Derivative in Experimental Pneumonitis in Rats.

We studied the effect of a new indolinone derivative GRS on animal survival and on functioning and histological structure of the lungs in rats with experimental pneumonitis. The rats of experimental groups were intratracheally administered 0.5% aqueous solution of carrageenan under intramuscular anesthesia. Compound GRS (10 mg/kg; a suspension in 0.5% aqueous solution of carboxymethyl cellulose) was orally administered for 4 days starting from the day of carrageenan administration; another rat group received the aqueous solution of carboxymethyl cellulose alone. Control rats received intratracheally isotonic solution of sodium chloride. Animal mortality was registered over 5 days; on day 5, the respiratory parameters were measured, the lungs were weighed, pulmonary edema was evaluated, and histological structure of the lungs was studied. GRS compound improved survival of animals with modeled pneumonitis, restored the respiratory parameters to the level of control animals, and reduced pulmonary edema by 35% and the severity of histological damage score in the lungs by 17% (p<0.05).

Anti-Atherosclerotic Action of a New Stimulator of Soluble Guanylate Cyclase in an Experiment.

We studied the effect of an indolinone derivative GRS on the development of experimental atherosclerosis in C57BL/6 mice. Atherosclerosis was modeled by intraperitoneal administration of endothelial lipoprotein lipase inhibitor Kolliphor P 407 micro Geismar over 5 months. GRS was administered orally in a dose of 10 mg/kg once a day throughout the experiment. In 5 months, the levels of total cholesterol, LDL, and triglycerides in blood serum, as well as histological composition of the ascending aorta were studied. In mice with experimental atherosclerosis, we observed pronounced dyslipidemia with an increase in serum cholesterol, LDL, and triglycerides and accumulation of xanthoma cells in the aorta wall. Repeat administration of GRS did not eliminate dyslipidemia, but prevented an increase in the number of xanthoma cells in the aorta wall (p<0.05). The stimulator of soluble guanylate cyclase GRS did not exhibit hypolipidemic activity, but restored impaired endothelial function in the atherosclerosis model and prevented atherosclerotic damage to blood vessels and vascular wall remodeling.

Antihypertensive Effects of a Soluble Guanylate Cyclase Stimulator.

We studied antihypertensive activity of an indolinone derivative (compound GRS), a soluble guanylate cyclase stimulator and a drug with previously proven antiaggregant effects. Contraction activity of isolated aorta segments of Wistar-Kyoto (WKY) rats was assessed in vitro using a mechanographic method. Addition of GRS (0.1-100 µÐœ) resulted in dose-dependent relaxation of endothelium-denuded aorta segments. Pretreatment of aorta smooth muscle segments with a specific inhibitor of soluble guanylate cyclase (ODQ, 1 µM) weakened the vasodilatory effect of GRS. Antihypertensive activity of the indolinone derivative GRS was studied in spontaneously hypertensive SHR rats. Single oral administration of 5 and 10 mg/kg GRS was followed by a significant dose-dependent reduction of systolic and diastolic BP in SHR rats. Antihypertensive effect of GRS in a dose of 5 mg/kg was more potent than that of the reference drug isosorbide dinitrate. GRS in a dose of 10 mg/kg did not affect systolic and diastolic BP in normotensive WKY rats.

Effect of Ester Derivative of Indomethacin on Immune Inflammation.

The anti-inflammatory effect of the ester derivative of indomethacin (IML) in doses of 6.25, 12.5, and 25 mg/kg was studied in rats with modeled rheumatoid arthritis (adjuvant arthritis) and compared to the effects of the reference drug indomethacin in a dose of 1 mg/kg. IML in doses of 12.5 and 25 mg/kg reduced joint inflammation and promoted recovery of the microstructure of the synovial membrane and articular cartilage better than indomethacin. IML produced no ulcerogenic effect, while indomethacin concentration in the stomach wall after administration of IML was 1.8-3.4 times lower than after administration of the reference drug (p<0.05).

Effects of Levofloxacin on Blood Lymphocyte Apoptosis in Patients with Pulmonary Tuberculosis: an In Vitro Study.

The effects of a fluroquinolone levofloxacin on apoptosis of peripheral blood lymphocytes from patients with infiltrative pulmonary tuberculosis were studied in vitro. It was found that levofloxacin stimulated apoptotic cell death in tuberculosis. Addition of levofloxacin to cell suspension from patients with drug-susceptible form of tuberculosis led to an increase in the number of CD95+ and AnnV+ lymphocytes. In patients with drug-resistant form of tuberculosis, only the number of apoptotic lymphocytes, but not the count of CD95+ cells increased under these conditions.

In Vitro Study of the Modulatory Effects of Levofloxacin and BCG on Secretion of Proinflammatory Cytokines in Infiltrative Pulmonary Tuberculosis.

The effects levofloxacin (fluoroquinolone) and vaccinal BCG strain on cytokine production by blood mononuclear leukocytes was studied in patients with infiltrative pulmonary tuberculosis. Combined treatment with levofloxacin and vaccinal BCG strain suppressed the production of TNFα in drug-resistant pulmonary tuberculosis and production of IL-12 and IFNγ in drug-sensitive tuberculosis.

[INFLUENCE OF MEDICINAL PLANT EXTRACTS ON THE FUNCTIONS AND ANTIOXIDANT PROTECTION OF ERYTHROCYTES IN RATS WITH EXPERIMENTAL DIABETES MELLITUS].

Experiments on rats with diabetes mellitus model induced by streptosotocin and high (30%) fat diet showed that the daily treatment with aqueous extracts of great nettle leaves (100 mg/kg) and common burdock roots (25 mg/kg) for a period of 10 days led to a decrease in the glycemic index and triglyceride level and produced protective action on erythrocytes both in animals kept on a fat-rich diet and on the background of a low-caloric ration. Both medicinal plant extracts were comparable with reference drug metformin in reducing the concentration of glycosylated hemoglobin (by 12-31%) and ectoglobular hemoglobin (1.7-1.8 times, p <0.05), decreasing the content of malonic dialdehyde in erythrocytes (1.3 times, p < 0.05), and increasing erythrocyte deformability (1.3-1.4 times, p < 0.05) and activity of their antioxidant enzymes glutathione peroxidase, glutathione reductase, glutathione-S-transferase, catalase, and supe- roxide dismutase (1.2-2.6 times, p < 0.05). A diet with usual (8%) fat content improved the metabolic indices to a lower degree (on the average by 13-21%, p < 0.05) than did the proposed phytotherapy.

[Prolonged interferon papillomavirus infection treatment].

Prolonged interferon papillomavirus infection treatment. In patients with recurrent genital HPV caused by human papillomavirus types 6 and 11, the use of genferon suppository according to prolonged scheme (500 000 IU 2 times a day for 10 days and further 500 000 IU 2 times a week for 3 months) in comparison with a short scheme (500 000 IU, 2 times a day for 10 days) is more effective in preventing recurrence of infection due to the normalization, an immune and cytokine status, as well as the elimination of the infectious agent from the affected tissues. Prolongation of the drug use did not cause undesirable side effects. The effectiveness of prolonged treatment regimes is determined by the pharmacological properties genferon components that provide systemic and local effects.

[Molecular mechanisms of action of bisphosphonates and strontium ranelate].

Bisphosphonates are chemical analogs of isoprene lipids, which competitively decrease the activity of farnesyl diphosphate synthase in osteoclasts and thus retard prenylation. The non-prenylated small GTPases cannot attach to the membrane of osteoclasts, which decreases their resorptive function and accelerates apoptosis. Strontium ranelate activates the Wnt signal pathway (with participation of calcium-sensitive receptor), increases the replication activity (by changing the function of RANKL/RANK/OPG system) thus suppressing the apoptosis of osteoblasts, and retards the resorptive function by accelerating the apoptosis of osteoclasts.

Modulating effect of matrices with calcium phosphate coating on cytotoxicity of strontium ranelate and ibandronic acid in vitro.

Strontium ranelate (29 µg/ml) and ibandronic acid (50 µM) produced a cytotoxic effect on rat bone marrow myelokaryocytes in vitro. Strontium ranelate increased the number of myelokaryocytes with signs of necrosis, ibandronic acid increased the number of apoptotic and necrotic cells in the 9-day 2D culture of bone marrow cells on the plastic surface of the wells of culture plates. Co-culturing of the bone marrow with 3D matrices with microarc calcium phosphate coating that simulated bone mineral matrix increased intracellular ROS concentration, but abolished the cytotoxic effect of these drugs.

[Influence of a drug with anticonvulsant action on the level of bioelectric activity and ion content in brain structures].

1-[(3-chlorophenyl)phenylmethyl]urea--a compound possessing anticonvulsant activity, which has been selected by screening among 100 linear and cyclic urea derivatives, produces synchronization of spontaneous bioelectric activity, increased convulsion threshold in the motor cortex, dorsal hippocampus, and basolateral nuclei of amygdala, increased the index of low-frequency flicker acquisition, and reduced response to high-frequency oscillations in the visual cortex of rabbits. This compound also increased the extracellular content of sodium ions and reduced intracellular content of potassium ions in the motor cortex, dorsal hippocampus, and amygdala.

[Antiproliferative effect of polar lipids of maral antlers and peat in prostate benign hyperplasia model].

Lipids isolated from maral antlers and peat decreased the prostate posterior and lateral lobule mass and normalized its acinar and stromal histological structure, reduced protein content, decreased formation of lipid peroxidation products, and intensified antioxidant protection in homogenates, decreased prolactine and 5a-dihydrotestosterone blood level, and increased testosterone blood content in male rats of late reproductive age with prostate benign hyperplasia model caused by sulpiride injections. Polar lipids of maral antlers and peat more effectively suppress prostate hyperplasia and hyperprolactinemia development in comparison to the action of Serenoa repens extract (permixon).

[Effects of strontium ranelate on mononuclear leukocyte culture].

Strontium ranelate (SR) effect on the functional parameters of human blood mononuclear leukocytes culture has been investigated. SR in concentrations of 2.9, 29, and 290 mg/ml produces a dose-dependent decrease in the activity of alkaline phosphatase and the content of calcium and potassium ions in supernatants. In concentrations of 2.9 and 29 mg/ml, SR decreases, while in a concentration of 290 mg/ml it increases the intercellular phosphate ion content. Fibroblast- and osteoblast-like cells, which are capable of regulating mineral compound of intercellular liquid, are SR cellular targets in human blood mononuclear leukocytes culture.

[Influence of neuroprotectors with choline-positive action on the level of brain-injury markers during acute ischemic stroke].

Choline-positive neuroprotectors citicoline and choline alfoscerate decreased blood concentration of protein S100 in clinical trial on 52 patients in the first days after acute ischemic stroke. Neuroprotective therapy has also produced stabilization of blood-brain barrier.

[The effect of phospholipid hepatoprotectors on lipid peroxidation in liver and content of cytokines in the blood in experimental pathology caused by isoniazid].

The purpose--to investigate the influence of hepatoprotective agents of phospholipids'structure essentiale, eplir and its combinations with amber acid on rats liver functional state, lipoperoxidation and bioenergetics, also tumor necrosis factor-a and interleukin-10 blood content in experimental isoniazid intoxication. These agents demonstrated antioxidant action, decreased the common and indirect bilirubine, tumor necrosis factor-alpha blood content, aminotransferase and alkaline phosphatase activity, increased the interleukin-10 blood content. Isonoazid uncoupled the substrate oxidation with ADP phosphorylation and inhibited the respiratory activity of liver mitochondrions. Essentiale and eplir increased the coupling of oxidation with ATP synthesis, in combination with amber acid improved kinetic characteristics of liver mitochondrions.

[Correction of experimental anxiety behavior by meadowsweet (Filipendula vulgaris) extracts].

Influence of aqueous and aqueous-ethanol extracts of meadowsweet (Filipendula vulgaris) on the behavior of albino mice in anxiety models has been studied. It is established that the aqueous and 95% aqueous ethanol extracts of meadowsweet produce the most expressed anxiolytic action in the elevated plus-maze, open field, and emotional reaction tests. The anxiolytic activity of these extracts exceeds that of the reference valerian extract.

[Treatment of chlamydial infection in chronic prostatitis].

Clinical efficacy of cycloferon (solution for injections) in combination with azitromycin was studied in males with newly diagnosed chronic prostatitis of chlamydial etiology and silent urogenital chlamydial infection. Administration of cycloferon in recommended regimen promotes clinical recovery and prevents recurrences. High clinical efficacy of cycloferon results from immunotropic activity of the drug which normalizes immune response and leads to elimination of the pathogen 3-6 months after the end of the treatment.

[Gastroprotective action of the nettle extract in experimental peptic ulcer].

Nettle extract produced from leaves crushed to 40-70 nm fragments protects the stomach mucous membrane, and does it better than the extract derived from same leaves crushed to 1 mm fragments, on the models of peptic ulcers caused by acetylsalicylic acid, histamine, prednisolone, and immobilized stress. The antiulcer activity of the nettle extract from 40-70 nm fragments is comparable with the effect of buckthorn oil. Nettle extracts also hinder the excess acid secretion and diminish the acidity of stomach juice in experimental peptic ulcer caused by pylorus ligation.