Intermittent hypoxia-hyperoxia exposures improve cardiometabolic profile, exercise tolerance and quality of life: A preliminary study in cardiac patients
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01.01.2018 |
Glazachev O.
Susta D.
Dudnik E.
Zagaynaya E.
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Indian Journal of Public Health Research and Development |
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0 |
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© 2018, Indian Journal of Public Health Research and Development. All rights reserved. Study design: randomized controlled before-and-after and in follow-up trial. Forty-six CAD patients volunteered to take part in the study: a group of 27 patients undertook an Intermittent Hypoxia (O2 at 10%) - Hyperoxia (O2 at 30%) Training (IHHT), while a control group (CTRL) of 19 patients was allocated to sham IHHT treatment (breathing via face mask by room air, O2 at 21%). Exercise performance, blood and metabolic profile, quality of life (MOS SF-36, Seattle Angina Questionnaire, SAQ) were measured before and after IHHT/sham IHHT in both groups; the intervention group was also assessed one month after completing the IHHT. The IHHT intervention group showed improved exercise capacity (+1,8 ml O2/min/kg, p=0,02), reduced resting systolic and diastolic blood pressures (151/85 before vs 130/73 after p<0,01), enhanced Left Ventricle Ejection Fraction (62,6±5,5% vs 58±6,2%, p<0,01), glycemia was significantly reduced only at 1-month follow-up (6,18±1,7 after vs 7,10±2,34 mmol/l at baseline, p=0,037). Frequency of angina as reason to stop exercising was significantly reduced after treatment and at 1-month follow-up. In CAD patients an Intermittent Hypoxia-Hyperoxia Training program is associated with improved exercise tolerance, risks factors profile and quality of life (SF-36, SAQ). IHHT has proved to be safe, well tolerable and easily applicable in cardiac patients.
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CYP3A Activity and Rivaroxaban Serum Concentrations in Russian Patients with Deep Vein Thrombosis
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01.01.2018 |
Sychev D.
Vardanyan A.
Rozhkov A.
Hachatryan E.
Badanyan A.
Smirnov V.
Ananichuk A.
Denisenko N.
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Genetic Testing and Molecular Biomarkers |
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2 |
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© Copyright 2018, Mary Ann Liebert, Inc. 2018. Background: Rivaroxaban is metabolized in the liver via CYP3A4, the cytochrome involved in the metabolism of nearly 50% of all medications. Thus, its effective concentration depends on multiple pharmacologic parameters. Methods: The primary goal of our research was to study the correlation between the CYP3A family activity and the safety and efficacy of anticoagulant therapy with rivaroxaban in patients with deep vein thrombosis (DVT). Thirty one patients with DVT aged 21-83 years, 18 men and 13 women, received rivaroxaban (Xarelto) 30 mg/day for 21 days after diagnosis and 20 mg/day for the follow-up period of 6 months. During the study period, Doppler ultrasound was performed weekly to assess the clot dynamics and recanalization time. Results: We found a direct statistically reliable correlation between CYP3A4 activity and both peak and trough rivaroxaban levels. A correlation was also found between the initial clot length and the time to full recanalization r = 0.764 (0.554-0.883), p < 0.0001. No significant link was found between either the glomerular filtration rate and peak rivaroxaban concentrations or between CYP3A4 activity and the treatment effectiveness parameters. No connection between renal function and rivaroxaban concentration was established in our study, which agrees with the clinical trials data that allow unlimited rivaroxaban use in patients with glomerular filtration rate >30 mL/min. Conclusions: The direct link between the initial clot length and time to full recanalization that has been found means that patients with more advanced stages of thrombosis need more time to reach recanalization than their counterparts with a less severe condition.
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Mechanical stress-induced subcellular re-localization of N-terminally truncated tobacco Nt-4/1 protein
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01.01.2018 |
Atabekova A.
Lazareva E.
Strelkova O.
Solovyev A.
Morozov S.
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Biochimie |
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1 |
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© 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM) The Nicotiana tabacum 4/1 protein (Nt-4/1) of unknown function expressed in plant vasculature has been shown to localize to cytoplasmic bodies associated with endoplasmic reticulum. Here, we analyzed molecular interactions of an Nt-4/1 mutant with a deletion of 90 N-terminal amino acid residues (Nt-4/1d90) having a diffuse GFP-like localization. Upon transient co-expression with VAP27, a membrane protein known to localize to the ER, ER-plasma membrane contact sites and plasmodesmata, Nt-4/1d90 was concentrated around the cortical ER tubules, forming a network matching the shape of the cortical ER. Additionally, in response to mechanical stress, Nt-4/1d90 was re-localized to small spherical bodies, whereas the subcellular localization of VAP27 remained essentially unaffected. The Nt-4/1d90-containing bodies associated with microtubules, which underwent noticeable bundling under the conditions of mechanical stress. The Nt-4/1d90 re-localization to spherical bodies could also be induced by incubation at an elevated temperature, although under heat shock conditions the re-localization was less efficient and incomplete. An Nt-4/1d90 mutant, which had phosphorylation-mimicking mutations in a predicted cluster of four potentially phosphorylated residues, was found to both inefficiently re-localize to spherical bodies and tend to revert back to the initial diffuse localization. The presented data show that Nt-4/1 has a potential for response to stresses that is manifested by its deletion mutant Nt-4/1d90, and this response can be mediated by protein dephosphorylation.
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Genetic analysis of melanocortin 1 receptor red hair color variants in a Russian population of Eastern Siberia
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01.01.2018 |
Motorina A.
Palkina N.
Komina A.
Ruksha T.
Artyukhov I.
Kozlov V.
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European Journal of Cancer Prevention |
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2 |
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© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. The melanocortin 1 receptor is a G s protein-coupled receptor implicated in melanogenesis regulation. The receptor gene is highly polymorphic, which accounts for the association of several of its single-nucleotide polymorphisms (SNPs) with an increased risk of melanoma. The present study aimed to evaluate the distribution of melanocortin 1 receptor gene variants R151C, R160W, and D294H within the Russian population of Eastern Siberia and its association with melanoma development. Melanoma patients (n=95) admitted to Krasnoyarsk Territorial Oncological Center and healthy controls (n=334) were enrolled in the study. A clinical examination of patients was performed to evaluate the phenotypic features of melanoma patients. SNPs were analyzed by real-time PCR. Clinical examination indicated a more frequent occurrence of fair skin type, blue eyes, blonde and red hair, and more frequent localization of freckles on the neck, trunk, and extremities in the melanoma group of patients. The R151C melanocortin 1 receptor gene variant was found in 18% of melanoma patients and associated with an increased likelihood of melanoma development (odds ratio=6.4; 95% confidence interval: 2.8-14.3; P=0.0001). The two remaining variant alleles of the melanocortin 1 receptor gene occurred with low frequency both in controls and in the melanoma group. The R160W SNP was identified neither in controls nor in melanoma patients. The D294H heterozygous variant was observed in 0.3% of individuals in the control group and in 1.1% of the patients in the melanoma group. Such an asymmetric distribution of the melanocortin 1 receptor within red hair color genotypes in the population under study compared with other populations may be because of Russian genetic homogeneity. Carriers of the mutant R151C allele should exercise caution in terms of exposure to the sun to avoid the risk of melanoma development.
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Invasive mosquito species Aedes albopictus and Aedes aegypti on the Black Sea coast of the Caucasus: genetics (COI, ITS2), Wolbachia and Dirofilaria infections
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01.01.2018 |
Shaikevich E.
Patraman I.
Bogacheva A.
Rakova V.
Zelya O.
Ganushkina L.
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Vavilovskii Zhurnal Genetiki i Selektsii |
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0 |
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© AUTHORS, 2018. The area of invasive species Aedes albopictus and Aedes aegypti is expanding. Precise identification and understanding of the genetic diversity of invasive mosquito populations allows us to develop appropriate control methods. Endosymbiotic bacterium Wolbachia pipientis has different effects on their arthropod hosts and can influence the transmission and spread of the pathogens. The objective of the presented study was molecular-genetic identification of the Aedes mosquitoes collected in sampling sites on the Black Sea coast from 2007 to 2017; determination of genetic variability of Ae. aegypti, Ae. albopictus and their symbiotic bacteria Wolbachia; assessment of mosquitoes ability to be infected and to spread parasitic Dirofilaria. Another objective was obtaining the genetic characteristic of laboratory strain Ae. aegypti IMPITM. We investigated two markers of nuclear and mitochondrial DNA from Ae. albopictus and Ae. aegypti and compared them to DNA from Ae. cretinus and Ae. koreiсus sympatrically inhabiting the territory, as well as to one of Ae. aegypti from a laboratory line. The study of nuclear and mitochondrial DNA revealed a low level of variability in the invasive mosquitoes Ae. albopictus and Ae. aegypti collected at different collection sites and in different years. More than a half of Ae. albopictus were infected with Wolbachia, two strains of bacteria, wAlbA and wAlbB, occur in the Ae. albopictus population on the Black Sea coast. Total infection of Ae. aegypti and Ae. albopictus with dirofilariae was 1.8 %. Dirofilaria immitis was found only in mosquito abdomen, larvae of infective stage L3 were not found. D. repens larvae developed to the infective stage in the mosquitoes of both species.
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Therapy with canakinumab for adult-onset Still's disease.
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01.01.2018 |
Nasonov E.
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Nauchno-Prakticheskaya Revmatologiya |
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0 |
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© 2018 Ima-Press Publishing House. All rights reserved. Still's disease in children (systemic-onset juvenile idiopathic arthritis, SoJIA) and in adults (adult-onset Still's disease) are considered as non-familial systemic autoinflammatory diseases of unknown etiology driven by similar immunopathogenetic mechanisms. The adult-onset Still's disease pathogenesis is based on genetically determined innate immunity disturbances and molecular basis of immunopathogenesis consists of NLRP3 inflammasome-dependent mechanisms of inflammation characterized by hyperproduction of proinflammatory cytokines interleukin (IL) 1 and IL18. Nonsteroidal anti-inflammatory drugs, glucocorticoids, methotrexate and other disease modifying drugs are considered as «first line» medications for the treatment of adult-onset Still's disease and if they fail biologi-cals are recommended. A review of the literature data concerning anti-IL1 monoclonal antibodies administration in adult-onset Still's disease is presented, indicating good prospects for the use of canakinumab not only in case of resistance to standard therapy, but also as a «first-line» therapy in the onset of the disease.
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Role of interleukin 1 in the development of atherosclerosis
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01.01.2018 |
Nasonov E.
Popkova T.
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Nauchno-Prakticheskaya Revmatologiya |
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0 |
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© 2018 Ima-Press Publishing House. All rights reserved. Atherosclerosis is now considered as chronic inflammatory vascular disease connected to «pathological» activation of innate and adaptive immunity, characterized by lipid deposition, leukocyte infiltration and proliferation of vascular smooth muscle cells. Subclinical (low grade) inflammation plays fundamental role at all stages of atherosclerotic process progression and determines cardiovascular catastrophes development and mortality. Proinflammatory cytokines including interleukin (IL) 1, IL6, tumor necrosis factor α (TNFα), IL17, IL18, IL27, IL33, IL37 tightly interacting within cytokine network occupy an important place among numerous mediators participating in immunopathogenesis of atherosclerosis and rheumatoid arthritis. IL1β playing an important role in the development of many acute and chronic immunoinflammatory diseases attracts particular attention. IL1β significance in the development of atherosclerosis is determined by many mechanisms including procoagulant activity, enhancement of monocytes and leucocytes adhesion to vascular endothelium, vascular smooth muscle cells growth and others. Fundamental role of inflammation in the development of atherosclerosis is well proved in investigations of anti-atherosclerotic effect of canakinumab. Randomized placebo-controlled trial CANTOS (Canakinumab ANti-inflammatory Thrombosis Otcomes Study) assessing efficacy of canakinumab as new tool for secondary prophylaxis cardiovascular complications in general population of patients with severe atherosclerotic vascular damage. CANTOS results in combination with accumulated in rheumatology data on cardiovascular effects of anti-inflammatory drugs are of great importance for personification of approach to secondary prophylaxis of caused by atherosclerosis cardiovascular complications. They also contribute to the development of inflammatory theory of atherosclerosis pathogenesis in the whole.
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The role of interleukin 1 in the development of human diseases
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01.01.2018 |
Nasonov E.
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Nauchno-Prakticheskaya Revmatologiya |
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0 |
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© 2018 Ima-Press Publishing House. All rights reserved. Human immuno-inflammatory diseases (IID), depending on the predominant mechanisms of immune activation, are divided into two main categories: autoimmune and autoinflammatory. It is assumed that hyperproduction of "proin-flammatory" and immunoregulatory cytokine-interleukin 1 (IL 1) largely determines the "intersection" between the mechanisms underlying autoimmunity and autoinflammation in many IID. This review discusses the role of IL1 in the pathogenesis of IID, primarily those associated with the activation of NLRP3-inflammasome, and therapeutic perspectives of IL1β inhibition with monoclonal antibodies to IL1β - canakinumab. The study of the IL1 role in the regulation of interactions between innate (TLR activation, inflammasome) and adaptive (Th1 - and Th17-types of immune response) immunity and the efficacy of IL1 inhibitors may be important in terms of decoding the patho-genetic mechanisms of IID and the development of new approaches to personalized therapy.
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The microsurgical tissue autotransplantation in the treatment of late radiation tissue injuries with complicated osteomyelitis of the tibia
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01.01.2018 |
Zelyanin A.
Filippov V.
Dubrov V.
Meskhi K.
Kelban D.
Zelyanin D.
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Clinical and Experimental Surgery |
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© 2018 GEOTAR Media. All rights reserved. Aim. Study of the remote results free flaps usage in treatment of patients with the late radiation injuries complicated by tibial bone osteomyelitis. Material and methods. Our work is based on a retrospective study of treatment of eight patients with late radiation tissue injuries and chronic osteomyelitis of the tibia. In them we performed 9 operations using free, vascularized flaps. According to RTOG/EORTC Late Radiation Morbidity Scoring Scheme, skin lesions corresponded to grade IV, bone damage – grade II–III. In the zone of the late radiation injuries, the lesion of the cortical plate of the tibia was detected in 5 patients, a lesion that occurred more than a third of the tibial circumference – in 3 patients. 6 patients had cicatricial osteomyelitis form, and 2 had osteomyelitis with the inclusion of a chronic draining fistula. Late radiation ulcer was emerged in all patients after previous radiotherapy in a total dose of 40 to 60 Gy for different types of neoplasms. For 7 patients, the timing of the previous radiotherapy ranged from 5 to 19 years before the appearance of a late radiation tissue injury. Three patients received radiotherapy in childhood. In one patient, with posttraumatic osteomyelitis of the tibia, in remission, squamous cell carcinoma was diagnosed. Patients underwent radiation therapy in a total dose of 60 Gy. Later it was associated a radiation ulcer with open defects of the tibia. The objectives of surgical treatment included the preservation of the limb, adequate surgical debridement and the replacement of the tissues defect. The surgical technique included a radical resection of the affected areas of the bone tissue. To fill dead space, a musculo-fasciocutaneous thoracodorsal flap was used in all paients. In 2 out of 3 patients with localized form of osteomyelitis, the autograft complex, supplementary to the thoracodorsal component, included additionally a fragment of the anterior serratus muscle for tamponade of the osteomyelitis cavity. For one patient with localized osteomyelitis, a tamponade method of the post osteomyelitis bone defects included use of the distal part of the fragment of the latissimus muscle flap. 1 patient originally addressed concerning a late radiation ulcer on the back surface of a crus without involvement of bone structures. Two years after elimination of cicatricial and ulcer defect the torakodorsal skin and muscular flap, created a late radiation ulcer on the forward surface of a shin with defeat of a cortical plate of a tibial bone. Discussion. Fundamental difference of patients with local radiation injury from patients with traumatic osteomyelitis and investing tissue extensive defects is the feature of a course of wound process against the background of the progressing depression of a reparation both in the focus, and in surrounding tissues with lack of a clear boundary defeat. Morphological basis of local late radiation defeat are permanent damages of blood and lymphatic vessels with tissue fibrosis progressing. In the conditions of local reserve opportunities decrease, free revascularised flaps application, with one's own axial blood supply, allows to save an extremity, to receive the best immediate and long-term results of tissues defects elimination in the irradiated zone. It can be confirmed with the fact that directly under the replaced skin and muscular revascularised flap the covered functional structures purulent defeat stopped and patients achieved osteomyelitic process permanent remission. Results. In all observations the full flap engraftment has received. All patients have achieved osteomiyelitic process remission. Conclusions. The radical debridement of the affected zones, followed by the filling of the bone defect with muscle tissue and the defect elimination of the tissues by the skin portion of the vascularized musculocutaneous autograft is the method of choice in the treatment of patients with local post radiation injuries, complicated by osteomyelitis of the tibia.
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Depression is not the only cause of cognitive impairment in chronic migraine
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01.01.2018 |
Latysheva N.
Filatova E.
Osipova D.
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Nervno-Myshechnye Bolezni |
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0 |
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© 2018 ABV-Press Publishing House. All rights reserved. Background. Patients with the chronic migraine frequently present with memory and attention complaints. However, the prevalence and phenotype of such impairment in chronic migraine have not been studied. Objective-to evaluate the prevalence of the objective cognitive deficit in patients with chronic migraine and factors underlying its etiology. Materials and methods. We recruited 62 subjects with chronic migraine and 36 gender-and age-matched controls with low-frequency episodic migraine (not more, then 4 headache days per month) aged 18-59. All patients filled in the Hospital Anxiety and Depres sion Scale (HADS) and Sheehan Disability Scale. Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA), Digital Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and the Perceived Deficits Questionnaire (PDQ-20). Results. In this study 58 % of patients with chronic migraine complained of memory loss. Cognitive impairment was also found with PDQ-20. Objectively, we found a significant decrease in 90-second DSST results and RAVLT total recall and learning rate. In 40 % of subjects with chronic migraine scored lower than 26 points on MoCA. Patients with chronic migraine more frequently had lower DSST rates as compared to episodic migraine (odds ratio 5.07 (95 % confidence interval-1.59-16.17); p = 0.003). Depression and anxiety did not correlate with performance on cognitive tests. Chronic migraine (frequent headache) and longer headache history, but not depression, anxiety or medication overuse were independent predictors of cognitive impairment. Conclusion. Subjective and objective cognitive deficits are prevalent in the chronic migraine population. Most often memory and attention are impaired. Longer headache history and presence of chronic migraine are independent risk factors for cognitive impairment in patients with chronic migraine.
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Chemical and toxicological diagnosis of acute poisonings with phenazepam
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01.01.2018 |
Belova M.
Klyuyev E.
Melnikov E.
Yeliseyeva D.
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Sklifosovsky Journal Emergency Medical Care |
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0 |
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© 2018 Sklifosovsky Research Institute for Emergency Medicine. All rights reserved. BACKGROUND The relative availability of Phenazepam makes it a frequent cause of overdose, suicide and non-medical use. At the same time, it remains insufficiently studied in chemical and toxicological terms. THE AIM OF STUDY to create an accessible, rapid method for detecting Phenazepam in biological matrices of patients with acute poisoning. MATERIALS AND METHODS We used thin-layer chromatography (TLC), gas chromatography with a mass selective detector (GC-MS), high performance liquid chromatography with a tandem mass-selective detector (LC-MS/MS) and immunochromatographic analysis (ICA). The preparation of samples of intact urine with the addition of standard solutions of Phenazepam and real urine samples of patients with acute poisoning with Phenazepam was carried out using liquid-liquid extraction or precipitation of related components of the sample with acetonitrile. Hydrolysis and derivatization were also added in GC-MS analysis. RESULTS The analysis of statistics of the Department of Acute Poisonings of the N.V. Sklifosovsky Research Institute for Emergency Medicine in 2014–2016 showed that Phenazepam poisonings averaged 9.2% of the total number of admissions and mainly occurred as suicidal attempts. A technique has been developed for the detection of Phenazepam by TLC, which gives more objective results than ICA. For confirmatory analysis, it is advisable to use LC-MS/MS method for the native substance and GC-MS for the products of hydrolysis after derivatization. Compared to confirmatory methods, the developed TLC-screening technique is expressive, does not require the use of expensive high-tech equipment, difficult sample preparation, and makes it possible to reliably detect toxic and lethal concentrations of Phenazepam.
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Toxic epidermal necrolysis as a variant of severe skin lesions in systemic lupus erythematosus
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01.01.2018 |
Vorobyeva L.
Aseeva E.
Solovyev S.
Belousova T.
Lopatina N.
Sazhina E.
Serikova G.
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Nauchno-Prakticheskaya Revmatologiya |
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0 |
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© 2018 Ima-Press Publishing House. All rights reserved. Toxic epidermal necrolysis (TEN) has been long believed to be the most severe manifestation of drug allergy. However, cutaneous changes as TEN in systemic lupus erythematosus (SLE) were first described in the late 1970s. As of now, the English-language literature published reports of 30 cases of such lesions in SLE. This paper describes a clinical case of TEN as a direct manifestation of SLE; the positive experience has been first depicted in using not only intravenous immunoglobulin, but also rituximab with a good therapeutic effect in Russian clinical practice.
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Psoriatic arthritis: Pathogenetic features and innovative therapies
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01.01.2018 |
Lila A.
Nasonov E.
Korotaeva T.
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Nauchno-Prakticheskaya Revmatologiya |
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1 |
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© 2018 Ima-Press Publishing House. All rights reserved. The paper considers the modern concepts of the etiology and pathogenesis of psoriatic arthritis (PsA). The latter is currently indicated as a T-cell-mediated disease that is based on the activation of cellular immunity, followed by the hyperproduction and imbalance of key pro- A nd anti-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1â (IL-1â), IL-6, IL-12/23, and IL-17. The paper presents the basic principles of diagnosis and clinical manifestations of the disease and notes the importance of screening questionnaires, the use of which allows specialists to diagnose PsA early, by actively identifying articular complaints, the characteristic clinical and radiological signs of damage to the joint, spine, and entheses. It is pointed out that the key target of pharmacotherapy for PsA is to achieve remission or minimal activity of the main clinical manifestations of the disease, to slow down or prevent its radiographic progression, to increase the length and quality of life in patients, and to reduce the risk of comorbidities. The authors characterize the major groups of used drugs: Nonsteroidal anti-inflammatory drugs, conventional and targeted synthetic disease-modifying antirheumatic drugs, and biological drugs (inhibitors of TNF-α, IL-12/23, and IL-17). The key Treat-to-target principles of patient management are considered; it is noted that strict control over disease activity and treatment results provides suppression of all major clinical manifestations of PsA. The paper also shows the basic principles of the creation and further development of the All-Russian Registry of PsA patients, which makes it possible to optimize management decision-making on the provision of high-tech medical care and drugs for this cohort of patients.
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Effect of various agents on the direction of THP-1 cell differentiation
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01.01.2018 |
Zubova S.
Radzyukevich Y.
Grachev S.
Prokhorenko I.
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Serbian Journal of Experimental and Clinical Research |
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0 |
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© 2018, University of Kragujevac, Faculty of Science. All rights reserved. The ability of physiological (1α,25-dihydroxyvitamin D3, retinoic acid) and non-physiological (various LPS) agents and their combinations to influence the direction of pro-monocytic THP-1 cell differentiation was studied. The differentiating activity of the agents was evaluated by the expression and the ratio of surface receptors (TLR4, CD11b, and CD14) as well as by the change in THP-1 cell phagocytic activity of different degree of differentiation by Flow cytometry. The THP-1 cell differentiation by VD3 was shown to lead probably to the formation of classical monocytes. Summarizing we can conclude that VD3 induces the THP-1 cells differentiation with the formation of classical monocytes and the sequence of 1α, 25-dihydroxyvitamin D3 and non-toxic LPS R. capsulatus PG causes the THP-1 cells differentiation with the formation of inflammatory or intermediate monocytes.
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B-lymphocyte subpopulations in patients with rheumatoid arthritis and the effect of an interleukin-6 receptor inhibitor on them
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01.01.2018 |
Gerasimova E.
Popkova T.
Aleksankin A.
Martynova A.
Nasonov E.
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Nauchno-Prakticheskaya Revmatologiya |
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0 |
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© 2018 Ima-Press Publishing House. All rights reserved. The clinical efficacy and safety of interleukin-6 (IL-6) receptor blockade have been well studied, but the data on the impact of therapeutic inhibition of IL-6 on B cells are scarce and contradictory. Preliminary reports have shown that B cell function and a humoral immune response may be modulated by an IL-6 receptor inhibitor. Objective: to assess the effect of 12-month tocilizumab (TCZ) therapy on B-cell phenotype and gene expression in RA and to analyze the association between B-cell subsets and RA activity. Subjects and methods. Examinations were made in 24 active RA patients (20 women and 4 men) (median age, 55 [49; 64] years; disease duration, 72 [24; 108] months; DAS28 5.8 [5.3; 6.3]; the patients were seropositive for rheumatoid factor (RF) (100%) and for anti-cyclic citrullinated peptide antibodies (87.3%). The patients received TCZ 8 mg/kg every 4 weeks. After 12 months of therapy, 54% of patients were categorized as good responders, 46% as moderate responders according to the EULAR response criteria. A control group consisted of 29 volunteers (21 women and 8 men; median age, 58.5 [53.0; 62.0] years). Peripheral blood lymphocytes were immunophenotyped at the time of enrollment and after 12 months. The absolute and relative counts of CD19+B lymphocytes, memory B cells (CD19+CD27+), non-switched memory B cells (CD19+IgD+CD27+), switched memory B cells (CD19+IgDCD27+), naive (CD19+IgD+CD27-), double-negative (CD19+IgD-CD27-), transitional (CD19+IgD+CD10+CD38++CD27) B cells, plasma cells (CD19+CD38+), and plasmablasts (CD19+CD38+++IgD-CD27+CD20-) were estimated using multicolor flow cytometry. Results and discussion. The relative and absolute counts of memory B cells (CD19+CD27+) (1.3 [0.9; 1.7]%, 0015 [0.001; 0.003]•10 9 /l), switched memory B cells (CD19+IgD-CD27+) (6.8 [3.6; 11.6]%, 0.01 [0.005; 0.02]•10 9 /l), and the absolute number of transitional B cells (CD19+CD38++CD10+IgD+CD27-) (0.00009 [0; 0.00028]•10 9 /l) were found to be lower in RA patients than in donors: 2.2 [1.1; 3.0]%, 0.003 [0.001; 0.007]•10 9 /l; 12.8 [9.3; 17.0]%, 0.02 [0.01; 0.04]•10 9 /l; 0.0001 [0; 0.0003]•10 9 /l, respectively (p<0.05 for all cases). After 12 months of TCZ therapy initiation, there were decreases in the relative and absolute counts of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) from 0.15 [0.1; 0.3] to 0.1 [0.01; 0.1]% and from 0.0003 [0.00007; 0.004]•10 9 /l to 0.0001 [0; 0.0003]•10 9 /l, respectively (p<0.05). At the same time, the relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) remained lower in RA patients than in donors: 1.0 [0.7; 1.2] and 2.2 [1.1; 3.0]%; 0.001 [0.006; 0.003]•10 9 /l and 0.003 [0.001; 0.007]•10 9 /l; 3.1 [1.1; 4.2] and 12.8 [9.3; 17.0]%; 0.003 [0.002; 0.006]•10 9 /l and 0.02 [0.01; 0.04]•10 9 /l, respectively (p<0.05 for all cases). Following 12 months of TCZ therapy, the numbers of other B-cell subpopulations were not considerably altered. When included in the study, the patients with RA showed correlations between the absolute count of memory B cells (CD19+CD27+) and the level of C-reactive protein (r=0.50; p<0.05); between the absolute count of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) and the level of RF (r=0.41 and r=0.52; p<0.05). There were no correlations of B cell subsets with clinical and laboratory findings after 12 months of TCZ initiation. Conclusion. Immunophenotyping of peripheral blood B lymphocyte subsets showed the lower relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) in RA patients than in healthy donors. The found correlations between the counts of memory B cells and plasmablasts and the values of laboratory parameters in patients with high RA activity may suggest that B lymphocytes are involved in the pathogenesis of RA. There was a decline in plasmablast levels after 12 months of TCZ therapy.
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Risk factors for venous thromboses in patients with rheumatoid arthritis
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01.01.2018 |
Satybaldyeva M.
Reshetnyak T.
Seredavkina N.
Glukhova S.
Nasonov E.
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Nauchno-Prakticheskaya Revmatologiya |
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© 2018 Ima-Press Publishing House. All rights reserved. Objective: to determine risk factors (RFs) for venous thromboembolic events (VTE) in patients with rheumatoid arthritis (RA). Subjects and methods: The investigation enrolled 374 patients (311 women and 63 men) with a reliable diagnosis of RA who met the 2010 ACR/EULAR classification criteria. The patients' mean age was 53.7±13.6 years; the disease duration was 12.1±10.7 years. All the patients were treated at the V.A. Nasonova Research Institute of Rheumatology Clinic during the period from 2014 to 2017. A standard clinical examination of the peripheral joints was performed. RA activity was measured using DAS28. A survey was made using a questionnaire including questions on traditional RFs for VTE and RFs that might be caused by RA and its therapy. Results and discussion. VTE were recorded in 45 (12%) out of the 374 patients. Group 1 included 45 patients with VTE; Group 2 consisted of 329 patients without VTE. Multidimensional analysis showed an increased risk of developing VTE in RA under the influence of the following factors: high inflammatory activity; lower extremity varicose veins; hypercholesterolemia; and hypertension. Their weighted coefficients were 1.1, 2.5, 1.0, and 0.9, respectively. According to the obtained model (p<0.001), the risk of VTE in RA can be predicted by the following formula: Z = 1.1 • high RA activity (Yes = 1/No = 0) + 2.5 • lower extremity varicose veins (Yes = 1/No = 0) + + 1.0 • hypercholesterolemia (Yes = 1/No = 0) + 0.9 • hypertension (Yes = 1 / No = 0). Conclusion: The increased risk for VTE in RA patients determines the need for its timely assessment, by taking into account the known risk factors as both standard ones and those caused by the disease itself and its therapy. This risk assessment is necessary for the timely adequate treatment and prevention of thrombotic events in RA.
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Medicine during world war i: Commission for the revision of sanitary and medical supply standards of the Russian army (1915–1917)
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01.01.2018 |
Yaroshenko A.
Shok N.
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History of Medicine |
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© AA Yaroshenko, NP Shok. The lessons learned from the last wars of the second half of the 19th to early 20th centuries influenced the organization of the troop command and control. The latest inventions, mass outbreaks of infectious diseases among the troops and the population of countries at war, as well as a number of other factors, led to changes in army management mechanisms. Given the experience gained from initial hostilities, the Russian government decided to review its approach to medical support for the field army and the organization of the medical supply system for troops. This was due to the unsatisfactory state of the Russian military-indus-trial complex at the beginning of World War I. At the beginning of the war, Russia was forced to seek help from France, Britain, the United States, and Japan, and to take urgent measures to expand its own production of medical equipment. Emergency measures were taken to facilitate the production of medical equipment on the territory of the Russian Empire. During the reign of Nicholas II, in June 1915, a Special council was set up. The council oversaw the activities of industrial enterprises that produced war supplies, distributed military orders between Russian and foreign factories and facilitated the opening of new ones. The Special council entrusted the provision of medical supplies for the Russian army to the Commission for the Revision of Sanitary and Medical Supply Standards, which was established on October 24, 1915. As a result of the work of the commission during the war, the medical support system for the troops was improved, production of domestic versions of medical equipment was established, the procedure for dispensing medical supplies was simplified, and standards were increased.
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Clinical efficacy of the rituximab biosimilar Acellbia® 600 mg in patients with active rheumatoid arthritis in clinical practice
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01.01.2018 |
Kusevich D.
Avdeeva A.
Rybakova V.
Chichasova N.
Nasonov E.
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Nauchno-Prakticheskaya Revmatologiya |
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© 2018 Ima-Press Publishing House. All rights reserved. Objective: to evaluate the clinical efficacy of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval in patients with active rheumatoid arthritis (RA) 12 and 24 weeks after initiation of treatment. Subjects and methods. Examinations were made in 20 active seropositive RA patients who had not been previously treated with biological agents (BAs), but received two infusions of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval during stable therapy with methotrexate (MT) and glucocorticoids (GCs). The European League Against Rheumatism (EULAR) response criteria (Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index) and the American College of Rheumatology (ACR) criteria were used to evaluate the efficiency of Acellbia® therapy. Disease remission was identified by DAS28 and 2011 ACR/EULAR criteria. The safety profile (the frequency of all reported adverse events) corresponds to the data on the safety of rituximab (MabThera®). Results and discussion. At the time of inclusion, median DAS28 was 5.6 [4.9; 6.8], SDAI - 27.1 [23.0; 39.9], and CDAI - 26.6 [22.2; 37.0]. At week 12 after initiation of Acellbia® therapy, they decreased to 4.2 [3.24; 4.75], 14.4 [8.5; 20.7], and 13.2 [7.9; 19.0] respectively, which remained at 24-week follow-up (p<0.01). At week 12, the frequencies of ACR 20%, 50%, 70% improvements were 70, 55, and 5%; at week 24, these were 75, 45, and 15%, respectively. A good or moderate EULAR response at week 24 was observed in 25 and 60% of patients, respectively. At week 24, DAS28, SDAI, and CDAI remissions were achieved by 4 (20%), 2 (10%), and 1 (5%); low disease activity - by 4 (20%), 5 (25%), and 6 (30%) patients, respectively; high disease activity as measured by SDAI and CDAI remained in 3 (15%) patients. Two patients (10%) met the 2011 ACR/EULAR remission criteria at 24 weeks. Conclusion. The rituximab biosimilar Acellbia® 600 mg used in patients with active seropositive RA is clinically effective and comparable in the safety profile as shown in investigations of the brand-name MabThera® (F. Hoffman-La Roche Ltd., Switzerland) at a low dose (500 mg), as well as the first BA.
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Radical prostatectomy performed via robotic, transperitoneal and extraperitoneoscopic approaches: Functional and early oncological outcomes
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01.01.2018 |
Rapoport L.
Yossepowitch O.
Shpot E.
Chinenov D.
Chernov Y.
Yurova M.
Enikeev D.
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Central European Journal of Urology |
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© 2018, Polish Urological Association. All rights reserved. Introduction Oncological remission along with high postoperative functionality [continence and erectile function (EF)] are the main aspects of prostate cancer (PCa) treatment. The aim of this study was to compare functional and oncological treatment results achieved after a nerve-sparing radical prostatectomy (RP) via transperitoneal (TPRP), extraperitoneal (EPRP) and robot-assisted (RARP) approach. Material and methods From March 2015 to March 2016, 507 RP were performed at the Institute for Urology and Reproductive Health (Moscow, Russia). A total of 264 patients with localized (cТ1а–2с) prostate cancer [prostate-specific antigen (PSA) <20 ng/ml, Gleason score ≤7], intact prostate capsule (according to MRI), International Index of Erectile Function (IIEF-5) ≥19 and a life expectancy >10 years were included into the retrospective study. All the surgeries were performed by a single surgeon. The outcomes were evaluated after urethral catheter removal and 3–6–12 months after RP. Results Nerve preservation (NP) was performed for 153 patients without significant distinctions in time (р = 0.064) and blood loss (р = 0.073). The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) score was lower for NP: 9.23 ±6.59 and 3.86 ±5.38 after 3 and 12 months respectively compared with continence after RP without nerve preservation (NP): 14.27 ±5.1 vs. 6.15 ±4.76 (р <0.001). Continent was 52.2% vs. 83.3% vs. 81.8% in TPRP, RARP and EPRP groups; р <0.001. IIEF-5 scores were 14.67 ±9.4, 4.2 ±4.26 and 4.0 ±2.07 after RARP, TPRP and EPRP respectively (р = 0.002). After 12 months the PSA: TPRP = 0.11 ±0.19, RARP = 0.03 ±0.05 and EPRP = 0.53 ±1.87 ng/ml (р <0.001). Outcomes depend on surgical approach and was better in the RARP-group (AUC = 0.768 ±0.034 (CI 95% 0,701–0.834; р <0.001). Conclusions We suggest RARP with NP as a method of choice for treatment of prostate cancer in patients interested in preservation of EF and quality of life in general.
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Hygienic characteristics of the chemical composition of groundwater in Ryazan region
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01.01.2018 |
Solovyev D.
Dementiev A.
Kluchnikova N.
Prokhorov N.
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Bulletin of Russian State Medical University |
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© 2018 Istituto Superiore di Sanita. All Rights Reserved. Among the factors that have a strong impact on public health the environment, living conditions, food and water quality are just as important as socio-economic forces. Providing the population with access to safe potable water has become a socioeconomic priority in Russia. The aim of this work was to characterize the aquifers supplying the population of Ryazan region with water for personal and domestic needs and to compare their chemical composition. Sample collection was performed in cooperation with the Center for Hygiene and Epidemiology (Ryazan region). The obtained data were processed using ANOVA. The Kashirsky and Ozersko-Khovansky aquifers turn to be the most commonly used ones supplying water to 30.7% and 27.3% of the total artesian wells. The Oksko-Tarussky and Podolsko-Myachkovsky aquifers rank second, feeding 21% and 18.9% of the wells, respectively. The share of the Kasimovsky aquifer in the total water supply is only 2.1%. Although the recommended lifespan of an artesian well is 25 years, two-thirds of the wells in Ryazan region have been in service for 26 to 50 years, and one in every 4 wells is over 50 years old. The chemical composition of the groundwater drawn from different aquifers is different. High concentrations (0.7 mg/l) of iron (Fe 2+ ) are present in the water from the Ozersko-Khovansky aquifer (р ≥ 0.05). Sulfates are found in abundance in the Podolsko-Myachkovsky and Ozersko-Khovansky aquifer. The water from the Oksko-Tarussky aquifer contains high concentrations of ionized ammonia.
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