A multi-scale model of the coronary circulation applied to investigate transmural myocardial flow
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01.10.2018 |
Ge X.
Yin Z.
Fan Y.
Vassilevski Y.
Liang F.
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International Journal for Numerical Methods in Biomedical Engineering |
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5 |
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© 2018 John Wiley & Sons, Ltd. Distribution of blood flow in myocardium is a key determinant of the localization and severity of myocardial ischemia under impaired coronary perfusion conditions. Previous studies have extensively demonstrated the transmural difference of ischemic vulnerability. However, it remains incompletely understood how transmural myocardial flow is regulated under in vivo conditions. In the present study, a computational model of the coronary circulation was developed to quantitatively evaluate the sensitivity of transmural flow distribution to various cardiovascular and hemodynamic factors. The model was further incorporated with the flow autoregulatory mechanism to simulate the regulation of myocardial flow in the presence of coronary artery stenosis. Numerical tests demonstrated that heart rate (HR), intramyocardial tissue pressure (Pim), and coronary perfusion pressure (Pper) were the major determinant factors for transmural flow distribution (evaluated by the subendocardial-to-subepicardial (endo/epi) flow ratio) and that the flow autoregulatory mechanism played an important compensatory role in preserving subendocardial perfusion against reduced Pper. Further analysis for HR variation-induced hemodynamic changes revealed that the rise in endo/epi flow ratio accompanying HR decrease was attributable not only to the prolongation of cardiac diastole relative to systole, but more predominantly to the fall in Pim. Moreover, it was found that Pim and Pper interfered with each other with respect to their influence on transmural flow distribution. These results demonstrate the interactive effects of various cardiovascular and hemodynamic factors on transmural myocardial flow, highlighting the importance of taking into account patient-specific conditions in the explanation of clinical observations.
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Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice
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01.10.2018 |
Cole L.
Kim J.
Amoscato A.
Tyurina Y.
Bayır H.
Karimi B.
Siddiqui T.
Kagan V.
Hatch G.
Kauppinen T.
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Biochimica et Biophysica Acta - Molecular Basis of Disease |
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3 |
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© 2018 Elsevier B.V. Cardiolipin (CL) is a key mitochondrial phospholipid essential for mitochondrial energy production. CL is remodeled from monolysocardiolipin (MLCL) by the enzyme tafazzin (TAZ). Loss-of-function mutations in the gene which encodes TAZ results in a rare X-linked disorder called Barth Syndrome (BTHS). The mutated TAZ is unable to maintain the physiological CL:MLCL ratio, thus reducing CL levels and affecting mitochondrial function. BTHS is best known as a cardiac disease, but has been acknowledged as a multi-syndrome disorder, including cognitive deficits. Since reduced CL levels has also been reported in numerous neurodegenerative disorders, we examined how TAZ-deficiency impacts cognitive abilities, brain mitochondrial respiration and the function of hippocampal neurons and glia in TAZ knockdown (TAZ kd) mice. We have identified for the first time the profile of changes that occur in brain phospholipid content and composition of TAZ kd mice. The brain of TAZ kd mice exhibited reduced TAZ protein expression, reduced total CL levels and a 19-fold accumulation of MLCL compared to wild-type littermate controls. TAZ kd brain exhibited a markedly distinct profile of CL and MLCL molecular species. In mitochondria, the activity of complex I was significantly elevated in the monomeric and supercomplex forms with TAZ-deficiency. This corresponded with elevated mitochondrial state I respiration and attenuated spare capacity. Furthermore, the production of reactive oxygen species was significantly elevated in TAZ kd brain mitochondria. While motor function remained normal in TAZ kd mice, they showed significant memory deficiency based on novel object recognition test. These results correlated with reduced synaptophysin protein levels and derangement of the neuronal CA1 layer in hippocampus. Finally, TAZ kd mice had elevated activation of brain immune cells, microglia compared to littermate controls. Collectively, our findings demonstrate that TAZ-mediated remodeling of CL contributes significantly to the expansive distribution of CL molecular species in the brain, plays a key role in mitochondria respiratory activity, maintains normal cognitive function, and identifies the hippocampus as a potential therapeutic target for BTHS.
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Comparison of short-term and medium-term swimming training on cardiodynamics and coronary flow in high salt-induced hypertensive and normotensive rats
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01.10.2018 |
Plecevic S.
Jakovljevic B.
Savic M.
Zivkovic V.
Nikolic T.
Jeremic J.
Milosavljevic I.
Srejovic I.
Tasic N.
Djuric D.
Jakovljevic V.
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Molecular and Cellular Biochemistry |
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0 |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The aim of present study was to evaluate the effects of 3- and 6-week swimming exercise on cardiodynamics and coronary flow in high salt-induced hypertensive and normotensive rats. 80 male Wistar albino rats (6 weeks old) were divided into 8 groups: hypertensive animals that swam for 3 weeks; hypertensive animals that swam for 6 weeks and their respective sedentary controls; normotensive animals that swam for 3 weeks; normotensive animals that swam for 6 weeks and their respective sedentary controls. Hypertensive animals were on high sodium (8% NaCl solution) diet for 4 weeks, and these animals did not drink tap water during the experimental protocol. After sacrificing, hearts were isolated and perfused according to Langendorff technique at gradually increased coronary perfusion pressure (40–120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of pressure development in LV, systolic, and diastolic left ventricular pressure, and heart rate. Coronary flow was measured flowmetrically. Findings of the present study may help in better understanding of short- to medium-term exercise-induced direct effects on cardiac function and perfusion. Generally viewed, swimming of both durations did not change myocardial function and perfusion in hypertensive and normotensive conditions.
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Large-scale production of stem cells utilizing microcarriers: A biomaterials engineering perspective from academic research to commercialized products
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01.10.2018 |
Tavassoli H.
Alhosseini S.
Tay A.
Chan P.
Weng Oh S.
Warkiani M.
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Biomaterials |
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9 |
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© 2018 Elsevier Ltd Human stem cells, including pluripotent, embryonic and mesenchymal, stem cells play pivotal roles in cell-based therapies. Over the past decades, various methods for expansion and differentiation of stem cells have been developed to satisfy the burgeoning clinical demands. One of the most widely endorsed technologies for producing large cell quantities is using microcarriers (MCs) in bioreactor culture systems. In this review, we focus on microcarriers properties that can manipulate the expansion and fate of stem cells. Here, we provide an overview of commercially available MCs and focus on novel stimulus responsive MCs controlled by temperature, pH and field changes. Different features of MCs including composition, surface coating, morphology, geometry/size, surface functionalization, charge and mechanical properties, and their cellular effects are also highlighted. We then conclude with current challenges and outlook on this promising technology.
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Introducing Anatomically Correct CT-Guided Laparoscopic Right Colectomy with D3 Anterior Posterior Extended Mesenterectomy: Initial Experience and Technical Pitfalls
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01.10.2018 |
Gaupset R.
Nesgaard J.
Kazaryan A.
Stimec B.
Edwin B.
Ignjatovic D.
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Journal of Laparoendoscopic and Advanced Surgical Techniques |
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1 |
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© 2018, Mary Ann Liebert, Inc. Background: Laparoscopic D3 anterior posterior extended mesenterectomy (D3APEM) in right colectomy has received increased attention. The aim of this study is to prove feasibility, systemize technical accomplishment, and provide short-term outcomes data. Methods: From July 2013 to February 2017, 18 patients with adenocarcinoma in the right colon underwent right colectomy with laparoscopic D3APEM, including lymph nodes anterior and posterior to the superior mesenteric vessels. A reconstructed three-dimensional anatomy map derived from the staging computed tomography was used as a road map at surgery. The procedure was systematized into seven operative steps: Step 1, trocar placement and inspection; Step 2, release of the transverse colon; Step 3, identification of the terminal mesenteric vessels; Step 4, release of the anterior flap; Step 5, division of the transverse mesocolon; Step 6, release of the posterior flap; and Step 7, anastomosis and specimen removal. Patient disposition and variations regarding vascular anatomy and ability to expose consequentially may necessitate a variation in the sequence of the steps. Results: A total of 7 (39%) cases were converted, 3 due to bleeding and 4 due to challenging dissection. Median operative time and blood loss were 276 minutes (168-439 minutes) and 200 mL (< 50-1300 mL), respectively. Postoperative complications occurred in 6 (33%), including 2 (11%) major complication requiring reoperation. Median hospital stay was 5 days (3-13 days). R0 resection was achieved in all cases. Median number of the lymph nodes harvested was 40 (25-86), including 11.5 (4-35) in the D3 volume. Six patients (33%) had positive nodes, 3 of them affecting the D3 zone, including 1 case of a skip metastasis. There was no mortality, and at present all the patients are alive. One patient developed distant lymph node metastases. Conclusion: Laparoscopic right colectomy with D3APEM is feasible, associated with acceptable morbidity and fast recovery; now in readiness for introduction in specialized colorectal institutions.
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Oncobox bioinformatical platform for selecting potentially effective combinations of target cancer drugs using high-throughput gene expression data
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01.10.2018 |
Sorokin M.
Kholodenko R.
Suntsova M.
Malakhova G.
Garazha A.
Kholodenko I.
Poddubskaya E.
Lantsov D.
Stilidi I.
Arhiri P.
Osipov A.
Buzdin A.
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Cancers |
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5 |
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© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Sequential courses of anticancer target therapy lead to selection of drug-resistant cells, which results in continuous decrease of clinical response. Here we present a new approach for predicting effective combinations of target drugs, which act in a synergistic manner. Synergistic combinations of drugs may prevent or postpone acquired resistance, thus increasing treatment efficiency. We cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and obtained cell lines demonstrating increased drug resistance. We investigated gene expression profiles of intact and resistant cells by microarrays and analyzed alterations in 378 cancer-related signaling pathways using the bioinformatical platform Oncobox. This revealed numerous pathways linked with development of drug resistant phenotypes. Our approach is based on targeting proteins involved in as many as possible signaling pathways upregulated in resistant cells. We tested 13 combinations of drugs and/or selective inhibitors predicted by Oncobox and 10 random combinations. Synergy scores for Oncobox predictions were significantly higher than for randomly selected drug combinations. Thus, the proposed approach significantly outperforms random selection of drugs and can be adopted to enhance discovery of new synergistic combinations of anticancer target drugs.
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Radioactive (<sup>90</sup>Y) upconversion nanoparticles conjugated with recombinant targeted toxin for synergistic nanotheranostics of cancer
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25.09.2018 |
Guryev E.
Volodina N.
Shilyagina N.
Gudkov S.
Balalaeva I.
Volovetskiy A.
Lyubeshkin A.
Sen A.
Ermilov S.
Vodeneev V.
Petrov R.
Zvyagin A.
Alferov Z.
Deyev S.
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Proceedings of the National Academy of Sciences of the United States of America |
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10 |
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© 2018 National Academy of Sciences. All rights reserved. We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 (90Y) fractionally substituting yttrium in UCNP, and a fragment of the exotoxin A derived from Pseudomonas aeruginosa genetically fused with a targeting designed ankyrin repeat protein (DARPin) specific to HER2 receptors. The resultant hybrid complex UCNP-R-T was tested using human breast adenocarcinoma cells SK-BR-3 overexpressing HER2 receptors and immunodeficient mice, bearing HER2-positive xenograft tumors. The photophysical properties of UCNPs enabled background-free imaging of the UCNP-R-T distribution in cells and animals. Specific binding and uptake of UCNP complexes in SK-BR-3 cells was observed, with separate 90Y- and PE40-induced cytotoxic effects characterized by IC50 140 μg/mL (UCNP-R) and 5.2 μg/mL (UCNP-T), respectively. When both therapeutic agents were combined into UCNP-R-T, the synergetic effect increased markedly, ∼2200-fold, resulting in IC50 = 0.0024 μg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo.
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Rational Surface Design of Upconversion Nanoparticles with Polyethylenimine Coating for Biomedical Applications: Better Safe than Brighter?
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10.09.2018 |
Guller A.
Nadort A.
Generalova A.
Khaydukov E.
Nechaev A.
Kornienko I.
Petersen E.
Liang L.
Shekhter A.
Qian Y.
Goldys E.
Zvyagin A.
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ACS Biomaterials Science and Engineering |
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2 |
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Copyright © 2018 American Chemical Society. Upconversion nanoparticles (UCNPs) coated with polyethylenimine (PEI) are popular background-free optical contrast probes and efficient drug and gene delivery agents attracting attention in science, industry, and medicine. Their unique optical properties are especially useful for subsurface nanotheranostics applications, in particular, in skin. However, high cytotoxicity of PEI limits safe use of UCNP@PEI, and this represents a major barrier for clinical translation of UCNP@PEI-based technologies. Our study aims to address this problem by exploring additional surface modifications to UCNP@PEI to create less toxic and functional nanotheranostic materials. We designed and synthesized six types of layered polymer coatings that envelop the original UCNP@PEI surface, five of which reduced the cytotoxicity to human skin keratinocytes under acute (24 h) and subacute (120 h) exposure. In parallel, we examined the photoluminescence spectra and lifetime of the surface-modified UCNP@PEI. To quantify their brightness, we developed original methodology to precisely measure the colloidal concentration to normalize the photoluminescence signal using a nondigesting mass spectrometry protocol. Our results, specified for the individual coatings, show that, despite decreasing the cytotoxicity, the external polymer coatings of UCNP@PEI quench the upconversion photoluminescence in biologically relevant aqueous environments. This trade-off between cytotoxicity and brightness for surface-coated UCNPs emphasizes the need for the combined assessment of the viability of normal cells exposed to the nanoparticles and the photophysical properties of postmodification UCNPs. We present an optimized methodology for rational surface design of UCNP@PEI in biologically relevant conditions, which is essential to facilitate the translation of such nanoparticles to the clinical applications.
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Synthesis, antibacterial and antitumor activity of methylpyridinium salts of pyridoxine functionalized 2-amino-6-sulfanylpyridine-3,5-dicarbonitriles
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02.09.2018 |
Grigor’ev A.
Shtyrlin N.
Gabbasova R.
Zeldi M.
Yu. Grishaev D.
Gnezdilov O.
Balakin K.
Nasakin O.
Shtyrlin Y.
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Synthetic Communications |
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3 |
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© 2018, © 2018 Taylor & Francis. A library of 29 2-amino-6-sulfanylpyridine-3,5-dicarbonitriles functionalized with a pyridoxine moiety was synthesized using a three-component one-pot reaction of aldehyde derivative of pyridoxine, malononitrile, and thiophenol. The obtained bipyridine structures were converted into methylpyridinium salts. Several compounds demonstrated expressed antibacterial activity with MICs (minimum inhibitory concentrations) in the range of 0.5–4 µg/mL against the three studied Gram-positive strains and 8–64 µg/mL against the Gram-negative E. coli strain, which was comparable or better than the activity of the reference antimicrobial agents. At the same time, all the synthesized compounds were inactive against the Gram-negative P. aeruginosa. Several compounds also demonstrated high cytotoxic activity against the studied tumor cells, but without selectivity for the normal HSF (human foreskin fibroblast) cells. Despite the preliminary character of the performed biological studies, the obtained results make the obtained structural chemotype a promising starting point for the design of physiologically active compounds.
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Changes in the dentoalveolar system in children with chronic kidney disease
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01.09.2018 |
Morozova N.
Mamedov A.
Morozova O.
Maslikova E.
Elovskaya A.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018; Pediatria Ltd. All rights reserved. Among the leading forms of socially significant pathology is chronic kidney disease (CKD), which has a variety of causes and often originates in early childhood. Risk factors and causes of CKD in children are associated with congenital anomalies in urinary tract (UT) development, accompanied by a persistent chronic infection, urodynamic disorder, remodeling of renal blood flow. Kidneys homeostatic functions disorder causes morphofunctional changes in various organs and tissues, incl. dentoalveolar system (DAS). The negative effect of CKD on the formation of maxillofacial region in children is studied. The data on disorders of jaw bones structures, temporomandibular joint (TMJ) and its function, oral cavity mucous membrane pathology, periodontal diseases, quantitative and qualitative changes in saliva, the defects of teeth hard tissues, pulp calcification caused by this pathology are systematized. The lack of a holistic view of DAS abnormalities development mechanisms in children with kidney damage makes it difficult for the dentist to conduct a timely diagnosis and combine work with doctors of other specialties, such as a pediatrician and a pediatric nephrologist. An integrated approach to managing children with CKD would allow to personify patient management tactics and improve treatment and rehabilitation results.
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Synchronous primary-multiple malignant tumor: Bifenotypic synonasal sarcoma and colorectal cancer
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01.09.2018 |
Reshetov Igor V.
Bykov Igor I.
Shevalgin Alexandr A.
Kurochkina Juliya S.
Nekrasova Tatiyana P.
Mikerova Maria S.
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Novosti Khirurgii |
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0 |
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© 2018 Vitebsk State Medical University. All rights reserved. Primary-multifocal malignant tumors hold a specific place in oncology. Present case report describes the combination of two neoplastic processes with different anatomic localization, the analogues to which have not been found either in the domestic literature or foreign sources. The article presents the case of a synchronous primary-multiple malignant neoplasm - malignant tumor from the membranes of the peripheral nerves of the nasal cavity with expansion into the right maxillary sinus, the cells of the ethmoidal sinus т2bN0M0 and moderately differentiated adenocarcinoma of the sigmoid colon т4аN0M0. Physical examination and positron emission tomography combined with the computed tomography confirmed a hypervascular tumor of the posterior cells of the ethmoidal sinus and a nasal cavity without hypermetabolism and the circular tumor of the sigmoid colon with hypermetabolism. Taking into account the primary-multiple character of the lesion and the clinic of intestinal obstruction, a tactic of the treatment was a combined surgery - the removal of the neoplasm of the nasal cavity with resection of the right maxillary sinus with microsurgical technique and a reconstructive-plastic component using a coronary access, laparotomy, resection of the sigmoid colon, lymphadenectomy. The chosen treatment allowed eliminating both of the tumors in a short time and moving on to a further stage of treatment. The patient is under the supervision, there is no recurrence of the disease at the moment.
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Urinary indicators of inflammation and fibrosis in children with congenital uropathies
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01.09.2018 |
Morozov D.
Morozova O.
Maltseva L.
Lakomova D.
Palatova T.
Morozov K.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018; Pediatria Ltd. All rights reserved. Congenital uropathies (CU) are anomalies associated with impaired patency of the upper and lower urinary tract and include congenital hydronephrosis, megaureter, primary vesicoureteral reflux (VUR), infravesical obstruction with prevalence in the pediatric population up to 1,4-2,8%. The most dangerous complication of CU is the development of kidney fibrosis in 30-60% of children combined with a persistent urinary system infection (USI). The lack of effective methods for early diagnosis and evaluation of renal parenchyma fibrosis treatment efficacy dictates the need for further search for molecular indicators of kidney injury. The article describes the study of inflammation biomarkers (interleukin 6 (IL6), inertleukin 8 (IL8), interleukin 10 (IL10)) and fibrosis (monocyte chemoattractant protein 1 (MCP1), transforming growth factor Β1 (TGFΒ1), vasculoendothelial growth factor (VEGF)) in urine in children with CU for diagnosis, monitoring and predicting the course of pathology. The study included 255 patients with various variants of CU (congenital hydronephrosis - 75, VUR - 169, infravesical obstruction - 11). The mean age of the patients was 4,3±3,2 years. The comparison group included 20 almost healthy children stratified by sex and age without USI. Biomarkers were determined by the method of enzyme immunoassay (ELISA) in the dynamics of pathology. All patients had an increase in urinary levels of proinflammatory cytokines (IL6, 8), even without clinical picture of USI. The increase in the concentration of MCP1 and TGFΒ1 in the urine is proportional to the degree and duration of VUR before its treatment, their content increased after 6 months after the correction of VUR and indicated the persistence of latent pyelonephritis and fibrosis progression. Molecular diagnosis of inflammation and fibrosis markers n the urine is a promising noninvasive method for assessing the pathological process in kidneys, the effectiveness and adequacy of the treatment.
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Complex method for calculating total serum calcium concentration
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01.09.2018 |
Eremenko N.
Shikh E.
Serebrova S.
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Drug Metabolism and Personalized Therapy |
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0 |
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© 2018 2018 Walter de Gruyter GmbH, Berlin/Boston. Calcium drugs are analogs of endogenous substances. The baseline concentration of endogenous substances in the body and homeostasis mechanisms of regulation make the bioavailability and bioequivalence (BE) evaluation of these drugs very difficult. The aim of the study was to assess the pharmacokinetic parameters of calcium in the studies of comparative bioavailability combined with the assessment of homeostatic regulation mechanisms. The study included 42 healthy male volunteers. We studied the composition of 1000 and 1200 mg of calcium, and 800 and 1000 IU of cholecalciferol. Blood sampling was carried out at 8 a.m. and 0.5, 1, 2, 3, 4, 6, 8 h after administering the drugs. Calcium pharmacokinetic parameters were measured: the area under the curve (AUC) "concentration-time", and maximum concentration (Cmax) in volunteers. The excretion of calcium in urine in terms of creatinine clearance and parathyroid hormone (PTH) levels was assessed. The maximum excretion of calcium was converted to creatinine (calcium/creatinine). Enzyme-linked immunosorbent assay (ELISA) was used to determine the PTH and the o-cresolphthalein method to quantitatively measure the total calcium serum and urine. Results indicated that both the AUC and the excretion of calcium are comparable, and the differences are not statistically significant, p>0.05 (the ratio of calcium and creatinine in the urine maintained within physiological levels). The comparable dynamics of PTH concentration is an indirect measure of the amount of absorbed calcium. The study demonstrates that, along with the standard way of calculating the area under the curve "concentration-time" (total calcium in serum), it is important to assess the calcium excretion in urine in terms of creatinine excretion, as well as focusing on the changes in the PTH levels in volunteers, which could be considered as a marker of the calcium level in the blood.
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Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice
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01.09.2018 |
Glezer M.
Vygodin V.
Nekrasova E.
Khlopina I.
Nubret K.
Agafonova Y.
Ternavsky S.
Bardukova O.
Kutyakova N.
Berestennikova Y.
Ustyugova V.
Filatova T.
Khalturina I.
Ishchenko K.
Karutskaja O.
Panikar V.
Bolkhovitina O.
Bondarev E.
Eremin I.
Kadashova S.
Frolova O.
Petukhova I.
Suvorov A.
Zhuchkova Y.
Kuhl M.
Rodionova L.
Musurok T.
Ivkova I.
Ermakov A.
Stukalova E.
Chumakov V.
Rubezhanskaja E.
Kotlova A.
Pushkareva A.
Dmitrieva L.
Bel’kina E.
Solov’eva O.
Panyulaytenene S.
Sarkisyan O.
Konovalova G.
Kuznetsova S.
Nikolaeva S.
Trubitsyna I.
Alekseeva O.
Kozmina M.
Babautseva N.
Kochetkova I.
Anokhin A.
Vovk E.
Buyko A.
Malahatka E.
Iskra M.
Shilonosov S.
Moiseenko G.
Tomm Y.
Stopyatuk N.
Grigorieva E.
Zaitseva A.
Zaitseva N.
Sirotkina I.
Kiyanichenko R.
Grigoriev S.
Medvedeva N.
Svatkov M.
Golubeva L.
Kozhevnikova L.
Chernova A.
Dolbilkin A.
Palvinskaya A.
Baranova T.
Habeeva T.
Khodus D.
Ermolaeva G.
Arbatskaja I.
Idiatullina V.
Egorova M.
Galimova I.
Kuklina M.
Mamatadzhiev A.
Rahmatullina R.
Kim Z.
Stepanova V.
Gerr I.
Levchenko G.
Dubinkina S.
Zoob R.
Krokhmal O.
Lisina S.
Kudryavtseva N.
Sitnikov D.
Lunegov D.
Evdokimova N.
Ivanova I.
Manilova A.
Bessergeneva O.
Mokhova E.
Kulchytska O.
Shulikina O.
Ananenko V.
Ivanova O.
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Advances in Therapy |
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0 |
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© 2018, The Author(s). Introduction: Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients’ satisfaction and adherence. Methods: ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting. Results: A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p < 0.001) decrease in angina attack frequency (from 4.7 ± 3.5 to 0.9 ± 1.3/week) and SAN use (from 4.5 ± 3.9 to 0.7 ± 1.3/week). Overall tolerability and effectiveness were rated as “very good” by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p < 0.0001) and non-adherence by 3% (vs. 36% at baseline, p < 0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p < 0.01), slight limitation (46% vs. 5% at baseline, p < 0.001) or moderate limitation (30% vs. 23%, p < 0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p < 0.001) or very marked reduction (1% vs. 19% at baseline, p < 0.01) at month 3. Conclusion: In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients. Trial Registration: ISRCTN registry Identifier, ISRCTN97780949. Funding: Servier. Plain Language Summary: Plain language summary available for this article.
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The ABCB1, CYP2C19, CYP3A5 and CYP4F2 genetic polymorphisms and platelet reactivity in the early phases of acute coronary syndromes
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01.09.2018 |
Mirzaev K.
Rytkin E.
Ryzhikova K.
Grishina E.
Sozaeva Z.
Fedorinov D.
Konova O.
Giliarov M.
Belyakova G.
Andreev D.
Sychev D.
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Drug Metabolism and Personalized Therapy |
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1 |
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© 2018 2018 Walter de Gruyter GmbH, Berlin/Boston. The aim was to study seven polymorphic markers of genes encoding proteins involved in the absorption, metabolism and pharmacokinetics of clopidogrel among patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Eighty-one ACS and PCI patients older than 18 years and treated with dual antiplatelet therapy were enrolled in the study. Platelet function testing and ABCB1, CYP2C19, CYP3A5 and CYP4F2 genotyping were performed. The predictive role of categorical variables, such as genotypes (carriers and non-carriers of polymorphism), on platelet reactivity (platelet reactivity units [PRU] platelet inhibition [PI]) was assessed by logistic regression (for categorical outcomes) and linear regression (for continuous outcomes) analysis. A p-value<0.05 was considered significant. The allele frequencies were estimated by gene counting, and Hardy-Weinberg equilibrium was tested using the chi-square test. Regarding clopidogrel response, 62 patients (76.5%) were clopidogrel responders and 19 were non-responders (23.5%). Mean PRU value and the percentage of platelet inhibition were 170.0±50.9 PRU and 28.6±19.9%, respectively. The effects of the CYP2C19∗2 polymorphisms on PRU (166.0±50.8 vs. 190.7±48.2, p<0.038) and PI (30.6±20.0 vs. 18.1±16.3, p<0.013) were observed, and the rates of high platelet reactivity (HPR) were lower in CYP2C19∗1/∗1 than those in CYP2C19∗1/∗2+CYP2C19∗2/∗2 (16.2% vs. 53.8% p<0.0067). In comparison, no significant difference in PRU value and PI was observed at <5 days between the rest of polymorphisms (p>0.05). Based on the logistic regression analysis, CYP2C19∗2 (OR: 4.365, CI: 1.25-17.67, p=0.022) was an independent predictor of HPR at <5 days, as was the stent diameter (OR: 0.219, CI: 0.002-0.229, p=0.049). The remaining polymorphisms had no influence. The reactivity of the on-clopidogrel platelet in the early phase of ACS is influenced primarily by the CYP2C19 polymorphisms. We believe that the findings of the present study could supply additional evidence regarding the clinical appropriateness of the CYP2C19 genetic testing for designing suitable antiplatelet therapy in the early phase of ACS.
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Analysis of literature sources on the problem of quality of life of children with urinary system chronic pathology
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01.09.2018 |
Kosyreva M.
Guseva N.
Korsunskiy A.
Zaykova N.
Orekhova S.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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© 2018; Pediatria Ltd. All rights reserved. Chronic pathology of the urinary system (US) among children is widespread. Continuously relapsing course of the disease significantly reduces the quality of life (QOL) of patients and their caregivers. Objective of the research - to analyze the necessity of QOL study of children with US chronic pathology. The article presents modern methods, approaches to the assessment of QOL of children of this group. It explains the need to study the evaluation of QOL in children in pediatric practice. QOL indicators of children with chronic diseases are presented as a criterion for assessing the effectiveness of their treatment and socialization. The revealed flaws of QOL of children of different medical and social groups testify to the need to include this indicator in their survey program to optimize medical care for these patients.
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Clinical diagnosis of lipocalin 2 detection associated with neutrophil gelatinase (UNGAL) in urine in children with pyelonephritis debut
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01.09.2018 |
Yeremeyeva A.
Dlin V.
Korsunskiy A.
Zaykova N.
Bondarenko E.
Turina I.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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© 2018; Pediatria Ltd. All rights reserved. Search for biomarkers, reflecting the severity of inflammation and damage to kidney tissue in children with pyelonephritis is very important. Objective of the research - to study clinical significance of lipocalin 2 associated with neutrophil gelatinase (uNGAL) in urine as a marker of renal parenchymal lesion severity in children with pyelonephritis debut. Study materials and methods: 73 children with pyelonephritis debut hospitalized in the nephrologic department were examined. Children were divided into 2 groups: 1st group - 41 children with acute pyelonephritis (without USO abnormalities), 2nd group - 32 children with acute pyelonephritis combined with various abnormalities of urinary system organs. In all patients, the levels of urea, creatinine, cystatin C, procalcitonin, renal concentration capacity, uric excretion of lipocalin 2 associated with neutrophil gelatinase (uNGAL) were assessed. Results: the study revealed that the level of uNGAL/Cr excretionat the admission in children of both main groups did not differ significantly. A positive correlation was found between uNGAL/Cr value and cystatin C level in patients of the 2nd group. All children had a direct correlation between the duration of febrile fever from the onset of antibiotic therapy and the uNGAL/Cr excretion level. The study also revealed a correlation between uNGAL/Cr excretion level in the acute period of the disease and the degree of renal parenchymal lesion in children from the first and second groups confirmed by static DMCA nephroscintigraphy. Conclusion: a high urinary excretion of uNGAL/Cr in patients with acute pyelonephritis indicates a marked renal parenchyma lesion and requires static nephroscintigraphy with further observation, but not earlier than 6 months after the normalization of clinical-laboratory indicators.
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Heart phantom with electrical properties of heart muscle tissue
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01.09.2018 |
Korn L.
Lyra S.
Rüschen D.
Pugovkin A.
Telyshev D.
Leonhardt S.
Walter M.
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Current Directions in Biomedical Engineering |
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© 2018 Leonie Korn et al. The weakened heart is supported by a left ventricular assist device (LVAD) to supply the heart muscle with oxygenated blood. In case the heart muscle recovers during LVAD therapy, the patient has to be weaned from the device. To date, there is no adequate method to detect heart muscle recovery in LVAD therapy. In order to establish a novel method based on the measurement of electric conductivity, this study presents a silicone model of a ventricle mock-up to simulate the electrical properties of cardiac muscle tissue. Previously, it has been shown that the electrical properties of myocardial tissue change during ischemia, so that these changes are a possible estimate for measuring the condition of myocardial tissue. To this purpose, this study presents a casting process for a ventricle model and describes the materials used to imitate the electrical properties of the heart muscle to obtain conductive material. Initial results showed that the higher the carbon concentration in the silicone, the higher the conductivity of the silicone samples. The measurements were performed at different frequencies and the samples were analyzed for homogenization.
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The earthworm species Eisenia fetida modulates greenhouse gas release and carbon stabilization after rice straw amendment to a paddy soil
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01.09.2018 |
Zaitsev A.
Gorbunova A.
Korobushkin D.
Degtyarev M.
Zhadova A.
Kostina N.
Gongalsky K.
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European Journal of Soil Biology |
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© 2018 Elsevier Masson SAS We performed a mesocosm experiment with rice paddy soils of three different soil types which were collected in the three major regions of rice production in Russia: Krasnodarsky Krai, the Republic of Kalmykia and Primorsky Krai. We used the earthworm species Eisenia fetida (Savigny 1826), introduced at different densities (0, 2, 4 and 6 individuals per mesocosm with an area of 69.4 cm2 and a soil column height of approximately 10 cm) to assess rice straw decomposition and carbon stabilization in the three soil types. After 20 days of the experiment, straw amendment consistently increased CO2 release from all three soil types. The effect was highest in the soil of Krasnodarsky Krai after a straw amendment was combined with 4 earthworms per mesocosm. The effect of earthworms on CH4 release remained soil type specific but did not demonstrate any synergy with the straw amendment. We also recorded the highest enrichment of soil with carbon from the rice straw when compared with the control mesocosms without straw amendment (the difference was 31.5 mg g−1 soil dwt) under the treatment with four earthworms, and this result was independent of soil type. We conclude that the practice of rice straw reincorporation with the amendment of a certain number of earthworms provides a potentially viable way to recycle crop residue.
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Patient-reported outcomes: A 5-year long study reveals previously unreported therapeutic, demographic, socio-economic, and other correlations in vitiligo
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01.09.2018 |
Valle Y.
Korobko I.
Sigova J.
Borodina M.
Lomonosov K.
França K.
Lotti T.
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Dermatologic Therapy |
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© 2018 Wiley Periodicals, Inc. Vitiligo is a non-lethal, non-communicable, immune-mediated, and generally progressive skin disease, with poorly understood etiopathogenesis and weak evidence base. The aim of the study is to contribute to the scant research on the patient-reported outcomes in vitiligo, and to examine the presence of associations between various inputs for possible use in clinical practice. The study was designed as a web-based questionnaire with 40 inputs across seven dimensions. The questions include demographics, skin type, eye and natural hair color, age of respondent and age of onset, possible triggers, disease extent, localization, progression and activity, the efficacy of most common treatment modalities, medication side-effects, heredity and diseases among parents, and out-of-pocket expenses for treatments to date. The analysis presented with this work contributes to the discussion about the relation between therapies, socio-economic factors, and treatment outcomes in vitiligo. All physicians should adequately manage patient expectations in terms of overall treatment duration and expected out-of-pocket expenses, and actively evaluate patients at shorter intervals. A more aggressive therapeutic approach using telehealth devices should be considered to supplement therapy, monitor treatment progress, and protocol compliance.
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