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of stage plaster casts; foot was fixed (27%) for 3-4 months. In the middle position we performed selective and pressure point massage, correction gymnastics. When start walking correspondingly to the age children were trained exercises for strengthening of muscles of shin and they were prescribed to wear orthopedic shoes with straight last, fornix and heel arch supporter laying out, external hard tibia, bearing of the heel inside and prolongation of the inner crocle. In the elder age (4-14 years old) there is necessity of longer therapeutic courses and continuous wearing of arch supporter inner sole. Course (4 times a year) administration of multi vitamin agents, correction massage, and therapeutic physical training stimulating exchange processes have quite positive effect on the restoration of ligament apparatus of sole and back surfaces of foot.
Complex therapy performed in compliance with the proposed strategy provided significant correction of the anatomic integrity of the feet, improvement of its physiologic status and mobility. Besides
that, the study of oxyprolinuria revealed the tendency for decrease of its amount dependently on sex and age peculiarities.
Conclusion. Versatility of the flat-footedness problem and formation of various forms of it, therapeutic problem should be solved in young age. Prevalence of flat-footedness is greater in 3-7 years old age group. Electric physiologic test of flat-footed-ness determines decrease of gastrocnemius activity 2 fold, and activity of foot extensors stayed in the limits of normal values. in cases of flat-footedness in children the symptoms of neurogenic pathology combined with dysplastic development of lumbar-sacral part of vertebral column. In computer planography we revealed diminishing of longitudinal and transverse foot sizes to 1/3 as a result of equines of heel bone and pronation of the anterior part. Conservative therapeutic methods applied at early stages of flat-footedness formation provide correction of anatomical integrity and mobility of feet.
References:
1. Yemelyanov A. S. The role of family in the prophylaxis of impairments of skeletal apparatus of schoolboy/A. S. Yemelyanov, A. N. Stro-kina//Collection of materials of the XI congress of Russian pediatricians "Actual problems of pediatrics". - M., 2007. - 226.
2. Ivanov A. V. Non-invasive method of sovial-hygienic monitoring of children's population/A. V. Ivanov, N. V. Rilova//Hyg. And san. -2004. - № 6. - P. 56-58.
3. Kuznetsova M. N. Rehabilitation of children in kindergarten conditions/M/N, Kuznetsova, N. S. Davidova, I. T. Korneyeva et al.//Prob-lems of modern pediatrics. - 2006. - V.5, № 1. - 300.
4. Kuchma V. P. Values of children and teenagers' health in the system of social-hygienic monitoring//Hyg. And san. - 2004. - № 6. - P. 14-16.
Zakirkhodjaev Sherzod, Department of Internal Medicine, Haematology, Tashkent Medical Academy, Republic of Uzbekistan Shamsutdinova Maksuda Ilyasovna, Department of Internal Medicine, Haematology, Tashkent Medical Academy, Republic of Uzbekistan Kamalov Zaynitdin Sayfutdinovich Iinstitute of Immunology Academy of Sciences of the Republic of Uzbekistan E-mail: zay_kamal@rambler.ru
Features the production of cytokines in chronic pancreatitis and pancreatic cancer
Abstract: With respect to the blood levels of pro- and anti-inflammatory cytokines in the 40 patients with chronic pancreatitis (CP), and pancreatic cancer (PC), there was a significant increase of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) as compared to healthy controls. Clinical and laboratory analyses revealed an enlargement of the pancreas in 32 (80%), and of the spleen in 3 (7%) patients, respectively. Elevated bilirubin was present in 17 patients (41%), significantly elevated lipase, gamma-glutamyltrans peptidase and alkaline phosphatase activities were found in 24 (62%) patients. ALT and AST activities were significantly elevated in 20 (50%), moderately elevated (3-5 xULN) in 6 (15%) patients and slightly elevated (1.5-3 x ULN) in 14 (35%) patients. Serum albumin levels were reduced in 21 (51%) patients. The tumor markers CA 19-9 was elevated in 15 (38%) patients with a tumor in the head of the pancreas that was confirmed by computer tomography. The results indicate that cytokines are activated in patients with CP and PC respectively. This activation is accompanied by an increased levels of pro-inflammatory cytokines IL-2R, IL-6, TNF-a and INF-y, which closely correlate with the major pathological clinical and laboratory parameters in these patients.
Keywords: Chronic pancreatitis, cytokines, pancreas carcinoma, pathogenesis.
Introduction. In recent years, the interest of clinicians in of CP has increased due to the better understanding of the pathogenesis of CP and PC. The role of cytokines as an important link the
regulation of inflammation and pancreas regeneration in patients with CP remains unclear however. All pro-inflammatory cytokines examined in this study (IL-2R, IL-6, TNF-a) have been shown to be
Features the production of cytokines in chronic pancreatitis and pancreatic cancer
produced within the pancreas during the early stages ofpancreatitis and show elevated levels in both blood and pancreatic tissue. With a correlation between serum levels and disease severity. In particular, serum levels of IL-6 are now regarded as a reliable clinical indicator the severity of acute pancreatitis. The major sources of IL-2R and IL-6 during pancreatic necrosis and inflammation are activated macrophages in the inflammatory infiltrate within the gland. However, the molecular targeted therapy of pancreas cancer is still at a conceptual level. The selective inhibition of IL-6 secretion by targeting specific integrin's was shown to significantly reduce metastasis but did not result in complete arrest of tumor growth. Similar studies suggested that the therapeutic targeting of cytokines which are directly involved in establishing the tumor microenvironment, serves as an essential convergence point for multiple cytokine pathways. The complex interaction of cytokines with pancreatic cancer cell-signaling pathways and the multitude of chemical cross-talks between microenvironment and tumor make it unlikely that a single molecular target will be effective. Rather, the most effective treatment will be one that combines multiple molecular therapeutic targets as well as the based on chemokine tumor markers. In this context, previous studies have shown a direct correlation betweenIL-6 levels and tumor growth and antigenic potential. An increased level of IL-6 is in part directly responsible for the oncogenic activity and aggressive metastasis seen in pancreatic tumors. These data indicate that IL-2R and IL-6 play a critical role in tumor pathogenesis and may be useful for the early diagnosis of pancreas cancer, using for example IL-6 as a marker. Cytokines are very complex interacting molecular signals, which are involved in the regulation of other. The aim of the study was the determination of the levels of standard laboratory parameters and of serum cytokines, respectively in patients with CP and PC.
Materials and methods. 40 patients with CP (12 men, 28 women) aged between 29 and 65 years (average 45±18 years) were examined in our clinic. The clinical duration of CP was
With respect to the blood levels ofpro- and anti-inflammatory cytokines in the 25 patients with CP, there was a significant elevation of IL-2R and IL-6 in patients as compared to healthy controls. The mean values ofTNF-a was increased in 16 (65%) and ofINF-y in 20 (82%) patients, respectively, the elevation of inflammatory cytokines closely correlated with the relevant clinical and laboratory parameters of CP of our patients (Table1).10 (42%) patients had drastically improved IL-6 and IL-2R levels and 14 (58%) showed only a moderate increase.
13±6 years. 15 patients with PC (8 men, 7 women) aged between and years (average 58±15 years) were included in the study. The control group consisted of 25 healthy volunteers (8 men,17 women) with an average age of 38±15years. The causes of CP were viral infections, alcohol, metabolic, or autoimmune diseases and others. In all patients the standard laboratory parameters amylase, lipase, AST, ALT, LDH, CRP and cancer-specific markers CA 19-9 were determined. In addition, the serum levels of TNF-a, IL-2R, IL-6, INF-y were determined enzyme immune assays.
Results and discussion. 30 (75%) patients with CP were overweight (BMI = 37,3±4 kg/m 2)and 10 (25%) patients were asthenic. Non-insulin dependent diabetes mellitus was diagnosed in 14 (35%) patients, gastric dyspepsia in 6 (15%) patients. Clinical and laboratory analyses revealed an enlarged pancreas in 32 (80%), and an enlarged spleen in 3 (7%) patients, respectively. Bilirubin was elevated in 17 (41%) patients. Serum lipase, Y-glutamyltrans peptidase (y-GT) and alkaline phosphatase (AP) activities were significantly elevated in 15 (62%) patients. ALT and AST activities were significantly increased in 12 (50%), moderately elevated (3-5 x ULN) in 6 (15%) and slightly elevated (1.5-3 xULN) in 14 (35%) patients. Serum albumin levels were reduced in 13 (51%) patients.
Patients with PC serum enzymes such as: lipase, y-GT and AP activities were significantly elevated in 14 (93%) patients. ALT and AST activities were significantly increased in 13 (86%), moderately elevated (6-8 x ULN) in 1 (10%) patients. Serum albumin levels were reduced in 12 (80%) patients. These data are summarized in (Table 1). The tumor marker CA 19-9 was elevated in 15 (38%) patients with a tumor in the head of the pancreas that was confirmed by computer tomography.
The comparison of the biochemical data revealed a direct association between amylase and lipase elevations with the levels of TNF-a and INF-y, and of the y-GT and AP elevation and the INF-y level in patients with CP and pancreas carcinoma (PC).
Patients with PC had a significant elevation of IL-2R and IL-6 compared to healthy controls in 14 (93%), moderately elevated (4-6 x ULN) in 1 (10%) patients. The mean values of TNF-a was increased in 14 (93%) and of INF-y in 13 (86%) patients, respectively, the elevation of inflammatory cytokines closely correlated with the relevant clinical and laboratory parameters of PC of our patients significantly elevated in 14 (93%) patients (Table 2).
Groups TNF-a INF-y IL-2R IL-6
Patients with CP (n=25) 158.7 ± 19.6* 823.3 ± 97.5* 1622.7 ± 23.4* 138.5 ± 2.6*
Patients with PC (n=15) 290.8 ± 21.4* 952.4 ± 85.3* 2212.56 ± 36.5* 245.6 ± 6.6*
Controls (n=25) 43.5 ± 6.1 38.9 ± 5.5 390 ± 15.5 28.5 ± 1.1
*p<0,001 relative to control
Table 1. - Standard laboratory analyses of serum in patients with CP and PC
Groups Lipase AP y-gt ALT AST LDH CRP Glucose
Patients with CP (n=25) 346.6± 15.6* 454.2± 15.9* 877.5± 30.7* 159.4 ± 6.7* 159.7± 7.2* 364.1± 13.8* 66.3 ± 2.4* 112.4± 4.5
Patients with Pancreas carcinoma (n=15) 450.5± 20.5* 506.4±8.5* 941.6± 24.8* 263.5± 7.2* 164.4± 4.1* 390.6± 34.1* 82.4± 6.4* 181.2± 6.2*
Controls (n=25) 60±2.7 130±3.5 60±2.1 50±2.1 50±2.2 22.5±8.5 5±1.8 106± 4.2
*p<0,001 relative to control
Table 2. - Serum levels of inflammatory cytokines (pg/ml) in patients with CP and PC
In the majority of our patients with CP the clinical symptoms werenon-specific with laboratory findings typical for CP (elevation of serum lipase and amylase). The most common clinical and laboratory findings were: malegender, overweight, an enlarged head of the pancreas and elevated serum levels of glucose and lipase and amylase. The normal function of the immune system is based on the balanced regulatory cytokine production. In patients with CP the serum levels of IL-2R, IL-6, TNF-a, and INF-y were elevated compared to the control group. High levels of TNF-a and INF-y in serum ofpatients with CP indicate a shift towards the production of pro-inflammatory cytokines. Thus, a vicious circle develops through the action of reactive oxygen species and pro-inflammatory cytokines. In addition to the above factors, insulin also stimulates the synthesis of TNF-a through the expression of TNF-receptors in adipose and muscle tissues [4; 7]. Pro-inflammatory cytokines, including TNF-a, may participate in the mechanism of insulin resistance. How TNF-a is involved in this process is not completely understood, but insulin receptors (IRS-1) are important targets for TNF-a [3; 4].
Conclution. The results of our study indicate that cytokines are involved in the pathogenesis of CP. This study has demonstrated that PSCs have the capacity to respond to cytokines known to be up regulated during pancreatitis. Persistent activation of PSCs by cytokines during acute pancreatitis may be a factor involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis [8]. The inflammatory IL-6 is often expressed by multiple cell types within the tumor microenvironment. IL-6 produced in the bone marrow microenvironment to bone metastasis and this cytokine has a strong pro-tumorigenic activity due to its multiple effects on bone metabolism, tumor cell proliferation and survival, angiogenesis, and inflammation. Supporting the role of IL-6 in human cancer is the observation of elevated serum levels of IL-6 and sIL-6R in patients with bone metastasis and their association with a poor clinical outcome. Thus, IL-6 emerges as a key player at all stages of the pathogenesis of pancreatic diseases, including carcinogenesis, and a potential molecular therapeutic target [2; 3; 6].
References:
1. Schultz N.A., Christensen I.J., Werner J., Giese N., Jensen B.V., et al (2013). Diagnostic and prognostic impact of circulatingYKL-40, IL-6, and CA 19-9 in patients with pancreatic cancer. PLoS One 8: e67059.
2. Matsuo Y., Takeyama H., Guha S. (2012) Cytokine network: new targeted therapy for pancreatic cancer. Curr Pharm Des 18: 24162419.
3. Zhang Y., Yan W., Collins M.A., Bednar F., Rakshit S et al (2013). Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Res 73: 6359-6374.
4. Guo Y., Xu F., Lu T., Duan Z., Zhang Z. (2012).Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev 38: 904-10.
5. Talukdar R., Saikia N., Singal D.K., Tandon R. (2006).Chronic pancreatitis: Evolving paradigms. Pancreatology 6: 440-9.
6. Tasnim Ara, T. Declerck Y.A. (2010). Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer 46: 1223-1231.
7. Talukdar R., Tandon R.K. (2008). Pancreatic stellate cells: New target in the treatment of chronic pancreatitis. J Gastroenterol Hepatol 23:34-41.
8. Apte M., Phillips P., Fahmy R. (2008). Alcohol directly stimulates rat pancreatic stellate cells. Gastroenterology 118: 780. - 94.
Zufarov Aziz Alimdjanovich, CMS, Assistant of the Department of Propaedeutics of children's diseases,
Tashkent Pediatric Medical Institute E-mail: mbshakur@mail.ru
Acute respiratory syndrome and spectral characteristics of cardiac rhythm in children and its cause-effect interrelations
Abstract: For the age peculiarities of the children with manifestations of ARS there was determined link with all spectral ranges of CR. From one side it determines the character of organism reaction and specificities of pathologic process, and from the other side it is linked with the processes of functional development (status).
Keywords: acute respiratory syndrome, the spectral characteristics of heart rate, children.
Topicality. In the structure of morbidity among children there is prevailing of acute respiratory infections of the upper respiratory ways with various etiologies and influenzae, taking more than 90% of all registered infectious and parasite diseases in children [3; 7]. These diseases prevail all other infections with the number of cases [4; 8].
During the last three decades significant interrelations were revealed between vegetative nerve system and cardiac vascular mortality rate including sudden deaths [2].
In the modern time one of the methods of study of vegetative nerve system and its functions in the mechanisms of development of diseases is application of cardiac rhythm variability methods, es-
pecially for the states when vagosympathetic factors probably play an important role [6].
In spite of the chosen approach to the study of the regularities linked with spectral characteristics of cardiac rhythm (CR) for acute respiratory syndrome (ARS), the strategy of the study requires consideration of the revealed peculiarities by means of correlation analysis methods [5; 7]. And the basic branches of the analysis shoukd be linked with group-forming criteria such as sex, age, preliminary and clinical diagnosis.
The objective: is to study cause-effect interrelations of acute respiratory syndrome and spectral characteristics of cardiac rhythm in children.
