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well-known that cytokines play a role in inflammation as well as in malignant transformation and the promotion of cancer progression and metastasis [6]. IL-8 is strongly associated with chronic pancreatitis which increases the risk of pancreas cancer by a factor of 20 or more due to the convergence of inflammatory mediators and cytokines into a common pathway [7]. Thus, IL-8 is activated by inflammation, which in turn acts through a positive paracrine feedback loop via up-regulation of several inflammatory mediators to locally maintain inflammation and promote angiogenesis [8]. Further, IL-6 also enhances the secretion of pro-inflammatory cytokines typically expressed in Th2 lymphocytes and plays a similarly important role in inflammation [4]. The current molecular therapeutic aims are targeted at the inhibition of these common pathways and thereby the malignant transformation ofpancreas cells the communication between the tumor cells and the stromal fibroblasts as well as the immune effectors is very complicated, however. For instance, IL-8 binds to multiple receptors, and is induced, apart from hypoxia, by several factors such as NO, oxidative stress, and acidosis. At the same time both IL-8 and IL-6 are induced TNF-a [2]. Therefore, the detailed understanding of the entirety of the wide spectrum of
chemical cross-talk involved in establishing the tumor microenvironment is key for future therapeutic strategies. Thus, with the more fundamental understanding of the pathogenesis ofpancreas cancer, novel diagnostic, therapeutic and preventive targets will be identified improving the prognosis of patients with pancreas diseases.
Conclusions and perspectives. The analysis of patients with chronic pancreatitis showed that even during remission there are significant alterations of the the 'cytokine network' and the balance between pro- and anti-inflammatory components. The data obtained open the possibility of predicting natural course of CP, including disease recurrence and progress based on cytokine levels and and their imbalance. The level of pro-inflammatory and antiinflammatory cytokines can predict clinical deterioration and the probability of relapse. The he study demonstrates that in patients with CP cytokines are more sensitive laboratory markers than the traditional parameters. Thus, as we begin to develop a more fundamental understanding of the mechanisms underlying the aggressive natural course ofpancreas cancer, novel diagnostic, therapeutic and preventive targets will be identified that will result in an improved prognosis of patients with diseases of the pancreas.
References:
1. Long J., Zhang Y., Yu X., Yang J., LeBrun D.G., et al. (2011) Overcoming drug resistance in pancreatic cancer. Expert Opin Ther Targets 15: 817-828.
2. Feurino L.W., Fisher W.E., Bharadwaj U., Yao Q., Chen C., et al. (2006) Current update of cytokines in pancreatic cancer: pathogenic mechanisms, clinical indication, and therapeutic values. Cancer Invest 24: 696-703.
3. Waugh D.J., C. Wilson (2008) The interleukin-8 pathway in cancer. Clin Cancer Res 14: 6735-6741.
4. Feurino L.W., Zhang Y., Bharadwaj U., Zhang R., Li F, et al. (2007) IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells. Cancer Biol Ther 6: 1096-1100.
5. Li M., Zhang Y., Feurino L.W., Wang H., Fisher W.E., et al. (2008) Interleukin-8 increases vascular endothelial growth factor and neuropilin expression and stimulates ERK activation in human pancreatic cancer. Cancer Sci 99: 733-737.
6. Patra C.R., Bhattacharya R., Wang E., Katarya A., Lau J.S., et al. (2008) Targeted delivery of gemcitabine to pancreatic adenocarcinoma using cetuximab as a targeting agent. Cancer Res 68: 1970-1978.
7. Yu H., Kortylewski M., Pardoll D. (2007) Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 7: 41-51.
8. Zhang Y., Bharadwaj U., Logsdon C.D., Chen C., Yao Q et al. (2010) ZIP4 regulates pancreatic cancer cell growth by activating IL-6/STAT3 pathway through zinc finger transcription factor CREB. Clin Cancer Res 16: 1423-1430.
Sharipova Nilufar Saidovna, Senior Research Scientist — researcher, State Medical Institute. Abu Ali Ibn Sina, Department of Public health, Ministry of Health of the Republic of Uzbekistan Bukhara E-mail: farhod.ahmedov.77@mail.ru
Life style of the patients suffering with bronchial asthma
Abstract: This article studied on the questionnaire lifestyle, medical activity in patients with bronchial asthma, the factors leading to the disease of 670 persons infected with asthma and 420 persons not infected with this disease, but living in the similar conditions.
Keywords: bronchial asthma, quality of life, mode of life, medical active.
Bronchial asthma is disease of respiratory ways, including the pathological process flowing with chronic persistor inflammation and obstruction of bronchial tubes that it is possible to observe at attack suffocation or asthmatic condition [1; 3; 6; 13; 14; 15].
Despite improvement of diagnostics and methods of treatment of the disease, on a global scale suffering a bronchial asthma, and also cases ofphysical inability and death rate as a result of this disease increases. Basically, the cases having risk in a life of patients — long
heavy attacks of suffocation which are resistant active broncholytic therapies, strongly expressed respiratory insufficiency because of what the present disease is vital topic of modern medicine [2; 5; 8; 11] amplify.
On threshold XXI in all potential researches 3 global problems get to eyes concerning bronchial asthma. First is disease very widespread and such tendency will proceed further the next decade, secondly — problem of bronchial asthma left because of limits of
medicine and has turned to extremely actual social and economic problem of the state importance, thirdly — at the decision of questions of bronchial asthma epidemiological researches and despite it have the important role, on global scale, especially in the CIS countries, the quantity of such researches has sharply decreased [4; 7; 9; 10; 12].
Objective: Studying of life style, quality of life and medical activity of the patients who are ill with bronchial asthma.
Materials and methods.
Risk factors, which are at the bottom of disease and its formations have been studied by application of method "event-control" of subject of medicine based on evidences. With a view of research of way of life, quality of life of patients and the risk factors leading to disease have been involved 670 patients who are ill with bronchial asthma (event group) and 420 patients living in oncological conditions, but not ill with bronchial asthma (control groups) in both areas. The patients involved in sociological research in the cities and districts of Bukhara and Tashkent Regions have been selected by «Strata» method. The patients who are ill with serious illness, being in the period of attack of bronchial asthma and patients accepting hospitalisation within 4 weeks have not been involved in research. So, the all-round reliable representative data by means of modern methods has been obtained.
Results and discussion.
Among the contingents involved in research quantity of women more than men (57:43), 20,7 percent of patients consist of young men at the age of20-39 whereas the contingent at this age is equal in control group to 36,2 percent. Also, aged people of40-49 years make 34,4 percent, is more senior 50 years — 44,5 percent. This indicator makes in control group of 30,4% and 33,4% accordingly.
67% of patients involved in research consist of agricultural population, and in control group they make 58,8%. On structure of families of 11,9% 67,4%-4-6 the person consist of 1-3 persons, families in number of 7 and more persons make 20,7%. In control group this indicator accordingly makes 9,8%, 69,9%, 20,3%.
12,7% of patients have higher education, 2,8% — incomplete higher education, 46,0% — secondary education, 28,8% secondary special education and 9,7% — elementary education. It is confirmed that 86,9% from them live 5 and more years in the present place.
On the basis of interrogations it is established that among close relations of patients there are persons suffering a bronchial asthma. In particular in Bukhara Region among close relations of 52,0% of patients, its registered presence of bronchial asthma. 48% of patients deny presence of bronchial asthma at close relations. Among close relations of 89,5% of patients from control group presence of bronchial asthma is not observed. In Tashkent Region 64,4% of the patients involved in research denied presence of illness among their close relations.
In Bukhara Region within 1 year 22.7% of the surveyed patients suffered with acute respiratory virus infection 4 and more times, 53,7% of them suffered 2-3 times, 23,6% of them once or less.
In Tashkent Region this situation equals accordingly 29,6%, 54,0% of 16,4%. Among patients of control group this indicator makes: 78,7% — are less than 1 time year, 15,2 5 2-3 times a year, 6,1% — more than 4 times a year.
Immediate causes illnesses leading to excitation share on 4 groups:
1. House and street dust, vegetative disputes and dust, tobacco smoke.
2. Allergens of pets covered with wool.
3. Some foodstuff (citron fruits, bean products, eggs, sweets, etc.).
4. Acute respiratory virus infections.
If in Bukhara Region among the reasons being infecting agent the highest indicator the House and street dust, vegetative disputes and dust, tobacco smoke (49,1%) has that in Tashkent Region prevails Acute Respiratory Virus Infection (42.0%). As sensitivity to dust of wool of animals, coleoptera insects, rodents, cockroaches among patients of Bukhara Region in comparison with patients from Tashkent Region is observed to bowl on 21,8 5.
It has been established that at 32.4% of working patients from Bukhara and 25.2% of patients from Tashkent the labour plan, in particular is not correctly organised: hygienic conditions do not correspond to requirements; with view of decrease of fatigue it is not mechanised and labour process (works in the industry and agriculture) connected with the big expense of forces and energy is not automated; microclimate of the enterprises does not meet the requirements ofhygiene — of place of work are shined not enough, it is lot of noise, ventilating systems on elimination of dust and air clearing well do not work, at some enterprises the sequence ofwork and rest is irrationally organised, workers in enough are not provided with special clothes and masks, at the enterprises working with harmful connections there are no gas masks. This situation is correctly organised in 25.7% of the enterprises (in Tashkent 25.2%). In 25.5% presence of harmful factors connected with a trade is established (In Tashkent 18,4%), in particular the working day ofpersons working with dangerous factors is not truncated, additional labour holidays do not give, not organized constant medical inspections of workers of the enterprises. In control group, these situations accordingly make 32.0%, 40.4%, 13.2%. By results it is visible that the labour mode working in Tashkent Region is organised partially correctly in comparison with Bukhara Region.
Among workers with presence of bronchial asthma 34.3% of workers of the industrial enterprises make, 28.1% of workers of agriculture, 5.1% of workers of building sphere, 5.9% of workers of motor transport, 10.9% of workers are connected with the grocery goods. In Tashkent Region, this indicator accordingly makes 29.2%, 32.0%, 4.8%, 4.8%, 6.8%. Apparently by results if in Bukhara Region among patients the majority is made by employees of the industrial enterprises in Tashkent Region workers of agriculture prevail.
By results of interrogations it is established that the basic part of patients works on textile and silk winding companies, Karakul tanning industrial complexes, shoe factories, brick-works, oil refining factories and in agriculture. At specified companies there is considerable quantity of allergens of top respiratory ways influencing mucous membranes. Long contact of patients to the specified allergens leads to illness strengthening.
In the course of the analysis of results of interrogations it has been established that the psychological environment at 45% of patients (Bukhara) and 57,8% at patients from (Tashkent) bad, including: disputes often arising between the head, workers and the serving enterprises, conflicts, wrong distribution of work, weak organisation offeedback between heads and workers of the enterprises, authoritative form of government, administrative bureaucracy. In control group this indicator makes 32.6%.
At the analysis of economic and living conditions of patients involved in researches it was found out that in houses on the ground areas from them lives 26.2% in Bukhara Region and 39.6% in Tashkent Region, and other part lives in multiroom apartment houses. It is confirmed that 59.8% from among patients of control group live in the houses on the ground areas. It has been found out that living conditions (floor space having per capita, household conveniences: potable water, heating sources, gas, illumination sources,
degree of security the water drain, sanitary-and-hygienic positions of dwelling: light exposure, humidity, cleanliness etc.) patients living in Tashkent is much better than living conditions of patients living in Bukhara.
Judging by results of analyses duration of walks in the open air and employment by physical culture in the basic group the below-mentioned: In Bukhara Region of respondents which time makes till 1 hour — 6.8%, till 2 hours-13.1%, till 3 hours-17,7%. (In Tashkent Region this indicator accordingly equals 12.8%, 14.4%, 18.8%.). 62.4% of patients in Tashkent Region and 54.8% of patients in Bukhara Region have underlined that at all are not engaged in physical training. In control group this indicator has made 38.5%.
The number of smokers among suffering from Bukhara Region is observed by a bronchial asthma in 2.7 times more often in comparison with patients from Tashkent Region. In particular the quantity of smokers to 10 times a day meets in 3.5 times, and the quantity of smokers to 20 times a day meets in 7.3 times more often. Among smokers of 2.8% of patients have begun smoking at the age of 10-14 years. In Tashkent Region smoking men begin at the age of 10-14 years is not observed at all. Smoking begun at the age of 15-19 years in the present area also is observed in 7.3 times to a bowl than in Tashkent Region. If to judge under the experience of smoking the experience till 5 years in Bukhara Region meets in 9 times less often than in Tashkent Region. In group with such case of 37.3% smokers with the experience of 20 and more years make, and in control group this indicator makes 6.1%. Their ratio accordingly equals 6.1:1.
In results of interrogations it is established that presence of disagreements, quarrels and scandals in families of patients suffering a bronchial asthma has strongly affected their mentality. Results of researches I show that in both areas the psychological environment in houses of patients in groups with the specified situation on 76% worse in comparison with control group.
Results of the spent researches have confirmed that 20.4% of patients suffering with an asthma in Bukhara and 22.8% in Tashkent at all do not read medical literature. In control group this indicator makes 7.8%. 17% of patients have told that read the special medical literature, 14.4% that are read by mass brochures, and 32.8% that are read by medical magazines. Patients have underlined that concerning care of patients they receive data from: (25.8%) from medical telecasts, (14.3%) from the popular literature, (13.5%) from seminars spent on work, (60%) from posters a dignity. The bulletin, (9.9%) from conversations with employees ofmedicine, (17.5%) from conversations with acquaintances and friends and (13.0 5) from members of families.
Concerning health services of 51.1% of patients from Bukhara Region and 60.0% of patients from Tashkent Region have under-
lined that regularly address and are completely satisfied by medical services. As 13.5% of patients have told that are not satisfied by medical services, 9.9% that address to receive only the sick-list, 26.5% that do not address at all to the doctor and are treated independently even when are ill. (In Tashkent Region this indicator accordingly equals 23.6%, 2.4%, 14.0%) Proceeding from results the relation of patients to medical services not positive becomes clear that in both regions.
The conclusion.
1. Registered presence of bronchial asthma among close relatives of patients in Bukhara Region is 52%, in Tashkent Region — 35.6%
2. It is confirmed disease of the top respiratory ways of 76.4% of patients with Acute Respiratory Virus Infection from 2-4 and more times a year. In Tashkent Region cases of disease of the top respiratory ways from 1 up to 4 times within a year are observed by acute respiratory virus infection on more on 30.4% than in Bukhara Region. In control group this indicator makes 6.1%.
3. Among dangerous factors, promoting occurrence of bronchial asthma in Bukhara Region leading position has houses, streets, vegetative dusts and tobacco smoke. This situation is observed more on 29.0% in comparison with Tashkent Region, but in Tashkent Region is more often observed on 70.7% prevalence system of respiratory virus infection of the top respiratory ways in comparison with Bukhara Region. As at patients from Bukhara Region in comparison with patients from Tashkent Region on 21.8% sensitivity to dust of animal wool, coleoptera insects, cockroaches and rodents is more often observed.
4. In both regions plan of work of 28.9% of patients suffering with bronchial asthma is not organised correctly. 21.9% have dangerous factors connected with work. In both below-mentioned cases in Bukhara Region the indicator has appeared the highest (57: 43). At 59.9% of patients living conditions don't meet the requirements. Positivity of quality of life in Tashkent Region is higher in comparison with Bukhara Region (60:40).
5. Psychological environment in houses of patients as has affected experience and illness blossoming. In both regions psychological conditions in houses of groups with similar situation on 76% are worse in comparison with control group.
6. In both regions, relation of patients to medical services not the positive. 26.5% of patients are not satisfied by health services. In comparison with Tashkent Region in Bukhara Region in 2 times there are more than patients which at all did not pass medical inspection, did not address to the doctor on aetiology and were treated independently even in disease cases.
References:
1. Abdusalamov A. B. The principles of social and labor rehabilitation of patients with bronchial asthma.//Pulmonologiya. - 2004. -№ 2. - P. 85-89.
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3. Loshkareva E. O. Combined use termogelioksa and inhalation therapy in patients with bronchial asthma. Abstract of diss ...MD Moscow. - 2011.
4. Sergeeva K. M., Belyakov A. V. Risk factors and age-related evolution of bronchial asthma in children.//Russian Pediatric zhurnal. -2008. - № 1. - P. 26-29.
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6. Chuchalin AG et al. Bronchial asthma in Russia: results of a national study of the quality of care to patients with bronchial asthma.//Pul-monology - 2007. - N 6. - C. 94-102.
7. Shokirov Sh. T. Nobar^aror-kuchli Continental i^limy sharoitda bronhial astmani orir ytuvchi shakllarini tar^alishi, rivozhi va clinics kechishi yysinlari. T. f.n. Uchun ABSTRACT. Andijon - 2006. 21 b.
8. Yatsyna IV, Kovaleva TA Epidemiology, risk factors and modern aspects of the prevention of allergic diseases in the industrial cen-ter.//Vestn. Ros. AMN. - 2005. - № 3. - P. 36-39.
9. Beydon N., Davis S. D., Lombardi E., et al. An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children.//Am.J. Respir. Crit. Care Med. 2007. V. 175, № 12. P. 1304-1345.
10. Devulapalli C. S., Carlsen K. C., Haland G. et al. Severity of obstructive airways disease by age 2 years predicts asthma at 10 years of age//Thorax. 2008. V. 63. № 1. P. 8-13.
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Yuldasheva Dilchehra Yusuphonovna, assistant of the Tashkent Medical Academy, Republic of Uzbekistan Sadykova Dilfuza Ravshanovna, Associate Professor of the Tashkent Medical Academy,
Republic of Uzbekistan E-mail: evovision@bk.ru
Studying the frequency of genotypes and allelic variants of the polymorphism rs1042522 gene TP53 in women with cervical intraepithelial neoplasia
Abstract: One of the earliest identified polymorphisms in the TP53 gene was Ex4 + 119 G> C (Arg72 Pro, rs1042522), the caller an amino acid substitution of arginine (p53Arg) proline (p53Pro) in protein p53 (1).It was subsequently found that the polymorphic variants Arg and Pro possess different abilities to activating transcription of target genes p53 and p53 startup-mediated processes.
Keywords: cervical intraepithelial neoplasia, polymorphism, allelic imbalance.
Thanks to functional differences between the polymorphic variants like p53Arg and p53Pro, in the world widely studied the role of this polymorphism in forming of diseases of various pathology.
The p53 protein has an increased affinity to the interaction with HPV E6 protein, leading to the degradation of the first and, respectively, a high risk of developing cervical cancer and with greater sensitivity to ultraviolet (skin cancer) [2].
We have studied frequency of genotypes and allelic variants of the polymorphism rs1042522 in gene TP53 in patients with CIN and their possible association with the formation and with course of the disease. The distribution of genotype frequencies of this polymorphism and their conformity population equilibrium Hardy-Weinberg (HVE) was carried out separately in the study and control groups.
It was found that the genotypic diversity of TP53 gene polymorphism Arg72Pro among patients and the control group, which was estimated based on the magnitude of the observed heterozygosity was close to the maximum possible dinucleotide loci.
Patients of the main group were found close to statistically significant difference observed distribution of genotypes of the expected under HVE (^2 = 3.6; P = 0.06).
This indicates a possible "allelic imbalance" in the locus of the gene TP53, underlying malignant transformation and appears as a genetic mechanism by which lost "functionally unfavorable" and selected the most "favorable" for the tumor growth of alleles (or accumulation in patients with relevant genotypes and their possible protective effect on the formation of the disease).
The population sample was a statistically significant deviation of the observed distribution of genotypes of the expected under Hardy-Weinberg equilibrium (HWE) by reducing the number of homozygotes.
Thus, the observed increase in the observed heterozygosity compared to their expected value. Such variations are due to the specifics of the control group: it included only provisionally healthy women — without of endometrial hyperplastic processes and cervical pathology. In the subgroups of patients with increasing stage ofdisease observed accumulation ofheterozygote from 45.6% (subgroup — A) to 53.3% (subgroup — B) due to a decrease frequency ofhomozygotes ofboth forms (wild and mutant). The frequency distribution of genotypes in both groups of patients with a statistically insignificant has deviated irom the expected under HWE (P> 0.05).
Analysis of the relationship associations of alleles and genotypes of the polymorphism rs1042522 gene TP53 at risk of developing CIN showed that the frequency of allele polymorphism rs1042522 gene TP 53 statistically significant differences between samples of patients with CIN and control was not (^2 = 0.6; P = 0.4; OR = 2.2; 95% CI 0.7692, 1.921). Since the analysis of the association of the allele does not give a complete picture of the nature of interconnection examined polymorphisms with predisposition to disease, we investigated the effect of the genotypes polymorphism rs1042522 TP53 gene on the develop risk of CIN. Statistically significant differences in the genotype frequencies between groups were found (P> 0.05) [6].
