Dynamics of endothelial and inducible synthase nitric oxide in experimental osteoarthritis and its correction

Study have been carried out on white Wistar line rats (age – 3 months, weight – 180-220 g). According to the tasks the animals were divided into 7 groups:1st group is intact (n = 20). 2nd group is rats, which were modeled osteoarthritis without further correction and were withdrawn from the experiment in the first stage (7th day) (n=40). 3rd group is rats, which were modeled osteoarthritis without further correction and removed from the experiment in the second stage (21st day) (n=40). 4th group is rats, in which experimental osteoarthritis was corrected with nonsteroidal anti-inflammatory drugs (NSAIDs) (Diclofenac) and aminoguanidine and removed from the experiment in the first stage (7th day) (n=20). 5th group is rats, in which experimental osteoarthritis was corrected with NSAIDs (Diclofenac) and aminoguanidine and withdrawn from the experiment in the second stage (21st day) (n=20). 6th group is rats, where experimental osteoarthritis was corrected using NSAIDs and a 7% L-arginine solution and withdrawn from the experiment in the first stage (7th day) (n=20)7th group is rats, in which experimental osteoarthritis was corrected with NSAIDs and 7% L-arginine solution and withdrawn from the experiment in the second stage (21st day) (n=20)Animals were withdrawn from the experiment for the 7th day and the 21st day after the simulation of the pathological condition. NSAIDs (Diclofenac), aminoguanidine and L-arginine were administered from the beginning of the study.During the experiment was found nitric oxide hyperproduction by increasing the activity of inducible NO synthase. It was found decreased endothelial NO synthase activity against the background of experimental osteoarthritis development and the induced inducible NO synthase activation. It has been proven aminoguadine correction effectiveness (inducible NO-synthase inhibitor) of endothelial dysfunction in osteoarthritis. It has been established the feasibility of using L-arginine as a corrective agent for endothelial dysfunction in experimental osteoarthritis. Correction agents comparative characteristics showed that the use of nitric oxide donor is more effective compared to  inducible NO synthase inhibition

Researc of pro- and anti-inflammatory cytokines dynamic on the background of endothelial dysfunction development induced by experimental osteoarthrosis

Study have been carried out on white Wistar line rats (age – 3 months, weight – 180-220 g). According to the tasks the animals were divided into 7 groups:1st group is intact (n = 20). 2nd group is rats, which were modeled osteoarthritis without further correction and were withdrawn from the experiment in the first stage (7th day) (n=40). 3rd group is rats, which were modeled osteoarthritis without further correction and removed from the experiment in the second stage (21st day) (n=40). 4th group is rats, in which experimental osteoarthritis was corrected with nonsteroidal anti-inflammatory drugs (NSAIDs) (Diclofenac) and aminoguanidine and removed from the experiment in the first stage (7th day) (n=20). 5th group is rats, in which experimental osteoarthritis was corrected with NSAIDs (Diclofenac) and aminoguanidine and withdrawn from the experiment in the second stage (21st day) (n=20). 6th group is rats, where experimental osteoarthritis was corrected using NSAIDs and a 7% L-arginine solution and withdrawn from the experiment in the first stage (7th day) (n=20). 7th group is rats, in which experimental osteoarthritis was corrected with NSAIDs and 7% L-arginine solution and withdrawn from the experiment in the second stage (21st day) (n=20). Animals were withdrawn from the experiment for the 7th day and the 21st day after the simulation of the pathological condition. NSAIDs (Diclofenac), aminoguanidine and L-arginine were administered from the beginning of the study.It were found during the experiment, increased levels of Interleukin 1β and Interleukin 10 in the simulated osteoarthrosis pathogenesis. It has been established positive dynamics of these cytokines in the endothelial dysfunction correction at osteoarthritis with the aminoguadine correction. It was revealed more pronounced efficacy of using L-arginine as a corrective means of impaired endothelial function in experimental osteoarthritis. Comparative characteristics of correction agents has shown that the use of nitric oxide donor is more effective than incubation of inducible NO synthase. It was proved  normalization of endothelial functional status indicators in the group of animals treated with L-arginine as a part of complex correction of osteoarthrosis was proved

Analysis interconnection level index marker by endothelial NOS, hypoxia and dysfunction in the pathogenesis of experimental diabetic retinopathy

The aim of the study was to analyze changes in erythrocyte diphosphoglycerate levels and Willebrand factor in the development of hypoxia and endothelial dysfunction in experimental diabetic retinopathy. The study was performed on white Wistar rats weighing 180-200 g. Our results indicate the development of hypoxia on the 30th day of development of experimental diabetic retinopathy with subsequent progression of pathological changes on the 60th and 180th day of the study, as evidenced by the decrease level of 2,3 diphosphoglycerate of erythrocytes in the 2nd group (p <0,001). The most pronounced increase in the studied marker of hypoxia was detected in the 3rd stage of the experiment (p <0,001). As a result of our study, a violation of the structural and functional state of the endothelium in experimental diabetic retinopathy was proved, as evidenced by an increase in the level of Willeband factor in group 2 (p <0.001), most pronounced in stage 3. The most pronounced increase in the level of Willebrand factor was detected in the 3rd stage of the experiment (p <0.001). Analyzing the data obtained, we can say that there is a relationship between the development of hypoxia and endothelial dysfunction in the pathogenesis of experimental diabetic retinopathy

Analysis of peroxidase activity in diabetic retinopathy and in applying various corrective means

Hyperglycemia stimulates the development of oxidative stress, which in turn is a powerful pathophysiological mechanism for the development of microvascular complications in diabetes. Increased production of reactive oxygen species is observed both during development and during the progression of diabetic retinopathy.The study was performed on white Wistar rats weighing 180-200 g. According to the tasks, the animals were divided into 7 groups: 1st group - 60 intact animals; Group 2 - 60 animals in which diabetic retinopathy was simulated without further correction. Group 3 - 60 animals, which simulated diabetic retinopathy with subsequent correction of hyperglycemia; Group 4 - 60 animals in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept and L-arginine solution; Group 5 - 60 animals in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept and bromfenac; Group 6 - 60 animals in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac; Group 7 - 60 animals, which simulated diabetic retinopathy with subsequent correction of hyperglycemia, the introduction of aflibercept, a solution of L-arginine and citicoline.The results indicate the development of oxidative stress from the 30th and with subsequent progression on the 60th and 180th days of experimental diabetic retinopathy, which is confirmed by a decrease in peroxidase activity in the 2nd group, the maximum of which is observed in the 3rd stage. Correction with hypoglycemic agents in group 3 had a positive effect, but was not able to restore the activity of the antioxidant enzyme, so there was a need for additional drugs. The use of aflibercept and nitric oxide donor in group 4 to correct the development of diabetic retinopathy had a positive effect on increasing the activity of peroxidase, which peaked on the 180th day of the experiment, but did not reach the control values. The combined administration of bromfenac and aflibercept in group 5 was shown to significantly increase antioxidant activity, but not as significantly as in group 4. Administration of aflibercept, L-carnitine, and bromfenac to group 6 animals was shown to restore antioxidant protection as early as day 30 and was continued on days 60 and 180 of the study, but the results did not reach control values. The combination of metformin, aflibercept, L-arginine and citicoline in rats of the 7th group proved to be the most effective correction, as evidenced by the normalization of peroxidase activity on the 30th and 60th day of the experiment, and on the 180th recovery of marker activity to control values was recorded

Study of endothelial dysfunction and asymmetric dimethylarginine levels

The aim of the study was to analyze changes in the level of endothelin-1 and asymmetric dimethylarginine in the development of endothelial dysfunction in experimental diabetic retinopathy and various methods of its correction.The study was performed on white Wistar rats weighing 180-200 g. According to the tasks of the animal were divided into 7 groups:As a result of our study proved a violation of the structural and functional state of the endothelium in experimental diabetic retinopathy, as evidenced by elevated levels of ADMA and endothelin-1 in 2nd group (p <0.001), most pronounced in the 3rd stage. It was confirmed that the correction of the studied complication of diabetes mellitus only with a hypoglycemic drug, even with long-term administration, does not correct the development of endothelial dysfunction (p <0.001).It was found that the addition of aflibercept and a solution of L-arginine in the correction to hypoglycemic drugs significantly (p <0.001) improves the condition of the endothelium, but does not solve the problem completely. It is observed that the correction of the simulated pathological condition by reducing hyperglycemia, administration of aflibercept and bromfenac (group № 5) has a positive effect on the normalization of endothelial function markers (p <0.001), but the effect is less pronounced than in the following groups. It was found that in rats in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac (group № 6), the reduction of pathologically elevated levels of markers of endothelial dysfunction is more pronounced compared to the 3rd group, which indicates the feasibility of this method of correction. It was found that the most effective method of correction was in the 7th group of the experiment in which hyperglycemia was corrected, aflibercept, L-arginine and citicoline were obtained to normalize the levels of endothelial dysfunction markers - endothelin 1 and asymmetric dimethylarginine

Metabolic syndrome: review

The psychosomatic component of the metabolic syndrome, historical aspect of the problem under study, physiological and biochemical mechanisms of pathogenesis are considered in the article. The symptomatic components of the metabolic syndrome and their interrelation are outlined, the ways of diagnosis and therapy and  directions of modern research in this field are outlined

Changes of inducible NO synthase and Interleukin-1β on the background of experimental rhegmatogenous retinal detachment

Purpose: inflammatory processes investigation in the rhegmatogenous retinal detachment pathogenesis and analysis of correction methods effectiveness. On the 7th day in experimental groups observed increase in the interleukin 1β level and inducible NOS activity. On 14th day of the research, as in the 7th, also confirms inflammatory process development. In addition to presence of statistically significant differences between iNOS and IL 1β indices of all experimental groups in comparison with the data of intact animals at the level of significance p <0,05 (and iNOS - at the level of significance p <0,01), the tendency towards increased activation of inflammation in the group that did not receive corrective therapy, and decrease - in group № 4. The most positive therapeutic effect was observed in the 4th group at 21st day. Compared with data of intact rats in group № 2, for given day, increased activity of e inducible NOS at the level of significance was already p <0.01. Differences of group № 3 remained at level of significance p <0,05. In this case, no differences were found when comparing inducible NO-synthase activity in animals of group number 4 and control group. At the same time, there are very significant differences in the comparison of data groups № 4 and № 2. the superiority of the proposed correction suggests decrease in iNOS pathological activity in the rats of the above group compared with the data of the third group (p <0,05). In the analysis IL 1β dynamics at the 21st day, there was no difference in the results of groups number 3 and number 4 in comparison with the values of intact animals. At the same time, difference between fourth group, which received the correction proposed by us in comparison with the data of the second group, in which the simulated pathology was not adjusted, increased. Foregoing confirms the effectiveness of cytokoline and D-asparagine use in complex with the administration of L-arginine 7% solution against the background of experimental rhegmatogenous retinal detachment

The choice of the optimal experimental model of myocardial infarction

Nowadays myocardial infarction has a high percentage of mortality [12], and is widespread inUkraine and Western countries [1, 2, 3]. Such a situation calls for the development of a new model of myocardial infarction, which would be as simple and effective as possible. In this article, a model of myocardial infarction with the use of inhalation anesthesia with chloroform is proposed

Changes in the functional state of the endothelium in conditions of experimental rhegmatogenous retinal detachment and its correction

RRD – photoreceptors detachment from retinal pigment epithelial by retrovitreal fluid, which penetrates through the breakdown of the neurosensory part. Purpose: investigation of endothelial dysfunction in rhegmatogenous retinal detachment pathogenesis and analysis of correction methods effectiveness. Von Willebrand factor (VWF) is common marker of endothelial dysfunction. It was established increase in its level in the 7th day of the research in all groups in which rats were modeled rhegmatogenous retinal detachment. Differences in the comparison of these groups among themselves have not been identified. At 14th day, it is observed endothelial dysfunction development in group 2 (differences in comparison with the data of intact animals already at the level of significance p <0.01). In group of rats receiving a two-component correction, decrease in the level of VWF was found. In the group receiving the three-component correction, the level of the von Willebrand factor is more strongly approximated to the norm (p <0.05 when comparing the data of this group and the animals that did not undergo correction of the experimental RRD) On 21st day no differences were found when comparing the results of intact animals with the data of each group receiving correction of the modeled RRD, indicating the normalization of endothelial cells functioning. It is worth noting that in the group in which animals received cytokoline, D-asparagine and L-arginine (group №4), most expressed normalized functional state of the endothelium, as evidenced by the differences in comparison with the data of 2nd and 3rd groups on levels of significance p <0.0

Changes in the functional state of the endothelium in conditions of experimental rhegmatogenous retinal detachment and its correction

Levytskyi I. М., Savytskyi I. V., Levytska G. V., Miastkivska I. V. Changes in the functional state of the endothelium in conditions of experimental rhegmatogenous retinal detachment and its correction. Journal of Education, Health and Sport. 2017;7(11):409-418. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.2784034 http://ojs.ukw.edu.pl/index.php/johs/article/view/6911 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 1223 (26.01.2017). 1223 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Authors 2017; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 06.11.2017. Revised: 20.11.2017. Accepted: 30.11.2017. CHANGES IN THE FUNCTIONAL STATE OF THE ENDOTHELIUM IN CONDITIONS OF EXPERIMENTAL RHEGMATOGENOUS RETINAL DETACHMENT AND ITS CORRECTION I. M. Levytskyi, I. V. Savytskyi, G. V. Levytska, I. V. Miastkivska Odessa National Medical University Abstract RRD – photoreceptors detachment from retinal pigment epithelial by retrovitreal fluid, which penetrates through the breakdown of the neurosensory part. Purpose: investigation of endothelial dysfunction in rhegmatogenous retinal detachment pathogenesis and analysis of correction methods effectiveness. Von Willebrand factor (VWF) is common marker of endothelial dysfunction. It was established increase in its level in the 7th day of the research in all groups in which rats were modeled rhegmatogenous retinal detachment. Differences in the comparison of these groups among themselves have not been identified. At 14th day, it is observed endothelial dysfunction development in group 2 (differences in comparison with the data of intact animals already at the level of significance p <0.01). In group of rats receiving a two-component correction, decrease in the level of VWF was found. In the group receiving the three-component correction, the level of the von Willebrand factor is more strongly approximated to the norm (p <0.05 when comparing the data of this group and the animals that did not undergo correction of the experimental RRD) On 21st day no differences were found when comparing the results of intact animals with the data of each group receiving correction of the modeled RRD, indicating the normalization of endothelial cells functioning. It is worth noting that in the group in which animals received cytokoline, D-asparagine and L-arginine (group №4), most expressed normalized functional state of the endothelium, as evidenced by the differences in comparison with the data of 2nd and 3rd groups on levels of significance p <0.01 Key words: experimental rhegmatogenous retinal detachment, endothelium dysfunction, correction, citokoline, D-asparagine, L-arginine