159 results on '"Andreeva, T"'
Search Results
2. Morphometric and Nanomechanical Screening of Peripheral Blood Cells with Atomic Force Microscopy for Label-Free Assessment of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis.
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Taneva SG, Todinova S, and Andreeva T
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- Humans, Microscopy, Atomic Force, Blood Cells, Parkinson Disease diagnosis, Amyotrophic Lateral Sclerosis diagnosis, Alzheimer Disease diagnosis
- Abstract
Neurodegenerative disorders (NDDs) are complex, multifactorial disorders with significant social and economic impact in today's society. NDDs are predicted to become the second-most common cause of death in the next few decades due to an increase in life expectancy but also to a lack of early diagnosis and mainly symptomatic treatment. Despite recent advances in diagnostic and therapeutic methods, there are yet no reliable biomarkers identifying the complex pathways contributing to these pathologies. The development of new approaches for early diagnosis and new therapies, together with the identification of non-invasive and more cost-effective diagnostic biomarkers, is one of the main trends in NDD biomedical research. Here we summarize data on peripheral biomarkers, biofluids (cerebrospinal fluid and blood plasma), and peripheral blood cells (platelets (PLTs) and red blood cells (RBCs)), reported so far for the three most common NDDs-Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). PLTs and RBCs, beyond their primary physiological functions, are increasingly recognized as valuable sources of biomarkers for NDDs. Special attention is given to the morphological and nanomechanical signatures of PLTs and RBCs as biophysical markers for the three pathologies. Modifications of the surface nanostructure and morphometric and nanomechanical signatures of PLTs and RBCs from patients with AD, PD, and ALS have been revealed by atomic force microscopy (AFM). AFM is currently experiencing rapid and widespread adoption in biomedicine and clinical medicine, in particular for early diagnostics of various medical conditions. AFM is a unique instrument without an analog, allowing the generation of three-dimensional cell images with extremely high spatial resolution at near-atomic scale, which are complemented by insights into the mechanical properties of cells and subcellular structures. Data demonstrate that AFM can distinguish between the three pathologies and the normal, healthy state. The specific PLT and RBC signatures can serve as biomarkers in combination with the currently used diagnostic tools. We highlight the strong correlation of the morphological and nanomechanical signatures between RBCs and PLTs in PD, ALS, and AD.
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- 2023
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3. Mosaic loss of the Y chromosome in human neurodegenerative and oncological diseases.
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Kuznetsova IL, Uralsky LI, Tyazhelova TV, Andreeva TV, and Rogaev EI
- Abstract
The development of new biomarkers for prediction and early detection of human diseases, as well as for monitoring the response to therapy is one of the most relevant areas of modern human genetics and genomics. Until recently, it was believed that the function of human Y chromosome genes was limited to determining sex and controlling spermatogenesis. Thanks to occurance of large databases of the genome-wide association study (GWAS), there has been a transition to the use of large samples for analyzing genetic changes in both normal and pathological conditions. This has made it possible to assess the association of mosaic aneuploidy of the Y chromosome in somatic cells with a shorter lifespan in men compared to women. Based on data from the UK Biobank, an association was found between mosaic loss of the Y chromosome (mLOY) in peripheral blood leukocytes and the age of men over 70, as well as a number of oncological, cardiac, metabolic, neurodegenerative, and psychiatric diseases. As a result, mLOY in peripheral blood cells has been considered a potential marker of biological age in men and as a marker of certain age-related diseases. Currently, numerous associations have been identified between mLOY and genes based on GWAS and transcriptomes in affected tissues. However, the exact cause of mLOY and the impact and consequences of this phenomenon at the whole organism level have not been established. In particular, it is unclear whether aneuploidy of the Y chromosome in blood cells may affect the development of pathologies that manifest in other organs, such as the brain in Alzheimer's disease, or whether it is a neutral biomarker of general genomic instability. This review examines the main pathologies and genetic factors associated with mLOY, as well as the hypotheses regarding their interplay. Special attention is given to recent studies on mLOY in brain cells in Alzheimer's disease., Competing Interests: The authors declare no conflict of interest., (Copyright © AUTHORS.)
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- 2023
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4. An Analysis of Genetic Predisposition to Hereditary Catalepsy in a Mouse Model of Neuropsychiatric Disorders Using Whole-Genome Sequencing Data.
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Andreeva TV, Gusev FE, Sinyakova NA, Kulikov AV, Grigorenko AP, Adrianova IY, Bazovkina DV, and Rogaev EI
- Abstract
Catalepsy is a behavioral condition that is associated with severe psychopathologies, including schizophrenia, depression, and Parkinson's disease. In some mouse strains, catalepsy can be induced by pinching the skin at the scruff of the neck. The main locus of hereditary catalepsy in mice has recently been linked to the 105-115 Mb fragment of mouse chromosome 13 by QTL analysis. We performed whole-genome sequencing of catalepsy-resistant and catalepsy-prone mouse strains in order to pinpoint the putative candidate genes related to hereditary catalepsy in mice. We remapped the previously described main locus for hereditary catalepsy in mice to the chromosome region 103.92-106.16 Mb. A homologous human region on chromosome 5 includes genetic and epigenetic variants associated with schizophrenia. Furthermore, we identified a missense variant in catalepsy-prone strains within the Nln gene. Nln encodes neurolysin, which degrades neurotensin, a peptide reported to induce catalepsy in mice. Our data suggest that Nln is the most probable candidate for the role of major gene of hereditary, pinch-induced catalepsy in mice and point to a shared molecular pathway between catalepsy in mice and human neuropsychiatric disorders., (Copyright ® 2023 National Research University Higher School of Economics.)
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- 2023
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5. Platelets' Nanomechanics and Morphology in Neurodegenerative Pathologies.
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Strijkova V, Todinova S, Andreeva T, Langari A, Bogdanova D, Zlatareva E, Kalaydzhiev N, Milanov I, and Taneva SG
- Abstract
The imaging and force-distance curve modes of atomic force microscopy (AFM) are explored to compare the morphological and mechanical signatures of platelets from patients diagnosed with classical neurodegenerative diseases (NDDs) and healthy individuals. Our data demonstrate the potential of AFM to distinguish between the three NDDs-Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), and normal healthy platelets. The common features of platelets in the three pathologies are reduced membrane surface roughness, area and height, and enhanced nanomechanics in comparison with healthy cells. These changes might be related to general phenomena associated with reorganization in the platelet membrane morphology and cytoskeleton, a key factor for all platelets' functions. Importantly, the platelets' signatures are modified to a different extent in the three pathologies, most significant in ALS, less pronounced in PD and the least in AD platelets, which shows the specificity associated with each pathology. Moreover, different degree of activation, distinct pseudopodia and nanocluster formation characterize ALS, PD and AD platelets. The strongest alterations in the biophysical properties correlate with the highest activation of ALS platelets, which reflect the most significant changes in their nanoarchitecture. The specific platelet signatures that mark each of the studied pathologies can be added as novel biomarkers to the currently used diagnostic tools.
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- 2022
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6. Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.
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Jorstad SG, Marscher AP, Raiteri CM, Villata M, Weaver ZR, Zhang H, Dong L, Gómez JL, Perel MV, Savchenko SS, Larionov VM, Carosati D, Chen WP, Kurtanidze OM, Marchini A, Matsumoto K, Mortari F, Aceti P, Acosta-Pulido JA, Andreeva T, Apolonio G, Arena C, Arkharov A, Bachev R, Banfi M, Bonnoli G, Borman GA, Bozhilov V, Carnerero MI, Damljanovic G, Ehgamberdiev SA, Elsässer D, Frasca A, Gabellini D, Grishina TS, Gupta AC, Hagen-Thorn VA, Hallum MK, Hart M, Hasuda K, Hemrich F, Hsiao HY, Ibryamov S, Irsmambetova TR, Ivanov DV, Joner MD, Kimeridze GN, Klimanov SA, Knött J, Kopatskaya EN, Kurtanidze SO, Kurtenkov A, Kuutma T, Larionova EG, Leonini S, Lin HC, Lorey C, Mannheim K, Marino G, Minev M, Mirzaqulov DO, Morozova DA, Nikiforova AA, Nikolashvili MG, Ovcharov E, Papini R, Pursimo T, Rahimov I, Reinhart D, Sakamoto T, Salvaggio F, Semkov E, Shakhovskoy DN, Sigua LA, Steineke R, Stojanovic M, Strigachev A, Troitskaya YV, Troitskiy IS, Tsai A, Valcheva A, Vasilyev AA, Vince O, Waller L, Zaharieva E, and Chatterjee R
- Abstract
Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales
1-3 . This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5 , plasma instabilities6,7 or orbital motion in an accretion disc7,8 . Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref.9 ). BL Lac, the prototype of a subclass of blazars10 , is powered by a 1.7 × 108 MSun (ref.11 ) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref.12 )). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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7. Immune Tolerance Induction (ITI) with a pdFVIII/VWF Concentrate (octanate) in 100 Patients in the Observational ITI (ObsITI) Study.
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Escuriola Ettingshausen C, Vdovin V, Zozulya N, Svirin P, Andreeva T, Benedik-Dolničar M, Jiménez-Yuste V, Kitanovski L, Zupancic-Šalek S, Pavlova A, Bátorová A, Montaño Mejía C, Abdilova G, Knaub S, Jansen M, Lowndes S, Belyanskaya L, Walter O, and Oldenburg J
- Abstract
Background Immune tolerance induction (ITI) with repeated factor VIII (FVIII) administration is the only strategy proven to eradicate inhibitors. The observational ITI study is evaluating ITI with a range of FVIII products. Methods This subgroup analysis reports prospective interim data for patients treated with a plasma-derived, von Willebrand factor-stabilized FVIII concentrate (pdFVIII/VWF, octanate). Complete success (CS) of ITI required achievement of three criteria: inhibitor titer < 0.6 BU/mL; FVIII recovery ≥ 66%; FVIII half-life ≥6 hours. Partial success (PS) required achievement of two criteria and partial response (PR) one. ITI success was defined as CS or PS. Data were analyzed for patients who achieved CS, had 36 months' observation, or failed ITI. Results One-hundred prospectively enrolled patients were included in the analysis; 91 had poor prognosis factors for ITI success. The mean (standard deviation) daily ITI dose was 116.4 (61.1) IU FVIII/kg in 14 low responders (< 5 BU/mL) and 173.7 (112.0) IU FVIII/kg in 86 high responders (≥ 5 BU/mL). Inhibitor titers < 0.6 BU/mL were achieved in 71% of patients in a median of 4.01 months, accompanied by a 93% reduction in bleeding rate. ITI success was achieved by 70% of patients and 56 of 72 (78%) primary (first-line) ITI patients. PR was achieved by 5 patients; ITI failed in 25 patients. PS and CS were achieved in a median of 5.55 and 11.25 months, respectively. Conclusions ITI with pdFVIII/VWF led to rapid eradication of FVIII inhibitors, normalization of FVIII pharmacokinetics in the majority of patients, and a significant reduction in bleeding rates., Competing Interests: Conflict of Interest C. Escuriola Ettingshausen has acted as a consultant and received speaker's fees and/or research funding from the following companies: Bayer, Biomarin, Biotest, Chugai, CSL Behring, Grifols, Kedrion, Novo Nordisk Octapharma, Roche, Swedish Orphan Biovitrum and Takeda. V. Vdovin has participated in studies sponsored by Bayer, Generium, Novo Nordisk, Octapharma and Roche. N. Zozulya has acted as a consultant and received speaker's fees and/or research funding from the following companies: CSL Behring, Generium, Novo Nordisk, Octapharma, Roche, SOBI and Takeda. T. Andreeva has received speaker's fees and/or research funding from Bayer, Baxalta, Biomarin, Catalis, CSL Behring, Generium, Grifols, Novo Nordisk, Octapharma and Roche, and has consulted for CSL Behring, Generium, Novo Nordisk, Octapharma, Roche, Shire and Swedish Orphan Biovitrum. V Jiménez-Yuste has acted as a consultant and/or received speaker's fees and/or research funding from the following companies: Bayer, Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. L. Kitanovski has acted as a consultant and received speaker's fees from the following companies: Bayer, Novo Nordisk, Octapharma, Roche, Takeda and Swedish Orphan Biovitrum. S. Zupančić Šalek has acted as a consultant and/or received speaker's fees and/or research funding from following companies: Bayer, Novo Nordisk, Octapharma, Roche, Swedish Orphan Biovitrum and Takeda. A. Pavlova has participated in studies sponsored by Octapharma AG. A. Bátorová has acted as a consultant and/or received speaker's fees and/or research funding from the following companies: Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. C. Montaño Mejía has received speaker's fees from Octapharma and Roche; travel support from CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche and Takeda. J. Oldenburg has acted as a consultant and/or received speaker's fees, honoraria and research funding from the following companies: Bayer, Biogen Idec, Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. S. Knaub, S. Lowndes, L. Belyanskaya and O. Walter are employees of Octapharma AG. M. Jansen is an employee of Octapharma Pharmazeutika Produktionsges.mbH. P. Svirin, M. Benedik-Dolničar and G. Abdilova stated that they had no conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2022
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8. Global Seroprevalence of Pre-existing Immunity Against AAV5 and Other AAV Serotypes in People with Hemophilia A.
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Klamroth R, Hayes G, Andreeva T, Gregg K, Suzuki T, Mitha IH, Hardesty B, Shima M, Pollock T, Slev P, Oldenburg J, Ozelo MC, Stieltjes N, Castet SM, Mahlangu J, Peyvandi F, Kazmi R, Schved JF, Leavitt AD, Callaghan M, Pan-Petesch B, Quon DV, Andrews J, Trinh A, Li M, and Wong WY
- Subjects
- Antibodies, Neutralizing, Antibodies, Viral, Genetic Vectors genetics, Humans, Prospective Studies, Seroepidemiologic Studies, Serogroup, Dependovirus genetics, Hemophilia A epidemiology, Hemophilia A genetics, Hemophilia A therapy
- Abstract
Adeno-associated virus (AAV)-mediated gene therapy may provide durable protection from bleeding events and reduce treatment burden for people with hemophilia A (HA). However, pre-existing immunity against AAV may limit transduction efficiency and hence treatment success. Global data on the prevalence of AAV serotypes are limited. In this global, prospective, noninterventional study, we determined the prevalence of pre-existing immunity against AAV2, AAV5, AAV6, AAV8, and AAVrh10 among people ≥12 years of age with HA and residual FVIII levels ≤2 IU/dL. Antibodies against each serotype were detected using validated, electrochemiluminescent-based enzyme-linked immunosorbent assays. To evaluate changes in antibody titers over time, 20% of participants were retested at 3 and 6 months. In total, 546 participants with HA were enrolled at 19 sites in 9 countries. Mean (standard deviation) age at enrollment was 36.0 (14.87) years, including 12.5% younger than 18 years, and 20.0% 50 years of age and older. On day 1, global seroprevalence was 58.5% for AAV2, 34.8% for AAV5, 48.7% for AAV6, 45.6% for AAV8, and 46.0% for AAVrh10. Considerable geographic variability was observed in the prevalence of pre-existing antibodies against each serotype, but AAV5 consistently had the lowest seroprevalence across the countries studied. AAV5 seropositivity rates were 51.8% in South Africa ( n = 56), 46.2% in Russia ( n = 91), 40% in Italy ( n = 20), 37.2% in France ( n = 86), 26.8% in the United States ( n = 71), 26.9% in Brazil ( n = 26), 28.1% in Germany ( n = 89), 29.8% in Japan ( n = 84), and 5.9% in the United Kingdom ( n = 17). For all serotypes, seropositivity tended to increase with age. Serostatus and antibody titer were generally stable over the 6-month sampling period. As clinical trials of AAV-mediated gene therapies progress, data on the natural prevalence of antibodies against various AAV serotypes may become increasingly important.
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- 2022
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9. CVD-Synthesis of N-CNT Using Propane and Ammonia.
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Skudin V, Andreeva T, Myachina M, and Gavrilova N
- Abstract
N-CNT is a promising material for various applications, including catalysis, electronics, etc., whose widespread use is limited by the significant cost of production. CVD-synthesis using a propane-ammonia mixture is one of the cost-effective processes for obtaining carbon nanomaterials. In this work, the CVD-synthesis of N-CNT was conducted in a traditional bed reactor using catalyst: (Al
0,4 Fe0,48 Co0,12 )2 O3 + 3% MoO3 . The synthesized material was characterized by XPS spectroscopy, ASAP, TEM and SEM-microscopy. It is shown that the carbon material contains various morphological structures, including multiwalled carbon nanotubes (MWCNT), bamboo-like structures, spherical and irregular sections. The content of structures (bamboo-like and spherical structure) caused by the incorporation of nitrogen into the carbon nanotube structure depends on the synthesis temperature and the ammonia content in the reaction mixture. The optimal conditions for CVD-synthesis were determined: the temperature range (650-700 °C), the composition (C3 H8 /NH3 = 50/50%) and flow rate of the ammonia-propane mixture (200 mL/min).- Published
- 2022
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10. Morphometry and Stiffness of Red Blood Cells-Signatures of Neurodegenerative Diseases and Aging.
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Strijkova-Kenderova V, Todinova S, Andreeva T, Bogdanova D, Langari A, Danailova A, Krumova S, Zlatareva E, Kalaydzhiev N, Milanov I, and Taneva SG
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- Adult, Aged, Aged, 80 and over, Elastic Modulus physiology, Erythrocyte Count methods, Female, Humans, Male, Middle Aged, Aging pathology, Erythrocytes pathology, Neurodegenerative Diseases pathology
- Abstract
Human red blood cells (RBCs) are unique cells with the remarkable ability to deform, which is crucial for their oxygen transport function, and which can be significantly altered under pathophysiological conditions. Here we performed ultrastructural analysis of RBCs as a peripheral cell model, looking for specific signatures of the neurodegenerative pathologies (NDDs)-Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), utilizing atomic force (AFM) and conventional optical (OM) microscopy. We found significant differences in the morphology and stiffness of RBCs isolated from patients with the selected NDDs and those from healthy individuals. Neurodegenerative pathologies' RBCs are characterized by a reduced abundance of biconcave discoid shape, lower surface roughness and a higher Young's modulus, compared to healthy cells. Although reduced, the biconcave is still the predominant shape in ALS and AD cells, while the morphology of PD is dominated by crenate cells. The features of RBCs underwent a marked aging-induced transformation, which followed different aging pathways for NDDs and normal healthy states. It was found that the diameter, height and volume of the different cell shape types have different values for NDDs and healthy cells. Common and specific morphological signatures of the NDDs were identified.
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- 2021
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11. Genetic Evidence of Authenticity of a Hair Shaft Relic from the Portrait of Tsesarevich Alexei, Son of the Last Russian Emperor.
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Andreeva T, Manakhov A, Kunizheva S, and Rogaev E
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- Humans, Russia, DNA, Mitochondrial genetics, Forensic Anthropology, Forensic Genetics, Hair, High-Throughput Nucleotide Sequencing
- Abstract
To determine the value of an art piece, authenticity of the artwork must be verified. We demonstrate here a genetic approach to determine origin of a historic relic in the museum piece. We tested two hair shafts of unknown origin framed into a watercolor portrait of Tsesarevich Alexei Romanov, son of the last Russian Tzar Nicholas II, which is a unique item kept in the State Historical Museum. Genetic identification of the hair shafts was performed by analysis of mitochondrial DNA (mtDNA) markers using both massive parallel genomic sequencing and multiplex targeted PCR, followed by Sanger sequencing. In previous works, we reconstructed the complete mtDNA sequence inherited to Alexei Romanov through the Queen Victoria lineage [Rogaev et al. (2009) Proc. Natl. Acad. Sci. USA, 106, 5258-5263]. DNA extracts were obtained from the two thin hair shafts and used for comparative genetic analysis. Despite the very low quantity and quality of the DNA templates retrieved from the historical single hair shaft specimen, informative mtDNA sequences were determined. The mtDNA haplotype in the hair shafts corresponds to the mtDNA haplotype of Tsarevich Alexei, his sisters, and his mother, Empress Alexandra Feodorovna. This haplotype remains unique in the currently available mtDNA databases. Our results reveal that the hair relic from the portrait is associated with the family of the last Russian Emperor Nicholas II. The study is an example of first application of the genetic methodology for verification of the value of museum artwork items.
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- 2021
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12. Publisher Correction: Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.
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Beidler CD, Smith HM, Alonso A, Andreeva T, Baldzuhn J, Beurskens MNA, Borchardt M, Bozhenkov SA, Brunner KJ, Damm H, Drevlak M, Ford OP, Fuchert G, Geiger J, Helander P, Hergenhahn U, Hirsch M, Höfel U, Kazakov YO, Kleiber R, Krychowiak M, Kwak S, Langenberg A, Laqua HP, Neuner U, Pablant NA, Pasch E, Pavone A, Pedersen TS, Rahbarnia K, Schilling J, Scott ER, Stange T, Svensson J, Thomsen H, Turkin Y, Warmer F, Wolf RC, and Zhang D
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- 2021
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13. Unprecedented formation of sterically stabilized phospholipid liposomes of cuboidal morphology.
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Bakardzhiev P, Forys A, Trzebicka B, Andreeva T, and Rangelov S
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- Doxorubicin, Lipid Bilayers, Polymers, Liposomes, Phospholipids
- Abstract
Sterically stabilized phospholipid liposomes of unprecedented cuboid morphology are formed upon introduction in the bilayer membrane of original polymers, based on polyglycidol bearing a lipid-mimetic residue. Strong hydrogen bonding in the polyglycidol sublayers creates attractive forces, which, facilitated by fluidization of the membrane, bring about the flattening of the bilayers and the formation of cuboid vesicles.
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- 2021
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14. Functionalization of Aminoalkylsilane-Grafted Bacterial Nanocellulose with ZnO-NPs-Doped Pullulan Electrospun Nanofibers for Multifunctional Wound Dressing.
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Shahriari-Khalaji M, Hu G, Chen L, Cao Z, Andreeva T, Xiong X, Krastev R, and Hong FF
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- Animals, Bandages, Glucans, Rats, Nanofibers, Nanoparticles, Zinc Oxide
- Abstract
High moisture permeability, excellent mechanical properties in a wet state, high water-holding capability, and high exudate absorption make bacterial nanocellulose (BNC) a favorable candidate for biomedical device production, especially wound dressings. The lack of antibacterial activity and healing-promoting ability are the main drawbacks that limit its wide application. Pullulan (Pul) is a nontoxic polymer that can promote wound healing. Zinc oxide nanoparticles (ZnO-NPs) are well-known as a safe antibacterial agent. In this study, aminoalkylsilane was chemically grafted on a BNC membrane (A- g -BNC) and used as a bridge to combine BNC with Pul-ZnO-NPs hybrid electrospun nanofibers. FTIR results confirmed the successful production of A- g -BNC/Pul-ZnO. The obtained dressing demonstrated blood clotting performance better than that of BNC. The dressing showed an ability to release ZnO, and its antibacterial activity was up to 5 log values higher than that of BNC. The cytotoxicity of the dressing toward L929 fibroblast cells clearly showed safety due to the proliferation of fibroblast cells. The animal test in a rat model indicated faster healing and re-epithelialization, small blood vessel formation, and collagen synthesis in the wounds covered by A- g -BNC/Pul-ZnO. The new functional dressing, fabricated with a cost-effective and easy method, not only showed excellent antibacterial activity but could also accelerate wound healing.
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- 2021
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15. Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.
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Beidler CD, Smith HM, Alonso A, Andreeva T, Baldzuhn J, Beurskens MNA, Borchardt M, Bozhenkov SA, Brunner KJ, Damm H, Drevlak M, Ford OP, Fuchert G, Geiger J, Helander P, Hergenhahn U, Hirsch M, Höfel U, Kazakov YO, Kleiber R, Krychowiak M, Kwak S, Langenberg A, Laqua HP, Neuner U, Pablant NA, Pasch E, Pavone A, Pedersen TS, Rahbarnia K, Schilling J, Scott ER, Stange T, Svensson J, Thomsen H, Turkin Y, Warmer F, Wolf RC, and Zhang D
- Abstract
Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak
1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2 , a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4 . The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5 . Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization., (© 2021. The Author(s).)- Published
- 2021
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16. Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia.
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Andreeva T, Komsa-Penkova R, Langari A, Krumova S, Golemanov G, Georgieva GB, Taneva SG, Giosheva I, Mihaylova N, Tchorbanov A, and Todinova S
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- Abortion, Habitual etiology, Abortion, Habitual metabolism, Adult, Blood Platelets metabolism, Case-Control Studies, Female, Humans, Pregnancy, Abortion, Habitual pathology, Blood Platelets pathology, Nanostructures chemistry, Polymorphism, Genetic, Thrombophilia complications
- Abstract
Pregnancy is associated with hypercoagulation states and increased thrombotic risk, especially in women with thrombophilia. We combine atomic force microscopy (AFM) and flow cytometry to examine the morphology and nanomechanics of platelets derived from women with early pregnancy loss (EPL) and control pregnant (CP) and non-pregnant (CNP) women. Both control groups exhibit similar morphometric parameters (height and surface roughness) and membrane stiffness of platelets. EPL patients' platelets, on the other hand, are more activated than the control groups, with prominent cytoskeletal rearrangement. In particular, reduced membrane roughness (22.9 ± 6 nm vs. 39.1 ± 8 nm) ( p < 0.05) and height (692 ± 128 nm vs. 1090 ± 131 nm) ( p < 0.05), strong alteration in the membrane Young modulus, increased production of platelets' microparticles, and higher expression of procoagulant surface markers, as well as increased occurrence of thrombophilia ( FVL , FII20210A , PLA1/A2 , MTHFR C677T or 4G/5G PAI-1 ) polymorphisms were found. We suggest that the carriage of thrombophilic mutations triggers structural and nanomechanical abnormalities in platelets, resulting in their increased activation. The activation state of platelets can be well characterized by AFM, and the morphometric and nanomechanical characteristics might serve as a new criterion for evaluation of the cause of miscarriage and offer the prospect of an innovative approach serving for diagnostic purposes.
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- 2021
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17. Novel Gene Mutations Regulating Immune Responses in Autoimmune Polyglandular Syndrome With an Atypical Course.
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Yukina M, Erofeeva T, Nuralieva N, Andreeva T, Savvateeva E, Dudko N, Troshina E, Rogaev E, and Melnichenko G
- Abstract
Context: Autoimmune polyglandular syndrome (APS) is a cluster of endocrine disorders arising from immune dysregulation, often combined with damage to nonendocrine organs. There are 2 types of APS: type 1 and type 2 (APS-1 and APS-2, respectively). In clinical practice, an atypical course of APS is often observed., Objective: This work aims to find a novel genetic predictor of APS., Methods: We performed exome sequencing in 2 patients with an atypical clinical APS picture and members of their families. Patient A presented with a manifestation of APS-2 in early childhood and patient B with a late manifestation of the main components of APS-1., Results: In patient B, we identified inherited compound mutations as a novel combination of the c.769C > T and c.821delG alleles of AIRE and genetic variation in the CIITA gene. No homozygous or compound mutations in AIRE were found in patient A, but we did reveal mutations in genes encoding regulatory proteins of innate and acquired immunity in this patient., Conclusion: Our data revealed novel combination of mutations in the AIRE gene in atypical APS and imply that mutations in immune-related genes may modify the clinical manifestation of APS in AIRE -mutation carriers and contribute to the development of autoimmune pathology in non-AIRE carriers with atypical APS., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
- Published
- 2021
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18. Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABA A and Nicotinic Acetylcholine Receptors.
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Son L, Kryukova E, Ziganshin R, Andreeva T, Kudryavtsev D, Kasheverov I, Tsetlin V, and Utkin Y
- Subjects
- Animals, Binding Sites, Binding, Competitive, Cell Line, Tumor, Cholinergic Agents metabolism, Cobra Neurotoxin Proteins metabolism, GABA-A Receptor Antagonists metabolism, Membrane Potentials, Mice, Protein Binding, Protein Conformation, Receptors, GABA genetics, Receptors, GABA metabolism, Structure-Activity Relationship, Torpedo, Xenopus laevis, alpha7 Nicotinic Acetylcholine Receptor metabolism, Cholinergic Agents pharmacology, Cobra Neurotoxin Proteins pharmacology, Elapid Venoms metabolism, GABA-A Receptor Antagonists pharmacology, Naja, Receptors, GABA drug effects, alpha7 Nicotinic Acetylcholine Receptor drug effects
- Abstract
Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABA
A receptors (GABAA Rs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAA R and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedo californica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAA Rs, showed that all toxins interacted with the GABAA R much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAA R was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAA R. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.- Published
- 2021
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19. Condensing Effect of Cholesterol on hBest1/POPC and hBest1/SM Langmuir Monolayers.
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Videv P, Mladenov N, Andreeva T, Mladenova K, Moskova-Doumanova V, Nikolaev G, Petrova SD, and Doumanov JA
- Abstract
Human bestrophin-1 protein (hBest1) is a transmembrane channel associated with the calcium-dependent transport of chloride ions in the retinal pigment epithelium as well as with the transport of glutamate and GABA in nerve cells. Interactions between hBest1, sphingomyelins, phosphatidylcholines and cholesterol are crucial for hBest1 association with cell membrane domains and its biological functions. As cholesterol plays a key role in the formation of lipid rafts, motional ordering of lipids and modeling/remodeling of the lateral membrane structure, we examined the effect of different cholesterol concentrations on the surface tension of hBest1/POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and hBest1/SM Langmuir monolayers in the presence/absence of Ca
2+ ions using surface pressure measurements and Brewster angle microscopy studies. Here, we report that cholesterol: (1) has negligible condensing effect on pure hBest1 monolayers detected mainly in the presence of Ca2+ ions, and; (2) induces a condensing effect on composite hBest1/POPC and hBest1/SM monolayers. These results offer evidence for the significance of intermolecular protein-lipid interactions for the conformational dynamics of hBest1 and its biological functions as multimeric ion channel.- Published
- 2021
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20. Opinion: Cultural and linguistic diversities are underappreciated pillars of biodiversity.
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Frainer A, Mustonen T, Hugu S, Andreeva T, Arttijeff EM, Arttijeff IS, Brizoela F, Coelho-de-Souza G, Printes RB, Prokhorova E, Sambou S, Scherer A, Shadrin V, and Pecl G
- Subjects
- Brazil, Europe, Humans, Linguistics, Senegal, Taiwan, Biodiversity, Cultural Diversity, Language
- Abstract
Competing Interests: The authors declare no competing interest.
- Published
- 2020
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21. Providers' Initial Trust on an Organization-Sponsored Sharing Platform: The Framing of Coworker Collaborative Consumption.
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Bhappu AD, Blomqvist K, Andreeva T, Zappa P, Yeo ML, and Lempiälä T
- Abstract
Organization-sponsored sharing platforms extend the sharing economy to workplaces by connecting employees in a private online community where they can socially exchange goods and services with coworkers. Employees share costs but do not earn income during this collaborative consumption. Furthermore, employers pay for their employees to have access to the platform technology and any related transaction fees. Trust is a crucial antecedent for engagement on sharing platforms because it helps mitigate risks during collaborative consumption. However, the literature on trust in the sharing economy has focused almost exclusively on platforms that broker peer-to-peer rental transactions rather than social exchanges. There is also a lack of research about providers' perspectives. We address these gaps by investigating the nature of trust among employees who initially provide goods and services on an organization-sponsored sharing platform. We also explore how these employees' initial trust influences their collaborative consumption with coworkers. Through abductive analysis of 22 interviews with 15 providers on an organization-sponsored sharing platform, we shed light on how employees initially develop trust when providing goods and services to coworkers. By integrating prior research on initial trust among employees and cognitive framing with in-depth qualitative insights, we develop a conceptual model depicting how identity, interaction and issue frames shape these providers' beliefs about coworker trustworthiness and intended sharing strategy. In particular, our empirical findings reveal that employees' social categorization, illusions of control and engagement motive framed their initial trust and enactment of collaborative consumption as citizens in a community or consumers in a marketplace., (Copyright © 2020 Bhappu, Blomqvist, Andreeva, Zappa, Yeo and Lempiälä.)
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- 2020
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22. The curly coat phenotype of the Ural Rex feline breed is associated with a mutation in the lipase H gene.
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Manakhov AD, Andreeva TV, and Rogaev EI
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- Animals, Keratins, Hair-Specific metabolism, Lipase metabolism, Mutant Proteins genetics, Mutant Proteins metabolism, Receptors, Lysophosphatidic Acid metabolism, Species Specificity, Cats genetics, Hair anatomy & histology, Keratins, Hair-Specific genetics, Lipase genetics, Mutation, Receptors, Lysophosphatidic Acid genetics
- Abstract
Mutations in lipase H (LIPH) and lysophosphatidic acid receptor 6 (LPAR6), which are essential for the lysophosphatidic acid (LPA) signalling pathway, are associated with hypotrichosis and wooly hair in humans. Mutations in LPAR6 and keratin 71 (KRT71), result in unusual fur growth and hair structure in several cat breeds (Cornish Rex, Devon Rex and Selkirk Rex). Here, we performed target sequencing of the LIPH, LPAR6 and KRT71 genes in six cat breeds with specific hair-growth phenotypes. A LIPH genetic variant (LIPH:c.478_483del; LIPH:p.Ser160_Gly161del) was found in Ural Rex cats with curly coats from Russia, but was absent in all other cat breeds tested. In silico three-dimensional analysis of the LIPH mutant protein revealed a contraction of the α3-helix structure in the enzyme phospholipid binding site that may affect its activity., (© 2020 Stichting International Foundation for Animal Genetics.)
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- 2020
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23. Genetic Association Between Alzheimer's Disease Risk Variant of the PICALM Gene and EEG Functional Connectivity in Non-demented Adults.
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Ponomareva N, Andreeva T, Protasova M, Konovalov R, Krotenkova M, Malina D, Mitrofanov A, Fokin V, Illarioshkin S, and Rogaev E
- Abstract
Genome wide association studies (GWAS) have identified and validated the association of the PICALM genotype with Alzheimer's disease (AD). The PICALM rs3851179 A allele is thought to have a protective effect, whereas the G allele appears to confer risk for AD. The influence of the PICALM genotype on brain functional connectivity in non-demented subjects remains largely unknown. We examined the association of the PICALM rs3851179 genotype with the characteristics of lagged linear connectivity (LLC) of resting EEG sources in 104 non-demented adults younger than 60 years of age. The EEG analysis was performed using exact low-resolution brain electromagnetic tomography (eLORETA) freeware (Pascual-Marqui et al., 2011). We found that the carriers of the A PICALM allele ( PICALM AA and AG genotypes) had higher widespread interhemispheric LLC of alpha sources compared to the carriers of the GG PICALM allele. An exploratory correlation analysis showed a moderate positive association between the alpha LLC interhemispheric characteristics and the corpus callosum size and between the alpha interhemispheric LLC characteristics and the Luria word memory scores. These results suggest that the PICALM rs3851179 A allele provides protection against cognitive decline by facilitating neurophysiological reserve capacities in non-demented adults. In contrast, lower functional connectivity in carriers of the AD risk variant, PICALM GG , suggests early functional alterations in alpha rhythm networks., (Copyright © 2020 Ponomareva, Andreeva, Protasova, Konovalov, Krotenkova, Malina, Mitrofanov, Fokin, Illarioshkin and Rogaev.)
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- 2020
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24. Dissection of the Human T-Cell Receptor γ Gene Repertoire in the Brain and Peripheral Blood Identifies Age- and Alzheimer's Disease-Associated Clonotype Profiles.
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Aliseychik M, Patrikeev A, Gusev F, Grigorenko A, Andreeva T, Biragyn A, and Rogaev E
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- Adult, Aged, Aged, 80 and over, Complementarity Determining Regions genetics, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Pilot Projects, Receptors, Antigen, T-Cell, gamma-delta blood, Receptors, Antigen, T-Cell, gamma-delta immunology, Young Adult, Aging blood, Aging immunology, Alzheimer Disease blood, Alzheimer Disease immunology, Brain immunology, Clone Cells immunology, Genes, T-Cell Receptor gamma, Receptors, Antigen, T-Cell, gamma-delta genetics
- Abstract
The immune system contributes to neurodegenerative pathologies. However, the roles of γδ T cells in Alzheimer's disease (AD) are poorly understood. Here, we evaluated somatic variability of T-cell receptor γ genes (TRGs) in patients with AD. We performed deep sequencing of the CDR3 region of TRGs in patients with AD and control patients without dementia. TRG clones were clearly detectable in peripheral blood (PB) and non-neuronal cell populations in human brains. TRG repertoire diversity was reduced during aging. Compared with the PB, the brain showed reduced TRGV9 clonotypes but was enriched in TRGV2/4/8 clonotypes. AD-associated TRG profiles were found in both the PB and brain. Moreover, some groups of clonotypes were more specific for the brain or blood in patients with AD compared to those in controls. Our pilot deep analysis of T-cell receptor diversities in AD revealed putative brain and AD-associated immunogenic markers., (Copyright © 2020 Aliseychik, Patrikeev, Gusev, Grigorenko, Andreeva, Biragyn and Rogaev.)
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- 2020
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25. Dimeric Disintegrins from the Steppe Viper V. ursinii Venom.
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Kryukova EV, Potapenko AS, Andreeva TV, Ivanov IA, Ryabinin VV, Ziganshin RH, Starkov VG, Ayvazyan NM, Tsetlin VI, and Utkin YN
- Subjects
- Animals, Disintegrins pharmacology, Humans, MCF-7 Cells, Receptors, Vitronectin metabolism, Reptilian Proteins pharmacology, Viper Venoms pharmacology, Disintegrins chemistry, Protein Multimerization, Reptilian Proteins chemistry, Viper Venoms chemistry, Viperidae
- Abstract
Four dimeric disintegrins were isolated from the venom of the steppe viper V. ursinii using liquid chromatography. Disintegrins prevented adhesion of MCF7 cells to fibronectin, which indicates their interaction with integrin receptors of the αVβ1 type. According to mass spectrometry data, the molar masses of disintegrins are about 14 kDa. The method of peptide mapping established the structure of a new heterodimeric disintegrin weighing 13 995.5 Da and shows that it belongs to the class of RGD/KGD-containing disintegrins.
- Published
- 2019
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26. Cardiotoxins from Cobra Naja oxiana Change the Force of Contraction and the Character of Rhythmoinotropic Phenomena in the Rat Myocardium.
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Averin AS, Astashev ME, Andreeva TV, Tsetlin VI, and Utkin YN
- Subjects
- Animals, Dose-Response Relationship, Drug, Rats, Cobra Cardiotoxin Proteins pharmacology, Heart drug effects, Heart physiology, Myocardial Contraction drug effects, Naja naja
- Abstract
The study of the influence of cobra Naja oxiana cardiotoxins on the contractility of the rat papillary muscles and its rhythmoinotropic characteristics has shown that the presence of toxins induces a slight contractility decrease in the stimulation frequency range up to 0.1 Hz. In the stimulation frequency range from 0.1 to 0.5 Hz, a positive inotropic effect is found. However, the positive inotropic effect is replaced by a negative one with further increase in the frequency up to 3 Hz. In the presence of cardiotoxins, the positive force-frequency relationship in the region of 1-3 Hz, characteristic of healthy rat myocardium, disappears and the relationship becomes completely negative. L-type calcium channel blocker nifedipine does not affect the changes induced by toxins, while a high concentration (10 mM) of calcium prevents the effects of cardiotoxins on the muscle. The results obtained show that the impairment of the force-frequency relationship occurs long before the development of irreversible damage in the myocardium and may be the first sign of the pathological action of cardiotoxins.
- Published
- 2019
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27. Desiccation-induced alterations in surface topography of thylakoids from resurrection plant Haberlea rhodopensis studied by atomic force microscopy, electrokinetic and optical measurements.
- Author
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Doltchinkova V, Andreeva T, Georgieva K, Mihailova G, and Balashev K
- Subjects
- Craterostigma radiation effects, Droughts, Craterostigma metabolism, Desiccation, Light, Microscopy, Atomic Force methods, Thylakoids metabolism
- Abstract
With their ability to survive complete desiccation, resurrection plants are a suitable model system for studying the mechanisms of drought tolerance. In the present study, we investigated desiccation-induced alterations in surface topography of thylakoids isolated from well-hydrated, moderately dehydrated, severely desiccated and rehydrated Haberlea rhodopensis plants by means of atomic force microscopy (AFM), electrokinetic and optical measurements. According to our knowledge, so far, there were no reports on the characterization of surface topography and polydispersity of thylakoid membranes from resurrection plants using AFM and dynamic light scattering. To study the physicochemical properties of thylakoids from well-hydrated H. rhodopensis plants, we used spinach thylakoids for comparison as a classical model from higher plants. The thylakoids from well-hydrated H. rhodopensis had a grainy surface, significantly different from the well-structured spinach thylakoids with distinct grana and lamella, they had twice smaller cross-sectional area and were 1.5 times less voluminous than that of spinach. Significant differences in their physicochemical properties were observed. The dehydration and subsequent rehydration of plants affected the size, shape, morphology, roughness and therefore the structure of the studied thylakoids. Drought resulted in significant enhancement of negative charges on the outer surface of thylakoid membranes which correlated with the increased roughness of thylakoid surface. This enhancement in surface charge density could be due to the partial unstacking of thylakoids exposing more negatively charged groups from protein complexes on the membrane surface that prevent from possible aggregation upon drought stress., (© 2018 Scandinavian Plant Physiology Society.)
- Published
- 2019
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28. Aminated Graphene Oxide as a Potential New Therapy for Colorectal Cancer.
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Krasteva N, Keremidarska-Markova M, Hristova-Panusheva K, Andreeva T, Speranza G, Wang D, Draganova-Filipova M, Miloshev G, and Georgieva M
- Subjects
- Animals, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Shape, Cell Survival, Colorectal Neoplasms pathology, DNA Damage, Mice, Nanoparticles chemistry, Nanoparticles ultrastructure, Reactive Oxygen Species metabolism, Amines therapeutic use, Colorectal Neoplasms therapy, Graphite therapeutic use
- Abstract
Nanotechnology-based drug delivery systems for cancer therapy are the topic of interest for many researchers and scientists. Graphene oxide (GO) and its derivates are among the most extensively studied delivery systems of this type. The increased surface area, elevated loading capacity, and aptitude for surface functionalization together with the ability to induce reactive oxygen species make GO a promising tool for the development of novel anticancer therapies. Moreover, GO nanoparticles not only function as effective drug carriers but also have the potential to exert their own inhibitory effects on tumour cells. Recent results show that the functionalization of GO with different functional groups, namely, with amine groups, leads to increased reactivity of the nanoparticles. The last steers different hypotheses for the mechanisms through which this functionalization of GO could potentially lead to improved anticancer capacity. In this research, we have evaluated the potential of amine-functionalized graphene oxide nanoparticles (GO-NH
2 ) as new molecules for colorectal cancer therapy. For the purpose, we have assessed the impact of aminated graphene oxide (GO) sheets on the viability of colon cancer cells, their potential to generate ROS, and their potential to influence cellular proliferation and survival. In order to elucidate their mechanism of action on the cellular systems, we have probed their genotoxic and cytostatic properties and compared them to pristine GO. Our results revealed that both GO samples (pristine and aminated) were composed of few-layer sheets with different particle sizes, zeta potential, and surface characteristics. Furthermore, we have detected increased cyto- and genotoxicity of the aminated GO nanoparticles following 24-hour exposure on Colon 26 cells. The last leads us to conclude that exposure of cancer cells to GO, namely, aminated GO, can significantly contribute to cancer cell killing by enhancing the cytotoxicity effect exerted through the induction of ROS, subsequent DNA damage, and apoptosis.- Published
- 2019
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29. Impact of age and comorbidities on the efficacy of FC and FCR regimens in chronic lymphocytic leukemia.
- Author
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Strugov V, Stadnik E, Virts Y, Andreeva T, and Zaritskey A
- Subjects
- Adult, Aged, Comorbidity, Female, Humans, Male, Middle Aged, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell mortality
- Abstract
CLL is an aging-associated neoplasm with median age at diagnosis > 65 years. Little is known about safety and efficacy of FC/FCR regimens in elderly CLL patients with multiple comorbidities. We retrospectively revised medical records of 90 patients treated with FC/FCR regimens in our clinic. Data on demographic and biological characteristics, comorbidities, response to therapy, and treatment-associated adverse events were analyzed. Compared to FC, FCR yielded higher rates of OR (93.6 vs. 81.4%, p = .109) and CR (72.3 vs. 46.5%, p = .018). This translated in longer EFS (median 52 vs. 19 months, p = <.001) and OS (median 89 vs. 45 months, p = .001). Elderly patients (≥ 65 years) had more comorbidities and higher median CIRS-G score (7 vs. 4, p < .001). However, no association was found between CIRS-G score and survival. Decreased renal function was associated with dismal prognosis in patients treated with FCR.
- Published
- 2018
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30. Genetic Association between Alzheimer's Disease Risk Variant of the PICALM Gene and Auditory Event-Related Potentials in Aging.
- Author
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Ponomareva NV, Andreeva TV, Protasova MA, Filippova YV, Kolesnikova EP, Fokin VF, Illarioshkin SN, and Rogaev EI
- Subjects
- Adult, Aged, Alleles, Alzheimer Disease genetics, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Young Adult, Aging genetics, Alzheimer Disease pathology, Evoked Potentials physiology, Monomeric Clathrin Assembly Proteins genetics
- Abstract
Aging and genetic predisposition are major risk factors in age-related neurodegenerative disorders. The most common neurodegenerative disorder is Alzheimer's disease (AD). Genome-wide association studies (GWAS) have identified statistically significant association of the PICALM rs3851179 polymorphism with AD. The PICALM G allele increases the risk of AD, while the A allele has a protective effect. We examined the association of the PICALM rs3851179 polymorphism with parameters of the P3 component of auditory event-related potentials (ERPs) in 87 non-demented volunteers (age, 19-77 years) subdivided into two cohorts younger and older than 50 years of age. We found statistically significant association between the AD risk variant PICALM GG and increase in the P3 latency in subjects over 50 years old. The age-dependent increase in the P3 latency was more pronounced in the PICALM GG carriers than in the carriers of the PICALM AA and PICALM AG genotypes. The observed PICALM-associated changes in the neurophysiological processes indicate a decline in the information processing speed with aging due, probably, to neuronal dysfunction and subclinical neurodegeneration of the neuronal networks in the hippocampus and the frontal and parietal cortical areas. Such changes were less pronounced in the carriers of the PICALM gene A allele, which might explain the protective effect of this allele in the cognitive decline and AD development.
- Published
- 2018
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31. Immunogenetic Factors of Neurodegenerative Diseases: The Role of HLA Class II.
- Author
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Aliseychik MP, Andreeva TV, and Rogaev EI
- Subjects
- Adaptive Immunity, Alzheimer Disease genetics, Alzheimer Disease immunology, Alzheimer Disease pathology, HLA-DR alpha-Chains genetics, HLA-DRB1 Chains genetics, Histocompatibility Antigens Class II metabolism, Humans, Neurodegenerative Diseases genetics, Neurodegenerative Diseases immunology, Parkinson Disease genetics, Parkinson Disease immunology, Parkinson Disease pathology, Polymorphism, Single Nucleotide, Histocompatibility Antigens Class II genetics, Neurodegenerative Diseases pathology, Presenilins genetics
- Abstract
An increase in the life expectancy during the last decades in most world countries has resulted in the growing number of people suffering from neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and others. Familial forms of neurodegenerative diseases account for 5-10% of all cases and are caused by mutations in specific genes often resulting in pathological protein deposition. The risk factors for neurodegeneration include trauma, lifestyle, and allelic variants of disease-associated genes with incomplete penetrance. Many of these gene variants are located in immunity-related loci, particularly in the human leukocyte antigen locus (HLA class II) coding for proteins of the major histocompatibility complex class II (MHCII). HLA class II plays a key role in the antigen presentation and is expressed in microglial cells. Microglia is a component of innate immunity. On the one hand, microglial cells phagocytize pathological protein deposits; on the other hand, they produce proinflammatory factors accelerating neuronal death. The involvement of adaptive immunity mechanisms (antigen presentation, T cell response, antibody production) in the development of neurodegenerative diseases remains unclear and requires further research, including more detailed studies of the role of identified HLA class II genetic variants.
- Published
- 2018
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32. Peripubertal serum dioxin concentrations and subsequent sperm methylome profiles of young Russian adults.
- Author
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Pilsner JR, Shershebnev A, Medvedeva YA, Suvorov A, Wu H, Goltsov A, Loukianov E, Andreeva T, Gusev F, Manakhov A, Smigulina L, Logacheva M, Shtratnikova V, Kuznetsova I, Speranskiy-Podobed P, Burns JS, Williams PL, Korrick S, Lee MM, Rogaev E, Hauser R, and Sergeyev O
- Subjects
- Adolescent, Adult, Child, Environmental Monitoring, Humans, Male, Puberty, Russia, Whole Genome Sequencing, Young Adult, DNA Methylation, Endocrine Disruptors blood, Environmental Pollutants blood, Polychlorinated Dibenzodioxins blood, Spermatozoa metabolism
- Abstract
Background: The association of exposure to endocrine disrupting chemicals in the peripubertal period with subsequent sperm DNA methylation is unknown., Objective: We examined the association of peripubertal serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations with whole-genome bisulfite sequencing (WGBS) of sperm collected in young adulthood., Methods: The Russian Children's Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age and provided semen samples at 18-19 years of age. WGBS of sperm was conducted to identify differentially methylated regions (DMR) between highest (n = 4) and lowest (n = 4) peripubertal TCDD groups., Results: We found 52 DMRs that distinguished lowest and highest peripubertal serum TCDD concentrations. One of the top scoring networks, "Cellular Assembly and Organization, Cellular Function and Maintenance, Carbohydrate Metabolism", identified estrogen receptor alpha as its central regulator., Conclusion: Findings from our limited sample size suggest that peripubertal environmental exposures are associated with sperm DNA methylation in young adults., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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33. The First Recombinant Viper Three-Finger Toxins: Inhibition of Muscle and Neuronal Nicotinic Acetylcholine Receptors.
- Author
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Makarova YV, Kryukova EV, Shelukhina IV, Lebedev DS, Andreeva TV, Ryazantsev DY, Balandin SV, Ovchinnikova TV, Tsetlin VI, and Utkin YN
- Subjects
- Animals, Calcium Signaling, Cell Line, Tumor, Humans, Muscles cytology, Neurons cytology, Recombinant Proteins genetics, Toxins, Biological genetics, Muscles metabolism, Neurons metabolism, Receptors, Nicotinic metabolism, Recombinant Proteins metabolism, Toxins, Biological metabolism, Viperidae genetics
- Abstract
Genes encoding two three-finger toxins TFT-AF and TFT-VN, nucleotide sequences of which were earlier determined by cloning cDNA from venom glands of vipers Azemiops feae and Vipera nikolskii, respectively, were expressed for the first time in E. coli cells. The biological activity of these toxins was studied by electrophysiological techniques, calcium imaging, and radioligand analysis. It was shown for the first time that viper three-finger toxins are antagonists of nicotinic acetylcholine receptors of neuronal and muscle type.
- Published
- 2018
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34. Sexual Function, Mental Well-being and Quality of Life among Kurdish Circumcised Women in Iran.
- Author
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Daneshkhah F, Allahverdipour H, Jahangiri L, and Andreeva T
- Abstract
Background: Female genital mutilation is an intentional inhumane procedure that threatens girls and women's health. It is especially widespread in developing countries due to cultural, traditional and religious preferences. The aim of the current study was to investigate how circumcision affects women's sexual function., Methods: This cross-sectional study was conducted in the urban and rural area of Piranshahr County, Iran, in 2015 among convenience samples of 200 women, 15-49 yr old, who were applying to health care centers for receiving routine health care services. Data collection was conducted with the use of a self-administered written questionnaire to assess female sexual function, mental well-being, and quality of life., Results: Significant differences were found between circumcised and non-circumcised women in total score of female sexual function index (FSFI) in domains of desire, arousal, vaginal moisture, orgasm, satisfaction, and pain [( P <0.001), MD(95%CI)=5.64(3.64 to 7.64)] and based on Hotelling's T-square, significant differences were found in dimensions of quality of life and FSFI., Conclusion: The revealed sexual dysfunction among mutilated women gives ground to require that public health systems take actions aimed at implementing special sexual education program to improve sexual functions of mutilated women and changing beliefs and social norms in the community level., Competing Interests: Conflict of Interests The authors declare that there is no conflict of interest.
- Published
- 2017
35. Quantitative Analysis of L1-Retrotransposons in Alzheimer's Disease and Aging.
- Author
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Protasova MS, Gusev FE, Grigorenko AP, Kuznetsova IL, Rogaev EI, and Andreeva TV
- Subjects
- 5' Untranslated Regions, Aged, Alzheimer Disease metabolism, Case-Control Studies, Female, Frontal Lobe metabolism, Genome, Human, Humans, Male, Middle Aged, RNA, Ribosomal, 5S genetics, RNA, Ribosomal, 5S metabolism, Real-Time Polymerase Chain Reaction, Aging, Alzheimer Disease pathology, Long Interspersed Nucleotide Elements genetics
- Abstract
LINE1 retrotransposons are members of a class of mobile genetic elements capable of retrotransposition in the genome via a process of reverse transcription. LINE1 repeats, integrating into different chromosomal loci, affect the activity of genes and cause different genomic mutations. Somatic variability of the human genome is linked to the activity of some subfamilies of LINE1, in particular, a high level of LINE1 retrotranspositions has been observed in brain tissues. However, the contribution of LINE1 to genomic variability during normal aging and in age-related neurodegenerative diseases is poorly understood. We conducted quantitative real-time PCR analysis of active subfamilies of LINE1 repeats (aL1) using genomic DNA extracted from brain specimens of Alzheimer's disease (AD) patients and individuals without neuropsychiatric pathologies, as well as DNA extracted from blood specimens of individuals of different ages (healthy and AD subjects). Inter-individual quantitative variations of active families of aL1 repeats in the genome were observed. No significant age-dependent differences were identified. Likewise, no difference of aL1 copy number in brain and blood were indicated between AD patients and the aged-matched control group without dementia. These data imply that aging and the AD-associated neurodegenerative process are not the major factors contributing to the retrotransposition processes of active LINE1 repeats.
- Published
- 2017
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36. Biological Basis for Amyloidogenesis in Alzheimer's Disease.
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Andreeva TV, Lukiw WJ, and Rogaev EI
- Subjects
- Age Factors, Aging pathology, Alzheimer Disease epidemiology, Alzheimer Disease pathology, Animals, Humans, Risk Factors, Aging metabolism, Alzheimer Disease metabolism, Amyloid metabolism
- Abstract
Certain cellular proteins normally soluble in the living organism under certain conditions form aggregates with a specific cross-β sheet structure called amyloid. These intra- or extracellular insoluble aggregates (fibers or plaques) are hallmarks of many neurodegenerative pathologies including Alzheimer's disease (AD), Huntington's disease, Parkinson's disease, prion disease, and other progressive neurological diseases that develop in the aging human central nervous system. Amyloid diseases (amyloidoses) are widespread in the elderly human population, a rapidly expanding demographic in many global populations. Increasing age is the most significant risk factor for neurodegenerative diseases associated with amyloid plaques. To date, nearly three dozen different misfolded proteins targeting brain and other organs have been identified in amyloid diseases and AD, the most prevalent neurodegenerative amyloid disease affecting over 15 million people worldwide. Here we (i) highlight the latest data on mechanisms of amyloid formation and further discuss a hypothesis on the amyloid cascade as a primary mechanism of AD pathogenesis and (ii) review the evolutionary aspects of amyloidosis, which allow new insight on human-specific mechanisms of dementia development.
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- 2017
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37. Complete mitochondrial genome and evolutionary analysis of Turritopsis dohrnii, the "immortal" jellyfish with a reversible life-cycle.
- Author
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Lisenkova AA, Grigorenko AP, Tyazhelova TV, Andreeva TV, Gusev FE, Manakhov AD, Goltsov AY, Piraino S, Miglietta MP, and Rogaev EI
- Subjects
- Animals, Base Sequence, DNA, Mitochondrial genetics, Genes, Mitochondrial, Genetic Variation, Nucleotides genetics, Open Reading Frames genetics, Phylogeny, RNA, Ribosomal genetics, Biological Evolution, Genome, Mitochondrial, Life Cycle Stages genetics, Scyphozoa genetics, Scyphozoa growth & development
- Abstract
Turritopsis dohrnii (Cnidaria, Hydrozoa, Hydroidolina, Anthoathecata) is the only known metazoan that is capable of reversing its life cycle via morph rejuvenation from the adult medusa stage to the juvenile polyp stage. Here, we present a complete mitochondrial (mt) genome sequence of T. dohrnii, which harbors genes for 13 proteins, two transfer RNAs, and two ribosomal RNAs. The T. dohrnii mt genome is characterized by typical features of species in the Hydroidolina subclass, such as a high A+T content (71.5%), reversed transcriptional orientation for the large rRNA subunit gene, and paucity of CGN codons. An incomplete complementary duplicate of the cox1 gene was found at the 5' end of the T. dohrnii mt chromosome, as were variable repeat regions flanking the chromosome. We identified species-specific variations (nad5, nad6, cob, and cox1 genes) and putative selective constraints (atp8, nad1, nad2, and nad5 genes) in the mt genes of T. dohrnii, and predicted alterations in tertiary structures of respiratory chain proteins (NADH4, NADH5, and COX1 proteins) of T. dohrnii. Based on comparative analyses of available hydrozoan mt genomes, we also determined the taxonomic relationships of T. dohrnii, recovering Filifera IV as a paraphyletic taxon, and assessed intraspecific diversity of various Hydrozoa species., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
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38. Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A.
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Giangrande P, Andreeva T, Chowdary P, Ehrenforth S, Hanabusa H, Leebeek FW, Lentz SR, Nemes L, Poulsen LH, Santagostino E, You CW, Clausen WH, Jönsson PG, and Oldenburg J
- Subjects
- Adolescent, Adult, Aged, Child, Coagulants adverse effects, Coagulants pharmacokinetics, Drug Administration Schedule, Factor VIII adverse effects, Factor VIII pharmacokinetics, Hemophilia A blood, Hemophilia A diagnosis, Hemorrhage blood, Humans, Male, Middle Aged, Severity of Illness Index, Treatment Outcome, Young Adult, Coagulants administration & dosage, Factor VIII administration & dosage, Hemophilia A drug therapy, Hemorrhage prevention & control, Hemostasis drug effects
- Abstract
Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.
- Published
- 2017
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- View/download PDF
39. Recombinant B-domain-deleted porcine sequence factor VIII (r-pFVIII) for the treatment of bleeding in patients with congenital haemophilia A and inhibitors.
- Author
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Mahlangu JN, Andreeva TA, Macfarlane DE, Walsh C, and Key NS
- Subjects
- Adolescent, Adult, Animals, Factor VIII therapeutic use, Female, Humans, Male, Prospective Studies, Swine, Young Adult, Hemophilia A drug therapy, Hemorrhage drug therapy
- Abstract
Introduction: Development of inhibitors to human FVIII (hFVIII) significantly complicates the control of bleeding events in patients with haemophilia A., Aim: This prospective, multicentre, open-label, non-comparative, Phase II study evaluated the haemostatic activity of a recombinant B-domain-deleted porcine FVIII (r-pFVIII), in the treatment of non-life/non-limb-threatening bleeding in individuals with haemophilia A and FVIII inhibitors., Methods: Acute bleeding episodes in patients with pFVIII inhibitor titres <0.8 BU mL
-1 were treated with 50 U kg-1 body weight r-pFVIII. Those with pFVIII inhibitor titres of >0.8 BU mL-1 received an initial calculated r-pFVIII loading dose followed by 50 U kg-1 treatment dose. Treatment continued at 6-hourly intervals until bleeding was determined, controlled or till a maximum of eight doses was reached., Results: All 25 bleeding episodes in nine patients (mean age: 23.7 years; range: 14-34 years) were controlled successfully with eight or fewer injections of r-pFVIII. The median time from bleeding onset to the administration of r-pFVIII was 5.7 h (range: 1.5-20.0 h). Twenty of the bleeding episodes (80%) were controlled with one treatment dose of r-pFVIII (with or without a loading dose, median dose: 200.8 U kg-1 ; range: 50-576 U kg-1 ) regardless of pFVIII level. r-pFVIII was well tolerated and no treatment-emergent serious adverse events were considered by the investigator to be related to r-pFVIII administration., Conclusion: The results suggest that FVIII replacement therapy with r-pFVIII could be a viable alternative to bypassing agents for the treatment of bleeding episodes in individuals with haemophilia A and FVIII inhibitors., (© 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.)- Published
- 2017
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- View/download PDF
40. [Efficacy of a bendamustine and rituximab combination in first-line therapy for chronic lymphocytic leukemia: Results of the BEN-001 study].
- Author
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Stadnik EA, Strugov VV, Andreeva TO, Virts YV, Rumyantsev AM, Mirolyubova YV, Butylin PA, and Zaritsky AY
- Subjects
- Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Antineoplastic Combined Chemotherapy Protocols, Bendamustine Hydrochloride administration & dosage, Bendamustine Hydrochloride adverse effects, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Leukemia, Lymphocytic, Chronic, B-Cell psychology, Male, Middle Aged, Remission Induction methods, Rituximab administration & dosage, Rituximab adverse effects, Russia epidemiology, Treatment Outcome, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Neoplasm, Residual diagnosis, Neoplasm, Residual drug therapy, Neoplasm, Residual etiology, Quality of Life
- Abstract
Aim: To evaluate the efficacy and safety of the BR regimen containing bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not previously received specific therapy., Subjects and Methods: The results of the Russian prospective observational multicenter study BEN-001 (2012-2015) covering 196 CLL patients from 34 centers of the Russian Federation were analyzed. The diagnosis was confirmed by the results of peripheral blood lymphocyte immunophenotyping. A centralized approach was employed to make IGHV gene mutational status analysis, FISH examination, and minimal residual disease according to standardized methods. Quality-of-life (QOL) indicators were estimated using the EQ-5D and FACT-Leu questionnaires. Survival rates were calculated applying by the Kaplan-Meier method., Results: The patients' median age was 61 years. 41% of patients had a decline in estimated creatinine clearance less than 70 ml/min/1.73 m2. The combination of bendamustine and rituximab could achieve a common response in 83.2% of the patients, including complete remission in 59.7%. Eradication of minimal residual disease was achieved in 23 (27.4%) of 84 patients. Two-year progression-free survival rates were 85.9%. The QOL indicators were noted to be improved during the treatment., Conclusion: The investigation shows the good tolerability of bendamustine when it is used in clinical practice. Due to the high cost of new drugs (ibrutinib, obinutuzumab, ofatumumab, etc.) and toxicity of the FCR regimen, the combination including bendamustine can be the best first-line therapy option for all CLL patients, regardless of their age and comorbidity.
- Published
- 2017
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41. Overview of diagnostic performance and results for the first operation phase in Wendelstein 7-X (invited).
- Author
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Krychowiak M, Adnan A, Alonso A, Andreeva T, Baldzuhn J, Barbui T, Beurskens M, Biel W, Biedermann C, Blackwell BD, Bosch HS, Bozhenkov S, Brakel R, Bräuer T, Brotas de Carvalho B, Burhenn R, Buttenschön B, Cappa A, Cseh G, Czarnecka A, Dinklage A, Drews P, Dzikowicka A, Effenberg F, Endler M, Erckmann V, Estrada T, Ford O, Fornal T, Frerichs H, Fuchert G, Geiger J, Grulke O, Harris JH, Hartfuß HJ, Hartmann D, Hathiramani D, Hirsch M, Höfel U, Jabłoński S, Jakubowski MW, Kaczmarczyk J, Klinger T, Klose S, Knauer J, Kocsis G, König R, Kornejew P, Krämer-Flecken A, Krawczyk N, Kremeyer T, Książek I, Kubkowska M, Langenberg A, Laqua HP, Laux M, Lazerson S, Liang Y, Liu SC, Lorenz A, Marchuk AO, Marsen S, Moncada V, Naujoks D, Neilson H, Neubauer O, Neuner U, Niemann H, Oosterbeek JW, Otte M, Pablant N, Pasch E, Sunn Pedersen T, Pisano F, Rahbarnia K, Ryć L, Schmitz O, Schmuck S, Schneider W, Schröder T, Schuhmacher H, Schweer B, Standley B, Stange T, Stephey L, Svensson J, Szabolics T, Szepesi T, Thomsen H, Travere JM, Trimino Mora H, Tsuchiya H, Weir GM, Wenzel U, Werner A, Wiegel B, Windisch T, Wolf R, Wurden GA, Zhang D, Zimbal A, and Zoletnik S
- Abstract
Wendelstein 7-X, a superconducting optimized stellarator built in Greifswald/Germany, started its first plasmas with the last closed flux surface (LCFS) defined by 5 uncooled graphite limiters in December 2015. At the end of the 10 weeks long experimental campaign (OP1.1) more than 20 independent diagnostic systems were in operation, allowing detailed studies of many interesting plasma phenomena. For example, fast neutral gas manometers supported by video cameras (including one fast-frame camera with frame rates of tens of kHz) as well as visible cameras with different interference filters, with field of views covering all ten half-modules of the stellarator, discovered a MARFE-like radiation zone on the inboard side of machine module 4. This structure is presumably triggered by an inadvertent plasma-wall interaction in module 4 resulting in a high impurity influx that terminates some discharges by radiation cooling. The main plasma parameters achieved in OP1.1 exceeded predicted values in discharges of a length reaching 6 s. Although OP1.1 is characterized by short pulses, many of the diagnostics are already designed for quasi-steady state operation of 30 min discharges heated at 10 MW of ECRH. An overview of diagnostic performance for OP1.1 is given, including some highlights from the physics campaigns.
- Published
- 2016
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- View/download PDF
42. Clusters of alpha satellite on human chromosome 21 are dispersed far onto the short arm and lack ancient layers.
- Author
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Ziccardi W, Zhao C, Shepelev V, Uralsky L, Alexandrov I, Andreeva T, Rogaev E, Bun C, Miller E, Putonti C, and Doering J
- Subjects
- Base Sequence, Chromosomes, Artificial, Bacterial genetics, Humans, In Situ Hybridization, Fluorescence, Phylogeny, Repetitive Sequences, Nucleic Acid, Centromere genetics, Chromosome Mapping, Chromosomes, Human, Pair 21 genetics, DNA, Satellite genetics, Evolution, Molecular, Multigene Family genetics
- Abstract
Human alpha satellite (AS) sequence domains that currently function as centromeres are typically flanked by layers of evolutionarily older AS that presumably represent the remnants of earlier primate centromeres. Studies on several human chromosomes reveal that these older AS arrays are arranged in an age gradient, with the oldest arrays farthest from the functional centromere and arrays progressively closer to the centromere being progressively younger. The organization of AS on human chromosome 21 (HC21) has not been well-characterized. We have used newly available HC21 sequence data and an HC21p YAC map to determine the size, organization, and location of the AS arrays, and compared them to AS arrays found on other chromosomes. We find that the majority of the HC21 AS sequences are present on the p-arm of the chromosome and are organized into at least five distinct isolated clusters which are distributed over a larger distance from the functional centromere than that typically seen for AS on other chromosomes. Using both phylogenetic and L1 element age estimations, we found that all of the HC21 AS clusters outside the functional centromere are of a similar relatively recent evolutionary origin. HC21 contains none of the ancient AS layers associated with early primate evolution which is present on other chromosomes, possibly due to the fact that the p-arm of HC21 and the other acrocentric chromosomes underwent substantial reorganization about 20 million years ago.
- Published
- 2016
- Full Text
- View/download PDF
43. Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies.
- Author
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Andreeva TV, Tyazhelova TV, Rykalina VN, Gusev FE, Goltsov AY, Zolotareva OI, Aliseichik MP, Borodina TA, Grigorenko AP, Reshetov DA, Ginter EK, Amelina SS, Zinchenko RA, and Rogaev EI
- Subjects
- Anoctamins chemistry, Cementoma genetics, Child, Female, Genetic Association Studies, Humans, Male, Models, Molecular, Osteogenesis Imperfecta genetics, Pedigree, Russia, Anoctamins genetics, Jaw Neoplasms genetics, Muscular Dystrophies genetics, Mutation, Missense, Sequence Analysis, DNA methods, Exome Sequencing methods
- Abstract
Tumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G > A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260), and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene.
- Published
- 2016
- Full Text
- View/download PDF
44. Fast bistable intensive light scattering in helix-free ferroelectric liquid crystals.
- Author
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Andreev A, Andreeva T, Kompanets I, Zalyapin N, Xu H, Pivnenko M, and Chu D
- Abstract
A new type of ferroelectric liquid crystal (FLC) is considered, where the reorientation of the director (main optical axes) at the interaction of an electric field with the FLC's spontaneous polarization is due to the movement of spatially localized waves with a stationary profile: solitons arise at the transition due to the Maxwellian mechanism of energy dissipation. Under certain conditions, the appearance of such waves leads to the formation of a structure of transient domains, and as a consequence, to the scattering of light. The Maxwellian mechanism of energy dissipation allows one to reduce the electric field strength at which the maximum efficiency of light scattering is achieved down to 2-3 V/μm and to increase the frequency of light modulation up to 3-5 kHz. Intensive bistable light scattering in an electro-optical cell filled with a specially designed helix-free FLC was studied, and a stable scattering state can be switched on and off for a few tens of microseconds and memorized for a few tens of seconds.
- Published
- 2016
- Full Text
- View/download PDF
45. First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study.
- Author
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Kreuz W, Escuriola Ettingshausen C, Vdovin V, Zozulya N, Plyushch O, Svirin P, Andreeva T, Bubanská E, Campos M, Benedik-Dolničar M, Jiménez-Yuste V, Kitanovski L, Klukowska A, Momot A, Osmulskaya N, Prieto M, Šalek SZ, Velasco F, Pavlova A, Oldenburg J, Knaub S, Jansen M, Belyanskaya L, and Walter O
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Drug Combinations, Factor VIII adverse effects, Female, Hemophilia A complications, Hemorrhage complications, Humans, Infant, Male, Prognosis, Prospective Studies, Risk Factors, Safety, Young Adult, von Willebrand Factor adverse effects, Antibodies, Neutralizing immunology, Factor VIII immunology, Factor VIII therapeutic use, Hemophilia A drug therapy, Hemophilia A immunology, Immune Tolerance drug effects, von Willebrand Factor immunology, von Willebrand Factor therapeutic use
- Abstract
Introduction/background: Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment., Aim: The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors., Patients/methods: Forty-eight prospective patients in this interim analysis received a single plasma-derived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start (<5 BU) received 50-100 IU FVIII kg(-1) daily, or every other day; 'high responders' (≥5 BU) received 100 IU FVIII kg(-1) every 12 h., Results: Forty of 48 patients (83.3%), had at least one risk factor for poor ITI-prognosis at ITI start (i.e. age ≥7 years, >2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success. ITI outcome was significantly associated with inhibitor titre level at ITI start (P = 0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P = 0.0007). Twenty-two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success., Conclusion: Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success., (© 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.)
- Published
- 2016
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- View/download PDF
46. [THE STATE OF TRAFFIC TRAUMATISM ACCORDING DATA OF OFFICIAL MEDICAL STATISTICS].
- Author
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Kakorina EP, Andreeva TM, Polikarpov AV, and Ogryzko EV
- Subjects
- Humans, Russia epidemiology, Accidents, Traffic statistics & numerical data, Emergency Medical Services statistics & numerical data, Epidemiological Monitoring, Hospitals statistics & numerical data, Wounds and Injuries epidemiology, Wounds and Injuries etiology, Wounds and Injuries therapy
- Abstract
The article presents situation with traffic accident traumatism and medical care support of victims of traffic accidents at pre-hospital and hospital stages. The recommendations are proposed concerning insertion of additions into reporting forms of federal (sectoral) monitoring to guarantee fullness of information.
- Published
- 2015
47. [THE STATE AND PERSPECTIVES OF DEVELOPMENT OF TRAUMATOLOGICAL ORTHOPEDIC OUT-PATIENT CARE TO POPULATION OF THE PRIVOLJSKII FEDERAL OKRUG].
- Author
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Norkin IA, Baratov AW, Andreeva TM, Yushina BS, and Fedonnikov AS
- Subjects
- Humans, Russia, Workforce, Ambulatory Care, Orthopedics, Traumatology
- Abstract
The article presents the results of analysis ofmanpower support of specialized out-patient traumatological orthopedic care in the Privoljskii federal okrug. The manpower deficiency of traumatologist-orthopedist at the out-patient stage was established especially especially in rural area. This is cause of low indicators ofdispensary monitoring of patients with consequences of traumas and diseases of musculo-skeletal system and factual unavailability of rehabilitation care to patients of given profile. The experience oftraining and re-training of traumatologist-orthopedist is presented. The organization of hospital-substituting forms of medical service of profile patients in the Saratovskaia oblast. The directions of development of organization of specialized out-patient care to population of the region.
- Published
- 2015
48. Real-life evidence in evaluating effectiveness of treatment in Haemophilia A with a recombinant FVIII concentrate: a non-interventional study in emerging countries.
- Author
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Gouider E, Rauchensteiner S, Andreeva T, Al Zoebie A, Mehadzic S, Nefyodova L, Brunn M, Tueckmantel C, and Meddeb B
- Subjects
- Adolescent, Adult, Aged, Blood Coagulation Factor Inhibitors, Child, Child, Preschool, Factor VIII administration & dosage, Factor VIII adverse effects, Hemophilia A complications, Humans, Infant, Infections etiology, Isoantibodies, Joint Diseases etiology, Male, Middle Aged, Premedication, Sucrose administration & dosage, Sucrose adverse effects, Treatment Outcome, Young Adult, Factor VIII therapeutic use, Hemophilia A drug therapy, Sucrose therapeutic use
- Abstract
Some progress has been made regarding availability of recombinant factor VIII concentrates and prophylaxis for haemophilia A in emerging countries, where plasma-derived concentrates were used in the vast majority. Clinical studies to document their introduction and effectiveness are so far not widely available in literature. This non-interventional study evaluates the real-life effectiveness and safety of prophylactic and on-demand treatment with recombinant factor VIII formulated with sucrose (rFVIII-FS) for bleed control and preservation of joints in emerging countries from Eastern Europe, North Africa and Middle East area. One hundred and eighty-six patients from 11 countries were enrolled, mean ± SD age 12.8 ± 12.7 years. At enrolment, majority (79.6%) had severe haemophilia A (<2% IU mL(-1) ), 47.8% had a target joint, 15% had an inhibitor history and one patient was on immune tolerance induction. During the 24-month observation period, 58.1% of the patients were prescribed prophylaxis at every visit, 31.7% were on an on-demand regimen. Patients with severe haemophilia A on prophylaxis (n = 82) had a mean annual rate of treated bleeds of 2.8 ± 4.4, whereas it was 19.1 ± 32.0 for the on-demand group (n = 31), and a mean total Gilbert Score of 9.9 ± 10.3 at baseline and 4.1 ± 6.7 at study end; vs. 15.2 ± 17.3 and 13.7 ± 17.1 for on-demand respectively. The majority of the bleeds (91.1%) were treated with one or two infusions. Four patients without inhibitor history had a first positive inhibitor test during the study. This study demonstrates the effective use of rFVIII-FS in emerging countries and adds to the established safety profile of rFVIII-FS., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2015
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- View/download PDF
49. [Non-Hodgkin lymphoma (a case of simultaneous ocular and orbital involvement)].
- Author
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Saakyan SV, Amiryan AG, Andreeva TA, Sklyarova NV, Zhil'tsova MG, and Zakharova GP
- Subjects
- Combined Modality Therapy, Diagnosis, Differential, Eye Neoplasms therapy, Humans, Lymphoma, Non-Hodgkin therapy, Male, Middle Aged, Ophthalmoscopy, Orbital Neoplasms therapy, Tomography, X-Ray Computed, Ultrasonography, Doppler, Duplex, Eye Neoplasms diagnosis, Lymphoma, Non-Hodgkin diagnosis, Orbital Neoplasms diagnosis
- Abstract
The paper presents an integrated analysis of clinical, instrumental, and morphological data on a very rare pathological condition-- simultaneous ocular and orbital involvement in a lymphoproliferative disorder.
- Published
- 2015
- Full Text
- View/download PDF
50. Recombinant factor IX (BAX326) in previously treated paediatric patients with haemophilia B: a prospective clinical trial.
- Author
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Urasinski T, Stasyshyn O, Andreeva T, Rusen L, Perina FG, Oh MS, Chapman M, Pavlova BG, Valenta-Singer B, and Abbuehl BE
- Subjects
- Adolescent, Age Factors, Child, Child, Preschool, Female, Hemophilia B blood, Hemophilia B complications, Hemorrhage drug therapy, Hemorrhage etiology, Hemorrhage prevention & control, Humans, Infant, Male, Premedication, Retreatment, Time Factors, Treatment Outcome, Factor IX pharmacology, Factor IX therapeutic use, Hemophilia B drug therapy, Recombinant Proteins pharmacology, Recombinant Proteins therapeutic use
- Abstract
A newly developed recombinant factor IX (BAX326(1) ) was investigated for prophylactic use in paediatric patients aged <12 years with severe (FIX level <1%) or moderately severe (FIX level 1-2%) haemophilia B. The aim of this prospective clinical trial was to assess the safety, haemostatic efficacy and pharmacokinetic profile of BAX326 in previously treated paediatric patients. BAX326 was administered as prophylaxis twice a week for a period of 6 months, and on demand for treatment of bleeds. Safety was assessed by the occurrence of related AEs, thrombotic events and immunologic assessments. Efficacy was evaluated by annualized bleeding rate (ABR), and by treatment response rating (excellent, good, fair, none). PK was assessed over 72 h. None of the 23 treated paediatric subjects had treatment-related SAEs or AEs. There were no thrombotic events, inhibitory or specific binding antibodies against FIX, rFurin or CHO protein. Twenty-six bleeds (19 non-joint vs. 7 joint bleeds) occurred (mean ABR 2.7 ± 3.14, median 2.0), of which 23 were injury-related. Twenty subjects (87%) did not experience any bleeds of spontaneous aetiology. Haemostatic efficacy of BAX326 was excellent or good for >96% of bleeds (100% of minor, 88.9% of moderate and 100% of major bleeds); the majority (88.5%) resolved after 1-2 infusions. Longer T1/2 and lower IR were observed in younger children (<6 years) compared to those aged 6 to 12 years. BAX326 administered as prophylactic treatment as well as for controlling bleeds is efficacious and safe in paediatric patients aged <12 years with haemophilia B., (© 2014 John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
- View/download PDF
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