EFFECTIVENESS OF EDUCATIONAL PROGRAMS ON EARLY DIAGNOSIS OF ANKYLOSING SPONDYLITIS FOR PRIMARY CARE PHYSICIANS IN KAZAN

The diagnosis of ankylosing spondylitis (AS) in the real-life practice is delayed for 7–8 years on average. Educational programs for primary care physicians may promote the disease diagnosis. Objective. To analyze the effectiveness of the educational programs for the early diagnosis of AS for primary contact physicians in the real-life clinical practice in Kazan. Material and methods. The development of the educational programs and determination of their effectiveness com- prised three stages: 1) determination of the level of knowledge and problems in the diagnosis and treatment of AS among primary care physicians and neurologists; 2) development of educational programs suitable to be used in the real-life clinical practice; 3) analysis of the effectiveness of implementing the programs according to the reports on work of the City Rheumatology Center in 2009–2011. Results. After running the courses, the number of patients with AS at the Kazan City Rheumatology Center increased almost twofold, from 378 in 2009 to 683 in 2011; the period from the onset of the disease to diagnosis was simultane- ously reduced from 8.4 to 3.5 years. Conclusion. The educational programs for primary care physicians and neurologists in Kazan have promoted shorten- ing of the AS diagnosis time

New phosphorus dithioacids and their derivatives containing chiral centers and pharmacophoric groups

© 2016 Taylor & Francis Group, LLC.New phosphorus dithioacids, their ammonium salts and S-silyl and plumbyl derivatives containing asymmetric carbon atoms and pharmacophoric groupswere obtained by the reactions of tetraphosphorus decasulfide and 1,3,2,4-dithiadiphosphetane-2,4-disulfides with chiral natural terpenyl alcohols, diols, carboxylic acid esters, amino acids and monosaccharides as well as synthetic chiral amines and 1-phenylethanol. The biological activity of the ammonium salts and S-esters of phosphorus dithioacids were studied

Chiral Salts of Phosphorus Dithioacids Based on Quinine

© 2018, Pleiades Publishing, Ltd. Reactions of quinine with dithioacids based on (1R)-endo-(+)-fenchol, (1S)-endo-(–)-borneol, and (S)-(–)-menthol have afforded optically active quinine salts. Chiral diquinine salts have been obtained in the reactions of quinine with bisthiophosphonic acids based on triethylene glycol and resorcinol

Optimization of the Conditions for Cultivation of Yersinia pseudotuberculosis in the Process of Obtaining Cell Mass

Objective of the study was to optimize the conditions of submerged recurrent cultivation and the composition of the nutrient medium for obtaining the cell mass of Yersinia pseudotuberculosis strains, used as an adsorbent in the preparation of diagnostic plague immunoglobulins. Materials and methods. We utilized Y. pseudotuberculosis adsorbent strains 6; 31; 68; 69; and 70 belonging to V, I, III, IV, and V serotypes, respectively, received from the State Collection of Pathogenic Bacteria at the premises of the RusRAPI “Microbe”. The cultivation process was carried out on an incubator-shaker, laboratory and pilot fermenters with variation of the process parameters, different options for feeding and nutrient media. Results and discussion. In the course of work, the optimal parameters of recurring submerged cultivation have been established. It was found that the highest biomass yield is provided by a combination of a nutrient medium – a carbon substrate in the form of a broth, based on an enzymatic fibrin hydrolysate, with the addition of galactose as a substrate feeding. Thereat, the morphology and immunochemical properties of microbial cells obtained through modified preparation process do not differ from those produced in the control run. The optimization of the parameters for Y. pseudotuberculosis cell mass cultivation with subsequent upscaling has been performed

Efficacy and tolerability of adalimumab (humira) in patients with active rheumatoid arthritis

Objective: to evaluate the efficacy and tolerability of adalimumab alone and in combination with basic anti-inflammatory drugs (BAIDs) in patients with rheumatoid arthritis (RA), by taking into account the specific features of the course of the disease. Subjects and methods. The study enrolled 30 patients with a verified diagnosis of RA, its high activity by DAS 28, and ineffective previous therapy with standard BAIDs. At the beginning of the study, 20 (66.7%) patients continued taking BAIDs. According to therapy, the patients were divided into 3 groups: 1) 10 (33.3%) patients received subcutaneous adalimumab injections only; 2) 12 (40%) took adalimumab+methotrexate (MT); 3) 8 (26.7%) had adalimumab+leflunomide. The patient groups were matched for age, the duration and activity of RA (by DAS 28), its X-ray stage and seropositivity. Nine (37.5%) patients took oral glucocorticoids (GCs) and 25 (83.3%) received non-steroidal anti-inflammatory drugs (NSAIDs). Two (8.3%) patients had previously been prescribed biological therapies. Adalimumab was subcutaneously injected every 2 weeks for 24 weeks. The quantitative parameters of articular syndrome and blood and urine biochemical and clinical analyses were used to evaluate therapeutic effectiveness. The effect of therapy was evaluated by the ACR and EULAR (DAS 28) criteria. The efficiency of therapy was evaluated 12 and 24 weeks after therapy. Results. The clinical and laboratory effect of adalimumab was noted in 29 (96.7%) of the 30 patients. All the assessed parameters of articular syndrome became significantly lower (p<0.001) by week 12 of therapy and to a greater extent by week 24. Evaluation of the efficiency of adalimumab therapy by the ACR criteria showed that following 12-week therapy, the parameters were decreased by 20% in 87% of the patients and 50% in 16.7%; after 24 weeks, 23.3, 70 and 96.7% achieved very good (ACR 70), good (ACR 50), and satisfactory (ACR 20) effects. Estimation of the time course of changes in the disease activity index (DAS 28) revealed that adalimumab significantly reduced disease activity. Therapeutic effectiveness was also shown as reduced needs for NSAIDs and GCs. Positive clinical and laboratory changes during adalimumab+ MT combination therapy were also demonstrated to be significantly higher than those during adalimumab monotherapy or adalimumab + leflunomide combination therapy. Conclusion. Adalimumab is an effective disease-modifying biological agent. Its benefits may include the rapid development (on days 4-5 on average) and long retention (for 6 months or more) of an effect, a good safety profile (adverse reactions occurred only in 16.7% of the patients), and easiness-to-use

Применение растительного препарата Урисан в качестве базисной терапии подагры

Objective: to evaluate the efficacy, safety, and tolerance of the herbal complex Urisan used in patients with gout. Subjects and methods. Thirty allopurinol-untreated patients with a verified diagnosis of gout (by the ACR criteria) were followed up during a relapse-free interval. Subjective appraisals of the tolerance of Urisan were provided by a physician and a patient. General clinical examination, anthropometry, monitoring blood pressure and uric acid (UA) in blood and urine, and lipid metabolism were made to define the efficiency of therapy before and after it. Results. Urisan exhibited a positive effect in reducing the blood levels of UA (p< 0,003). For more detailed evaluation of the effect of Urisan on hyperuricemia, the patients were divided into 3 groups in accordance with the baseline level of UA; positive changes were observed in all the groups. Significantly lower UA levels were seen in Groups 1 and 2 (p< 0,007 and p< 0,04, respectively). The remedy was found to have no effect on UA excretion. Its tolerance was good. Conclusion. Urisan has a positive effect, by lowering hyperuricemia despite the latter's baseline valuesЦель исследования - оценка эффективности, безопасности и переносимости растительного комплекса Урисан у больных подагрой. Материал и методы. Под наблюдением находилось 30 больных с верифицированным диагнозом подагра (по критериям ACR) в межприступном периоде, не принимающих аллопуринол. Проводилась субъективная оценка переносимости препарата врачом и пациентом. Для определения эффективности терапии до ее начала и через 1 мес осуществляли общеклиническое обследование, антропометрию, контроль АД, уровня мочевой кислоты (МК) в крови и моче, липидного обмена Результаты исследования. Отмечен положительный эффект Урисана, проявившийся в снижении уровня МК в крови (р<0,003). Для более детальной оценки влияния Урисана на гиперурикемию пациентов разделили на 3 группы в зависимости от первоначального уровня МК, во всех группах отмечалась положительная динамика. Достоверное снижение показателей МК наблюдалось в 1-й и 2-й группах (р<0,007 и р<0,04 соответственно). Влияния на выделение МК не установлено. Переносимость препарата была хорошей. Заключение. Урисан оказывает положительное действие, снижая гиперурикемию независимо от ее исходных значени

ДЕВОН-КАМЕННОУГОЛЬНЫЙ МАГМАТИЗМ И ОРУДЕНЕНИЕ ЮЖНО-УРАЛЬСКОЙ АККРЕЦИОННО-КОЛЛИЗИОННОЙ СИСТЕМЫ

The oceanic stage in the history of the South Urals completed in the Ordovician – Early Silurian. The Ordovician through Devonian events in the region included the formation of an island arc in the East Ural zone from the Middle Ordovician to Silurian; westward motion of the subduction zone in the Late Silurian – Early Devonian and the origin of a trench along the Main Ural Fault and the Uraltau Uplift; volcanic eruptions and intrusions in the Magnitogorsk island arc system in the Devonian. The Middle-Late Paleozoic geodynamic evolution of uralides and altaides consisted in successive alternation of subduction and collisional settings at the continent-ocean transition. The greatest portion of volcanism in the major Magnitogorsk zone was associated with subduction and correlated in age and patterns of massive sulfide mineralization (VMS) with Early – Middle Devonian ore-forming events in Rudny Altai. Within-plate volcanism at the onset of volcanic cycles records the Early (D1e2) and Middle (D2ef2) Devonian slab break off. The volcanic cycles produced, respectively, the Buribay and Upper Tanalyk complexes with VMS mineralization in the Late Emsian; the Karamalytash complex and its age equivalents in the Late Eifelian – Early Givetian, as well as the lower Ulutau Formation in the Givetian. Slab break off in the Late Devonian – Early Carboniferous obstructed the Magnitogorsk island arc and supported asthenospheric diapirism. A new subduction zone dipping westward and the Aleksandrovka island arc formed in the Late Devonian – Early Carboniferous. The Early Carboniferous collision and another event of obstructed subduction led to a transform margin setting corresponding to postcollisional relative sliding of plates that produced another slab tear. Postcollisional magmatism appears as alkaline gabbro-granitic intrusives with related rich Ti-magnetite mineralization (C1). Transform faulting persisted in the Middle Carboniferous through Permian, when the continent of Eurasia completed its consolidation. The respective metallogenic events included formation of Cu-Ni picritic dolerites (C2–3), as well as large-scale gold and Mo-W deposits in granites (P1–2).Завершение океанической стадии на Южном Урале произошло в ордовик – раннесилурийское время. В среднем ордовике в Восточно-Уральской зоне начала формироваться среднеордовикско-силурийская островная дуга. В позднем силуре – раннем девоне произошел перескок зоны субдукции на запад, формирование глубоководного желоба в зоне Главного Уральского разлома – Уралтауского антиклинория и началось образование вулкано-интрузивных формаций Магнитогорской островодужной системы (D1–D3). В среднепозднепалеозойской геодинамической эволюции уралид и алтаид произошло последовательное чередование субдукционных и трансформно-коллизионных обстановок в зоне перехода континент – океан. На Южном Урале с субдукционной обстановкой связан главный объем вулканических ассоциаций Магнитогорской мегазоны. В раннем (D1e2) и среднем (D2ef2) девоне произошли разрывы слэба, фиксирующиеся проявлениями внутриплитного вулканизма, приуроченного к начальным этапам раннедевонского позднеэмсского и позднеэйфельско-раннеживетского колчеданоносных вулканических циклов. В позднем девоне – раннем карбоне произошла блокировка Магнитогорской островной дуги с разрывом слэба, и, как следствие, – главный этап астеносферного диапиризма. На рубеже позднего девона – раннего карбона сформировалась новая зона субдукции западного падения и возникла Александровская редуцированная островная дуга. Раннекаменноугольная коллизия и повторная блокировка субдукционной зоны привели к трансформной обстановке, отвечавшей постколлизионному скольжению литосферных плит, и вновь – к появлению астеносферного окна («slab-tear»). В этой обстановке были сформированы габбро-гранитные интрузивы повышенной щелочности и связанные с ними Ti-Mgt месторождения мирового класса (С1). Трансформная геодинамическая обстановка оставалась ведущей на протяжении среднего карбона – перми, когда произошла окончательная консолидация Евразийского континента

Experimental Substantiation of Feasibility of Using Enzymatic Fibrin Hydrolyzate-Based Medium to Obtain Components of Chemical Cholera Vaccine

The aim of the study was to experimentally substantiate the possibility of using a nutrient medium based on enzymatic fibrin hydrolyzate in order to obtain specific components of chemical cholera vaccine: cholerogen-anatoxin and O-antigen. Materials and methods. We used production strains of Vibrio cholerae 569B and V. cholerae M-41. Submerged low-volume cultivation was carried out in a laboratory fermenter for 8 hours, with automatic maintenance of cultivation parameters and feeding with glucose on the nutrient medium based on enzymatic fibrin hydrolyzate, containing (1.0±0.1) g/l of amine nitrogen, pH being (8.0±0.1). Cholerogen-anatoxin and O-antigens were obtained from detoxified formalin-treated centrifugates of culture liquids. The specific activity of V. cholerae antigens at the stages of cultivation and isolation was determined applying immunochemical methods. The preparation of the finished dosage form of the cholera vaccine and the coating of the tablets with an enteric coating was carried out in accordance with the regulatory documentation. Results and discussion. It has been shown that cultivation on the medium based on enzymatic fibrin hydrolyzate provides a stable growth of the biomass of V. cholerae production strains with a high level of specific activity of antigens. Comparative analysis of the main properties of the finished dosage form of laboratory batches with a commercial batch of chemical cholera vaccine has demonstrated compliance with the requirements of regulatory documentation. The results obtained has led us to conclusion that it is feasible to use the nutrient medium based on enzymatic fibrin hydrolyzate for cultivating production strains and obtaining specific components of the cholera vaccine

Эффективность и переносимость адалимумаба (Хумира) у пациентов с активным ревматоидным артритом

Objective: to evaluate the efficacy and tolerability of adalimumab alone and in combination with basic anti-inflammatory drugs (BAIDs) in patients with rheumatoid arthritis (RA), by taking into account the specific features of the course of the disease. Subjects and methods. The study enrolled 30 patients with a verified diagnosis of RA, its high activity by DAS 28, and ineffective previous therapy with standard BAIDs. At the beginning of the study, 20 (66.7%) patients continued taking BAIDs. According to therapy, the patients were divided into 3 groups: 1) 10 (33.3%) patients received subcutaneous adalimumab injections only; 2) 12 (40%) took adalimumab+methotrexate (MT); 3) 8 (26.7%) had adalimumab+leflunomide. The patient groups were matched for age, the duration and activity of RA (by DAS 28), its X-ray stage and seropositivity. Nine (37.5%) patients took oral glucocorticoids (GCs) and 25 (83.3%) received non-steroidal anti-inflammatory drugs (NSAIDs). Two (8.3%) patients had previously been prescribed biological therapies. Adalimumab was subcutaneously injected every 2 weeks for 24 weeks. The quantitative parameters of articular syndrome and blood and urine biochemical and clinical analyses were used to evaluate therapeutic effectiveness. The effect of therapy was evaluated by the ACR and EULAR (DAS 28) criteria. The efficiency of therapy was evaluated 12 and 24 weeks after therapy. Results. The clinical and laboratory effect of adalimumab was noted in 29 (96.7%) of the 30 patients. All the assessed parameters of articular syndrome became significantly lower (p<0.001) by week 12 of therapy and to a greater extent by week 24. Evaluation of the efficiency of adalimumab therapy by the ACR criteria showed that following 12-week therapy, the parameters were decreased by 20% in 87% of the patients and 50% in 16.7%; after 24 weeks, 23.3, 70 and 96.7% achieved very good (ACR 70), good (ACR 50), and satisfactory (ACR 20) effects. Estimation of the time course of changes in the disease activity index (DAS 28) revealed that adalimumab significantly reduced disease activity. Therapeutic effectiveness was also shown as reduced needs for NSAIDs and GCs. Positive clinical and laboratory changes during adalimumab+ MT combination therapy were also demonstrated to be significantly higher than those during adalimumab monotherapy or adalimumab + leflunomide combination therapy. Conclusion. Adalimumab is an effective disease-modifying biological agent. Its benefits may include the rapid development (on days 4-5 on average) and long retention (for 6 months or more) of an effect, a good safety profile (adverse reactions occurred only in 16.7% of the patients), and easiness-to-use.Цель наблюдения - оценка эффективности и переносимости адалимумаба у больных РА как при монотерапии, так и в комбина- ции с базисными противовоспалительными препаратами (БПВП) с учетом особенностей течения заболевания. Материал и методы. В наблюдение было включено 30 больных с достоверным диагнозом РА и высокой активностью болезни по DAS 28 и неэффективностью предшествующей терапии стандартными БПВП. К моменту начала наблюдения продолжали принимать БПВП 20 (66,7%) пациентов. В соответствии с терапией пациенты были разделены на три группы: только подкожные инъекции адалимумаба по- лучали 10 (33,3%) больных, адалимумаб+метотрексат (МТ) - 12 (40%) и адалимумаб+лефлуномид - 8 (26,7%). Группы пациентов бы- ли сопоставимы по возрасту, длительности, активности РА (по DAS 28), его рентгенологической стадии и серопозитивности. Пероральные глюкокортикоиды (ГК) получали 9 (37,5%) больных, нестероидные противовоспалительные препараты (НПВП) - 25 (83,3%). Терапию биологическими агентами в прошлом назначали 2 (8,3%) пациентам. Адалимумаб вводили подкожно каждые 2 нед в течение 24 нед. Для оценки эффективности лечения использовали количественные параметры суставного синдрома, биохимические, клинические анализы крови и мочи. Эффект терапии оценивали по критериям ACR и EULAR (DAS 28). Оценку эффективности проводили через 12 и 24 нед терапии. Результаты. Клинико-лабораторный эффект адалимумаба отмечен у 29 (96,7%) из 30 больных. Все оцениваемые параметры сус- тавного синдрома достоверно (p<0,001) уменьшались к 12-й неделе и еще в большей степени - к 24-й неделе терапии. Оценка эф- фективности лечения адалимумабом по критериям ACR показала, что через 12 нед терапии уменьшение параметров на 20% от- мечалось у 87% больных, на 50% - у 16,7%; через 24 нед ответ на терапию зарегистрирован у 96,7% больных (ACR 20), 70% (ACR 50) и 23,3% (ACR 70). При оценке динамики индекса активности болезни (DAS 28) выявлено, что адалимумаб достоверно снижал активность заболева- ния. Эффективность терапии проявлялась также в снижении потребности в НПВП и ГК. Положительная динамика клинико-ла- бораторных показателей на фоне комбинированной терапии адалимумабом+МТ была достоверно выше, чем при монотерапии ада- лимумабом или использовании комбинации адалимумаб + лефлуномид. Заключение. Адалимумаб - эффективный болезнь-модифицирующий биологический препарат. К его преимуществам можно отне- сти быстрое развитие (в среднем на 4-5-й день) и длительное сохранение (6 мес и более) эффекта, хороший профиль безопасности (побочные явления возникли лишь у 16,7 больных), удобство введения