Catastrophic antiphospholipid syndrome (Ronald Asherson syndrome) and obstetric pathology
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24.05.2018 |
Makatsariya A.
Khizroeva J.
Bitsadze V.
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Journal of Perinatal Medicine |
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1 |
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© 2018 Walter de Gruyter GmbH, Berlin/Boston. Catastrophic antiphospholipid syndrome (CAPS) is an uncommon, often fatal, variant of the antiphospholipid syndrome (APS) that results in a widespread coagulopathy and high titres of antiphospholipid antibodies (aPL) and affects predominantly small vessels supplying organs with the development of multiorgan failure. It remains unclear why some patients develop the typical clinical picture of APS (thrombosis of large vessels), whereas others show the development of progressive microthrombosis, which the authors called "thrombotic storm" and multiple organ failure, that is, CAPS. Since 2001-2016, we discovered 17 patients with CAPS development. CAPS is life-threatening condition, but optimal treatment for CAPS is not developed yet and the mortality rate is as high as 30%-40%.
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Versatile Platform for Nanoparticle Surface Bioengineering Based on SiO <inf>2</inf> -Binding Peptide and Proteinaceous Barnase, Barstar Interface
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23.05.2018 |
Shipunova V.
Zelepukin I.
Stremovskiy O.
Nikitin M.
Care A.
Sunna A.
Zvyagin A.
Deyev S.
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ACS Applied Materials and Interfaces |
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7 |
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© 2018 American Chemical Society. Nanoparticle surface engineering can change its chemical identity to enable surface coupling with functional biomolecules. However, common surface coupling methods such as physical adsorption or chemical conjugation often suffer from the low coupling yield, poorly controllable orientation of biomolecules, and steric hindrance during target binding. These issues limit the application scope of nanostructures for theranostics and personalized medicine. To address these shortfalls, we developed a rapid and versatile method of nanoparticle biomodification. The method is based on a SiO 2 -binding peptide that binds to the nanoparticle surface and a protein adaptor system, Barnase∗Barstar protein pair, serving as a "molecular glue" between the peptide and the attached biomolecule. The biomodification procedure shortens to several minutes, preserves the orientation and functions of biomolecules, and enables control over the number and ratio of attached molecules. The capabilities of the proposed biomodification platform were demonstrated by coupling different types of nanoparticles with DARPin9.29 and 4D5scFv - molecules that recognize the human epidermal growth factor receptor 2 (HER2/neu) oncomarker - and by subsequent highly selective immunotargeting of the modified nanoparticles to different HER2/neu-overexpressing cancer cells in one-step or two-step (by pretargeting with HER2/neu-recognizing molecule) modes. The method preserved the biological activity of the DARPin9.29 molecules attached to a nanoparticle, whereas the state-of-the-art carbodiimide 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysulfosuccinimide method of conjugation led to a complete loss of the functional activity of the DARPin9.29 nanoparticle-protein complex. Moreover, the method allowed surface design of nanoparticles that selectively interacted with antigens in complex biological fluids, such as whole blood. The demonstrated capabilities show this method to be a promising alternative to commonly used chemical conjugation techniques in nanobiotechnology, theranostics, and clinical applications.
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Design, in silico prioritization and biological profiling of apoptosis-inducing lactams amenable by the Castagnoli-Cushman reaction
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15.05.2018 |
Krasavin M.
Gureyev M.
Dar'in D.
Bakulina O.
Chizhova M.
Lepikhina A.
Novikova D.
Grigoreva T.
Ivanov G.
Zhumagalieva A.
Garabadzhiu A.
Tribulovich V.
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Bioorganic and Medicinal Chemistry |
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1 |
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© 2018 Elsevier Ltd Five lactam chemotypes amenable by the Castagnoli-Cushman reaction of imines and cyclic anhydrides have been investigated for their ability to activate p53 tumor suppressing transcription factor thus induce apoptosis in p53 + cancer cells. A virtual library of 1.07 million chemically diverse compounds based on these scaffolds was subjected to in silico screening first. The compounds displaying high docking score were visually prioritized to identify the best-fitting compounds, i. e. the ones which adequately mimic the interactions of clinical candidate inhibitor Nutlin-3a. These 38 compounds were synthesized and tested for apoptosis induction in p53 + H116 cancer cells to identify 9 potent apoptosis-inducers (two of them exceeding the activity of Nutlin-3a) which belonged to four different chemotypes. The activation of p53 involved in the proapoptotic activity observed was supported by effective induction of EGFP expression in human osteocarcinoma U2OS-pLV reporter cell line. Moreover, the two most potent apoptosis inducers displayed antiproliferative profile identical to several known advanced p53 activators: they inhibited the growth of p53 +/+ HCT116 cells in much lower concentration range compared to p53 −/− HCT116 cells.
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Risk factors for growth retardation in patients with juvenile scleroderma
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01.05.2018 |
Bokareva E.
Podchernyaeva N.
Vitebskaya A.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018, Pediatria Ltd.. All rights reserved. Objective of the research: to dentify risk factors for growth retardation in patients with juvenile scleroderma (JSD). The presented data show that the most unfavorable factors for growth retardation in patients with JSD are the systemic form of the disease, debut age less than 4 years. Other unfavorable factors of growth retardation developing are father's height less than 175 cm and a mother's height less than 165 cm. Analysis of the effect of glucocorticoid saverage daily dose during the year on the growth rate in patients with JSD, normalization of growth rates was noted with its decrease to 0,2 mg/kg/day or less.
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Selection and switching of genetically engineered biological agents in treatment of juvenile arthritis
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01.05.2018 |
Zholobova E.
Ignatova A.
Seylanova N.
Golubeva A.
Shpitonkova O.
Afonina E.
Nikolaeva M.
Chebysheva S.
Meleshkina A.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018, Pediatria Ltd.. All rights reserved. Therapy with genetically engineered biological preparations (GEBP) significantly improved the prognosis and quality of life of patients with juvenile idiopathic arthritis (JIA). However, primary or secondary in efficiency, the development of undesirable phenomena require switching to another GEBP. Objective of the research – to determine optimal GEBP preparations when selecting and switching therapy based on the analysis of prescribed GEBP in real practice, depending on the clinical version of the JIA and the presence of uveitis. Materials and methods: the study included 322 patients with JIA on GEBP therapy, observed in the Pediatric Rheumatology Department of Children's Clinical Hospital of the I.M. Sechenov First Moscow State Medical University from Jan. 1, 2015 to Dec. 31, 2017. Retrospective, continuous observational clinical study. Of 322 patients, 70 (21,74%) had systemic JIA, 155 patients (48,14%) had polyarterial seronegative for rheumatoid factor (RF–) variant of JIA, 9 patients (2,8%) – polyarticular seropositive for rheumatoid factor RF+) variant of JIA, 55 patients (17,08%) – oligoarticular (persistent and spreading) variant of JIA, 26 patients (8,07%) – enthesitis (juvenile spondylitis), 7 patients (2,17%) – psoriatic variant of JIA. Results: as the first biological preparation were prescribed: etanercept to 177 (54,97%) patients; adalimumab to 51 (15,84%); tocilizumab to 44 (13,66%); abatacept to 39 (12,11%); infliximab to 11 (3,42%) patients. Transition to the second line of biological therapy was performed in 51 patients (in 15,8% of cases), on the third line of therapy in 13 patients (in 4,04% of cases), on the fourth line in 3 patients (in 0,93% of cases). As the second-line GEBP adelimumab was prescribed in 22 cases (43,14%), tocilizumab in 13 (25,49%), etanercept in 11 (21,57%), abatacept in 5 (9,8%). GEBP inefficiency was the reason for switching to the second line in 32 cases (9,9%). Of these, secondary inefficiency in 22 cases (6,8%); primary inefficiency – in 4 (1,3%), low efficiency – in 6 (1,9%), development/exacerbation of uveitis – in 7 patients (2,2%), in 6 cases (1,9%) due to insufficient compliance, drug shortage in the community, etc. Adverse effects caused switching in 5 patients (1,6%), incl. in 4 children – infusion reactions, in one – tuberculosis. Analysis of GEBP choice depending on the disease form and the presence of uveitis, was performed in 3 groups. Group 1 (n=70) consisted of patients with systemic JIA. Group 2 (n=53) included patients with articular form of JIA and concomitant uveitis. Group 3 (n=199) included patients with articular form of JIA without concomitant uveitis. Patients with systemic JIA as the first-line GEBP tocilizumab was prescribed significantly more often – to 38 patients out of 70 (54,29±5,96%) than etanercept – to 19 patients (27,14±10,19%) (t=2, 3, p<0,05), and other drugs in total (infliximab, abatacept, adalimumab) – to 13 (18,57±10,88%) (t=2,9, p<0,05). Switching to GEBP second line in this group was performed in 20 patients (28,57%). Tocilizumab was the final choice drug (after 3 years of follow-up) at the time of samples collection in 50 patients (71,43%) with systemic JIA. In patients with articular forms of JIA and concomitant uveitis as the first-line GEBP, adalimumab was prescribed significantly more often – in 34 of 53 cases (64,15±8,23%) than other drugs (abatacept, etanercept, infliximab) in total – 19 of 53 cases (35,85±11,01%) (t=2,06, p<0,05). Adalimumab was the drug final choice at the time of sample collection for 43 (81,13%) patients with JIA and uveitis. Most patients with articular form without uveitis received etanercept as first-line GEBP, 150 of 199 (75,38±3,54%), and etanercept prescription frequency was significantly higher than that of other drugs (abatacept, adalimumab, tocilizumab, infliximab) in total – 49 of 199 (24,62±6,19%) (t=7,1, p<0,01). In this group, the switching frequency was the smallest and amounted only 8,54%. The number of patients who received etanercept at the end of the study actually remained unchanged – 148 patients (74,37%).
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Comparative results of cryoablation and laparoscopic radical prostatectomy in the treatment of localized prostate cancer
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01.05.2018 |
Chinenov D.
Rapoport L.
Shpot E.
Enikeev D.
Chernov Y.
Taratkin M.
Korolev D.
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Urologia |
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2 |
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AIM: To evaluate early prostate cancer cryoablation functional and oncological results in comparison with results of extraperitoneoscopic radical prostatectomy. MATERIALS AND METHODS: We analyzed early results of surgical treatment of 285 patients with prostate cancer: 42 of them had undergone total cryoablation (Group 1) while the rest of them had been treated by radical laparo- and extraperitoneoscopic prostatectomy. For comparative assessment of prostate cryoablation results, 42 patients from Group 2 randomized in accordance with their age, stage of disease, Gleason, prostate-specific antigen, and prostate volume were selected. In compliance with the results of pre-surgical examination, all the patients had low oncological risk and were not concerned in sexual function. Volume of prostate was from 22 to 65 cm3, prostate-specific antigen level was from 4.1 to 10 ng/mL, and level of neoplastic process differentiation using Gleason grading system was from 6 to 7a (3 + 4) scores. RESULTS: Patients after prostate cryoablation in early post-surgical period felt lower intensity of postoperative pain compared with those who had undergone prostatectomy. Follow-up period up to 12 months manifested significant true reduction of prostate-specific antigen level in both groups of patients. Frequency of stress-induced enuresis in Group 1 was not observed. CONCLUSION: Radical prostatectomy is still the traditional treatment of choice in the case of localized prostate cancer. But we can draw the conclusion that cryoablation is an effective low-invasive method for treatment of low oncological risk patients, which gives the opportunity both to achieve good oncological results and to preserve high life quality.
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Treatment of pulmonary tuberculosis: Past and present
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01.05.2018 |
Giller D.
Giller B.
Giller G.
Shcherbakova G.
Bizhanov A.
Enilenis I.
Glotov A.
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European Journal of Cardio-thoracic Surgery |
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6 |
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© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. OBJECTIVES: Surgical interventional has been key in the treatment of tuberculosis (TB) for a long time. Its importance diminished after the emergence of chemotherapy. However, the spread of rapid multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has led us to return to surgery to treat TB. Today, every second patient in Russia with destructive TB has either MDR or XDR TB, which is the reason for the low efficacy of conservative treatment. In 2015, treatment with drugs resulted in clinical recovery in only 29.8% of new cases of destructive TB acid-fast bacilli (AFB)+. METHODS: The author's data from 1999 to 2016 have been analysed. The author performed 5599 surgeries on patients with pulmonary TB aged from 1 to 87 years (mean age 34.6 years). The most common reasons for surgical treatment were fibrotic cavitary and cavitary pulmonary TB, tuberculoma with destruction, tuberculous pleural empyema, caseous pneumonia and intrathoracic lymph nodes. The strategy of early collapse therapy and the use of surgery to treat TB was proposed in the Penza region of Russia; the results were analysed to estimate the long-term outcomes of treatment. RESULTS: In 5599 surgeries, the full clinical effect was achieved in 93% of operated patients with MDR TB, in 92.1% of those with XDR TB and in 98% of patients without MDR or XDR resistance. According to the data from the Penza region, 3 years after surgery, 93.9% (149 of 159 cases) of the operated patients exhibited clinical recovery. CONCLUSIONS: Taking into account the data from the World Health Organization on the insufficient level of therapeutic success in the treatment of MDR and XDR pulmonary TB, surgical treatment is necessary in regions with a high frequency of drug-resistant cases.
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The risk of formation and complicated course of giant coronary aneurysms in kawasaki syndrome, the tactics of convalescent management
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01.05.2018 |
Lyskina G.
Shirinskaya O.
Bokeria O.
Kostina Y.
Shpitonkova O.
Gagarina N.
Satyukova A.
Trifonova L.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018, Pediatria Ltd.. All rights reserved. Objective of the research: to define peculiarities of Kawasaki syndrome (KS) course in patients with giant coronary artery aneurysms (GCAA) to assess risk factors for complicated course, frequency, development time, the dynamics of coronary thrombosis and stenosis, and to rationale for the examination and treatment of convalescents. Materials and methods: in 2003–2017 342 children with KS were examined, GCAA was found in 17. Results: in all patients with GCAA KS treatment was started untimely (on the 12th–60th day of the KS). Thrombi in GCAA were found in 14, coronary arteries stenosis (CA) – in 6 patients. Thrombi regressed in 7, decreased – in 2, occlusion of right CA – in 2. Myocardial infarction was in one patient. Surgical treatment was in 5 patients: 3 – mammaroconary shunting (MSC), 2 – CA stenting, in one of them after 10 months – stent occlusion, MCS. Conclusion: to reduce the risk of life-threatening complications, timely treatment of KS, assessment of CA lesions nature for adequate thrombosis prophylaxis, detection of significant CA stenosis, timely consultation with cardiac surgeon are necessary.
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Retrospective Analysis of Short-Term Outcomes after Monopolar Versus Laser Endoscopic Enucleation of the Prostate: A Single Center Experience
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01.05.2018 |
Enikeev D.
Glybochko P.
Okhunov Z.
Alyaev Y.
Rapoport L.
Tsarichenko D.
Enikeev M.
Sorokin N.
Dymov A.
Taratkin M.
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Journal of Endourology |
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8 |
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© Mary Ann Liebert, Inc. Introduction: Endoscopic enucleation of the prostate (EEP) has been recognized as a viable treatment modality for men with benign prostatic hyperplasia (BPH). The aim of our study was to compare the efficacy and functional outcomes of three different techniques of EEP, including monopolar enucleation (MEP), holmium laser enucleation of the prostate (HoLEP), and thulium laser enucleation of the prostate (ThuLEP). Methods: The study consisted of a retrospective comparison of pre- and postoperative parameters in men undergoing three types of EEP: MEP, HoLEP, and ThuLEP. Functional parameters were evaluated before and 6 months after surgery, which included the International Prostate Symptom Score, maximum flow rate, postvoid residual volume, prostate volume, and sodium levels of all patients. Results: A total of 551 men with the mean age of 67.1 years were included in the study. Of these, MEP was performed on 95 patients, HoLEP was performed on 254 patients, and ThuLEP on 202 patients. The mean mass of morcellated tissue obtained during the three techniques did not differ significantly (p > 0.05). Mean procedure times of ThuLEP and HoLEP were shorter than MEP demonstrating 72, 76, and 86 minutes, respectively (p < 0.01). The mean catheterization time following laser EEPs was shorter than MEP as shown by 1.3, 1.3, and 3.8 days, respectively (p < 0.01). Hospital stay times of HoLEP and ThuLEP were shorter than MEP demonstrated by 3.3, 3.4, and 6.9 days, respectively (p < 0.01). Patients after MEP had significant decrease in postoperative hemoglobin and sodium levels. All the groups showed statistically significant improvement in the aforementioned parameters following treatment. Conclusions: Both techniques of laser enucleation proved to be efficacious in the management of BPH. MEP of the prostate seems to be a highly promising addition to the list of enucleation techniques and was determined to be an effective and acceptable procedure, despite a higher complication rate.
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New biomarkers of acute mesenteric ischemia
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01.05.2018 |
Chernookov A.
Bozhedomov A.
Atayan A.
Belyx E.
Sylchuk E.
Khachatryan E.
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Novosti Khirurgii |
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0 |
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© 2018 Vitebsk State Medical University. All rights reserved. The acute mesenteric ischemia is one of the most complex problems in the urgent surgery because of the high mortality, the cause of which is late diagnosis. The operation treatment is often provided in the phase of diffuse peritonitis. This literature review is done in order to identify the most accessible and accurate methods of early diagnosis of the acute mesenteric ischemia. At present time rather a small number of biomarkers for diagnosing the acute mesenteric ischemia are used, such as α-glutamate-S-transferase, D-dimers, procalcitonin, D-lactate, intestinal fatty acid binding protein (I-FABP), ischemia-modified albumin. According to the literature the highest sensitivity and specificity were found in I-FABP (75-85% and 70-80% respectively), α-glutamate-S-transferase (67.8% and 84.2%), ischemia-modified albumin (94.7% and 86.4%). In addition, expensive and invasive methods are currently used for early diagnosis, such as CT angiography, contrast-enhanced MRI, selective angiography. However, these technologies are not available to all medical institutions. We should continue further search of various biomarkers and their more widespread introduction to clinical practice in order to solve the problem of early acute mesenteric ischemia diagnostics.
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Preparation of Low-Molecular-Weight Heparins by Radiation-Induced Destruction
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01.05.2018 |
Tuaeva N.
Trukhan V.
Kardonskii D.
Eganov A.
Grebenkina E.
Veselov V.
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Pharmaceutical Chemistry Journal |
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0 |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Low-molecular-weight heparins (LMWHs) are widely used in medical practice. LMWHs are produced using various methods of controlled depolymerization of unfractionated heparin (UFH). Herein, a method for radiation-induced destruction of aqueous heparin solutions using a 60Co gamma-irradiation source is presented. The optimal conditions for depolymerization of starting heparin were found. The anticoagulant activity of LMWHs was studied as a function of irradiation dose. The results allowed this LMWH production method to be recommended for development of new anticoagulants.
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Prognostic value of age, subglottic, and anterior commissure involvement for early glottic carcinoma treated with CO<inf>2</inf> laser transoral microsurgery: a retrospective, single-center cohort study of 261 patients
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01.05.2018 |
Carta F.
Bandino F.
Olla A.
Chuchueva N.
Gerosa C.
Puxeddu R.
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European Archives of Oto-Rhino-Laryngology |
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5 |
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© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: CO2 laser transoral microsurgery for glottic carcinoma, when indicated, has the well-established advantages of low morbidity and positive oncological outcomes. The present study aims to determine how patient age, and tumor site could negatively impact prognosis; other variables such as the status of the margins of resection, tobacco and alcohol intake, and the grade of differentiation of the tumors have been evaluated. Methods: This was a retrospective analysis on 261 patients with a glottic carcinoma who underwent CO2 laser transoral microsurgery. The impact of different variables was calculated using univariate and multivariate analyses. Results: The study included 248 males and 13 females. The median follow-up period was 4.3 years. Five-year disease-specific survival, recurrence-free survival, local control with laser alone, overall laryngeal preservation, and overall survival rates were 99.4, 92.2, 93.8, 97.6, and 85.5%, respectively. Equivalent results were observed in young and elderly patients. Patients with positive margins after CO2 laser transoral microsurgery showed a reduced local control with laser alone. T2 patients with true subglottic spreading and patients with anterior commissure involvement of grade 3 (Rucci’s classification) experienced worse local control rates, despite free surgical margins confirmed by histology. Conclusions: CO2 laser transoral microsurgery is an effective and reproducible single-stage modality therapy for young and elderly patients with glottic carcinoma. Superficial close margins can be managed by a careful wait-and-see policy, while positive margins should undergo surgical enlargement. In our experience, undifferentiated tumors, true subglottic extension, and anterior commissure involvement of grade 3 were associated with worse outcomes.
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Vitamin D receptor variants and uncontrolled asthma
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01.05.2018 |
Hutchinson K.
Kerley C.
Faul J.
Greally P.
Coghlan D.
Louw M.
Elnazir B.
Rochev Y.
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European Annals of Allergy and Clinical Immunology |
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4 |
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© 2018, EDRA S.p.A. All rights reserved. Background. Asthma is a common childhood respiratory disease, affecting around 20% of Irish children. In other populations, vitamin D receptor (VDR) polymorphisms have been associated with asthma risk. We aimed to investigate the association between 2 VDR polymorphisms and uncontrolled paediatric asthma. Methods. 44 asthmatic children and 57 healthy volunteers were studied. The VDR TaqI gene variant in exon 9 (T/C) (rs731236) and ApaI (rs7975232) in intron 8 (C/T) were determined, using TaqMan® Assays. The lung function, serum 25-hydroxyvitamin D (25OHD) levels and other biomarkers of allergy, immunity, airway and systemic inflammation were assessed. Results. The distribution of T and C alleles and genotype frequencies differed significantly between asthmatics and controls for both polymorphisms (p < 0.05). A significant association was found between both TaqI (OR = 2.37, 95% CI (1.27 - 4.45), p = 0.007) and ApaI polymorphisms, and asthma risk (OR = 2.93, 95% CI (1.62 - 5.3), p = 0.0004). No association was observed between genotypes and 25OHD levels, lung function and other biomarkers, with the exception of Interleukin-10 (IL-10) and white blood cells count (WBC). IL-10 levels were lower in asthmatics with TC genotype for TaqI polymorphism (p < 0.01) and were higher in patients with TT genotype for ApaI (p < 0.01). WBC were higher in patients with TC and CC genotypes for TaqI (p < 0.05) and lower in TT genotype for ApaI (p < 0.05). Conclusion. TaqI and ApaI polymorphisms are associated with asthma in Irish children. Further studies are warranted to investigate the importance of decreased IL-10 levels in paediatric asthmatics with specific genotypes.
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Anti-Inflammatory Action of Polyextract of Orthosiphon stamineus (Leaves), Arctostaphylos uva-ursi (Leaves), Polygonum aviculare (Herbs), Calendula officinalis (Flowers), and Glycyrrhiza uralensis (Root) on the Rat Prostate
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01.05.2018 |
Nikolaev S.
Nikolaeva G.
Mondodoev A.
Markaryan A.
Nikolaeva I.
Nagaslaeva O.
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Pharmaceutical Chemistry Journal |
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0 |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. A polyextract consisting of the extracts of the five title plants shows a marked prostate-protective effect in experimental chronic prostatitis. The pharmacotherapeutic efficacy of the phytoextract gives a basis to recommend its use in complex treatment and prophylaxis of prostatitis.
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Acute and Chronic Musculoskeletal Injury in Para Sport: A Critical Review
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01.05.2018 |
Tuakli-Wosornu Y.
Mashkovskiy E.
Ottesen T.
Gentry M.
Jensen D.
Webborn N.
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Physical Medicine and Rehabilitation Clinics of North America |
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2 |
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© 2018 Elsevier Inc. Sport-related injury patterns among Para athletes have been described with increasing frequency. This review summarizes musculoskeletal injuries in Para athletes. Seated Para athletes sustain upper extremity injuries more commonly; ambulant Para athletes frequently sustain lower extremity injuries. The upper extremity is the most commonly injured anatomic area in all Para athletes, unlike able-bodied athletes. Advanced age and spinal cord injury may increase the risk of upper extremity injury. Injury data for recreational and youth Para athletes are sparse. Summarizing current injury epidemiology data may help to accelerate the development of injury prevention strategies and lifetime injury models for Para athletes.
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Application of NIR spectroscopy and chemometrics for revealing of the ‘high quality fakes’ among the medicines
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01.05.2018 |
Rodionova O.
Balyklova K.
Titova A.
Pomerantsev A.
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Forensic Chemistry |
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6 |
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© 2018 Counterfeit medicines of ‘high quality’ are the most difficult to detect as they have the same chemical composition as the genuine ones, but they are produced by underground manufacturers who violate technological regulations. Our approach is to consider a remedy as a whole object, taking into account the complex composition of APIs, excipients and manufacturing conditions. For rapid testing, the Near Infrared (NIR)-based approach is applied. It entails the acquisition of NIR spectra and processing of the collected data using a modern one-class classifier method called data driven soft independent modeling by class analogy (DD-SIMCA). We present an exemplary analysis of the suspected drugs, which have the same designation and a very similar chemical composition to the brand of a widely used medication used to treat allergies. We recognized the counterfeits using a model that had been previously developed and stored in a library for everyday monitoring in drugstores. We also describe the steps taken in development and validation of DD-SIMCA library models. In the case under consideration, the NIR-based analysis reveals 100% of counterfeits, and this result surpasses the results of the routine compedial tests. Additionally, we present a new instrument, VisCam, that is used in visual analysis of the primary and secondary packages. This instrument combines a tenfold web-camera with different light sources. It is shown that VisCam helps to reveal hidden violations in the primary and secondary packages.
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Halobacterium salinarum storage and rehydration after spray drying and optimization of the processes for preservation of carotenoids
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01.05.2018 |
Kalenov S.
Gordienko M.
Murzina E.
Poberezhniy D.
Baurin D.
Suzina N.
Morozov A.
Yakubovich L.
Belov A.
Panfilov V.
Yarovaya O.
Il’in M.
Sorokin V.
Skladnev D.
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Extremophiles |
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0 |
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© 2018, Springer Japan KK, part of Springer Nature. Spray drying is appropriate for the preservation of halophilic microorganisms due to the nature of these microorganisms, as they survive in adverse environmental conditions by being encapsulated in salt crystals. Artificial neural networks were in this study used to optimize practically significant spray-drying regimes of the C50-carotenoids producer Halobacterium salinarum. Immediately after drying, the samples contained up to 54% halobacterial biomass and less than 5% moisture, and the level of preservation of carotenoids was 95–97%. The storage of biomass at 4 °C resulted in the gradual degradation of the carotenoids, which reached 58–64% in the best samples after 1 year. A comprehensive study of changes in halobacteria biomass after spray drying and the nature of the damage provided new data on the survival and preservation of cells and biologically active substances in the various spray-drying regimes and at different storage times.
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Cytokinin activity of N<sup>6</sup>-benzyladenine derivatives assayed by interaction with the receptors in planta, in vitro, and in silico
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01.05.2018 |
Savelieva E.
Oslovsky V.
Karlov D.
Kurochkin N.
Getman I.
Lomin S.
Sidorov G.
Mikhailov S.
Osolodkin D.
Romanov G.
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Phytochemistry |
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© 2018 Elsevier Ltd Biological effects of hormones in both plants and animals are based on high-affinity interaction with cognate receptors resulting in their activation. The signal of cytokinins, classical plant hormones, is perceived in Arabidopsis by three homologous membrane receptors: AHK2, AHK3, and CRE1/AHK4. To study the cytokinin–receptor interaction, we used 25 derivatives of potent cytokinin N6-benzyladenine (BA) with substituents in the purine heterocycle and/or in the side chain. The study was focused primarily on individual cytokinin receptors from Arabidopsis. The main in planta assay system was based on Arabidopsis double mutants retaining only one isoform of cytokinin receptors and harboring cytokinin-sensitive reporter gene. Classical cytokinin biotest with Amaranthus seedlings was used as an additional biotest. In parallel, the binding of ligands to individual cytokinin receptors was assessed in the in vitro test system. Quantitative comparison of results of different assays confirmed the partial similarity of ligand-binding properties of receptor isoforms. Substituents at positions 8 and 9 of adenine moiety, elongated linker up to 4 methylene units, and replacement of N6 by sulfur or oxygen have resulted in the suppression of cytokinin activity of the derivative toward all receptors. Introduction of a halogen into position 2 of adenine moiety, on the contrary, often increased the ligand activity, especially toward AHK3. Features both common and distinctive of cytokinin receptors in Arabidopsis and Amaranthus were revealed, highlighting species specificity of the cytokinin perception apparatus. Correlations between the extent to which a compound binds to a receptor in vitro and its ability to activate the same receptor in planta were evaluated for each AHK protein. Interaction patterns between individual receptors and ligands were rationalized by structure analysis and molecular docking in sensory modules of AHK receptors. The best correlation between docking scores and specific binding was observed for AHK3. In addition, receptor-specific ligands have been discovered with unique properties to predominantly activate or block distinct cytokinin receptors. These ligands are promising for practical application and as molecular tools in the study of the cytokinin perception by plant cells.
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A shared epitope of collagen type XI and type II is recognized by pathogenic antibodies in mice and humans with arthritis
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12.04.2018 |
Tong D.
Lönnblom E.
Yau A.
Nandakumar K.
Liang B.
Ge C.
Viljanen J.
Li L.
Bãlan M.
Klareskog L.
Chagin A.
Gjertsson I.
Kihlberg J.
Zhao M.
Holmdahl R.
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Frontiers in Immunology |
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© 2018 Tong, Lönnblom, Yau, Nandakumar, Liang, Ge, Viljanen, Li, Bãlan, Klareskog, Chagin, Gjertsson, Kihlberg, Zhao and Holmdahl. Background: Collagen XI (CXI) is a heterotrimeric molecule with triple helical structure in which the a3(XI) chain is identical to the a1(II) chain of collagen II (CII), but with extensive posttranslational modifications. CXI molecules are intermingled in the cartilage collagen fibers, which are mainly composed of CII. One of the alpha chains in CXI is shared with CII and contains the immunodominant T cell epitope, but it is unclear whether there are shared B cell epitopes as the antibodies tend to recognize the triple helical structures. Methods: Mice expressing the susceptible immune response gene Aq were immunized with CII or CXI. Serum antibody responses were measured, monoclonal antibodies were isolated and analyzed for specificity to CII, CXI, and triple helical collagen peptides using bead-based multiplex immunoassays, enzyme-linked immunosorbent assays, and Western blots. Arthritogenicity of the antibodies was investigated by passive transfer experiments. Results: Immunization with CII or CXI leads to a strong T and B cell response, including a cross-reactive response to both collagen types. Immunization with CII leads to severe arthritis in mice, with a response toward CXI at the chronic stage, whereas CXI immunization induces very mild arthritis only. A series of monoclonal antibodies to CXI were isolated and of these, the L10D9 antibody bound to both CXI and CII equally strong, with a specific binding for the D3 epitope region of a3(XI) or a1(II) chain. The L10D9 antibody binds cartilage in vivo and induced severe arthritis. In contrast, the L5F3 antibody only showed weak binding and L7D8 antibody has no binding to cartilage and did not induce arthritis. The arthritogenic L10D9 antibody bound to an epitope shared with CII, the triple helical D3 epitope. Antibody levels to the shared D3 epitope were elevated in the sera from mice with arthritis as well as in rheumatoid arthritis. Conclusion: CXI is immunologically not exposed in healthy cartilage but contains T and B cell epitopes cross-reactive with CII, which could be activated in both mouse and human arthritis and could evoke an arthritogenic response.
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The effects of PPAR stimulation on cardiac metabolic pathways in barth syndrome mice
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11.04.2018 |
Schafer C.
Moore V.
Dasgupta N.
Javadov S.
James J.
Glukhov A.
Strauss A.
Khuchua Z.
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Frontiers in Pharmacology |
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© 2018 Schafer, Moore, Dasgupta, Javadov, James, Glukhov, Strauss and Khuchua. Aim: Tafazzin knockdown (TazKD) in mice is widely used to create an experimental model of Barth syndrome (BTHS) that exhibits dilated cardiomyopathy and impaired exercise capacity. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that play essential roles as transcription factors in the regulation of carbohydrate, lipid, and protein metabolism. We hypothesized that the activation of PPAR signaling with PPAR agonist bezafibrate (BF) may ameliorate impaired cardiac and skeletal muscle function in TazKD mice. This study examined the effects of BF on cardiac function, exercise capacity, and metabolic status in the heart of TazKD mice. Additionally, we elucidated the impact of PPAR activation on molecular pathways in TazKD hearts. Methods: BF (0.05% w/w) was given to TazKD mice with rodent chow. Cardiac function in wild type-, TazKD-, and BF-treated TazKD mice was evaluated by echocardiography. Exercise capacity was evaluated by exercising mice on the treadmill until exhaustion. The impact of BF on metabolic pathways was evaluated by analyzing the total transcriptome of the heart by RNA sequencing. Results: The uptake of BF during a 4-month period at a clinically relevant dose effectively protected the cardiac left ventricular systolic function in TazKD mice. BF alone did not improve the exercise capacity however, in combination with everyday voluntary running on the running wheel BF significantly ameliorated the impaired exercise capacity in TazKD mice. Analysis of cardiac transcriptome revealed that BF upregulated PPAR downstream target genes involved in a wide spectrum of metabolic (energy and protein) pathways as well as chromatin modification and RNA processing. In addition, the Ostn gene, which encodes the metabolic hormone musclin, is highly induced in TazKD myocardium and human failing hearts, likely as a compensatory response to diminished bioenergetic homeostasis in cardiomyocytes. Conclusion: The PPAR agonist BF at a clinically relevant dose has the therapeutic potential to attenuate cardiac dysfunction, and possibly exercise intolerance in BTHS. The role of musclin in the failing heart should be further investigated.
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