Peculiarities of polyneuropathy in the peripheral t-cell lymphoma with cytostatics

This paper presents data on the occurrence and form of polyneuropathy in the peripheral T-cell lymphoma, and its main pathogenesis elements. Here the toxic effects of cytotoxic drugs and their role in the impairment of the nervous system have been describe

The definition of specific antiparkinsonian effects of Rapitalam

Previously, we identified a metabotropic glutamate receptor 4 (mGluR4) as a potential target for drugs and predicted that activation of mGluR4 could provide a palliative advantage in the treatment of Parkinson's disease. Determine the mechanism of action of Rapitalam in vitro on a cell culture with mGluR4 over expression. The HEK293T cell line expressing human mGluR4 was used in the wor

The Determinants of the 13-Year Risk of Incident Atrial Fibrillation in a Russian Population Cohort of Middle and Elderly Age

Atrial fibrillation (AF) is the most common arrhythmia and a predictor of the complications of atherosclerotic cardiovascular diseases (ASCVDs), particularly thromboembolic events and the progression of heart failure. We analyzed the determinants of the 13-year risk of incident AF in a Russian population cohort of middle and elderly age. A random population sample (n = 9360, age 45–69 years) was examined at baseline in 2003–2005 and reexamined in 2006–2008 and 2015–2017 in Novosibirsk (the HAPIEE study). Incident AF was being registered during the average follow-up of 13 years. The final analysis included 3871 participants free from baseline AF and cardiovascular disease (CVD) who participated in all three data collections. In a multivariable-adjusted Cox regression model, the 13-year risk of AF was positively associated with the male sex (hazard ratio (HR) = 2.20; 95% confidence interval (CI) 1.26–3.87); age (HR = 1.10 per year; 95% CI 1.07–1.14); body mass index (BMI), (HR = 1.11 per unit; 95% CI 1.07–1.15); systolic blood pressure (SBP), (HR = 1.02 per 1 mmHg; 95% CI 1.01–1.02), and it was negatively associated with total cholesterol (TC), (HR = 0.79 per 1 mmol/L; 95% CI 0.66–0.94). In women, the risk of AF was more strongly associated with hypertension (HT) and was also negatively related to total cholesterol (TC) level (HR = 0.74 per 1 mmol/L; 95% CI 0.56–0.96). No independent association was found with mean alcohol intake per drinking occasion. These results in a Russian cohort have an implication for the prediction of AF and ASCVD complications in the general population

THE CLINICAL SIGNIFICANCE OF MATRIX METALLOPROTEINASES IN RHEUMATOID ARTHRITIS PATIENTS (REVIEW OF THE LITERATURE AND OUR OWN DATA)

Matrix metalloproteinases (MMPs) are a group of over 20 proteolytic enzymes responsible for cleavage of protein components of the extracellular matrix. Three types of MMPs play an important role in the development of joint damage in patients with rheumatoid arthritis (RA): collagenases (MMP1, 8 and 13), stromelysins (MMP3), and gelatinases (MMP9). MMP3 is considered to be one of the key mediators of joint damage. Increased serum level of MMP is not specific for RA and may be registered in other rheumatic diseases (osteoarthritis, psoriatic arthritis, gout, ankylosing spondylitis, systemic lupus erythematosus); however, monitoring of the level of MMP is of particular clinical importance in patients with RA. MMP3 serum level may be a useful marker of disease activity. Several studies have shown a correlation of MMP3 concentration with clinical and laboratorial parameters of inflammatory activity (ESR and C-reactive protein – CRP) in RA patients. The elevated level of MMP3 is associated with radiological changes in joints and can also be a predictor of severe destructive lesions in RA patients. Evaluation of the MMP3 level can also be useful for monitoring the therapy effectiveness using both standard disease-modifying antirheumatic drugs (DMARDs) and genetically engineered biological drugs (GEBD). Thus, evaluation of MMP3 concentration is useful for assessing disease activity and efficacy of treatment with DMARDs and GEBD, as well as for predicting the severity of destructive changes in joints

Chemical analysis of bioactive substances in seven siberian Saussurea species

Main groups of biologically active substances of seven siberian Saussurea species (S. controversa DC., S. latifolia Ledeb., S. parviflora (Poir.) DC., S. frolowii Ledeb, S. amara (L.) DC., S. salicifolia (L.) DC. and S. daurica Adams) have been studied using paper, thin-layer, performance liquid chromatography, IR spectroscopy, spectrophotometry and mass spectrometry with inductively coupled plasma. Siberian Saussurea species have a rich elemental composition and contain a variety of phenolic compounds, amino acids, polysaccharides. The majority of polysaccharides are accumulated by S. controversa, S. salicifolia and S. frolowii. These plants contain a significant amount of calcium that may be a species characteristic. All plants contain quercetin and its glycosides, in some species luteolin, kaempferol, glycosides of apigenin and myricetin were revealed. Phenolic acids with predominant content of caffeic, chlorogenic and cinnamic acids were found in all the species. The maximum amount of phenolic acids and flavonoids was determined in the grass of S. latifolia, S. controversa and S. daurica. Characteristic absorption bands of lactone carbonyl of sesquiterpenoids in IR spectrum found in S. latifolia, S. controversa, S. daurica, S. amara and S. salicifolia. HPLC / UV analysis showed that peaks with absorption maxima of 242-246 nm due to the presence of α,β-unsaturated ketone group in the structure of ecdysteroids were found in S. salicifolia, S. controversa, S. daurica and S. latifolia

Evaluation of denitration of nitrocellulose by microbiological treatment for industrial waste effluents using calorimetry analysis

© 2018, Akadémiai Kiadó, Budapest, Hungary. The problem of utilization of the compounds present in the effluents of the production of cellulose nitrates (NC) is very important and complicated, and its decision is inextricably related to the environment. The process of heat release in the samples of nitrocellulose subjected to biological processing of different types was studied. Biological processing was conducted by incubation with sulfate-reducing bacteria Desulfovibrio desulfuricans BКMB-1388, microscopic fungi Fusarium solani BKM F-819, and their mixed culture. The studies were carried out on the native NC (13.38% nitrogen) and the NC processed (NCproc) using ultraviolet radiation and ozone (UV + ozone). It has been shown that the pretreatment of the NC by UV + ozone significantly increases the degree of decomposition of the NC during its subsequent biodegradation assisted by symbiotic microorganisms of D. desulfuricans and F. solani. A substantial result was achieved on the fifth day of NCproc incubation, which is promising from the viewpoint of practical applications

Экспрессия интерферон-стимулированных генов у пациентов с ревматоидным артритом на фоне анти-В-клеточной терапии (предварительные результаты)

Objective: to evaluate the expression of interferon-stimulated genes (ISG) – interferon (IFN) signature – in patients with rheumatoid arthritis (RA) and its dynamics during anti-B-cell therapy.Patients and methods.We examined 20 patients with RA who received two infusions of the biosimilar rituximab (RTM) Acellbia® in a total dose of 1200 mg. Five genes were selected to evaluate IFN signature: IFI44L, MX1, IFIT1, RSAD2, EPSTI1. The expression of IFI44L and IFIT1 could not be determined for technical reasons, and further analysis included three genes – MX1, EPSTI1, RSAD2. IFN signature was calculated as the average value of the expression of three selected genes (IFN-score).Results and discussion. The initial expression level of MX1 was 11.48 (5.45–19.38), EPSTI1 – 12.83 (5.62–19.64), RSAD2 – 5.16 (2.73–10.4) and IFN-score –10.3 (5.18–17.12), in patients with RA it was statistically significantly higher than in healthy donors: 1.26 (0.73–1.6); 1.06 (0.81–1.48); 0.93 (0.72–1.19) and 1.09 (0.92–1.42), respectively (p<0.05). The IFN-score was high in 15 (75%) patients, low in 5 (15%). The use of RTM was accompanied by a statistically significant decrease in disease activity and the level of acute phase parameters (ESR, CRP) after 12 and 24 weeks of therapy (p<0.05). In the group as a whole, as well as in patients with a moderate effect of therapy or its absence, by the 24th week of treatment, an increase in the expression of RSAD2 (p<0.05) and a tendency to an increase in the IFN-score level (p=0.06) were observed.Conclusion. In patients with RA, an increased expression of ISH was found compared to healthy donors. An increase in the expression of RSAD2 and IFN-score is observed both in patients with a satisfactory effect of RTM and with no effect. The obtained results can be important for predicting the course of the disease and personalizing therapy.Цель исследования – оценить экспрессию интерферон-стимулированных генов (ИСГ) – интерфероновый (ИФН) «автограф» – у пациентов с ревматоидным артритом (РА) и ее динамику на фоне анти-В-клеточной терапии.Пациенты и методы. Обследовано 20 больных РА, получивших две инфузии биоаналога ритуксимаба (РТМ) Ацеллбия® в суммарной дозе 1200 мг. Для оценки ИФН-«автографа» были отобраны пять генов: IFI44L, MX1, IFIT1, RSAD2, EPSTI1. Экспрессию IFI44L и IFIT1 определить не удалось по техническим причинам и в дальнейшем анализе учитывали три гена – MX1, EPSTI1, RSAD2. ИФН-«автограф» был рассчитан как среднее значение экспрессии трех выбранных генов (ИФН-score).Результаты и обсуждение. Исходный уровень экспрессии MX1 – 11,48 (5,45–19,38), EPSTI1 – 12,83 (5,62–19,64), RSAD2 – 5,16 (2,73–10,4) и ИФН- score – 10,3 (5,18–17,12) у пациентов с РА были статистически значимо выше, чем у здоровых доноров: 1,26 (0,73–1,6); 1,06 (0,81–1,48); 0,93 (0,72–1,19) и 1,09 (0,92–1,42) соответственно (р<0,05). Показатель ИФН-score был высоким у 15 (75%) больных, низким – у 5 (15%). Применение РТМ сопровождалось статистически значимым снижением активности заболевания и уровня острофазовых показателей (СОЭ, СРБ) через 12 и 24 нед терапии (p<0,05). В группе в целом, а также у пациентов с умеренным эффектом терапии или его отсутствием к 24-й неделе лечения отмечались повышение экспрессии RSAD2 (p<0,05) и тенденция к повышению уровня ИФН-score (р=0,06).Заключение. У пациентов с РА выявлена повышенная экспрессия ИСГ по сравнению со здоровыми донорами. При удовлетворительном эффекте РТМ или его отсутствии наблюдается повышение экспрессии RSAD2 и ИФН-score. Полученные результаты могут иметь значение для прогнозирования течения заболевания и персонификации терапии

Взаимосвязь лабораторных биомаркеров и ультразвуковых признаков воспаления у пациентов с ревматоидным артритом на фоне терапии биоаналогом ритуксимаба

Objective: to assess the relationship between laboratory biomarkers and ultrasonographic signs of inflammation in patients with rheumatoid arthritis during therapy with a rituximab (RTM) biosimilar.Patients and methods. 20 patients with definite diagnosis of RA were examined. All patients received 2 infusions of RTM (Acellbia®), at a dose of 600 mg intravenously 2 weeks apart during therapy with methotrexate, non-steroidal anti-inflammatory drugs and glucocorticoids. Clinical and laboratory parameters were analyzed immediately before the start of therapy, and then 12 and 24 weeks after the first infusion of the drug.Results and discussion. By the 24th week of RTM therapy, a good/moderate effect according to the EULAR criteria was registered in 17 (85%) patients; remission according to DAS28 (<2.6) was achieved in 4 (20%) patients, SDAI (≤3.3) – in 2 (10%), CDAI (≤2.8) – in 1 (5%). Prior to the start of treatment, active synovitis was detected in 13 (65%) patients by power Doppler imaging (PD), and in 20 (100%) patients by gray scale scanning. During therapy with the RTM biosimilar, a significant decrease in inflammatory changes in the joints was observed, and by the 24th week after the start of treatment, the median PD was 0.5; active inflammation persisted in 7 (35%) patients. As shown by ROC analysis, the initial level of interleukin (IL) 6 >100.0 pg/ml is associated with the persistence of inflammatory activity according to PD by the 24th week of therapy with the RTM biosimilar, while the sensitivity was 85% and the specificity was 62% (AUC 0.78, 95% CI 0.57–0.99)Conclusion. An association was found between an increased level of pro-inflammatory cytokines, mainly IL6, and the activity of synovial inflammation according to ultrasound data. IL6 is the most promising marker for predicting persistent inflammatory activity based on the results of PD; other analyzed parameters have worse sensitivity and specificity parameters.Цель исследования – оценить взаимосвязь лабораторных биомаркеров и ультразвуковых признаков воспаления у пациентов с ревматоидным артритом на фоне терапии биоаналогом ритуксимаба (РТМ).Пациенты и методы. Обследовано 20 больных с достоверным диагнозом РА. Всем пациентам проведено по 2 инфузии РТМ (Ацеллбия®) в дозе 600 мг внутривенно с интервалом в 2 нед на фоне терапии метотрексатом, нестероидными противовоспалительными препаратами и глюкокортикоидами. Клинические и лабораторные показатели анализировались непосредственно перед началом терапии, а затем через 12 и 24 нед после первой инфузии препарата.Результаты и обсуждение. К 24-й неделе терапии РТМ хороший/умеренный эффект по критериям EULAR зарегистрирован у 17 (85%) пациентов; ремиссия по DAS28 (<2,6) достигнута у 4 (20%) больных, SDAI ( ≤3,3) – у 2 (10%), CDAI ( ≤2,8) – у 1 (5%). До начала лечения активный синовит по данным энергетического допплеровского картирования (ЭД) выявлен у 13 (65%) пациентов, а при сканировании в режиме серой шкалы – у 20 (100%). На фоне терапии биоаналогом РТМ наблюдалось значимое уменьшение воспалительных изменений в суставах, и к 24-й неделе после начала лечения медиана ЭД составила 0,5; активное воспаление сохранялось у 7 (35%) больных. Как показал ROC-анализ, исходный уровень интерлейкина (ИЛ) 6 >100,0 пг/мл ассоциируется с сохранением воспалительной активности по данным ЭД к 24-й неделе терапии биоаналогом РТМ, при этом чувствительность составила 85% и специфичность – 62% (AUC 0,78, 95% доверительный интервал 0,57–0,99)Заключение. Выявлена ассоциация между повышенным уровнем провоспалительных цитокинов, в основном ИЛ6, и активностью синовиального воспаления по данным УЗИ. Для прогнозирования сохраняющейся воспалительной активности по результатам ЭД наиболее перспективным маркером является ИЛ6, другие анализируемые показатели имеют худшие параметры чувствительности и специфичности