Research of changes in the level of vascular endothelial growth factor in experimental diabetic retinopathy. comparison of methods of correction

The aim of work to investigate the changes in the vascular endothelium growth factor in experimental animals, which were simulated diabetic retinopathy and against the background of its correction. The results of the analysis of the vascular growth factor in the 2nd group confirm the development of diabetic retinopathy, a particularly pronounced increase in the marker was detected on the 180th day of the development of the pathological process. It was established analyzing the data of group No. 3 that the correction of the pathological condition with hypoglycemic agents has partial positive effect but requires the involvement of additional means of correction in addition to the normalization of the level of glycemia. The results of the 4th group indicate that the involvement of a nitric oxide donor and aflibercept in the correction of diabetic retinopathy has positive effect on the reduction of the level of vascular growth factor, more pronounced compared to the 3rd group, but it does not reach normative values. It is observed that the correction of the simulated pathological condition by reducing hyperglycemia, administration of aflibercept and bromfenac (group No. 5) gives positive results, but less pronounced, compared to the data of the 4th group. It was found that in rats in which diabetic retinopathy was modeled with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac (group No. 6) at the first stage, there is a pronounced effectiveness of the proposed method of correction in comparison with the previously considered methods, the established positive trend is being followed also at the 2nd and 3rd stages of the experiment, which indicates the effectiveness of this correction method. The most pronounced positive effect of normalizing the level of vascular growth factor is observed when using a hypoglycemic drug in combination with the administration of aflibercept, a solution of L-arginine and citicoline (in group No. 7)

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

The role of lipid peroxidation in the pathogenesis of experimental diabetic retinopathy

The aim of work – to analysis of changes in the level of primary products of lipid peroxidation in experimental animals were simulated diabetic retinopathy and against the background of its correction. The obtained results indicate an increase in the content of lipid peroxidation, starting from the 30th and with further progression on the 60th and 180th days of experimental diabetic retinopathy, which is confirmed by an increase in the level of diene conjugates in the 2nd group, the maximum of which is observed at the 3rd stage. Correction with hypoglycemic agents in the 3rd group had a positive effect, but was not able to reduce the level of primary products of lipid peroxidation and restore antioxidant activity, so the use of additional agents became necessary. The use of aflibercept and a nitric oxide donor in the 4th group to correct the development of diabetic retinopathy significantly suppressed oxidative stress, the maximum of which occurred on the 180th day of the experiment, but did not reach control indicators. It was proven that the combined administration of bromfenac and aflibercept in the 5th group significantly reduced the number of primary LPO products, but not as significantly as in the 4th group. It was proved that the administration of aflibercept, L-carnitine and bromfenac to the animals of the 6th group reduced the content of diene conjugates already on the 30th and continued on the 60th and 180th days of the study, but it also did not reach the control indicators. 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 the level of the studied indicators on the 30th and 60th days of the experiment, and on the 180th, a decrease in the content of markers was detected oxidative stress to control indicators

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

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

Results of construction of correlation fields with trend lines and determination of direction of relationships between studied indicators

The aim of work is construction of correlation fields with trend lines and determination of the directionality of relationships between the investigated indicators of endothelial dysfunction, hypoxia and oxidative stress. Our results indicate that Willebrand factor, endothelin-1, 2,3-diphosphoglycerate, MDA, diene conjugates and eNOS are informative markers in the pathogenesis of experimental diabetic retinopathy. As a result of the research, it was established that there is a direct linear relationship between the Willebrand factor indicator and malondialdehyde, since the points of the correlation field are practically located on a straight line. We trace a similar type of direct linear relationship between Willebrand factor and diene conjugates. The specified results confirm the mutually aggravating relationship between the development of endothelial dysfunction and oxidative stress. We trace an inverse linear relationship between Willebrand factor and peroxidase. With an increase in Willebrand factor indicators by stages, we trace a decrease in peroxidase indicators, which indicates a relationship between endothelial dysfunction and a weakening of antioxidant protection. As a result of the study, it was established that the first two indicators: malondialdehyde and diene conjugates have an almost direct linear relationship with endothelin-1 indicators. These results confirm the relationship between the functional and structural state of the endothelium and the development of oxidative stress. It was established that the peroxidase indicator has an inverse linear relationship with the endothelin-1 indicators, which, as in the case of the Willebrand factor, indicates a violation of antioxidant protection in the event of endothelial dysfunction. As a result of the analysis of the dependence of the indicators of 2,3 diphosphoglycerate, Willebrand factor and eNOS, it was found that in the first two pairs of indicators, there is an inverse linear relationship between the indicators. As eNOS levels increase by stage, levels of 2,3 diphosphoglycerate and Willebrand factor decrease. In the case of an inverse relationship between the parameters of the Willebrand factor and eNOS, a practically functional connection is observed, since the coefficient of determination is almost 1. The obtained results indicate that the violation of the structural and functional state of the endothelium and the development of hypoxia are interconnected with the violation of the physiological pathway of oxide synthesis nitrogen. The relationship between the indicators of 2,3 diphosphoglycerate and the Willebrand factor was revealed, which has a direct relationship between the variables, which once again confirms the aggravating interaction between hypoxia and endothelial dysfunction

Research of changes in the level of endothelin-1 in experimental diabetic retinopathy. comparison of methods of correction

Diabetic retinopathy (DR) according to the WHO is the main cause of decreased vision and blindness due to diabetes. The aim of the study: to compare the effectiveness of correction of vasoconstriction in experimental diabetic retinopathy under the influence of different methods of correction. Our results indicate a violation of the functional state of blood vessels on the 30th day of experimental diabetic retinopathy with subsequent progression of pathological changes on the 60th and 180th day of the study, as evidenced by a significant increase in endothelin-1 in the 2nd group (p <0.001), most pronounced in the 3rd stage.In the analysis of data of group №3 it was found that the correction of pathological conditions with hypoglycemic agents has a positive effect, but does not allow to significantly correct pathologically increased levels of endothelin-1, which indicates the need for additional correction tools other than hyperglycemia.The results of group 4 indicate that the involvement of a donor of nitric oxide and aflibercept in the correction of diabetic retinopathy corrects the level of the studied marker, the most pronounced effect is observed on the 180th day of the experiment, but normative values can not be achieved. It was found that in the 5th group, in which the correction of the simulated pathological condition was performed by reducing hyperglycemia, the introduction of aflibercept and bromfenac gives positive results, but less pronounced than in the 4th group, where L-arginine solution was added to the complex correction. .It was found that rats of group 6, which simulated diabetic retinopathy with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac have a pronounced effectiveness of the proposed method of correction compared to previous methods, the level of vasoconstriction stage and continues to recover in the following stages of the experiment, but does not reach the normative values. The obtained data suggest that the method of correction selected in group 7, which includes reduction of hyperglycemia, administration of aflibercept, solution of L-arginine and citicoline is most effective for normalizing vascular tone and structural and functional state of the endothelium

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

Dynamic of blood glucose levels in the model of experimental diabetic retinopathy and different ways to correct it

The aim of our study was to analyze the changes in the blood glucose level in experimental animals that simulated diabetic retinopathy and against the background of its correction. The obtained results show the development of experimental diabetes when streptozotocin is administered at a dose of 55 mg/kg of animal weight against the background of a high-fat diet. Correction with hypoglycemic agents in the 3rd group had a positive effect, but it was not able to completely normalize the level of glycemia, so the need arose for the use of additional agents. The use of aflibercept and a nitric oxide donor in the 4th group had a more pronounced positive effect compared to the 3rd group, but the result did not reach the control indicators. Combined administration of bromfenac and aflibercept in the 5th group showed itself to be less effective in the study of the blood glucose level at all stages in comparison with the data of the 4th group, in which the NO donor was involved in the correction. Administation of aflibercept, L-carnitine and bromfenac to the animals of the 6th group had a more pronounced positive effect in comparison with the group No. 5, but did not reach the values of the 4th group of the experiment. The most effective correction was the combination of metformin, aflibercept, L-arginine and citicoline in rats of the 7th group, which is evidenced by the normalization of the level of the studied indicators on the 30th and 60th days of the experiment, and on the 180th, the most pronounced decrease was recorded hyperglycemia