Успехи и проблемы в диагностике и лечении муковисцидоза в России (10-летие Российского центра муковисцидоза)

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Современные проблемы и достижения в области изучения муковисцидоза в России

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Improvement of nutrient absorption may enhance systemic oxidative stress in cystic fibrosis patients.

BACKGROUND: The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the pulmonary disease severity and progress. Malnutrition may be an important complicating factor in active and chronic lung disease. AIMS: The focus of this study was to investigate several inflammatory markers in pancreatic-insufficient CF patients with different enzyme treatment regimens. METHODS: CF patients with pancreatic insufficiency were examined at a time of symptomatic exacerbation of their lung disease. Group A (n = 11) regularly received microspheric enzymes. Group B (n = 8) were treated with enzymes during the hospitalization period only and demonstrated the presence of malnutrition. Inflammatory markers in the sputa (neutrophil elastase activity, interleukin-8 and tumour necrosis factor-alpha levels) and in the peripheral blood (plasma malondialdehyde (MDA), lymphocyte response to PHA, and the cell sensitivity to steroid suppression) have been investigated. RESULTS: During acute lung exacerbation, group B demonstrated reduced levels of lymphocyte proliferation. This parameter was normalized after combined antibiotic and pancreatic enzyme therapy. Simultaneously, plasma MDA in group B markedly increased following treatment. For this group, a significant positive linear association between values of plasma MDA and lymphocyte proliferation has been observed. For group A, neither the same correlation nor changes in MDA levels and lymphocyte proliferation have been found. CONCLUSIONS: Our data indicate that acute lung exacerbation in malnourished CF patients may be associated with alteration in T-lymphocyte activity. Adequate therapy normalizes lymphocyte function but results in systemic oxidative stress

Anti-inflammatory and immunomodulating effects of clarithromycin in patients with cystic fibrosis lung disease.

BACKGROUND AND AIM: Macrolide antibiotics are widely used in the treatment of suppurative lung diseases including cystic fibrosis (CF), the most common inherited fatal disease in the Caucasian population. This condition is characterized by secondary Pseudomonas infection resulting in neutrophil infiltration within the airways. The aim of the study was to investigate the evolution of inflammatory process in CF patients receiving long-term clarithromycin therapy. METHODS: Twenty-seven CF patients (mean age, 12 years) were enrolled into the study. Beside the basic therapy the patients were treated with clarithromycin at a dose of 250 mg every other day orally. All patients were routinely examined every 3 months. Blood and sputum were collected before clarithromycin treatment and then again 3, 6 and 12 months after the drug prescription. Cytokine concentrations (tumor necrosis factor-alpha, interleukin-8, interleukin-4, interferon-gamma) in the sputum and plasma were assayed. Peripheral blood lymphocyte response to phytohemagglutinin was also evaluated. RESULTS: Clarithromycin treatment resulted in a marked reduction of the cytokine levels both in the sputum and plasma specimens. At the same time, the interferon-gamma/interleukin-4 ratio has been significantly elevated. In addition, a sustained increase of peripheral blood lymphocyte response to phytohemagglutinin was demonstrated. These changes were associated with a significant improvement of the lung function. CONCLUSIONS: The beneficial effect of the prolonged treatment of CF patients with a 14-membered ring macrolide antibiotic clarithromycin seems to be associated not only with down-regulation of the inflammatory response, but also with immunological changes including the switch from Th2 to Th1 type response

РЕГИСТР КАК СРЕДСТВО УЛУЧШЕНИЯ КАЧЕСТВА МЕДИЦИНСКОЙ ПОМОЩИ БОЛЬНЫМ МУКОВИСЦИДОЗОМ

The creation of a register of mucoviscidosis (MV) patients is necessary for determining the epidemic situation in the region, evaluating the efficacy of therapeutic strategies and the quality of healthcare provided. The regional register of Yaroslavl contains information about 53 MV patients. The average age of these patients is 12.9 years, the amount of patients older than 18 is 22.7%, the average age of diagnosis is 3.4 years. The overall survival median is 26.8 years (by the beginning of 2012). The prevalence of the disease is 1:8005 newborns according to the results of neonatal screening. The amount of patients infected with Pseudomonas aeruginosa and Burkholderia cepacia is 30,2% and 2,5% respectively. The F508del mutation occurs in 43,4% of all cases. The next most prevalent mutations are N1303K, 394delTT, CFTRdele2,3 (21kb) (4,72% each), the number of unidentified mutations is only 8.49%. A comparative evaluation of therapeutic approaches (basic therapy) was conducted in the Yaroslavl region and in a number of European countries. Data obtained from the register allows to solve not only clinical and epidemiological problems, but also sort out organizational issues, plan medicine provisions and conduct medical and social rehabilitation.Создание регистра больных муковисцидозом (МВ) является необходимым для определения эпидемиологической ситуации в регионе, оценки эффективности терапевтических стратегий и качества оказания медицинской помощи. В Ярославском региональном регистре содержится информация о 53 больных МВ. Средний возраст больных 12,9 лет, количество пациентов старше 18 лет составляет 22,7%, средние сроки постановки диагноза 3,2 года. Общая медиана выживаемости на начало 2012 года — 26,8 лет. Распространенность заболевания согласно неонатальному скринингу составляет 1:8005 новорожденных. Число больных, инфицированных Pseudomonas aeruginosa и Burkholderia cepacia, — 30,2 и 2,5%, соответственно. Мутация F508del встречается в 43,4% случаев. Следующими по частоте являются мутации N1303K, 394delT, CFTRdele2,3 (21kb) (по 4,72%), число неидентифицированных мутаций составляет лишь 8,49%. Проведена сравнительная оценка терапевтических подходов (базисной терапии) в Ярославской области и ряде Европейских стран. Помимо клинико-эпидемиологических задач данные регистра позволяют решить организационные вопросы, планировать лекарственное обеспечение, осуществлять медико-социальную реабилитацию.

Inflammatory markers in cystic fibrosis patients with lung Pseudomonas aeruginosa infection.

Chronic endobronchial inflammation and bacterial infection are the main causes of morbidity and mortality in cystic fibrosis (CF), an autosomal recessive genetic disorder associated with improper function of chloride channels. Inflammation in CF lung is greatly amplified after Pseudomonas aeruginosa infection. In this study the relationship between P. aeruginosa status and inflammatory markers has been investigated. Seventeen CF children in acute lung exacerbation were examined. CF patients without P. aeruginosa infection were characterized by elevated activity of sputum elastase, reduced response of peripheral blood lymphocytes to PHA and significant resistance to the antiproliferative action of glucocorticoids. These parameters were normalized after antibiotic treatment. The patients with prolonged P. aeruginosa infection demonstrated extremely high levels of elastase activity and elevated amounts of sputum IL-8 and TNF-alpha. Although antibiotic treatment resulted in clinical improvement, it failed to suppress excessive immune response in the lung. The data indicate that CF patients with prolonged P. aeruginosa need the modified treatment, which should include immunomodulating drugs and protease inhibitors as well as antibacterial therapy

Contribution of Compton Scattering in Problems Associated with Measuring the Surface Density of Radiation Protection Coatings

The paper analyses the ratio between the number of Compton-scattered quanta excited in elements of radiation protection coatings by isotope Am-241 and the number of fluorescence quanta excited in in the same elements, taking into account the fluorescence yield coefficient and the distance between the energy of primary radiation quanta (60 keV) and the energy of absorption K-edge. The paper shows that the number of scattered quanta exceeds the number of fluorescent quanta from K-level in all elements. The obtained values define the ratio of scattered and fluorescent quanta in any radiation protection coatings with a known chemical composition

Tetrahedron and 3D reflection equations from quantized algebra of functions

Soibelman's theory of quantized function algebra A_q(SL_n) provides a representation theoretical scheme to construct a solution of the Zamolodchikov tetrahedron equation. We extend this idea originally due to Kapranov and Voevodsky to A_q(Sp_{2n}) and obtain the intertwiner K corresponding to the quartic Coxeter relation. Together with the previously known 3-dimensional (3D) R matrix, the K yields the first ever solution to the 3D analogue of the reflection equation proposed by Isaev and Kulish. It is shown that matrix elements of R and K are polynomials in q and that there are combinatorial and birational counterparts for R and K. The combinatorial ones arise either at q=0 or by tropicalization of the birational ones. A conjectural description for the type B and F_4 cases is also given.Comment: 26 pages. Minor correction