Changes of gas metabolism, gas homeostasis and tissue respiration in rats during prolonged hypokinesia

The oxygen uptake and tissue gas homeostasis of restrained albinic rats remained relatively constant during a 60 day experiment. The gas metabolism in some tissues changed, and O2 consumption increased in the liver and decreased in the myocardium. Capacity for physical work was reduced by five times. Hypokinesia for 60 days resulted in a delay in the animals growth

Changes of the body functions during long-term hypokinesia

Prolonged hypokinesis (100-170 days) studied in 2000 rats kept in cages limiting their mobility provoked considerable changes in the gaseous and energetic metabolism: an elevation of the total gaseous metabolism and of the rate of O2 requirement by the muscles (in the late periods of hypokinesis) and a change in the intensity of tissue respiration of the liver and myocardium. There also proved to be a reduction in the level of phosphorylation and separation of oxidative phosphorylation in the myocardium, liver, and partially in the skeletal muscle. Prolonged hypokinesia led to changes in tissue metabolism: a disturbance of development of the animals, a marked delay and an increase in the weight of the organism and the muscular system, and disturbances of the mineral and protein metabolism. Prolonged hypokinesis also lead to exhaustion of the hypothalamus-hypophysis-adrenal cortex system

MODERN IDEA ON THE PATHOGENESIS OF SPONDYLOARTHRITIS: MOLECULAR MECHANISMS

As of now, impaired immune homeostasis of the intestinal mucosa in genetically predisposed individuals is considered to be one of the major components in the pathogenesis of spondyloarthritis (SpA), which leads to systemic chronic inflammation. The results of recent studies may suggest that the interleukin-23/interleukin-17 (IL-23/IL-17) axis plays a leading role in the development of these diseases. The multifactorial components of the pathogenesis of SpA are characterized by not only the hyperproduction of IL-23, but also by the change in cell target susceptibility to this cytokine with aconcurrent increase in their number, resulting in the chronic autoinflammatory process that occurs via a wide spectrum of clinical manifestations of different types of Sp

«Гастроэнтерологическая» ревматология: дифференциальная диагностика ранних артритов

In real clinical practice, rheumatologists constantly face with the problem of differential diagnosis of rheumatic (RDs) and non-rheumatic diseases, as well as various RDs with similar symptoms. Most of the RDs are multisystemic and heterogeneous in clinical symptoms, course, and outcomes. Their clinical, laboratory, and instrumental signs that could be considered as the gold standard to confirm the diagnosis are not defined in all nosological entities. Therefore, the diagnostic process, especially in early arthritis caused by systemic inflammation, is complex cognitive in nature and requires the synthesis of many data that are usually not taken into account in a simple algorithm, the basis of which is a set of classification criteria.The review presents the issues of differential diagnosis of early arthritis in gastrointestinal tract diseases, such as celiac disease, microscopic colitis, PPP syndrome, etc.Ревматологи в реальной клинической практике постоянно сталкиваются с проблемой дифференциальной диагностики ревматических (РЗ) и неревматических заболеваний, а также разных РЗ со схожими признаками. Большинство РЗ мультисистемны и гетерогенны по клинической симптоматике, течению и исходам. Их клинические, лабораторные и инструментальные признаки, которые можно было бы считать «золотым стандартом» для подтверждения диагноза, не определены при всех нозологиях. Поэтому диагностический процесс, особенно в случае раннего артрита, обусловленного системным воспалением, носит комплексный познавательный характер и требует синтеза многих данных, обычно не учитываемых в простом алгоритме, основой которого является набор классификационных критериев.В обзоре представлены вопросы дифференциальной диагностики раннего артрита при таких заболеваниях желудочно-кишечного тракта, как целиакия, микроскопический колит, синдром ППП и др

Polarization sensitive spectroscopy of charged Quantum Dots

We present an experimental and theoretical study of the polarized photoluminescence spectrum of single semiconductor quantum dots in various charge states. We compare our high resolution polarization sensitive spectral measurements with a new many-carrier theoretical model, which was developed for this purpose. The model considers both the isotropic and anisotropic exchange interactions between all participating electron-hole pairs. With this addition, we calculate both the energies and polarizations of all optical transitions between collective, quantum dot confined charge carrier states. We succeed in identifying most of the measured spectral lines. In particular, the lines resulting from singly-, doubly- and triply- negatively charged excitons and biexcitons. We demonstrate that lines emanating from evenly charged states are linearly polarized. Their polarization direction does not necessarily coincide with the traditional crystallographic direction. It depends on the shells of the single carriers, which participate in the recombination process.Comment: 11 pages, 9 figures. Revised versio

RESULTS OF A CROSS-SECTIONAL EPIDEMIOLOGICAL STUDY DETERMINING THE NEEDS FOR GENETIC ENGINEERINGBIOLOGICALS FOR THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL CLINICAL PRACTICE IN RUSSIA(IRACL)COMMUNICATION 2. DETERMINATION OF NEEDS FOR GENETIC ENGINEERING BIOLOGICALS

Genetic engineering biologicals (GEBs) show promises in treating rheumatoid arthritis (RA), their efficacy and tolerability have been studied and indications and contraindications defined. However, the extensive application of GEBs is limited due to their high cost. In Russia, GEB therapy is paid by the government. To plan and optimize expenditures, it is necessary to have standardized indications and to know the number of patients who need biological therapy. Objective: To define a need for GEBs (tumor necrosis factor- (TNF-) inhibitors) in patients with RA in real clinical practice in Russia. Subjects and methods. The study comprised 2 stages. At Stage 1, the expert method was used to develop a standardized scale to define indications for GEB therapy in patients with RA (StansRA). Disease activity (DAS 28) and duration, progression rate, and tolerability of earlier used basic anti-inflammatory drugs, including methotrexate (MT) in a dose of ≥15 mg/week were considered. Each index was estimated as scores. According to the total scores (min 0, max 0), the patients were divided into 4 groups: 1) GEBs are absolutely indicated (≥7 scores); 2) more likely indicated (5-6 scores); 3) more unlikely indicated (3-4 scores); 4) absolutely contraindicated (5.1) RA activity (27 and 65%, respectively). 69% took MT (mean dose 12.52.5 mg). Results. 4.4% of the 1810 patients had contraindications for GEB therapy. According to the StansRA, GEB therapy is absolutely contraindicated in 6% of cases and 52.7% had indications for GEB use (absolutely and more likely indicated in 9.5 and 43%, respectively). Of them, only 7 (0.5%) patients collected the maximum (9) scores; 33 (2.2%) patients had 8 scores; 101 (6.8%) had 7 scores. Conclusion. The StansRA developed and tested at the population level aids in reducing subjectivism to use these medicines and in optimizing financial expenses on the treatment of patients with RA in real clinical practice in Russia

Труднолечимый ревматоидный артрит. Какой он?

The widespread introduction into clinical practice of modern approaches to the treatment of rheumatoid arthritis (RA), the rational use of traditional and targeted antirheumatic drugs can effectively suppress inflammatory activity, restrain the progression of the disease and improve the quality of life of patients. At the same time, in some patients, even after the repeated change of targeted drugs, it is not possible to achieve the target level of RA activity. Serious difficulties arising in the management of such patients raised the question of identifying a special variant of the disease – difficult-to-treat (D2T) RA. The presence of various variants of D2T RA and the need to use a personalized approach to therapy justify the creation of special recommendations for the management of this category of patients. The first step in preparing these recommendations was the definition of D2T RA recently presented by the EULAR working group. It includes three criteria: 1) insufficient effectiveness of the therapy; 2) the presence of an active symptomatic disease; 3) clinical perception.Широкое внедрение в клиническую практику современных подходов к лечению ревматоидного артрита (РА), рациональное использование традиционных и таргетных противоревматических препаратов позволяют эффективно подавлять воспалительную активность, сдерживать прогрессирование болезни и улучшать качество жизни больных. Вместе с тем у части пациентов даже после повторной смены таргетных препаратов не удается добиться целевого уровня активности РА. Серьезные затруднения, возникающие при ведении таких пациентов, поставили вопрос о выделении особого варианта болезни – труднолечимого (difficult to treat, D2T) РА. Наличие разнообразных вариантов D2T РА и необходимость использования персонифицированного подхода к терапии обосновывают создание специальных рекомендаций по ведению данной категории больных. Первым шагом к подготовке данных рекомендаций стало определение понятия D2T РА, недавно представленное рабочей группой EULAR. Оно предусматривает соответствие пациента трем критериям: 1) недостаточная эффективность проводимой терапии; 2) наличие активного симптоматического заболевания; 3) клиническое восприятие

Role of hepcidin in the development of anemia in patients with rheumatoid arthritis

Chronic disease anemia (CDA) diagnosed in many patients with rheumatoid arthritis (RA) was described in the early 1970s. As earlier noted, iron metabolic disturbances in CDA are its diagnostic feature and the discovery of hepcidin, an iron-regulatory acute-phase protein, could largely clarify an association between the immune mechanism of impaired iron homeostasis and the development of CDA. Objective: to define the role of hepcidin in the differential diagnosis of CDA and true iron deficiency in patients with RA. Subjects and methods. The investigation enrolled 76 patients with RA (1987 ACR criteria) admitted to the Research Institute of Rheumatology, Russian Academy of Medical Sciences, to be treated. The patients were divided into two groups. A study group comprised anemic patients (n = 47). The WHO criteria for anemia were considered to be hemoglobin (Hb) levels of below 120 g/l for women and below 130 g/l for men. A control group consisted of non-anemic patients (n = 29). The anemic and non-anemic patients were matched for age (45.5±14.3 and 49.8±14.3 years, respectively) and disease duration (2 months to 20 years) (p > 0.05). Iron metabolic parameters, such as serum iron, total serum iron-binding capacity (TSIBC), iron transferrin saturation (ITS), transferrin receptors, and serum ferritin (SF), were studied and the level of hepcidin prohormone was estimated by direct enzyme immunoassay (Hepcidin Prohormone Enzyme Immunoassay Kit, IBL, Germany) in all the patients to be analyzed. Cytokines, such as interleukin 6, tumor necrosis factor-а) were determined by enzyme immunoassay (Bender MedSystems, Austria). The Institute’s differential diagnostic algorithm involving SF, TSIBC, and ITS was used to diagnose iron deficiency. The diagnosis was based on two stages of estimating iron values: isolated iron-deficiency anemia (IDA) was diagnosed if SF was below the normal value (< 40 μg/l). If the patient had SF of μ40 μg/l with a simultaneous rise of TSIBC above the normal level (> 70 μg/l) and a drop of ITS (> 20%), he/she might be suspected as having the mixed genesis of anemia, in which both iron deficiency and CDA are detectable. The other patients could be diagnosed as having isolated CDA. Results. The study has established that irrespective of the hemoglobin level, the content of serum hepcidin prohormone in the examined patients with RA averaged 89.2±65.1 pg/ml and was much higher than that in donors (64.9+21.6 pg/ml; р < 0.05). An analysis of the blood biochemical parameters characterizing iron metabolism showed that, whether they were anemic or non-anemic, the patients with RA, as compared with donors, were found to have an elevated level of SF that is an acute-phase indicator and reflects the high activity of an inflammatory process. To rule out IDA, the anemic patients with RA were subdivided into 3 subgroups according to the differential diagnostic algorithm. Subgroup 1 included patients with isolated CDA (n = 13 patients (28% of those in the study group)); Subgroup 2 consisted of 17 (32%) patients with anemia of mixed genesis (CDA ± IDA), and Subgroup 3 comprised 17 patients with IDA. An analysis of the clinical and laboratory parameters in RA independent of the nature of anemia demonstrated that only the patients with isolated CDA had significantly higher mean values of hepcidin prohormone (120.3±56.1 pg/ml) as compared to the control group (90.3±37.9 pg/ml) and RA patients with iron deficiency (both isolated IDA and that of mixed genesis). The same subgroup had a higher inflammatory RA activity characterized by the highest values of DAS 28, C-reactive protein, and SF. Conclusion. Hepcidin is a negative regulator of iron metabolism and may be used for the differential diagnosis of CDA and true iron deficiency in patients with RA

Estimation of disease activity in patients with ankylosing spondylitis in the real practice of a rheumatologist in Russia (Part 2)

Objective: to compare different methods for estimating ankylosing spondylitis (AS) activity in the real practice of a rheumatologist in the Russian Federation. Subjects and methods. The investigation enrolled 464 patients with AS, who had consecutively visited rheumatologists for 4 months in 24 cities and towns of Russia. A specially designed clinical card was filled out for all patients. BASDAI and ASDAS scores were estimated by a physician and erythrocyte sedimentation rate (ESD) and C-reactive protein (CRP) were measured in all the patients. Mini-BASDAI scores were determined in patients with axial AS. The diagnosis of the disease was verified at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, according to the 1984 modified New York criteria, by including X-ray film estimation. All activity assessment methods were compared. Results. The valid diagnosis of AS was confirmed in 330 (71.1%) out of all 464 patients included into the study; axial AS was present in 178 of them; their mean age was 39.7+10.2 years; the mean duration of disease was 14.6+2.6 years; 86% were men and 14% were women. About 61 and 74% of the patients (n = 178) had high BASDAI and mini-BASDAI scores, respectively; 88% had high and very high ASDAI (ESR) scores; the mean ESR (Westergren method) was 33.8+29 mm/h and CRP (n = 249) was 30 mg/l. Conclusion. On assessing the activity of disease, rheumatologists are primarily oriented to total activity scores and blood acutephase indicators (ESR and CRP) in real clinical practice. Patients with high disease activity calculated from BASDAI and ASDAS scores proved to be more. In its turn, ASDAS more frequently reveals high AS activity than BASDAI