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of patients with purulent focus and a comprehensive traditional start of treatment for complex treatment of purulent wounds using therapy marked decrease LII values — to 3,2usl. Units, with an ad- a C02 laser and photodynamic therapy corresponded to the value ditional impact on the injury occurred PDT greater reduction in- of FRI normal numbers -1,56 ± 0,5 conv, while the control group dex LII — to 2,71usl. u Revealed changes suggest increasing non- remained elevated in patients — 2,14 ± 0.6 standard units specific resistance and decreasing toxicity. Within 7 days after the
Table 3. - Dynamics of FRI patients of the main and control group
Leukocyte index of intoxication (LII) Days of treatment
1 3 5 7
Main group 3,42±0,8777 2,71±0,81 1,71±0,59 1,56±0,5
Control group 3,34±1,19 3,2±1,10 2,32±0,54 2,14±0,6
Indicators of postoperative bed-days in the groups differed significantly. If the traditional treatment of patients with purulent wounds of the average hospital stay was 9 days, the patients of the main group of hospital stay was 7 days.
All 17 patients of the study group was well tolerated method of photodynamic therapy, side effects were observed. This allowed all 17 patients (100%) planned to undertake a full course of treatment, PDT. The use of PDT is not required additional analgesia.
Thus, the data prove conclusively on the basis of common assessment, local criteria and laboratory parameters ascertained a marked improvement in the results of treatment ofpatients with infected and purulent wounds when applied PDT. Clinical data correlate well with the results of bacteriological tests in vitro.
Conclusions
1. Antibacterial photodynamic therapy in complex treatment of patients with purulent destructive diseases of soft tissues allows an earlier date to achieve cleansing of purulent wounds and their healing.
2. Photodynamic therapy is a very effective non-invasive and gentle treatment of purulent wounds and serve as justification for the use of the method of photodynamic therapy in clinical practice for the treatment of acute inflammatory processes in combination with conventional treatments.
3. Experimental and clinical studies of the results of applying PDT showed its efficacy as an in vitro as in vivo.
References:
1. Abaev Y. K. Surgeon Directory. Wounds and wound infection/Rostov n/D: Phoenix - 2006.
2. Baranov E. V., Buravsky S. K., Tretyak S. I. Antimicrobial photodynamic therapy in complex treatment of patients with purulent septic pathology//Proceedings of the scientific-practical conference with international cooperation, Grodno, - 2011, P. 5-7.
3. Derbenyov V. A., Azimshoev A. M., Sharifov A. D. Photoditazine in the complex treatment of purulent wounds.//Ros. biotherapists. Jour. - 2007; 1: 14.
4. Izmailov S. G., Beschastnov V. V., Zharinov A. Y. Application of a new ointment formulations in the treatment of purulent wounds of soft tissues//Actual problems of septic diseases and postoperative complications: Abstracts of Novgorod, - 2007. - P. 51.
5. Surgical infections/Materials VII Russian scientific conference Moscow, November - 27-28. - 2008. - T. 6, Annex I. The - S. 76.
6. Ischuk A. V. The use of photodynamic therapy laser apparatus "Rodnik-1" with a photosensitizer "Chlorophillipt" in the treatment of purulent wounds and trophic ulcers of the lower limbs/AV Ischuk, SI Leonovich//Surgery News. - 2008. - № 1. - S. 44-54.
7. Saveliev V. S. Surgical infections of skin and soft tissues. Russian national guidelines. - Moscow, - 2009. - P. 8.
8. Stranadko E. F., Koraboev U. M., Thick M. P. Photodynamic therapy for purulent diseases ofthe soft tissues.//"Surgery", - 2000, - 9, P. 67-70.
9. Sadykov R. A., Kasymov K. R., Sadykov R. R. Technical and scientific aspects of the photodynamic therapy. - Tashkent, - 2012. - 167 p.
10. Sumlin R. M., Stenko A. A., Beetle I. G., Braga M. Y. The main directions of photodynamic therapy in medicine//News hirurgii. -2008. - № 3. - S. 155-162.
11. Jori G., Tonlorenzi D. Photodynamic therapy for the microbial infections.//Photodynamic News. - 1999; 2: 1: 2-3.
DOI: http://dx.doi.org/10.20534/ESR-16-9.10-116-119
Musakhodjaeva Diloram Abdullaevna, Doctor of Biological Science, professor Head of the Laboratory of Immunomorphology of the Institute of Immunology of the Academy of Sciences of the Republic of Uzbekistan, BD, Professor E-mail: [email protected] Fayzullaeva Nigora Yakhyaevna, senior researcher of the Laboratory of Immunomorphology of the Institute of Immunology of the Academy of Sciences of the Republic of Uzbekistan, PhD
The effectiveness of immunotherapy in children with cystic fibrosis
Abstract: We observed 48 children with CF aged from 4 to 8 years, as well as the indicators of 20 healthy children of the same age were studied. Based on the dynamics of immunological parameters the effectiveness of the drug polioxidonium was
The effectiveness of immunotherapy in children with cystic fibrosis
shown. After the course of treatment the T cell-mediated and humoral immunity were activated, and increased the activity of nonspecific protection factors, leading to the normalization of the IL-1 p and IL-8.
Keywords: children, cystic fibrosis, cellular and humoral, immunity, immunotherapy.
Cystic fibrosis (CF — is one of the most common mono-gene diseases with polihedral manifestation. CF is characterized by lesions of exocrine glands, organs and body systems, different heavy, flow and a poor prognosis [4; 9; 10; 11]. The disease is inherited in an autosomal recessive manner. The cause of CF — is the mutations of chloride channel gene (cystic fibrosis transmembrane conductance regulator) [8; 9]. Violation of transport of chloride ions leads to the breakdown of transport ofwater and dehydration secret. Secrets of the exocrine glands thicken, leading to the development of multisystem disease with a lesion of bronchopulmonary system, digestive system, reproductive system, etc., and, ultimately, to the patient's death [6; 7; 8].
In CF, in the pathological process involves the entire body, but the most — the respiratory and digestive (liver, pancreas, bile ducts), as well as sweat glands and sexual organs (especially in males) [9; 10]. The clinical picture is dominated by symptoms of bronchopulmonary and digestive systems, especially dysfunction of these systems in the greatest degree determine the tactics of treatment and outcome of this desease [2; 3; 5; 8].
The purpose of the research — is to study the performance of innate and adaptive immunity in children with cystic fibrosis to justify carrying out immunotherapy.
Material and methods. On the base of The Department of Pul-monology, the Republican Specialized Scientific and Practical Medical Center of Pediatrics (RSSPMCP) were examined 48 children with a mixed form of cystic fibrosis (intestinal and pulmonary) from 4 to 8 years. The survey was conducted in the acute phase in 29 (60.4%) patients, and in remission — in 19 (39.6%) patients. The control group consisted of 20 healthy children of the appropriate age.
Immunological studies carried out with the studying of the level of lymphocytes on the identification on the surface of the cluster differentiation CD3, CD4, CD8, CD16, CD20, CD95 and of CD25 with monoclonal antibodies of LT Series ("Sorbent"LLP, Moscow, Russia). The concentration of immunoglobulin A, M, G has been determined by Mancini's method. Neutrophil phagocytic activity has been determined using latex particles (1.5 md) by Kudryavtseva V. P. method. The concentration of cytokines: inter-leukin — 1 p (IL-1 p and interleukin-8 (IL-8) was determined by ELISA (reagents set of «Cytokine»LTD, Russia).
For statistical calculations used in standard programs (MS Excel 2002, Statistica 6,0). The reliability of differences between groups was assessed by the criterion of a Fischer — Student. Differences were considered statistically significant at P <0.05; P <0,01; P <0,001.
Results and their discussion. The analysis of comorbidities showed that 90% of children were observed ENT diseases. In 28.6% of the children there was a delay of physical development.
In the analysis of somatic diseases in history have 31.4% of the patients children rickets was diagnosed.
Analysis of the presence of bacterial and viral infections revealed the following pathogens: St.aureus, P.aeruginosa, E.coli, Klebsiella pneumonia, Herpes and Chlamydia and mycoplasma infection.
The data of the immunological examinations of children with cystic fibrosis show suppression of cell-mediated immunity. There has been a fairly low level of CD3 + -cells (44,2 ± 1,9% against 55,4 ± 1,2% in the control, p <0.01) and CD4 + -cells (25,4 ± 1,5% as opposed to 32, 1 ± 0,9%) (Table-1). By reducing the helper activity
was significantly depressed immunoregulatory index (1,2 ± 0,01 vs. 1,5 ± 0,02 p <0.05).
Also marked inhibition of the secretion of natural killer cells (8,2 ± 0,4% in comparison with control group values of 14.7 ± 0.5, p <0.05).
On the background of elevated level of CD20 + -cells in these children revealed disimmunoglobulinemia, i. e. a significant decrease of Ig G and Ig A, virtually unchanged values of IgM. Specific antibodies — the most powerful mechanism for binding and limiting the spread of pathogens of respiratory infections in children. When the primary immune response immunoglobulins M begin to form from the 4th day after exposure to antigens of the immune system. They capture free virions cover their surface, facilitate their recognition by phagocytic cells and "killer cells". The term life of Ig M on average is 7 days. If within the first 2 weeks of respiratory infections recorded the permanence and growth of concentrations of specific IgM, it can be assumed that it is this or that primary infection.
On the 14th day of antibody formation class G. This type of antibodies more effectively restrains and inhibits infection [7]. The life of any specific IgG in the average is 21 days. If, starting from the 4th week of the onset of infection seen a steady increase in IgG concentrations, it can be assumed that the development of primary infection continues. When re-exposed to the same antigens of pathogens of respiratory infections almost immediately formed of IgG antibodies [7].
One of the most important functional characteristics of a neutrophils is their phagocytic activity. The number of phagocytic neutrophil significantly reduced in children with cystic fibrosis (44,5 ± 1,9 vs. 54,8 ± 1,6%, p <0.01). Phagocytes being the first line of defense against infectious agents, in the most cases, protect the body against bacteria.
In children with CF is common a functional failure of phagocytes.
Table 1. - The status of innate and adaptive immunity of the surveyed children, (M ± m)
Indicators Control group, n=20 Children with CF, n=48
CD3+,% 54,8 ± 1,6 44,2 ± 1,3*
CD4+,% 32,3 ± 1,0 25,4 ± 0,9
CD8+,% 21,5 ± 0,8 20,7 ± 0,7
CD4/CD8 1,5 ± 0,02 1,22 ± 0,01*
CD16+,% 14,7 ± 0,5 8,2 ± 0,4*
CD20+,% 18,3 ± 0,9 25,8 ± 1,0*
IgG, mg/% 970 ± 37 695 ± 11,8*
IgA, mg/% 123,0 ± 7,2 86,5 ± 6,4*
IgM, mg/% 85,5 ± 4,9 87,8 ± 5,2
Phagocytosis,% 54,8 ± 1,6 44,5 ± 1,9*
IL-1p, pg/ml 22,7 ± 3,7 85,3 ± 5,6*
IL-8, pg/ml 14,8 ± 1,4 47,2 ± 2,2*
Note: * values are valid when comparing with the control group (p <0.05-0.001).
Current long-term immunosuppressive effect of the inflammatory process in lung tissue is manifested primarily in relation
to humoral immunity, increased production of proinflammatory cytokines (85,3 ± 1,3 pg / ml - IL-1|3; 47,2 ± 2,2 pg / ml IL-8 - in the study group compared with the control group - 22.7 ± 3.7 pg / ml and 14.8 ± 1.4 pg / ml, respectively, p <0.05-0.001) violation detection of microbial antigens inhibition of the cytotoxic effector function of NK-cells. A characteristic feature of chronic inflammation in the lungs of CF patients - persistent infiltration of the lung tissue with massive neutrophils in the airways.
Involvement of neutrophils into the lung tissue due to high levels ofIL-8- primary chemo attractant for neutrophils [1]. With increasing severity ofinflammation was a significant (p <0.01) increase in the levels ofpro-inflammatory cytokines: IL-1p and IL-8 [1]. Derivatives dying neutrophils - elastase, cathepsin G, proteinase, collagenase, gelatinase, factor plasminogen activation, free radicals, myeloperoxidase, oxidases, cytokines, endotoxin contribute to the development of "respiratory burst" and can directly destroy lung structure (elastin, fibronectin and other structural proteins) [1]. In addition, neutrophil elastase, - is potential stimulator of IL-8 production and bronchial secretions. Clinical manifestation ofthe vicious cycle ofinfection - inflammation - lung tissue damage is the progressive decline oflung function.
In this state of the immune system it becomes impossible elimination of intracellular pathological agent, in the body conditions for the spread ofchronic pathological focus in the lung tissue are formed.
The above led to the conclusion that in this cohort of patients have a place in violation of multivalent basic systems regulating the homeostasis of the immune system, which leads to a decrease in general resistance to infectious agents and the products of their metabolism.
Table 2. - Dynamics of immune parameters
Due to the fact that children with cystic fibrosis recorded marked deficiency in T-cells, their major subpopulations imbalance humoral defense reactions, decreased functional activity of leukocytes and phagocytic activity of neutrophils, due to which there was expression of proinflammatory cytokines using different Patient Therapy group of drugs that implement various ways pharmacokinetic effect.
To enhance the effectiveness of the base immunotropic treatment of cystic fibrosis, and in view of the typical changes in the immune status further recommended the appointment of drugs targeting T-B-dependent reactions. We proposed immunomodulatory drug Polioxidonium, which is an immunomodulator systemic action.
The data obtained after 3 months a course of treatment are presented in Table-2. Immunomodulating action Polioxidonium implemented through macrophage secretory activity affected the T-cell, a more pronounced against CD3 + lymphocytes (48,9 ± 1,4% in comparison with the group to treatment - 44,2 ± 1,9%, p <0.05). Positive shift CD4 + -cells resulting in increased immunoregulatory index. This effect is apparently due to the increased level of phagocytosis (49,8 ± 2,5% as compared to baseline - 44,5 ± 1,9%, p <0.05), which acts on and enhances production of interferon activity T-cell and killer activity (11,0 ± 0,9% in comparison with the values before the treatment - 8,2 ± 0,4%).
We would also like to note the positive impact Polyoxidonium the maintenance of serum immunoglobulins. There was a significant increase in their level (p <0.05).
during treatment Polyoxidonium, (M ± m)
Indicators Control group, n=20 Children with CF before treatment, n=48 After 3 months after treatment, n=42
CD3+,% 54,8 ± 1,6 44,2 ± 1,3* 48,9 ± 1,4**
CD4+,% 32,3 ± 1,0 25,4 ± 0,9* 29,5 ± 1,1**
CD8+,% 22,5 ± 0,8 20,7 ± 0,7 21,3 ± 0,9
CD4/CD8 1,4 ± 0,02 1,22 ± 0,01* 1,38 ± 0,02**
CD16+,% 14,7 ± 0,5 8,2 ± 0,4* 11,0 ± 0,9
CD20+,% 18,3 ± 0,9 25,8 ± 1,0* 22,3 ± 1,0
IgG, mg/% 970 ± 37 695 ± 11,8* 798 ± 12,5**
IgA, mg/% 123,0 ± 7,2 86,5 ± 6,4* 95,6 ± 7,2**
IgM, mg/% 85,5 ± 4,9 87,8 ± 5,2 88,2 ± 5,3
Phagocytosis,% 54,8 ± 1,6 44,5 ± 1,9* 49,8 ± 2,5**
IL-1ß, pg/ml 22,7 ± 3,7 85,3 ± 5,6* 55,8 ± 2,1**
IL-8, pg/ml 14,8 ± 1,4 37,2 ± 2,2 20,1 ± 1,2**
Note: * values are valid when compared with the control group (p <0.05-0.001) ** Values are valid when compared with the group to treatment (p <0.05-0.001).
Prediction of pulmonary disease in a child with immunodeficiency always serious, especially in children with combined immune deficiency.
When using immunomodulators is very important to the formation of a sustainable immunological memory, which has significant practical importance.
In conclusion, it should be emphasized the need to continue the search of individual immunotherapeutic approaches to this vast group ofpatients. When a prospective look at is a problem becomes even more obvious need for the modern understanding of the rules of academic therapeutic: «Treat not a disease, and the patient.»
References:
1. Activation of TLR-9 induces IL-8 secretion through peroxynitrite signaling in human neutrophils/J. Levent, K. Tarek, E. Driss et al.//J. Immunol. - 2006. - Vol. 176. - P. 1195-1202.
2. Cystic fibrosis (Current Developments and Challenges). Guidelines/Ed. Kapranov NI etc. - M., - 2005. - P. 104.
3. Gleeson M., Bishop N. C., Stensel D. J., Lindley M. R., Mastana S. S., Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. - 2011; 11 (9):607-615. doi: 10.1038/nri3041. [PubMed] [Cross Ref].
4. Kapranov N. I., Shabalova L. A., Kashirskaya N. Y. et al. Cystic fibrosis. Current achievements and problems. Guidelines. - Moscow, -2005.
Depressive disorders in patients after myocardial infarction
5. Mathur N., Pedersen B. K. Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm. - 2008; - 2008:109502. [PMC free article] [PubMed].
6. Practical pediatric pulmonology (reference)/Ed. VC. Tatochenko. - P. 161-169.
7. Ploeger H. E., Takken T., de Greef M. H. G., Timmons B. W. The effect of chronic and acute exercise on different inflammatory markers in children and adults with a chronic inflammatory disease: a systematic review. Exerc Immunol Rev. - 2009; - 15:6-41. [PubMed]
8. Sergienko D. F. Clinical features and mechanisms of immune regulation in children with cystic fibrosis (monograph)/D. F. Sergienko, O. A. Bashkina, H. M. Galimzyanov. Astrakhan: Publishing house ofAGMA, - 2010. - 139 c.
9. Walsh N. P., Gleeson M., Shephard R. J., Gleeson M., Woods J. A., Bishop N. C., Fleshner M., Green C., Pedersen B. K., Hoffman-Goetz L., Rogers C. J., Northoff H., Abbasi A., Simon P. Position statement. Part one: Immune function and exercise. Exerc Immunol Rev. - 2011; - 17:6-63. [PubMed].
10. Van de Weert-van Leeuwen P. B., Slieker M. G., Hulzebos H. J., Kruitwagen C. L., Van der Ent C. K., Arets H. G. Chronic infection and inflammation affect exercise capacity in cystic fibrosis. Eur Respir J. - 2012; - 39 (4):893-898. doi: 10. 1183/09031936. 00086211. [PubMed] [Cross Ref].
DOI: http://dx.doi.org/10.20534/ESR-16-9.10-119-120
Muxamadiyeva Nigina Bakhodirovna, Assistant of the Department of Psychiatry and Narcology, Bukhara State Medical Institute, Bukhara, Uzbekistan E-mail: [email protected]
Depressive disorders in patients after myocardial infarction
Abstract: In article the depressions arising at patients after a myocardial infarction (MI) are shined, necessity of overcoming stigma concerning weight of the transferred MI, rational under-standing of illness especially in early period of the post infraction is defined.
Keywords: depressive disorders, myocardial infarction (MI), work capacity of patients, post infarct depression, risk factors.
High prevalence of a mental pathology is noted both among a contingent of polyclinic establishments, and in versatile hospitals where basically mental frustration are presented by out-patient "neurotic" forms among which prevail somatic disturbing-depressive frustration. Depre-ssion, irrespective of its origin, developed against available heavy somatic disease, considerably burdens its current and rehabilitation of the patient. In a number of researches it is established that depression symptoms are authentic prognostic indicators of death rate from cardiovascular diseases after the transferred MI
[1; 4].
Nervous and mental disorders at a acute myocardium infarction (AMI) are connected substantially with infringement of brain blood circulation, more often functional character, and sometimes owing to a thrombosis or thromboembolism small vessels of a brain. In the acute period of a MI there can be the fear of death accompanied by anxiety, alarm, melancholy. Some patients are silent, motionless, others, on the contrary, are extremely irritable [2; 3].
In clinic of psychopathological infringements at a AMI the big place is occupied with emotional disorders. In the first days of a MI the disturbing-depressive syndrome more often is found out. The fear of death, melancholy, alarm, disturbing depression can be replaced by psychomotor excitation. Patients in such condition try to get up, go, speak much. The disturbing depression accompanied by steady and long melancholy, can be at the bottom of suicide actions [5].
The aim of the research — the analysis of influence of depressive disorders (DD) on clini-cal and social characteristics at patients with AMI.
Materials and methods. During the period of2010-2013 years, It is surveyed 121 patients in cardiological department of Bukhara branch ofRepublican centre ofscience of urgent medical aid. Patients have been divided into two groups: the first group have made 88 pa-
tients who have transferred a AMI at whom in the subsequent the DD have developed, the second group — 33 patients who also have transferred a AMI, but without depression symptoms. Re-search methods were: clinical and psychopathological, clinical catamnesis, reliability of results was estimated with use of criterion of Student.
Results and discussion. At the characteristic of clinical features of DD at patients in the period of post infarction it is necessary to note the allocated variants of depressions: disturbing (77.3%), melancholic (11.2%), dysphoretic (4.8%), masked (6.7%). Irrespective of a depression variant in conversation patients first of all showed complaints to pressing, compressing pains behind a breast, eccentric in characteristic zones, and aching, pricking in the left half of thorax. Patients passed an opinion experiences of the physical condition, painful sensations, prospects on the future. From shown complaints the sleeplessness was following. From the subjective comp-laints specifying in DD, depression, a breakdown, sensation of hopelessness are noted. In ex-periences with identical frequency the fear of repetition of a AMI, pessimistic views on the future and a low self-estimation were reflected.
A well educated person often occurs in 2 groups of survey is more often (72.7%), average vocational education is more characteristic for patients of 1 group (45.4%). Obviously, that fact matters that the person who is engaged in brainwork, does not think of possible loss of work whereas the person who is engaged more in a physical activity, is compelled to limit loadings after the transferred MI and to replace activity that conducts to decrease or change of qualifica-tion and can change not only a habitual rhythm oflife of the patient, but also indirectly affect a material prosperity.
Convinces of it and that the reason of depressions at patients with a AMI in most parts of cases (81.8%) is the present somatic disease (table № 1).
