CC BY
30
Table 2. - Dynamics of middle molecular peptides in separated parodontal pockets (g/l)
Group Term of exposition Research period MM260 MM280
Healthy, n = 20 - - 0.22 ± 0.01 0.32 ± 0.01
1st group, 1 hour Before treatment 0.56 ± 0.02 0.67 ± 0.01
n = 10 After treatment 0.44 ± 0.01* 0.52 ± 0.02*
2nd group, 2 hours Before treatment 0.58 ± 0.02 0.66 ± 0.03
n = 10 After treatment 0.31 ± 0.01* 0.34 ± 0.01*
3 rd group, 3 hours Before treatment 0.57 ± .02 0.68 ± 0.03
n = 10 After treatment 0.30 ± 0.01* 0.35 ± 0.01*
Note: * — P < 0.05 in relation to size before treatment.
References:
1. Gabrielyan N. I., Filatov V. I. Experience in using the indicator of middle molecules in the blood to diagnose diseases in children ne-phrology//Laboratory business. - 1984. - № 3. - P. 138-140.
2. Kovtunova M. E., Pankov V. N. Ceruloplasmin and middle molecules as criteria of acute myelogenous leucosis//Clinical and laboratory diagnosis. - 2003. - № 5. - P. 52-54.
3. Maksimovskiy Y. M., Sargsyan M. A., Voloshin E. V. Influence of detoxification therapy using enterosgelya the duration of remission of chronic generalized periodontitis in appointing him to the immunomodulator "Imudon"//Dentistry for all. - 2004. - № 4. - P. 22-25.
4. Mavlyanova S. Z., Abdullaev A. A., Ismailov A. I. A retrospective analysis of medical records of patients with various forms of pemphigus for the period 1997-2007 according to Research Institute of Dermatology and Venereology of the Republic of Uzbekistan//Abstracts of the X All-Russian Congress of Dermatologists. - M., 2008. - P. 12-14.
5. Shogenova A. R. Status of middle plasma peptides in patients with complex treatment of inflammatory diseases of the maxillofacial area. Thesis. - Nalchik, 2004. - P. 22.
6. Suzdaltseva I. V. The pathogenetic role of endogenous intoxication with true pemphigus, optimization of its treatment. Thesis. -2009. - P. 28.
7. Wikstrom M., Renvert S., Jonnsson T., Dahlen G. Microbial associations in periodontitis sites before and after treatment//Oral Microbial Immunol. - 1993. - № 8. - P. 213-238.
8. WolffL., Dahlen G., Aeppli D. Bacteria as risk markers for periodontics// J. Periodontol. - 1994. - № 64. - P. 498-510.
9. Zakharova N. B., Ivanova I. A. Profile of cytokines in gingival fluid in periodontal diseases. Standardization of pre-analytical phase of research//Vector-Best News. - 2009. - № 4(54). - P. 1-3.
Ibadov Ravshan Alievich, Head of Department of Intensive Care in the Republican Specialized Center of Surgery of the name Acad. V. Vahidov, Doctor of Medical Sciences
E-mail: [email protected].
Ahmedova Khalida Yuldashevna, Deputy Director in the Scientific Research Institute of Epidemiology Microbiology
and Infectious Diseases, Doctor of Medical Sciences E-mail: [email protected] Abralov Hakimjan Kabuljanovich, Head of the Department of Surgery of congenital heart defects in the Republican Specialized Center of Surgery of the name Acad. V. Vahidov, doctor of Medical Sciences
E-mail: [email protected]
Alimdjanova Nelya Yunusovna, doctor-intern of resuscitation and intensive care in the Republican Specialized Center of Surgery of the name Acad. V. Vahidov
E-mail: [email protected]
Value of lymphocytes antigen-binding indicators to the cellular antigen
of the different organs in patients with congenital heart failure, complicated pulmonary hypertension on stages of the surgical treatment
Abstract: On 52 patients between the ages of 3 to 14 with congenital heart failure, complicated pulmonary hypertension on 3rd degree are learned dynamic of Antigen binding lymphocytes (ABL), specific to sensibility to the Tissue Antigen (TA) of brain, heart, lungs, and kidneys depend on different methods of insertion. By adding to traditional treatment of iPDE-5 showed noticeable decrease of the ABL to TA of the lungs, endocardium, and myocardium in patients the
high effect of the medication. Studies of the indicators of ABL to TA of organs in these patients allow objectively assess the intensity of destruction process and necrosis of this structures in these organs, and also, show the effect of iPDE-5 on this process.
Keywords: congenital heart failure, lungs hypertension, antigen binding lymphocytes, tissue antigen, iPDE-5.
Frequency of congenital heart failure (CHF) among all malformations is high enough and composes of 30%. In different authors, assessment of the frequency of occurrence is varies, but on average it is consist of 0,8-1,2 % of all newborns. Congenital heart failure in more then 5-% cases accompanied by hypervolemia (fluid overload) of pulmonary circulation (PC) with formation of pulmonary hypertension (PH)[2, 64; 4, 9]. PH is the main cause of development different in the expression hypoxia and hypoxemia, accompanied by an imbalance almost all chains non specific and cellular immunity. Development of the immunological insufficiency is causing high susceptibility to the variety infections and exposure to the development of multiple organ disorders, allergic and autoimmune processes, and high risk complications during cardio surgical involvement. With defeat of various geneses in any kind of organs causing their cell damaging intracellular process leads to dystrophy of the cell. The increase in the degree of the dystrophy causes destruction and necrosis of the cell. In the inter environment enter molecules and fragments of structural and functional proteins, that specify as organic. Tissue protein and molecules are "foreign" for inner environment, and take place as tissue antigen (TA), which activates immune reaction for neutralizing and elimination. As TA are located in inner environment in any kind of organs, they are differentiate and circulate in the blood antigen binding lymphocytes (ABL) that have ability specifically bind to TA only to this specific organ. Level of ABL to TA reflects the intensity of the destruction process and necrosis of organ's structures: increasing ABL in dynamic show on increasing, and decreasing ABL- on extinction intensity these process, which allow assess the degree of the damage of this organs and also effectiveness of the therapy. The value of the method for determining ABL to TA is its high sensitivity and specificity: containing ABL to TA reaches the diagnostic level on the early stages and appears way before clinical symptoms of the damaged organ that create possibility for earlier prognosis of risk development of the organic insufficiency. Statement of the reaction ABL with TA for several organs allow detect multiple organic damage of body during development of the pathology [1, 22-24; 3,115-118; 5, 13-17]. Pharmacotherapy (Drug treatment) of the PH is crucial and in most cases is the main correction method directed on central formation of pathophysiological mechanism. Nowadays, the scheme of the combine therapy is the subject of intensive studies (for example, analog of prostacyclin + antagonist endotelin-1 + inhibitors phosphodiesterase-5 (iPDE-5). The literature suggests successful using (iPDE-5) in patient with primary and secondary pulmonary hypertension. However, information about using inhibitors phosphodiesterase-5 (iPDE-5) in early childhood time is not much and it indicates a selective reduction of pressure in pulmonary artery [6,110-118; 7,110-118; 8, 55-56].
Purpose of research : Evaluate the significance of the indicators ABL to TA of different organs for identify the level of damage in brain tissue, heart, lungs and kidney in patients with CHF with PH based on treatment with inhibitors phosphodiesterase-5 (iPDE-5) and inhibitors AFP (iAFP).
Materials and methods of studies. In total, 52 patients between the ages of 3 to 14 with congenital heart failure such as VCD-43 (82, 7%) and PDA-9 (17, 3%) with pulmonary hyperten-
sion (PH) on 3rd degree (medium pressure in pulmonary artery 70-100 mm Hg).
All patients depend on treatment after the surgery has been divided into 2 groups: 1st group (24 patients) - comparative group, that was giving traditional therapy during surgical treatment (cardiac glycosides, metabolic therapy, diuretics are as indicated, cardio tonics); 2nd group (28 patients) — main group, patients to whom was added (iFDE-5) (Revatio, Pfizer) 3 mg/kg/day and iAFP as additional to traditional therapy. All the results was comparing with control group- indicators of almost all healthy people (n=22).
To all the patients on admission to hospital, after preparation for the surgery, after 10-14 days and 3 month after surgery together with general blood count analyses and special clinical studies measure the level of antigen binding lymphocytes (ABL) to tissue antigen (TA) of the brain, to TA of the heart-endocardium and myocardium, TA lungs and kidneys [1, 22-24; 3,115-118; 5, 13-17].
The essence of the method lies in the fact that lymphocytes of the patient incubate with erythrocytes that fixed on the surface of the tissue membrane with specific Antigen. Receptors of the surface on lymphocytes specifically bind with antigen on the surface of erythrocytes, and form "outlet" from binding lymphocytes and erythrocytes. Next, on the stained smears are calculate the percentage amount of binding lymphocytes in relation to the total pool. Determination of the antigen binding lymphocytes based on method Garib F.Yu with coauthors [1, 22-24] with using specific tissue antigen of different organs.
Results and their discussion. Studies of the ABL specific to sensibility to the tissue antigen of the brain, endocardium, myocardium, lungs and kidneys, reflecting the depth of the destructive changes of tissues, CHF patients with PH on admission showed noticeable changes comparative to the value of the control group.
Thus, the content of the blood in ABL to TA of the brain in average 4,8 times higher than in healthy person, endocardium- 5,9, myocardium as well as to TA of the brain in 4,8 times higher than healthy people, lungs- 5,87 and ABL to TA of kidney higher that in healthy people into 2,6 times as it showed on diagram (fig.1).
Accordingly, we examined patients revealed the presence of the significant destructive pathological process in organs, that obviously the reason that causing a consequence of long-term functional overvoltage of the heart and lungs with development of hypoxia and destruction of metabolism in tissues.
We have also studied the dynamics of the immune system and level of ABL in these patients after 10-14 days before surgical preparation, and after 14 days and 3 month after surgical interaction.
Analysis comparing the level of ABL, specific to sensibility to the tissue antigen of the brain, heart, lungs and kidneys, on patients of comparison group, where have been used traditional before surgery preparation during 12-14 days, showed a significant decrease in relative performance on admission only ABL to TA of lungs (5,96+0,16 and 6,16= 0,20%, while the norm range are 1,18+0,25 , respectively, P<0,05) and kidneys ( 4,54+0,14 and 5,02+0,14%, when normal range is 1,93+0,33, respectively, P<0,05), maintaining high significant difference with performance of healthy people ( P<0,001) (Table №1).
Category 1 Category 2 Category 3 Category 4 Fig. 1. Antigen binding lymphocytes of CHF patients with PH on admission to clinic ( %) Table 1. - Dynamic of antigen binding lymphocytes in patients of comparison group (without iPDE-5 intake)
ABL to TA Control On admission Before surgery After surgery
n = 22 n = 52 n = 24 On 12-14 days after 3 month
Brain 1.29 ± 0.13 6.14 ± 0.26* 5.71 ± 0.19 * 5.29 ± 0.18 *' ** 3.47 ± 0.12 ****
Endocardium 1.09 ± 0.25 6.32 ± 0.30* 6.08 ± 0.22 * 5.71 ± 0.20 *' ** 4.18 ± 0.21 ****
Myocardium 1.00 ± 0.28 4.57 ± 0.19* 4.46 ± 0.19 * 3.96 ± 0.16 *' ** 3.29 ± 0.17 ****
Lungs 1.18 ± 0.25 6.93 ± 0.26* 5.96 ± 0.16 *, ** 5.58 ± 0.17 *' ** 3.76 ± 0.14 ****
Liver 1.93 ± 0.33 5.04 ± 0.19* 4.54 ± 0.14 *' ** 4.63 ± 0.12 *' ** *** 3.88 ± 0.19 ****
Note:
*
**
***
****
— P < 0.05: The accuracy of the performance in comparison
— P < 0.05: The accuracy of the performance in comparison
— P < 0.05: The accuracy of the performance in comparison
— P < 0.05: The accuracy of the performance in comparison
After 12-14 days after surgery in this group of patients there is further reduction from baseline ABL to TA of the brain, heart, lungs and kidneys, but multiplicity reduction slightly higher figures only on ABL to TA of brain, myocardium and lungs (in 1.2 times, P < 0.05), remained meaningfully higher compared to the control group — in 4.1; 3.96 and 4.7 times (P < 0.05).
In this group of patients after surgery there is a slight increase ABL to TA of kidneys compare to previous survey, that possible connect to the own cardio surgical interventions and complicated process offunc-tional recovery of organs and systems of children organism (Table 2).
with control group; with on admission; with before surgery; with all studies and controls.
Dynamic od ABL to TA studied organs in this particular group of patients after 3 month after surgery show significantly decrease of indicators compare on admission, multiplicity reduction in this slightly higher on ABL to TA of brain and lungs - 1.8 times slightly decrease ABL to TA of endocardium - 1.5 times, TA of myo-card - 1.4 times, and kidneys - 1.3 times. In this, even after 3 month normalization of parameters is not happening yet. Thus, the level of the ABL to TA of the brain 2.7 times, endocardium and lungs -3.8 times, myocardium - 3.3 times, kidney - 2.0 times remain higher compare to control signs.
Brain Endocardium Myocardium Lungs Kidneys
Fig. 2. Dynamic indicators of ABL to TA in patients with traditional before surgery preparation ( %)
Table 2. - Dynamic of antigen binding lymphocytes in CHF patients with PH of 3rd degree ( %)
ABL to TA Control On admission Before surgery After surgery
n = 22 n = 52 n = 24 On 12-14 days after 3 month
Brain 1.29 ± 0.13 6.14 ± 0.26* 5.71 ± 0.19 * 4.93 ± 0.21 * 5.29 ± 0.18 *, ** 3.21 ± 0.15 * 3.47 ± 0.12 **** 2.48 ± 0.13 *
Endocardium 1.09 ± 0.25 6.32 ± 0.30* 6.08 ± 0.22 * 5.14 ± 0.18 * 5.71 ± 0.20 *, ** 4.86 ± 0.21 * 4.18 ± 0.21 **** 2.71 ± 0.14 *
Myocardium 1.00 ± 0.28 4.57 ± 0.19* 4.46 ± 0.19 * 4.14 ± 0.16 * 3.96 ± 0.16 *, ** 3.71 ± 0.18 * 3.29 ± 0.17 **** 2.33 ± 0.11 *
Lungs 1.18 ± 0.25 6.93 ± 0.26* 5.96 ± 0.16 *, ** 5.25 ± 0.21 * 5.58 ± 0.17 *' ** 4.75 ± 0.18 * 3.76 ± 0.14 **** 3.00 ± 0.14 *
Liver 1.93 ± 0.33 5.04 ± 0.19* 4.54 ± 0.14 *' ** 3.89 ± 0.19 * 4.63 ± 0.12 *, ** *** 4.82 ± 0.15 * 3.88 ± 0.19 **** 2.71 ± 0.14 *
Nate:
— P < 0.05: The accuracy of the performance in comparison with control group;
— P < 0.05: The accuracy of the performance in comparison with on admission;
— P < 0.05: The accuracy of the performance in comparison with before surgery;
— P < 0.05: The accuracy of the performance in comparison with all studies and controls.
In numerous there is indicators of the 1st group, and in dominant-indicators of the 2nd group.
Based on results of dynamic ABL to TA of the organs such as (brain, endocardium, myocardium, lungs, kidneys) in patients during pre-surgical period we may conclude that iPDA-5 intake show effective results (Table 2). The results as showed in diagram illustrate that the most effect noticeable in dynamic of indicators ABL to TA of lungs, endocardium and kidneys as compared
to initial parameters, and the relative performance of the 1st groups (Table 2, Fig. 3).
Analysis of the results that take place on 12-14 days after the surgery, showed the positive dynamic of indicators ABL to TA of the studied organs, exceeding in severity in 2nd groups ofpatients, except for the ABL to TA of the kidneys, where is show slight increase with respect to preoperative data as in the 1st and 2nd groups, possibly associated with the after surgery period (Table 2, Fig. 4).
Fig. 3. Dynamic of indicators Antigen binding lymphocytes before surgery of the 1st and 2nd groups ( %o)
A comparative analysis of the results ABL to TA of the organs (brain, endocardium, myocardium, lungs, and kidneys) was complete in patients that during 3 month continue to get traditional therapy (1st group, n = 17)and in patients which was added iPDA-5 to traditional therapy (2nd group, n = 21).
The results of the studies showed that indicators of ABL to tissue antigen of all named organs statistically (significantly) reduced with respect to all previous studies as in 1st and 2nd groups, but reduction of the severity differs significantly in 2nd group. So, if the indictors ABL to TA of the brain in 1st group in 1.8 times below baseline values, then in 2nd it will be 2.5 times; shows in 1.5 times decrease from baseline ABL to TA of the endocardium in 1st group and in 2.3 times in 2nd; in 1.4 times in 1st, 2.0 in 2nd in ABL to TA of the myocardium; in 1.8 and 2.3 times in ABL to TA of the lungs,
respectively 1.3 and 1.9 times bellow the degree of the ABL to TA of the kidneys in patients of the 1st and 2nd group, respectively relative to baseline values (Table 2, Fig. 5).
The results of the studies, as showed above, demonstrate that all values have tendency to normal, more it seen in 2nd group of patients, but continue to stay statistically (significant) high respectively to control values.
Therefore, immunological research studies on ABL in patients of CHF (Congenital Heart Failure) with PH (Pulmonary Hypertension) shows the present of the multiple organic lesions. A disorder of homeostasis and endogen intoxication of the organs contributes significantly to the development of the processes of destructions ad necrosis of the structures; significantly — in tissues of the heart, lungs, kidneys, and in moderate degree — in tissue of the brain.
V-
****
Fig. 4.
Meanwhile, sets the significant positive dynamic of the indicators of ABL to TA of organs, particularly, lungs and endocardium, patients of the main group (with iPDA-5 intake) on all the levels of the studies (during surgery preparation, after 12-14 days after the surgery and after 3 month after the surgery), with significant tendency to normalization, probably due to the mechanism of action, resulting in a decrease in pulmonary hypertension, improving homeostasis and significant decrease of the ABL level, specifically sensitized to tissue antigen of the inner organs, shows rapid decrease of the intensity of destructive processes.
Conclusions:
1. High level of ABL, specifically sensitized to TA of the brain, endocardium, myocardium and kidneys in patients with CHF with PH shows development of multi organic lesions, (ABL to TA of the brain and myocardium in average in 4.8 times, endocardium in 5.9 times,
2nd groups ( %)
lungs in 5.87 times and ABL to TA of kidneys in 2.6 times higher than in healthy individuals, P < 0.05)
2. Significant decrease ABL, specifically sensitized to TA of the lungs, endocardium, myocardium in patients with adding iPDA-5 in traditional treatment shows high effectively of medication (ABL to TA of the brain in 2.5 times; ABL to TA of endocardium in 2.3 times; in 2.0 times ofABL to TA of myocardium, 2.3 times ABL to TA of lungs, in 1.9 times decrease the level of the ABL to TA of kidneys relative to baseline values).
3. Studies of the ABL to TA of the lungs, heart, kidneys, and brain in patients with CHF with PH allows objectively evaluate intensity of the destruction process and necrosis of the structures in these organs, and also effect of iPDA-5 on this processes.
Dynamic of indicators of the antigen binding lymphocytes on 12—14th day after the surgery in 1st and
References:
1. Garib F. Y., Gurariy N. I., Gornina L. G. Quantitative methods of registration antigen binding lymphocytes outlet-forming lymphocytes in human. Thesis of 5th Republic conference CNIL medical university of Uzbekistan. - Tashkent, 1981. - P. 22-24.
2. Gorbachevskiy C. V., Belkina M. V. Examination of the patient with pulmonary hypertension in heart surgery clinic: methodical recommendation for physicians/written by academic RAMN K. A Bokereya. - M.: NCSSH named by Bakuleva RAMN, 2008. - P. 64, № 3 - P. 115-118.
3. Gulyamov N. G., Ahmedov H. Yu., Dalimov T. K., Imamova I. A. Diagnostic value of indicators antigen binding lymphocytes in assessment of the leasion of organs in infection and non infections pathology//Inf., immunity and pharmacology.
4. Ivanickiy A. V., Garbachevskiy S. V., Sobolev A. V. and etc. Integrated approach in diagnostics and treatment of congenital heart failure with high pulmonary hypertension//6th All-Russian Congress of heart surgeons: Thesis made. - M., 2000. - P. 9.
5. Leyderman I. N. Multi organic syndrome deficiency: Metabolic basis//Magazine Intensive therapy. - M., 1999. - № 2. - P. 8-13; № 3. - P. 13-17.
6. Yanulevich O. S. Using inhibitor of Phosphodiesteraze in diagnostic and treatment of pulmonary hypertension in children with congenital heart failure. Dissertation made by candidate of researcher in Tomsk. - 2010. - P. 110-118.
7. Garcia Martinez E., Ibarra De La Rosa I., Perez Navero J. L. et al. Sildenafil in the treatment of pulmonary hypertension//An Pediatr (Bare). - 2003, Jul. - V. 59, № 1. - P. 110-113.
8. Kleinsasser A., Loeckinger A., Hoermann C. et al. Sildenafil modulates hemodynamics and pulmonary gas exchange//Am J Respir Crit Care Med. - P. 55-56.
