Prenatal Atrioventricular Septal Defect (AVSD) as a planned congenital heart disease with different outcome depending on the presence of the coexisting extracardiac abnormalities (ECA) and/or malformations (ECM)
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01.01.2018 |
Słodki M.
Soroka M.
Rizzo G.
Respondek-Liberska M.
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Journal of Maternal-Fetal and Neonatal Medicine |
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© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Introduction: Prenatal atrioventricular septal defect (AVSD) on frequent occasions coexists with other cardiac or extracardiac abnormalities or malformation which may change the prognosis and the management with the fetus and the newborn. The aim of the research was to assess the prognosis and the outcome of prenatally diagnosed AVSD based on the classification which also includes coexisting extracardiac abnormalities and malformations as well as its influence on the prenatal consultation. Methods: It was a retrospective analysis of 113 patients with prenatally diagnosed AVSD. The group was selected out of 871 patients with CHD. Out of 113 fetuses with AVSD we exclude those in whom AVSD was coexistent with other cardiac malformations (n = 41). Extracardiac abnormalities [ECA] were defined as problems which do not require surgical intervention after delivery, they were usually markers of a genetic syndrome. Extracardiac malformations [ECM] were defined as problems requiring surgical interventions after delivery or lethal malformations. All 72 fetuses with an isolated AVSD were classified to one of the three groups: (1) Simple AVSD–(sAVSD)–a fetus with isolated AVSD without coexisting ECA and ECM (n = 6), (2) sAVSD + ECA–a fetus with isolated AVSD, with coexisting ECA (n = 28), (3) sAVSD + ECM–a fetus with isolated AVSD, with coexisting ECM (n = 38). Results: The pregnancy from the groups sAVSD + ECM were, in fact, more often referred to the prenatal cardiology centers on account of the existing ECM (p=.03). There were no differences between the two subgroups in regard to: the mean age of the pregnancy, the mean age of the fetus at the time of diagnosis and during diagnostic testing at the referral center, the gender of the fetus. An increased nuchal translucency (NT) was most often found in fetuses from the group AVSD + ECA (n = 13/23), which was connected with more frequent occurrence of abnormal karyotype (p=.048). The trisomy 21 more frequently referred to pregnancy with sAVSD + ECA than those with sAVSD + ECM (p=.0006). In the group sAVSD + ECM there was the highest number of fetuses small for the gestational age detected −48.65% (p=.01). Most often premature deliveries were found in the group sAVSD + ECM (72.73%). The duration of gestation in the group sAVSD + ECM turned out to be much shorter than that in the group with the isolated sAVSD (p=.01) and sAVSD + ECA (p=.03). The lowest Apgar score was in the newborns from the group sAVSD + ECM (p=.002). Longer period of gestation was connected with the higher score on Apgar scale (R = 0.541; p=.001). The average delivery weight of the newborns was the lowest in the group sAVSD + ECM (p=.04). sAVSD + ECM was connected with the significantly higher death rate than the isolated sAVSD (p=.0047) or sAVSD + ECA (p<.00001). The fatality rate of the newborns/ fetuses from the pregnancies lasting less than 37 weeks turned out to be much higher than in the case of the remaining pregnancies (sAVSD p=.002). Conclusions: (1) The majority of fetuses with AVSD remained the patients of just obstetricians and prenatal cardiologists because of highly heterogeneous of the coexisting malformations and abnormalities and since they perish in the period of fetal or neonatal life usually they are not seen by the pediatricians or cardiac surgeons. (2) The classification of the AVSD in fetus to a particular group of the prognostic classification of the fetal heart defects helps to plan perinatal management and supplies information regarding the prognosis. (3) The highest mortality rate was in a group of AVSD + ECM, probably due to shorter time of pregnancy duration, fetuses grow restriction and low Apgar score in 1 minute of life.
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Synthesis and biological activity of 7(7,11)-hydroderivatives of oligomycin A
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01.01.2018 |
Omelchuk O.
Lysenkova L.
Belov N.
Korolev A.
Dezhenkova L.
Grammatikova N.
Bekker O.
Danilenko V.
Shchekotikhin A.
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Macroheterocycles |
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© ISUCT Publishing. Macrolide antibiotics represent a valuable class of broad-spectrum, high active natural compounds with polyketide structure. A well-known FOF1 ATP-synthase inhibitor,[1] namely oligomycin A (1), is a 26-membered α,β-unsaturatedpolyketide lactone with conjugated diene, fused to spiroketal moiety. Oligomycin A possesses strong antifungal, antiactinomycotic and cytotoxic activity, but lacks antibacterial activity. According to recent investigations, the development of anti-cancer drugs based on oligomycin A is quite perspective due to its high cytotoxic activity toward tumor cells, ability to inhibit a multidrug resistance protein p-gp and to prevent an activation of oncogenic K-Ras by inhibition of its localization at the plasma membrane.[2-4] However, high toxicity for mammalian cells and low water solubility are significant limitations of oligomycin A, making it unacceptable for clinical application. Chemical modification is a promising way to improve pharmacological properties of natural compounds. Recently we have found that site-selective modifications of oligomycin A afforded semi-synthetic derivatives with high antiproliferative activity against tumor cell lines[5-7] or selective antifungal activity against Candida spp.[8] and, at the same time, with lower toxicity toward mammalian cells. Also, semi-synthetic oligomycin A derivatives are useful tools for molecular genetic studies of additional targets for this family of antibiotics.[9,10] Previously Ramirez F. et al. have described the reaction of oligomycins with sodium borohydride resulting in mixture of diastereomeric 7-dihydro-and 7,11-tetrahydro derivatives without further separation and characterization of individual products.[11] Also, there is no data on biological activity of these reduced oligomycins against fungal/actinomycetes strains and tumor cell lines in article mentioned above. Thus, in this paper we report regio-and stereoselective methods for borohydride reduction of oligomycin A, structure determination of obtained derivatives and investigation of theirs antiproliferative, antifungal and antiactinomycotic properties. The feasibility of regio-and stereoselective reduction of C7-carbonyl group in a core structure of oligomycin A was proposed due to the presence of haptophilic hydroxyl groups[12] at C5 and C9 positions and sterical hindrance of C-11 carbonyl group. Actually, treatment of oligomycin A with bulky sodium triacetoxyborohydride in acetic acid according to the method[13] led to (7S)-dihydrooligomycin A (2) in a good yield. The second carbonyl group (C-11) reduced in more harsh conditions: only the extended treatment of (7S)-dihydrooligomycin A with sodium borohydride in ethanol give (7S,11R)-7,11-tetrahydrooligomycin A (3) as major product. Reaction proceeds with acceptable stere-oselectivity and gives tetrahydro derivative 3, but in low yield (35 %), which associated with low stability of oligomycins in basic conditions.[14] Structure of compounds 2 and 3 was confirmed by high resolution mass spectrometry (HRMS ESI) and NMR spectroscopy. Absolute configurations at C7 and C11 positions of obtained derivatives were unambiguously confirmed by observed interactions between neighboring protons in corresponding1H-1H ROESY spectra. Testing of antimicrobial properties of oligomycins 2 and 3 against Candida spp., filamentous fungi and S. fradiae (strain, extremely sensitive to oligomycins) that of the parent antibiotic in comparison with starting oligomycin A revealed that reduction of carbonyl groups led to decreasing of activity (except strain M. canis). Also, reduced derivatives 2, 3 were less potent against human colon carcinoma cell line HCT116 and its doxorubicin-resistant subline HCT116(-/-), while activity against leukemia cell line K562 and doxorubicin-resistant subline K562/4 retained at the same level as for 1. It might be pointed that biological properties of (7S)-dihydrooligomycin A and (7S,11R)-7,11-tetrahydrooligomycin A are quite similar, consequently C7-carbonyl group has a greater influence on biological activity of oligomycin A than C-11 carbonyl group.
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Dynamic of cerebrovascular disorders in patients with carotid stenosis
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01.01.2018 |
Pyshkina L.
Abieva A.
Yasamanova A.
Darvish N.
Kamchatnov P.
Kabanov A.
Tyazhelnikov A.
Silina E.
Shurygin S.
Osmaeva Z.
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Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova |
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AIM: To study the state of cerebral hemodynamics and platelet hemostasis in patients with carotid stenosis (CS). MATERIAL AND METHODS: The prospective study included 123 patients with atherosclerotic CS. The 1st group included 53 patients (mean age 52±12.5 yrs) who underwent carotid endarterectomy (CEA); the 2nd group - 70 patients who were treated conservatively (mean age 58.5±15.9 yrs). The state of blood flow through the main arteries of the head (Doppler flowmetry), platelet aggregation induced by adrenaline, the frequency of acute cardiovascular events that occurred during 12 months were evaluated. RESULTS AND CONCLUSION: The severity of neurological deficits and cognitive impairment increased with increasing of the degree of CS. CEA leads to an improvement of cerebral hemodynamics and stabilization of cognitive functions. The adverse course of the disease occurred in 23.6% of patients (stroke/heart attack during the year in 5.7%, progression of cerebral ischemia in 20%, restenosis within 5 years after CEA in 15%). Hyperaggregation of platelets induced by ADP and epinephrine and decreased aggregation of platelets induced by collagen in patients receiving ASA were identified in 53% of the operated and in 60% of non-operated patients. The use of combined antiplatelet therapy normalize the platelet hemostasis and reduce the frequency of acute cardiovascular events.
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Endometriosis, adenomyosis, chronic endometritis: Clinical and pathogenetic relationships and reproductive failures
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01.01.2018 |
Unanyan A.
Sidorova I.
Kogan E.
Belogubova S.
Demura T.
Elisavetskaya A.
Sizova N.
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Akusherstvo i Ginekologiya (Russian Federation) |
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© Bionika Media Ltd. The article highlights the clinical and pathogenetic relationships between endometriosis/adenomyosis and chronic endometritis (CE) within reproductive failures. It describes a cause-and-effect relationship between endometriosis/ adenomyosis and CE by the example of its clinical symptomatology and the pathogenic mechanisms involving an autoimmune process, aseptic inflammation, and altered endometrial receptivity. Endometriosis/adenomyosis and CE have a number of common pathogenetic mechanisms of development and clinical manifestations (infertility, miscarriages, and assisted reproductive program failures). This implies the necessity to qualitatively assess the endometrium in women with endometriosis and adenomyosis during pregravid preparation, as well as the search for new therapeutic ways to correct autoimmune disorders. The use of sodium desoxyribonucleate (derinat) showing the pharmacological properties of an activator of the cellular and humoral immune system and a stimulator of reparative and regenerative processes is a promising approach to drug therapy.
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Сross-analysis of big data in accreditation of health specialists
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01.01.2018 |
Chelyshkova M.
Semenova T.
Naydenova N.
Dorozhkin E.
Malygin A.
Akhunov V.
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Electronic Journal of General Medicine |
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2 |
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© 2018, Modestum Ltd.. All rights reserved. Objective: The relevance of this study is due to the mass accreditation of health professionals that is developing in Russia, which requires innovative measurement tools and opens new opportunities for a well-founded cross-analysis of specialists’ professional readiness quality. Purpose of the study: The purpose of this article is to present approved methodical approaches to the transformation of accreditation data into a format suitable for secondary analysis of medical schools graduates quality based on the requirements of Professional Standards. Method: The leading methods of secondary data analysis are: a) codification of indicators in the primary data accumulation array; b) statistical processing of study results (evaluation of the relationships between the arrays of primary data accumulation and instrumental data, the correlation of test scores obtained by accreditation results with the labor functions of Professional Standards); c) the creation of representative samples for data analysis. The implementation of methods is carried out in the mode of working with arrays of big data, which also uses the method of cross-analysis to identify additional factors that affect to specialists’ professional readiness quality. Results: As a results of the research, there were: 1) approaches to the codification of data in the array and their secondary analysis were developed; 2) three samples were constructed with an estimation of representativeness for different strata, including subjects, assignments and corresponding labor functions; 3) the matrix of primary data in the specialty “Pediatrics” was verified using the example of the results of students from 50 medical universities in Russia. Conclusion: Approbation of methods of secondary data analysis conducted on representative samples of the subjects showed the effectiveness of the developed approaches that should be used when analyzing large data sets in the procedures of certification or accreditation. The materials of the article can be useful for specialists in the field of assessing the quality of education or assessing the professional readiness of health professionals, managers, professors and pedagogical staff of medical schools, specialists of centers for independent assessment of qualifications.
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Clinical and radiological manifestations and anatomical and topographical rationale for a possible combined injury of the hip joint and proximal part of the sciatic nerve (clinical and experimental study)
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01.01.2018 |
Nikolenko V.
Chekhonatskiy A.
Osadchuk M.
Ilyasova E.
Osadchuk A.
Chekhonatskiy V.
Reshetnikov A.
Levchenko K.
Bahteeva N.
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Russian Electronic Journal of Radiology |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: To study peculiarities of clinico-radiological and anatomico-topographic relationship of sciatic nerve and acetabulum. Materials and Methods: Two stages experimental research was conducted in vitro on 20 human corpses, died due to various reasons. Clinico-radiological study was carried out in vivo on 41 patients with injuries of sciatic nerve and acetabulum. Results: Research data can confidently state that topographic proximity of sciatic nerve to acetabulum especially to its posterior-upper edge determines high risk of nerve lesion at acetabulum fractures due to influence of bone fragments, formed hematoma, forming scars. Conclusion: Acetabulum fractures are potentially dangerous for possibility of simultaneous injury of sciatic nerve; in this case a patient has to be subjected to special examination with the purpose of his sciatic nerve status evaluation.
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Main directions of reducing patient irradiation doses in computed tomography
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01.01.2018 |
Matkevich E.
Sinitsyn V.
Zelikman M.
Kruchinin S.
Ivanov I.
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Russian Electronic Journal of Radiology |
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2 |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: To analyze and organize the basic techniques to reduce radiation exposure to patients with computed tomography (CT) scan of the head, chest, abdomen and pelvis. Materials and methods: The analysis of publications was carried out on the databases Scopus, Web of Science, MedLine and RINC. Results: The variants of the use of CT of the head, chest, heart, abdominal and pelvic organs in multidisciplinary institutions with different methods of reducing the dose burden on patients have been analyzed. Conclusion: The factors used to reduce the dose for CT can be systematized in three main ways: 1) methods that depend on the attending physician, radiologist and CT staff; 2) parameters of the research protocol; 3) features of CT-devices and software. Considering the factors reducing the radiation dose of patients in support of the need for CT examination, choice of parameters of the CT protocol, CT devices and software allows to significantly reduce the radiation burden on patients (by 10-78%) without compromising the quality of CT images. The development of methods to reduce the dose of irradiation of patients is extremely urgent, especially in screening, multiple CT studies and CT with contrast.
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Orthostatic hypotension: Definition, pathophysiology, classification, prognostic aspects, diagnostics and treatment
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01.01.2018 |
Ostroumova O.
Cherniaeva M.
Petrova M.
Golovina O.
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Rational Pharmacotherapy in Cardiology |
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1 |
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© 2018 Stolichnaya Izdatelskaya Kompaniya. All rights reserved. The urgency of the problem of orthostatic hypotension (OH) has increased in recent years. It was due to the high prevalence and its adverse effect on the prognosis and quality of life of patients, especially the elderly and oldest old. The purpose of this review was to summarize the contemporary domestic and foreign literature data about disease. The article presents an updated definition of OH, modern classification, pathophysiology, feature of the course of OH in the elderly, recommendations for diagnosis and treatment. Particular attention is paid to reviewing the results of scientific research on the influence of OH on the risk of developing coronary and cerebrovascular events and overall mortality. OH is one of the forms of orthostatic tolerance and diagnostic criteria were determined by the 2011 Consensus as a sustained fall of systolic blood pressure by at least 20 mm Hg and/or a diastolic blood pressure by 10 mm Hg within 3 min of standing. The prevalence of OH ranges depending on the age of the patients and the presence of a number of concomitant diseases: from 6% in healthy people without arterial hypertension up to 50% or more in people older than 75 years with a comorbid pathology. OH is an independent predictor of overall mortality and adverse cardiovascular events. OH is associated with an increased risk of serious adverse cerebrovascular and coronary events, and may also contribute to cognitive impairment and the development of dementia. For today, we have three clinical options OH: classical, early and delayed OH. In addition, OH is classified based on etiology-primary and secondary; and pathophysiological principle-neurogenic OH and not a neurogenic OH (or functional). The algorithm for identifying patients with a high risk of development of OH and diagnostic methods are also presented. Non-medicamentous and medicamentous methods of OH treatment are considered.
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Focus on Internal Urethrotomy as Primary Treatment for Untreated Bulbar Urethral Strictures: Results from a Multivariable Analysis
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01.01.2018 |
Barbagli G.
Fossati N.
Montorsi F.
Balò S.
Rimondi C.
Larcher A.
Sansalone S.
Butnaru D.
Lazzeri M.
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European Urology Focus |
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© 2018 European Association of Urology Background: The use of internal urethrotomy for treatment of urethral stricture remains a controversial topic in urology. Objective: To investigate outcomes and predictors of failure for internal urethrotomy as primary treatment for untreated bulbar urethral strictures. Design, setting, and participants: We performed a retrospective analysis of patients who underwent internal urethrotomy. Patients with bulbar urethral stricture who did not receive any previous treatment were included. Patients with traumatic, penile or posterior urethral strictures, lichen sclerosus, failed hypospadias repair, or stricture length >4 cm were excluded. Outcome measurements and statistical analysis: The primary outcome was treatment failure. Kaplan-Meyer plots were used to depict treatment failure–free survival. Univariate and multivariable Cox regression analyses were used to test the association between predictors (age, body mass index, diabetes, history of smoking, etiology, stenosis type and length, preoperative maximum flow [pQmax]) and treatment failure. Results and limitations: Overall, 136 patients were included. The median stricture length was 2 cm. Median follow-up was 55 mo. At 5-yr follow-up the failure-free survival rate was 57%. On univariate analysis, diabetes, nonidiopathic etiology, stricture length of 3–4 cm, and pQmax were significantly associated with treatment failure. These predictors were included in a multivariable analysis, in which pQmax was the only significant predictor of treatment failure. Conclusions: Failure of internal urethrotomy for untreated bulbar urethral strictures greatly depends on pQmax flow at uroflowmetry. Patients with pQmax > 8 ml/s have a high probability of success, while patients with pQmax <5 ml/s have a low probability of success. Patient summary: The use of internal urethrotomy in patients with an untreated bulbar urethral stricture should only be considered in selected cases. The use of internal urethrotomy in patients with untreated bulbar urethral stricture should be suggested only in selected cases.
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Characteristics of Bacillus pumilus B-13176 strain producing metabolites with fungicide and antibacterial activities to Aspergillus niger and Staphylococcus aureus (MRSA)
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01.01.2018 |
Kuzin A.
Tagaev A.
Ovchinnikova T.
Kuznetsova N.
Nikolaenko M.
Morozova O.
Azizbekyan R.
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Biotekhnologiya |
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© 2018. A strain B-13176 that manifested the antibacterial and fungicidal activities has been isolated by screening of sporiferous bacteria and identified as Bacillus pumilus on the basis of the analysis of variable regions of 16S RNA sequences. Cultural and morphological characteristics of the strain were studied, the dynamics of the synthesis of fungicidal and antibacterial metabolites and their location in culture were determined, and their resistance to physicochemical factors was investigated. It was shown that the strain possesses a pronounced activity against the fungi of Aspergillus niger and the methycillinresistant bacteria of Staphylococcus aureus strain (MRSA). The culture liquid of the strain was fractioned using centrifugation, ultrafiltration, extraction and HPLC. Mass-spectrometry was used to show that the Bacillus pumilus B-13176 strain produces active thermostable protease-resistant metabolites of the peptide origin that are located in the CL pellet (the fungicidal component) and in the CL supernatant (the antibacterial component).
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60S dynamic state of bacterial ribosome is fixed by Yeast mitochondrial initiation factor 3
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01.01.2018 |
Levitskii S.
Derbikova K.
Baleva M.
Kuzmenko A.
Golovin A.
Chicherin I.
Krasheninnikov I.
Kamenski P.
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PeerJ |
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2 |
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Copyright © 2018 Levitskii et al. The processes of association and dissociation of ribosomal subunits are of great importance for the protein biosynthesis. The mechanistic details of these processes, however, are not well known. In bacteria, upon translation termination, the ribosome dissociates into subunits which is necessary for its further involvement into new initiation step. The dissociated state of the ribosome is maintained by initiation factor 3 (IF3) which binds to free small subunits and prevents their premature association with large subunits. In this work, we have exchanged IF3 in Escherichia coli cells by its ortholog from Saccharomyces cerevisiae mitochondria (Aim23p) and showed that Yeast protein cannot functionally substitute the bacterial one and is even slightly toxic for bacterial cells. Our in vitro experiments have demonstrated that Aim23p does not split E. coli ribosomes into subunits. Instead, it fixes a state of ribosomes characterized by sedimentation coefficient about 60S which is not a stable structure but rather reflects a shift of dynamic equilibrium between associated and dissociated states of the ribosome. Mitochondria-specific terminal extensions of Aim23p are necessary for “60S state” formation, and molecular modeling results point out that these extensions might stabilize the position of the protein on the bacterial ribosome.
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Inhibition of HIF-prolyl 4-hydroxylases as a promising approach to the therapy of cardiometabolic diseases
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01.01.2018 |
Aitbaev K.
Murkamilov I.
Fomin V.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group. All rights reserved. Prolyl-4-hydroxylases of hypoxia-inducible factor (HIF-P4Hs) are enzymes that, under the conditions of normoxia, cause degradation of the HIF-transcriptional protein, which regulates a number of metabolic processes, including erythropoiesis, glucose level and lipid metabolism. In hypoxic conditions, on the contrary, their activity is suppressed and HIF stabilization takes place. This mechanism, i.e. stabilization of HIF by inhibition of HIF-P4Hs was the basis for the development of drugs designed for treatment of renal anemia, which are currently in stages 2 and 3 of clinical trials and are showing encouraging results. Recently, it has also been reported that inhibition of HIF-P4Hs can be effective in treatment of cardiometabolic diseases - coronary heart disease, hypertension, obesity, metabolic syndrome, diabetic cardiomyopathy and atherosclerosis. The review, based on the most recent data, discusses in detail molecular mechanisms of therapeutic effect of HIF-P4Hs inhibition in these pathological conditions and provides evidence that these mechanisms are associated with HIF stabilization and gene expression, improving perfusion and endothelial function, reprogramming metabolism from oxidative phosphorylation to anaerobic glycolysis, reducing inflammation and having beneficial effect on the innate immune system.
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LC-MS/MS identification and structural characterization of main biodegradation products of nitroproston-A novel prostaglandin-based pharmaceutical compound
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01.01.2018 |
Mesonzhnik N.
Moskaleva N.
Shestakova K.
Kurynina K.
Baranov P.
Gretskaya N.
Serkov I.
Lyubimov I.
Bezuglov V.
Appolonova S.
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Drug Metabolism Letters |
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© 2018 Bentham Science Publishers. Background: Nitroproston is a novel prostaglandin-based compound modified by NO-donating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. Objective: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products. Methods: The principal biodegradation products of Nitroproston were identified in vitro using liquid chromatography/ion trap – time-of-flight mass-spectrometry. The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by liquid chromatography/triple –stage quadrupole mass spectrometry. Results: Nitroproston is rapidly hydrolyzed in rat plasma to generate glycerol-1,3-dinitrate and prostaglandin E2 . The latter can undergo conversion to cyclopentenone prostaglandins A2 and B2 . Thereby less than 5% of the parent compound was observed in rat plasma at the first moment of incubation. A similar pattern was observed for rabbit plasma where half-life (T1/2) of Nitroproston was about 2.0 minutes. Nitroproston biodegradation rate for human plasma was the slowest (T1/2 = 2.1 h) among tested species, occurred more rapidly in whole blood (T1/2 = 14.8 min). Conclusion: It was found that Nitroproston is rapidly hydrolyzed in rodent compared to human plasma incubations. Whereas Nitroproston is relatively stable in human plasma an enhanced hydrolytic activity was observed in whole human blood incubations. Extensive metabolism of Nitroproston in human whole blood was mainly associated with red blood cells. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies.
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Association of polymorphisms of HLA-DRB1 and TNF-308 G/A with radiographic joint damage in patients with early rheumatoid arthritis with high inflammatory activity, treated according to the principle of "Treat to target" (REMARKA study)
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01.01.2018 |
Guseva I.
Smirnov A.
Demidova N.
Krylov M.
Avdeeva A.
Samarkina E.
Luchikhina E.
Karateev D.
Abramov D.
Nasonov E.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group. All rights reserved. Objective. To clarify the association between HLA-DRB1 and TNFα (-308G>A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (<6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to "Treat to target" strategy. Materials and Methods. The study included 85 patients with early RA and duration of symptoms <6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G>A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of ∗04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1∗01, ∗04:01, ∗04:04, ∗04:05, ∗04:08, ∗10 alleles were categorized as SE+ (Shared Epitope) alleles. Results. As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (ρ<0,005, and ρ<0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (Δ) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1∗(SE) genotypes: The carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (ρ<0,028, ρ<0,019, ρ<0,035 respectively). Conclusion. Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G>A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to "Treat to target" stratagy.
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Application of flow systems in laboratory diagnostics for the integral evaluation of the hemostatic system
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01.01.2018 |
Ushakova O.
Nechipurenko D.
Butylin A.
Panteleev M.
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Pediatric Hematology/Oncology and Immunopathology |
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0 |
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© 2018, Dynasty Publishing House. The assessment of thrombosis and bleeding risks is one of the most important tasks of laboratory diagnostics of disorders in the hemostasis system. For this purpose the highly specialized tests are not always appropriate, because these assays are focused on specific markers or pathologies of individual links: the level of coagulation factors, the level of D-dimers, ADP- and serotonininduced platelet activation, effects of acetyl salicylic acid on aggregation. Nowadays, integral assays are the most promising approach, simulating hemostatic process in vivo - thromboelastography, thrombodynamics, thrombin generation. These tests are designed to specify the risk of thrombosis or bleeding with co-origin, as well as screening and monitoring of drug therapy. One of the approaches in the development of integral assays are flow systems where plasma or whole blood flow is formed over the hemostatic activator, and the growth of the thrombus is recorded on the video. There are commercially available samples of such devices, and some experience of its application in clinic. However, there are no uniform standards and clinical guidelines. This review describes examples of flow chambers exploitation for diagnosis, existing problems of its usage and the opportunities that it can provide to the clinicians.
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Results of testing paediatricians on problems of antimicrobial therapy of respiratory tract infections
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01.01.2018 |
Dronov I.
Meshcheryakov V.
Elkina T.
Shulyak I.
Fayzullina R.
Izotova L.
Kovtun O.
Rodina E.
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Voprosy Prakticheskoi Pediatrii |
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© 2018 Dynasty Publishing House. All rights reserved. The objective. To study the level of knowledge of paediatricians on problems of antimicrobial therapy of respiratory tract infection with determination and analysis of the most common mistakes. Materials and methods. In 2016-2017, knowledge of antimicrobial therapy of respiratory tract infections in children was tested among 238 paediatricians in five cities (Yekaterinburg, Kirov, Novosibirsk, Surgut, Ufa). Testing included twenty stem questions composed according to modern clinical guidelines. Five answer choices were offered to each question, of which one or several were correct. Assessment of the results took into account both chosen and unchosen answers (maximally possible score was 100). The result of 91-100 scores was assessed as «excellent », 81-90 - «good», 71-80 - «satisfactory», 70 and less - «unsatisfactory». Results. The average score was 70.5. In different cities the average score was as follows: in Yekaterinburg - 71.7, in Kirov - 73.8, in Novosibirsk - 74, in Surgut - 69.3, in Ufa - 63.5. Only one physician's answers were assessed as «excellent» (0.42%), answers of 40 physicians were «good» (16.81%), 88 answers - «satisfactory» (36.97%) and 109 answers - «unsatisfactory» (45.8%). Conclusion. The study has shown insufficient knowledge of paediatrician on problems of antimicrobial therapy of respiratory tract infections. These data may be used in preparing educational programmes for physicians.
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A concept of cryoapplicator based on sapphire shaped crystal enabling control of the ice ball formation using spatially resolved elastic backscattering of light
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01.01.2018 |
Dubyanskaya E.
Chernomyrdin N.
Dolganova I.
Kuznetsov A.
Mukhina E.
Safonova L.
Donodin A.
Shikunova I.
Zaytsev K.
Kurlov V.
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Proceedings of SPIE - The International Society for Optical Engineering |
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© 2018 SPIE. We have proposed a concept of monitoring ice ball formation in biological tissues during cryodestruction process via spatially-resolved detection of elastic light backscattering. For this purpose, we developed an experimental setup for study cryodestruction by using applicators based on sapphire shaped crystals with internal channels for optical irradiation of biotissues and detection of backscattered light. Due to the unique physical properties of sapphire, i.e. high thermal, mechanical, and chemical strength, high thermal conductivity and optical transparency, the sapphire cryoapplicators yield combination of the tissue cryodestruction with the optical control of tissue freezing. We have shown experimentally that using the proposed concept of applicator with several channels, it is possible to monitor changes of the ice ball during the cryodestruction process.
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Analgesic activity of a natural peptide capable of specific binding to purinergic (P2x3) receptors
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01.01.2018 |
Palikova Y.
Zharmukhamedova T.
Palikov V.
Khokhlova O.
Osipova G.
Andreev Y.
Logashina Y.
Kozlov S.
Yavorskii A.
Murashev A.
D'Yachenko I.
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Eksperimental'naya i Klinicheskaya Farmakologiya |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. Results of investigation of the analgesic activity of the natural recombinant peptide PT1, which specifically binds to P2X3 receptors, are presented. The test for hypersensitivity provoked by complete Freund's adjuvant (CFA) showed evidence of the analgesic activity of PT1 peptide in CD-I mice after single intravenous administration in a dose range of 0.01-1 mg/kg.
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Prospects for drugs based on the mitochondria-targeting antioxidant SkQ1 in treatment of wounds with impaired healing
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01.01.2018 |
Zinovkin R.
Popova E.
Pletjushkina O.
Ilyinskaya O.
Pisarev V.
Chernyak B.
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Obshchaya Reanimatologiya |
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© 2018, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved. Chronic wounds with impared wound healing that require prolong time for healing remain unsolved problem of modern medicine. Excessive oxidative stress plays an important role in the pathogenesis of chronic wounds caused by aging, diabetes and other pathologies. This review is aimed at the role of mitochondria in oxidative stress and to the future prospects for using the innovative mitochondria targeted antioxidants for treatment of impaired wounds. Recent studies in old mice and mice with type 2 diabetes showed that the mitochondrial antioxidant SkQ1 [10- (6'- plastoquinonyl) decyltriphenylphosphonium] stimulates healing of full-thickness dermal wounds. SkQ1 accelerates inflammatory stage of wound healing, maturation of granulation tissue, angiogenesis and epithelization of wounds. The anti-inflammatory effect of SkQ1 is possibly connected to decreased inflammatory activation of the vascular endothelium, which is typical for aging, diabetes and other pathologies. Local administration of SkQ1 also accelerates wound healing and provides strong anti-inflammatory effect in the model of acute aseptic inflammation. In addition, SkQ1 to stimulate apoptosis of neutrophils and suppresses their activation, as well as suppresses inflammatory activation of mast cells. In the wound model in vitro, SkQ1 accelerates movement of epithelial cells and fibroblasts into the «wound» and stimulates differentiation of human subcutaneous fibroblasts to myofibroblasts. Reviewed data suggest that SkQ1-based topical drugs have a great potential to treat wounds that exhibit impaired healing also in patients suffering from chronic critical illness.
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Social and philosophical understanding of national and civic identity in the context of interethnic and interreligious conflict risks
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01.01.2018 |
Ryabchenko O.
Prokopyev A.
Romanchenko L.
Korzhuev A.
Krokhina J.
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XLinguae |
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7 |
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© 2018, Slovenska Vzdelavacia Obstaravacia. All rights reserved. Inter-ethnic and inter-confessional peace is an essential factor for sustainable development, civil society, and preservation of statehood. The most significant challenges we face today, especially the last few years, are closely connected with an acute problem of avoiding ethnic and inter-confessional conflict risks, and erosion of national and civic identity as a result of globalization. Social philosophy approach to the understanding of national and civic identity is important because any identity is a social construct formed in social interaction, and the use of philosophical methods can provide the study involving all factors that influence this phenomenon: political, economic, social, psychological, and others. The purpose of this article is to study possible targets to prevent ethnic and confessional conflict risks and preserve the unique national and civic identity of each nation and each state. Methodological basis for the research comprises philosophical principles, including dialectic synthesis, the transformation of quantity into quality and vice versa, and dialectical contradictions; a philosophical principle of determinism; and a system activity approach. The leading theoretical method to study the problem is a content analysis of scientific papers relevant to the issue under consideration, and factors affecting and contributing to distortion of national and civic identities. The article discusses the definition of identity as the protean term self, self-identity of an individual, a particular group affiliation according to the person's nationality, religion, social status, profession, etc. The inadequate treatment and false interpretation of history, the absence of a national or patriotic idea that is able to unite the people, the insufficient role of the state, and enforcing unconventional views, norms and values have been considered as risks encouraging national and civic identity distortion. The risk of ethnic and religious conflicts occurs when there is a discrepancy between national and civic identities, or their distortion due to economic, political, social crises, or, as it sometimes happens, external influence.
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