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The influence of sulfaporine on indicators of nitric oxide system at experimental hypercholesterolemia
in north Albania. The geographic distribution was correlated caused by these viruses are seen in people living in or having vis-with the seasonality and profession of patients. The diseases ited these areas.
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Kutlikova Guzalhon Mahamadzhanovna, Assistant of the Department of Organic and Biological Chemistry, Andijan Medical Institute E-mail: [email protected]
The influence of sulfaporine on indicators of nitric oxide system at experimental hypercholesterolemia
Abstract: At the heart of the development of endothelial dysfunction at HCS an important role plays decrease of the synthesis of endothelial nitric oxide and increase its active radicals, causing a modification of low density lipoproteins. Sulfated chitosan reduces high levels of peroxynitrite and endothelin-1, increase the activity of eNOS and nitric oxide. Keywords: Nitric oxide system, sulfaporine, hypercholesterolemia.
So far, cardiovascular disease remains the leading cause of death in most developed countries in Europe, accounting for 40 % of all deaths. To date, set a number of factors of different nature [1], contributing to the development and progression of coronary heart disease — dyslipidemia, hypertension, overweight tala, smoking, physical inactivity, diabetes. Much attention is paid to the cellular and molecular bases of endothelial dysfunction [4; 5]. An important role in endothelial dysfunction belongs nitrogen oxide [6; 7].
The pathogenesis of atherosclerosis is quite difficult, but important role in this belongs to, is dyslipidemia that defines initiation of inflammation cascade mechanism. Therefore, an important role in the development of therapeutic measures belongs to lower cholesterol and other saturated fats [2; 7]. Last years much attention is paid to a natural biodegradable compounds, in particular chitosan and its derivatives. The Institute of Polymer Chemistry and Physics, Academy of Sciences of Uzbekistan under the leadership of SS Rashidova developed various chitosan derivatives.
Research objective: to evaluate the impact of sulfaporina on the system nitric oxide at experimental hypercholesterolemia (HCS).
Materials and research methods. To solve the problems, experiments were performed on 46 rabbits Chinchilla average weight of 2.5-3.0 kg., contained in the standard power mode. Experimental
Model HCS at experimental animals is reproduced by introduction by orally dissolved cholesterol (LDL) in sunflower oil in the ratio 0.2 g. per 1 kg. ofbody weight per day for 3 months. On the development of HCS was judged by the increase in total cholesterol and LDL (LDL) and high (HDL) density, which is determined on a biochemical analyzer.
After 2 months from the start of the experiment rabbits were divided into five groups:
• Group 1 — intact (rabbit 6), which through the mouth daily entered sunflower oil 1.0 ml/kg;
• Group 2 — HCS + H2 O — control (8 rabbit);
• Group 3 — HCS + gemfibrazil on100 mg/kg (8 rabbits);
• Group 4 — GCN + chitosan sulfate 25 mg/kg (rabbit 8);
• Group 5 — HCS + chitosan sulfate 50 mg/kg (rabbit 8).
Action of preparations is investigated in dynamics: an initial
3-month's condition and after one month ofintroduction of preparations. On the state of NO-ergic system judged by the level of nitric oxide metabolites [9], the activity of nitric oxide synthase (eNOS), the activity of nitrate reductase (NR) [10] and the level of peroxynitrite (ONOO) [9].
Results of investigation and discussion
The most important role in the implementation ofvascular endothelium function and dysfunction is plays a NO-ergic system.
Section 4. Medical science
During the development of the pathology of the vascular system is disturbed intracellular signaling system involving the synthesis of NOx eNOS. Actually carried out in this respect, the study showed a significant decrease in the content of the end products of nitric oxide, which corresponds to the progression of the severity of hypercholesterolemia. So, the content of the nitric oxide, as measured by the number of end products, on the 30th, 60th and 90th day of the experiment is reduced to 1.29 (p < 0.05); 1.53 (P < 0.01) and 2.11 (P < 0.001) times, respectively, the values of intact rabbits.
Such changes of nitrogen oxide levels in the blood serum may be due to the inhibition of endothelial nitric oxide synthase.
Indeed, the definition of eNOS activity showed its progressive decline of 1.25 (P < 0.05); 1.36 (P < 0.05) and 1.94 (p < 0.001) times, respectively, relative values of intact animals. Overall, we detected changes in the activity of the enzyme NOS consistent with shifts from the NO-ergic system level product — NOx. Thus, the lower the NOS enzyme activity, the lower the level of NOx.
In contrast to the content of NO , in the serum of rabbits with
x '
hypercholesterolemia observed increase in NOx bioconversion product — ONOO-. So, if the level of the latter on the 30 th day of entering exogenous cholesterol increases of 1.33 (P < 0.05) times the value of intact rabbits, then on the 60 th and 90 th day of the experiment — respectively 1.93 (P < 0.001) and 2.47 (P < 0.001) times.
Given that the conditions of HCS level of ONOO in the serum is significantly higher than in intact rabbits, we also determined the activity of another enzyme NO-ergic system involved in the bioconversion of nitric oxide to NR. At HCS NR enzyme activity in blood serum at 30 hours administration of exogenous cholesterol increased only 1.15 (P < 0.05) times, on the 60 th and 90 thday of administration — 1.3 (P < 0.05), and 1.76 (P < 0.01) times.
At HCS occur noticeable disturbances in NO-ergatic blood system. Given that NO is involved in blood serum, especially in the realization of a fur-organisms maintain the functional activity of the vascular endothelium, it becomes in-understand the genesis of hypertension in the studied pathologies. This is proved by the decrease in blood serum levels of NOx experimental animals due to their inhibition activity of the enzyme eNOS. And raising per-oxynitrite evidence of the negative role of the implementation of NO-ergic system and indicates a pathological role of these disorders in the genesis and progression of atherosclerosis.
Studies have shown that at level of cholesterol in LDL 2.38 ± 0.27 mmol/l, the content of nitrogen oxide and the activity of the enzyme constitute 16.68 ± 0.28 pg/ml and 35.05 ± 0.76 mmol/ min x mg. protein.
At the level of cholesterol in LDL 4.08 ± 0.10; 5.97 ± 0.09 and 6.48 ± 0.11 mmol/l of nitrogen oxide is progressively decreased to 12.94 ± 0.10; 10.91 ± 0.15 and 7.89 ± 0.31 mmol/l, respectively, nitric oxide synthase activity to 28.29 ± 0.49; 25.80 ± 0.73 and 18.05 ± 0.70 mmol/min x mg. protein, respectively, the concentration of cholesterol in LDL.
Analysis of the level of peroxynitrite and HF activity depending on the content of cholesterol in LDL showed that the cholesterol level in LDL 2.38 ± 0.27 mmol/L, content and activity ofperoxynitrite constitute NR0.15 ± 0.01 mmol/l and 2.72 ± 0.19 mu. mol/min x mg. protein, respectively. At the level of LDL cholesterol and 4.08 ± 0.10; 5.97 ± 0.09 and 6.48 ± 0.11 mmol/l peroxynitrite content increased to 0.20 ± 0.01; 0.29 ± 0.02 and 0.37 ± 0.01 mmol/l and the HF activity- up to 3.12 ± 0.11; 3.54 ± 0.10 and 4.78 ± 0.14 mmol/min x mg. protein, respectively, shall drop in LDL cholesterol.
Therefore, the progression of hypercholesterolemia and hyperbeta lipoproteinemia production of nitric oxide and its synthase
activity in endothelial cells is inhibited, the content of his active radicals increases progressively. In the dynamics of serum HCS occur noticeable disturbances in NO-ergic system. These disorders are characterized by a deficiency of NOx , due to low activity of NOS, as well as the accumulation in them bioconversion product of nitric oxide-peroxynitrite by increasing the activity of nitrate reductase and probably insolvency antioxidant defense system. Undoubtedly, the definition of nitric oxide in the blood serum followed by defective functioning of mechanisms to regulate the functional activity of not only the vascular endothelium, but also blood cells, contribute to the launch of the corresponding endothelial mechanisms of feedback , which negatively affects the course and outcome of the study of pathology. This circumstance requires consideration by us ofviolations in the choice of strategy and tactics of the treatment of hypercholesterolemia.
Pharmacotherapy gemfibrazil for 1 month resulted in a significant increase in the level of the end products of nitric oxide to 1.18 times the value of the control group of animals. However, despite this increase, their content remained low (reduced to 1.79 times, P < 0.001), indicating that the low activity of endothelial cells that produce nitric oxide. Proofs of this are the low values of eNOS activity. The values it increased only 1.24 (P < 0.05) times compared to the control group values, but remained significantly lower than in intact rabbits to 1.57 (P < 0.01) times.
Pharmacotherapy by sulfaporin at doses of 25 and 50 mg/kg was significantly increased the value of the control group the level of nitric oxide in the 1.56 and 2.26 times, respectively. If the dose of 25 mg/kg nitric oxide levels remained low at 1.36 (P < 0.05) times as compared with the intact rabbits, using the dose of 50 mg/kg, it was not different from the above parameters. At the same time, compared with gemfibrozil was more effective in correction of nitric oxide. Nitric oxide was 1.32 (P < 0.05) and 1.92 (P < 0.001) times higher than in the group of rabbits treated with gemfibrazil.
Along with this, we also observed activation of nitric oxide synthase. So, activity of eNOS significantly increased 1.37 (P < 0.05) and 1.41 (P < 0.05) times relative control group values doses respectively of 25 and 50 mg/kg. These figures remained below the guideline values of 1.42 (P < 0.05) and 1.38 (P < 0.05) times, respectively. It should be noted that these values are only slightly exceeded the indicators of the group of rabbits treated with gemfibrazil.
Experimental hypercholesterolemia pharmacotherapy with gemfibrazil peroxynitrite leads to a decrease in the level of 1.21 times the NR activity and 1.2 times the values of untreated group of animals. The studied indicators remained high, exceeding the values of intact rabbits to 2.07 (P < 0.001) and 1.47 (P < 0.01) times, respectively. Pharmacotherapy sulfaporin hypercholesterolemia in doses 25 and 50 mg/kg reduced the high values of peroxynitrite in 1.38 and 1.73 times, respectively, relative to the values of untreated group. Compared to the group receiving gemfibrozil, this reduction amounted to 1.15 and 1.45 times, respectively doses.
However, it should be noted that the relative values of intact rabbits peroxynitrite levels using sulfaporina 1.81 and 1.43 times higher than, respectively, the doses 25 and 50 mg/kg. Pharmacotherapy sulfaporinom at doses 25 and 50 mg/kg reduced the high activity of nitrate and 2.05 to 1.64 times the values of the untreated animal group. In this respect values animals treated with gemfibrozil, this reduction amounted to 1.37 and 1.71 times, respectively doses.
From these data it is evident that the HCS pharmacotherapy Sulfargin more effectively corrects the violations of nitric oxide system. Its effect is more pronounced manifested in the correction level of nitrogen oxide and nitrate. At the same time, the nitric oxide synthase
Integrated immunotherapy when nosocomial pneumonia in infants
activity remained low. Apparently, a significant decrease in the level of nitric oxide in the background of continuing high activity of nitric oxide synthase, is associated with accelerated its interaction with active forms of oxygen and the formation ofperoxynitrite. This is confirmed by peroxynitrite maintaining high values in the blood serum of experimental animals. In our view, a more efficient system in terms of nitrogen oxide correction it is advisable to use a dose of 25 mcg/kg .
The following conclusions can be drawn from the data:
1. On the basis of the development of endothelial dysfunction at HCS play an important role decrease the synthesis of endothelial nitric oxide and increase its active radicals, stipulated modification of low density lipoproteins.
2. Sulfated chitosan reduces high levels of peroxynitrite and endothelin-1, increase the activity of eNOS and nitric oxide.
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Movlanova Shakhnoza Sobirovna, senior staff scientist of Republican Specialized Scientific and Practical Medical Center of Pediatric, Republic of Uzbekistan
E-mail: [email protected]
Integrated immunotherapy when nosocomial pneumonia in infants
Аbstract: In the present study we examined 150 patients, including 110 children with NoP and 40 children with community-acquired pneumonia. There was a significant decrease in CD3+ lymphocytes to 43.4 ± 0.8 % (61.5 ± 1.2 %) (P < 0.001), CD4+ lymphocytes to 27.1 ± 0.7 % (39.1 ± 0.5 %), CD8+ lymphocytes to 15.2 ± 0.5 % as compared to the indices CAP 19.5 ± 1.1 % (P < 0.01), a significant increase in the relative number of CD20+ lymphocytes, which amounted to 28.6 ± 0.5 % compared with CAP index — 16.4 ± 1.1 % (P < 0.01) and CD16+ lymphocytes to the 16.8 ± 0.4 % compared with the CAP 10.2 ± 0.5 (P < 0.001). From the humoral immunity, which is expressed in a decrease in the level of serum IgA and IgM, which amounted to 44.5 ± 2.5 mg., %; 92.4 ± 3.1 mg., % respectively, compared with CAP (78.4 ± 3.2 mg., %; 121.4 ± 4.9 mg., %, P < 0.01).
Differentiated methods of treatment potentiate the efficacy of antibiotic treatment of NoP, allowing faster return to normal changes in laboratory and immunological parameters of blood, reducing the number of bed-days, reduced the risk of severe and protracted forms of adverse outcomes NoP.
Keywords: nosocomial pneumonia, immunology, cytokines.
Actuality
The nosocomial pneumonia (NoP), which develops against the background of secondary immunodeficiency states, worsens the prognosis and creates threat to a child's life. It is known that the immune response includes multidirectional types of effector mechanisms, each of which is optimal in respect of certain pathogens. Analysis of published data shows that in the children's NoP dysfunction of the immune system are varied, complex, contradictory and not fully understood.
The purpose of study is to develop treatment regimen of nosocomial pneumonia in young children based on interdependence received clinical and laboratory data.
Material and methods
In the present study we examined 150 patients, including 110 children with NoP and 40 children with community-acquired pneumonia (CAP) who treated at the intensive care units and intensive therapy, pulmonology of infants departments of RSSPMC Pediatrics MoHRoUz. Conducted clinical, laboratory methods of research, studied in detail immunological methods by immunoferment method.
Depending on the type of therapy examined children were divided into three groups: I — group consisted of 40 children patients with NoP which had received basic therapy. II — group consisted of 35 children patients with NoP which had received with basic therapy
