Patologicheskaia fiziologiia i eksperimental'naia terapiia最新文献

The purpose: to ascertain possible cardioprotective effect of Sodium-L-arginine Succinate in case of myocardial lesions caused by Doxorubicin in rats. Methods. The effectiveness of the drug was assessed by morphometric and biochemical changes reflecting peroxidation intensity and structural and functional changes in myocardium. Results. Sodium-L-arginine Succinate used for the treatment and prophylaxis of antracyclic cardiomyopathy was demonstrated to decrease Doxorubicin effects lessening cardiomyocytal destruction and the left ventricular dysfunction with myocardial hypertrophy.

The purpose: Studying of efficiency of the combined application of the citicoline possessing nootropic and anticonvulsive action and antiepileptic drug of diazepam on the acute generalized convulsions (AGC) caused by a convulsant pentylentetrazole (PTZ).

Methods: Experiments are executed on the male Wistar rats (n = 68) weighing 160-190 g on the AGС model caused by of PTZ in a dose of 80 mg/kg, intraperitoneally (i.p.). For studying of efficiency of the combined use of drugs determined the minimum anticonvulsive action of a citicoline (Tserakson, «Nicomed Ferrer Internacional, S.A.») and diazepam (Relanium, Warsaw pharmaceutical plant of Polf AO, Warsaw, Poland). For this citicoline were administered i.p. in doses 500 and 300 mg/kg 1 hour before the PTZ and diazepam - in doses of 0,5 and 0,25 mg/kg 30 min before administration of PTZ. Control animals were injected with saline to the same extent and under the same experimental conditions.

Results: It is shown that the combined administration of a citicoline and diazepam in minimum active doses (300 and 0.25 mg/kg respectively), increases anticonvulsive properties of both drugs.

Conclusion: The combined administration of citicoline with diazepam in minimally active doses enhances anticonvulsant properties of both drugs, thereby reducing the risk of development of side effects. In addition, the research may serve as experimental justification for the use of drugs in case of convulsions for the purpose beneficial effect on cognitive function and delays of progressing of neurodegenerative processes.

Incidence of gastric ulcer is high in almost all countries of the world. On the development and course of the disease affect the state acid- and enzymes production stomach, immune status. The purpose was to determine the presence and power of correlative links secretory activity of the stomach and immune changes in the peripheral blood during exacerbation of ulcer disease stomach.

Methods: Surveyed in obtaining informed consent 42 patients with gastric ulcer in the acute phase prior to the eradication and antisecretory therapy and 40 healthy volunteers. On the state of function acid- and enzymes production of the gastric mucosa judged by the results of a 2-hour intragastric pH-metry and serum concentration pepsinogen, gastrin before the start of active treatment. Immunophenotype lymphocytes on CD-antigens (CD3, CD4, CD8, CD16, CD19, CD45, CD56) was measured by immunofluorescence, levels immunoglobulin isotype M, G, A, E - ELISA method.

Results: When short-term intragastric pH-metry of the stomach hyperacidity patients recorded 6.7 times more likely than healthy, normacidity - 12.3 times less. Reduction of acid production was observed up to 8.6 times more, indicating the development of mucosal atrophy. Basal pH in the antrum was lower by 54.5% than in the control group, with stimulation increased by 33.6%, but remained lower than the values of healthy individuals by 48.7%. When ELISA amount pepsinogen patients showed significant increase in serum levels of PG-I relative to the control group at 33.4%, PG-II - 52%. In assessing the immune status of patients were identified changes in system phagocytes, cellular and humoral links, most pronounced for severe current peptic ulcer disease.

Conclusion: The results indicate the presence of positive and negative correlative links mild to moderate force between indicators of secretory activity of gastric mucosal innate and adaptive immunity in patients with acute exacerbation of peptic ulcer disease. The presence and nature of these relationships should be taken into account when appointing antisecretory drugs.

The purpose: The purpose of research is to study cardiocytoprotective effect of cytoflavin in terms of aperinatal hypoxia in experiment.

Methods: During research the offspring (22 pups) of 15 females of white Wistar line rats aged 3-4 months were involved. The hypoxia was recreated by daily intraperitoneal introduction of sodium nitrite (NaNO2) in a dose of 5 mg/100 g of the body weight causing a moderately severe hypoxia. To females of the first group, and also their posterity medicamental correction wasn’t carried out. To females of the second group (8 females) after administration of sodium nitrite Cytoflavin was injected intraperitoneally. For an assessment of consequences of a perinatal hypoxia pups aged 7 days were slaughtered by means of a fast decapitation under ethereal anesthesia.

Results: It is taped that the hypoxia induced by nitrobonds has the expressed damaging effect on cardiomyocytes of newborn infant rats which is shown in the form of the hypoxemic and ischemic changes caused, first of all, by disturbance of integrity of cellular and mitochondrial membranes causes formation of hypoxemic type of a metabolism in a cardiac muscle, disturbance of energy balance in it found reflection in disturbance of automatism of a myocardium of experimental animals. Cytoflavin at pregnant females in experiment allows to lower a damage rate of cardiomyocytes at newborn animals, first of all, at the expense of his protective properties.

Conclusion: Membrane-protective properties of the drug along with its anti-hypoxic and antioxidant effects can put Cytoflavin in a number of promising drugs with cardiological and cytological protective action, leading to the optimization of energy metabolism in ischemic myocardium and allows it to take its rightful place among the modern drugs which are used to correct disorders of energy metabolism in the ischemic myocardium including pathologies in the neonatal period.

Research objective consisted in detection of nature of the changes of the myothermiс and the ergometric parameters of the contraction of the forward tibial muscle of rats in the course of performing of the tiring work at the saturation of an organism by therapeutic doses of dexamethasone.

Method: The experiments were performed on sexually mature rats-females (200-220 g), divided into control (n = 10) and experimental (n = 60) groups. The animals of experimental group received dexamethasone (D, KRKA, Slovenia) in a dose of 0,25 mg/kg (intraperitoneal, 1 time in 2 days) during from 10 to 60 days. On anesthetized animals (sodium thiopental, 100 mg/kg) with the use of myothermia and ergographia the nature of change of power of the muscle’s contraction in the course of the performance of the tiring work (3 six-second tetanus with external loading of 80 g) was studied.

Restults: At the initial stage of the development of iatrogenic hypercorticoidism (after 5-20 injections of D) the initial value of the external work of the muscle in comparison with the control is significantly lower (for 30-52%) and the temperature cost of the unit of the work (TCMW), on the contrary, - is higher (for 26-82%). On the end of the 2-month period of application of D the initial values of the power parameters of the muscle came back to control level. During the performance of the tiring tetanus in animal experimental groups the decline of the external work of the muscle is greater (69-73%) compared with the control (55%). This effect does not depend of the number of injections of D, which indicates about a high pathophysiological activity of glucocorticoid concerning working capacity of the muscle. At expressed fatigue the TCMW always increases from 104% (5 injections of D) to 230% (20 injections); at control animals the effect of the tiring work on TCMW is significantly weaker (28%). At long-term application of D (2 months) the described effect of the preparation is weakened, though remains accurately expressed.

Conclusion: The obtained data are considered from the point of view of formation at the hypercorticoidizm of the pathophysiological mechanism - the increase of power cost of muscular work. The revealed effect of D can be the cornerstone of the formation of the number of the pathophysiological mechanisms in neuromuscular system including causing the development of the myopathy at the hypercorticoidizm.

Kisspeptins, ligands of G protein-coupled receptor 54 (GPR54) encoded by the KiSS-1 gene, have recently emerged as key gatekeepers of the gonadotropic axis. Unlike its role at the hypothalamus on GnRH secretion, the effects of kisspeptins on gonadal and other peripheral tissues need to be clarified.

The purpose: To investigate the impact of experimentally induced hypogonadism in male rats on kisspeptins signaling in androgen-dependent tissues and blood.

Methods: Wistar male rats (total number 31) were used. Rats were divided into four groups. Group 1 (control, prepubertal rats aged 2 months, n = 7). Group 2 (control, pubertal rats aged 4 months, n = 6). Group 3 (unilaterally gonadectomized (ULG) in neonatal period). Group 4 (ULG testosterone-treated with testosterone (T) propionate 5 mg/kg/d during 10 days). In all the four groups density of GPR54 in testes and muscle and serum kisspeptin levels and T levels were estimated. The data was expressed as median values (Me) that were compared by Wilkokson criterion.

Results: Density of GPR54 in gonads in group 3 was lower than in group 2 (Me 0,88 ng/mg vs 1,13 ng/mg, p<0,05) and similar to group 1(Me 0,92 ng/mg). Unlike above, density of GPR54 in muscle in all groups 1,2,3 was not any differences (Me 0,1; 0,12; 0,13 ng/mg, p>0,05).Generally, density of GPR54 in group 2 in gonads was significantly higher than in the same group in muscle (Me 0,784 ng/mg vs 0.114 ng/mg, p<0,01). In the group 3 a significant decrease in serum levels of T (Me 15,39 ng/mg) in comparison with group 2 (Me 20,02 ng/mg, p<0,01) was invented. However, serum levels of kisspeptins in both groups had not any differences (0,27 ng/mg and 0,26 ng/mg, p>0,05). Treatment with testosterone propionate of the rats of group 4 lead to increase of serum level of T (from 15,39 ng/mg to 26,26 ng/mg, p<0,01), but didn`t modify the density of GPR54 in gonads (Me 0,79 ng/mg).

Conclusions: Hypogonadism lead to decrease of kisspeptins signaling in peripheral androgen-dependent tissues. Serum level of kisspeptins is physiologically low and, probably, it can not be used as a marker of activity of kisspeptins system. Efficacy of treatment with testosterone is not enough that is required a novel therapeutic resources.

The ischemic stroke is the reason of high mortality and population disability worldwide and it is closely connected with endothelium dysfunction (ED). The endothelium carries out regulation of specific functions, generally the universal modulator - nitrogen oxide. A number of enzymes participates in a production of nitric oxide, but specific for an endothelium is endothelial NO synthase (eNOS), which violation of regulation is observed at an ischemic stroke. Significant role in activity of eNOS regulation plays protein kinase C (PKC). In this review the following processes were investigated: ED and nitric oxide interrelation at an ischemic stroke; some features of biological activity of nitric oxide depending on a place of synthesis and on time of ischemic damage; eNOS activity regulation by means of PKC; interrelation between ED and PKC activity at oxidative stress; the main alarm ways including activation of eNOS and PKC which regulate microvascular permeability and a tone of vessels of a brain. Being guided by the carried-out analysis of theoretical data, it should be noted that at development of ED the PKC hyperactivity is observed, therefore, the search of the substances possessing inhibiting influence on activity of PKC for treatment of the majority of cardiovascular diseases and an ischemic stroke has become particularly important and perspective.

The purpose to identify key morphological features of the Astrocytes and Neurons in the acute local cerebral ischemia human cortex.

Subjects and methods: Left middle cerebral artery ischemic stroke died persons (n = 9) brain tissue samples from 3 zones: 1st - contiguous to the tissue necrotic damage site zone, 2nd - 5-10 cm distant from the previous one, 3rd - the damage site symmetrical zone of the contralateral hemisphere. For GFAP, MAP-2, NSE, p53 detection indirect immunoperoxidase immunohistochemical staining method has been used. Also, the samples were Nissl and Hematoxylin-Eosin stained.

Results: The most pronounced changes in the quantity and morphological structure of astrocytes and neurons are found in directly adjacent to the necrotic core region of theleft middle cerebral artery ischemic stroke brain. This indicates the prevalence of the inflammation processes around the area of nerve tissueischemic destruction. Morphological changes of neurons and astrocytes, apoptosis, enhanced neuron-astrocyte interaction found in the area bordering on necrotic core (5-10 cm from it), as well as ischemic hearth symmetrical sites of the contralateral hemisphere. This interaction is essential for the neuroplasticityrealization in the local ischemic brain injury.

Conclusion: The results obtained were shown the nerve tissue morphological characteristics changes occur in local cerebral cortex ischemic injury not only in the lesion, but also in the contralateral hemisphere. These changes are probably related to the implementation of neuroplasticity.

The purpose: The purpose of the study was to investigate the effect of the scheme autohemochemotherapy ATS on redox-dependent processes in red blood cells of tumor-bearing organism at an experimental ovarian cancer.

Methods: We studied the dynamics of redox-dependent processes in red blood cells of rats with experimental ascitic ovarian tumor during CAP-regimen autohemochemotherapy (cyclophosphamide, doxorubicin and cisplatin). We assessed the indicators of oxidative modification of proteins in erythrocytes - carbonyl derivatives at l = 346 nm, 370 nm, 430 nm and 530 nm, the parameters of lipid peroxidation - malondialdehyde, ketodienes, diene conjugates, Schiff bases; the enzymatic part of antioxidant system - the activity of catalase, glutathione transferase and superoxide dismutase biochemically.

Results: The red blood cells of tumor-bearing animals were found having increased the products of lipid peroxidation and oxidative modification of proteins while reducing the activity of antioxidant enzymes, suggesting a state of oxidative and carbonyl stress.

Conclusion: We showed that extracorporeal incubation of cytotoxic drugs used in the CAP scheme with autoblood prior to infusion - the method of autohemochemotherapy - either in monochemotherapy, or in CAP-regimen, decreases the levels of lipid peroxidation, oxidative modification of proteins and increases activity of first line antioxidant defense enzymes - catalase and superoxide dismutase in circulating red blood cells. Such dynamics of redox-dependent processes suggests a stabilizing effect of autohemochemotherapy on circulating erythrocytes in a tumor-bearing organism.

Purpose: Purpose. This article describes the use of capillary electrophoresis with UV detection to determine the ratio of protein-bound homocysteine and cysteine concentrations in human plasma.

Methods: Plasma samples were reduced with dithiothreitol and derivatized by thiocarbonyldiimidazole before being filtered again for purification of proteins. The pre-concentration of analytes was carried out directly in the capillary (48.5 cm in length and an inner diameter of 50 mkm) by NaOH post-injection. The eletrophoretic separation of analytes was carried out using 0.2 M ammonium acetate with 25 mM hexadecyltrimethylammonium bromide.

Results: Limit of quantitation for homocysteine was 0.8 mkM, reproducible ratio of cysteine/homocysteine <5%, full analysis time 15 min.

Conclusion: The ratio of bound cysteine to homocysteine is characterized by the same regularity as the ratio of their total content. It has a fairly high degree of correlation with the level of bound homocysteine and it is characterized by less variability than the level of total homocysteine. This has the advantage of use the bound cysteine/homocysteine ratio for assessing the risk of cardiovascular disease complications.