42 research outputs found

    Место комбинированной терапии М-холинолитиком и β2-адреномиметиком короткого действия в терапии бронхообструктивного синдрома

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    A role of combined therapy with M-cholinolytic and β2-adrenomimetic drugs for bronchial obstruction.Место комбинированной терапии М-холинолитиком и β2-адреномиметиком короткого действия в терапии бронхообструктивного синдрома

    Оценка влияния длительного приема фенспирида (Эреспала) на клинико-функциональное состояние больных хронической обструктивной болезнью легких

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    This open comparative randomized study has shown that fenspiride is an effective and well-tolerated drug while being administered in combined therapy of COPD for 3 to 12 months. The anti-inflammatory action of fenspiride 80 mg t. i. d. significantly reduced cough in COPD patients and enhanced the effect of bronchodilators. Fenspiride (Erespal) can be included in standards of combined treatment of patients with mild, moderate and severe COPD.В открытом сравнительном рандомизированном исследовании фенспирида (Эреспала) были показаны эффективность и хорошая переносимость при его включении в комплексную терапию больных хронической обструктивной болезнью легких (ХОБЛ) в течение как 3, так и 12 мес. Исследование подтвердило достоверное влияние Эреспала (80 мг 3 раза в день) на частоту кашлевого синдрома у больных ХОБЛ за счет противовоспалительного действия. Противовоспалительным эффектом можно объяснить также и потенцирование бронхолитического ответа. Эреспал может быть рекомендован для включения в протоколы комплексного лечения больных ХОБЛ легкой, среднетяжелой и тяжелой степени тяжести

    Оценка клинико-функционального состояния и качества жизни больных хронической обструктивной болезнью легких до и после комплексной медикаментозной терапии в амбулаторных условиях

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    A comparative randomised trial of fenspirid (Erespal) had been administered for 3 months together with bronchodilating and mycolytic drugs involved 45 patients with chronic obstructive pulmonary disease (COPD). Clinical status, forced expiratory values and quality of life (QoL) were studied using World Organization of Health questionnaire (W H O Q O L -100). Thirty four patients completed the examination (24 males and 10 females, the average age was 52.7±1.9 yrs). The comparative group included 25 healthy non-smokers. The trial demonstrated that the therapy resulted in improvement of QoL in physical and psychical health scales. The patients becam e more active, their sleep becam e better. Their attention was transferred from their physical status to the surroundings. The application of fenspirid (Erespal) facilitated the improvement in the forced expiratory values and ESR. The drug was well tolerated and caused only mild adverse effects which rates were equal to those in patients not received fenspirid. The results permit fenspirid to be included to modern treatment protocols for patients with mild to moderate COPD when combined with bronchodilators.В сравнительное рандомизированное исследование препарата фенспирид (эреспал), применявшегося в течение 3 мес в сочетании с бронхолитическими и муколитическими средствами, было включено 45 больных хронической обструктивной болезнью легких (ХОБЛ). Изучали клинический статус пациентов, параметры форсированного выдоха и качество жизни больных ХОБЛ с помощью опросника Всемирной организации здравоохранения W H O Q O L-100. Полностью обследование завершили 34 больных ХОБЛ (24 мужчин и 10 женщин), средний возраст которых составил 52,7±1,9 года. 25 здоровых не курящих людей составили группу сравнения. Проведенное исследование показало, что после лечения качество жизни (КЖ), оцененное по методике, рекомендованной ВОЗ, улучшилось по шкалам, отражающим физическое и психическое здоровье. Больные стали более активными, у них улучшился сон. Акцентуация была перенесена с собственного физического состояния на окружающую среду. Использование фенспирида (эреспал) в лечении больных ХОБЛ потенцировало улучшение параметров форсированного выдоха, нормализацию СОЭ. Препарат хорошо переносился, вызывал только легкие побочные реакции, которые встречались не чаще, чем у пациентов, не получавших фенспирид. Полученные данные позволяют рекомендовать включение фенспирида (эреспал) в современные протоколы лечения больных ХОБЛ при легком и среднетяжелом течении в сочетании с бронхолитическими препаратами

    Оценка клинической эквивалентности Беклазона Эко Легкое Дыхание и ДАИ флутиказона пропионата у больных бронхиальной астмой

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    It is well known that efficacy of asthma treatment depends on a choice of a basic medication as well as on a delivery system. The aim of this study was a comparison of clinical efficacy of equal doses of beclomethasone dipropionate (Beclasone Eco Easi Breathe) and fluticasone propionate (Flixotide) via MDI. The study was designed as a randomized open prospective comparative trial. Findings of 26 patients with moderate and severe asthma of > 18 yrs old were analyzed, such as medical history, physical findings, spirometric and bronchodilating test results, heart beat rate and blood pressure, quality of life (QoL) using Russian version of AQLQ questionnaire. After the run-in period the patients randomly received Beclasone Eco Easi Breathe 500 to 1000 μg daily or Flixotide at the same doses for 4 weeks followed the cross-over change of the drugs for the next 4 weeks. After 1 month of the treatment, significant improvements in airflow parameters, need in short-acting β2 -agonists and QoL have been reported. After changing the drugs these effects have been maintained with no further reliable improvement. Thus, the study demonstrated similar efficacy and safety of these inhaled steroids that could be considered as being clinically equal in treatment of moderate and severe asthma.Известно, что эффективность лечения бронхиальной астмы (БА) зависит не только от выбора базисной терапии, но и от способа доставки лекарственного средства. Целью данного исследования было сравнение клинической эффективности равных доз беклометазона дипропионата (Беклазона Эко в системе доставки Легкое Дыхание) и флутиказона пропионата в виде ДАИ (Фликсотид). Исследование было рандомизированным, перекрестным, открытым, проспективным, сравнительным. Анализировали данные 26 больных со среднетяжелой и тяжелой БА в возрасте >18 лет: данные анамнеза и врачебного осмотра, спирометрии с бронходилатационным тестом, пульса и АД, качества жизни (КЖ), которое оценивали с помощью русской версии опросника AQLQ. После вводного периода больные рандомизированно получали в течение 4 нед. либо Беклазон Эко Легкое Дыхание 500-1000 мкг/сут., либо Фликсотид в тех же дозах с последующей сменой препаратов еще на 4 нед. Через 1 мес. лечения в обеих группах произошло достоверное улучшение показателей бронхиальной проходимости, снижение потребности в бронхолитиках короткого действия и улучшение КЖ. После смены препаратов этот эффект был сохранен без дальнейшего существенного прироста. Таким образом, исследование показало равную клиническую эффективность и безопасность этих двух форм ингаляционных глюкокортикостероидов, что позволяет считать их клинически эквивалентными при среднетяжелой и тяжелой БА

    Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs

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    <p>Abstract</p> <p>Background</p> <p>Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs) and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF) binding sites (TFBSs). Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed.</p> <p>Results</p> <p>We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was 21-75% more precise than a related CRM predictor. The sensitivity of the system to locate known human heart enhancers reached up to 83%. CrmMiner precision reached 82% while mining for CRMs specific to the human CD4<sup>+ </sup>T cells. On several data sets, the system achieved 99% specificity.</p> <p>Conclusion</p> <p>These results suggest that CrmMiner predictions are accurate and likely to be tissue-specific CRMs. We expect that the predicted tissue-specific CRMs and the regulatory signatures broaden our knowledge of gene transcription regulation.</p

    Состояние больных саркоидозом исходно и 10 лет спустя при различной тактике их ведения (мультицентровый анализ)

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    Summary. A multicenter (12 centers) retrospective analysis of health status of 83 sarcoidosis patients in time of diagnosis and after 10 years of treatment has been performed. In 10 years after diagnosis, 47 % of the patients had complete remission of pulmonary manifestations; mean forced spirometric values have not reduced in 10 years (excluding patients initially treated with anti-TB drugs). Patients treated with systemic steroids initially or during 10 yrs were less likely to have the complete remission (36.5 %) and more likely to have recurrent sarcoidosis course (57.1 %) compared to those not treated with systemic steroids. Pentoxifylline administration positively influenced the remission rate (71.4 %) and relapse rate in patients who had not received immunosuppressive therapy (28.6 %). A tendency has been found to positive effects of essential phospholipids on relapse rate and remission rate in sarcoidosis. Anti-TB therapy or treatment of sarcoidosis patients in TB centers negatively influenced the outcome of sarcoidosis. The results disclose an urgent need to imply new approaches to treatment of sarcoidosis, eg. anti-TNF-α drugs

    A Selection Index for Gene Expression Evolution and Its Application to the Divergence between Humans and Chimpanzees

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    The importance of gene regulation in animal evolution is a matter of long-standing interest, but measuring the impact of selection on gene expression has proven a challenge. Here, we propose a selection index of gene expression as a straightforward method for assessing the mode and strength of selection operating on gene expression levels. The index is based on the widely used McDonald-Kreitman test and requires the estimation of four quantities: the within-species and between-species expression variances as well as the sequence heterozygosity and divergence of neutrally evolving sequences. We apply the method to data from human and chimpanzee lymphoblastoid cell lines and show that gene expression is in general under strong stabilizing selection. We also demonstrate how the same framework can be used to estimate the proportion of adaptive gene expression evolution

    The Genetic Signatures of Noncoding RNAs

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    The majority of the genome in animals and plants is transcribed in a developmentally regulated manner to produce large numbers of non–protein-coding RNAs (ncRNAs), whose incidence increases with developmental complexity. There is growing evidence that these transcripts are functional, particularly in the regulation of epigenetic processes, leading to the suggestion that they compose a hitherto hidden layer of genomic programming in humans and other complex organisms. However, to date, very few have been identified in genetic screens. Here I show that this is explicable by an historic emphasis, both phenotypically and technically, on mutations in protein-coding sequences, and by presumptions about the nature of regulatory mutations. Most variations in regulatory sequences produce relatively subtle phenotypic changes, in contrast to mutations in protein-coding sequences that frequently cause catastrophic component failure. Until recently, most mapping projects have focused on protein-coding sequences, and the limited number of identified regulatory mutations have been interpreted as affecting conventional cis-acting promoter and enhancer elements, although these regions are often themselves transcribed. Moreover, ncRNA-directed regulatory circuits underpin most, if not all, complex genetic phenomena in eukaryotes, including RNA interference-related processes such as transcriptional and post-transcriptional gene silencing, position effect variegation, hybrid dysgenesis, chromosome dosage compensation, parental imprinting and allelic exclusion, paramutation, and possibly transvection and transinduction. The next frontier is the identification and functional characterization of the myriad sequence variations that influence quantitative traits, disease susceptibility, and other complex characteristics, which are being shown by genome-wide association studies to lie mostly in noncoding, presumably regulatory, regions. There is every possibility that many of these variations will alter the interactions between regulatory RNAs and their targets, a prospect that should be borne in mind in future functional analyses
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