The role of innate immunity receptors (TLRs) in maintaining the homeostasis of the female genital tract in developing pregnancy and intrauterine infection
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01.01.2018 |
Karaulov A.
Afanasiev S.
Aleshkin V.
Bondarenko N.
Voropaeva E.
Afanasiev M.
Nesvizhsky Y.
Borisova O.
Aleshkin A.
Urban Y.
Borisova A.
Voropaev A.
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Russian Journal of Infection and Immunity |
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© Saint Petersburg Pasteur Institute. All rights reserved. The aim of the present systematic literature review is to summarize data on the role of TLRs in maintaining homeostasis of the female genitals, in maintaining the physiological development of pregnancy, provision of anti-infective resistance in pregnant women with intrauterine infection. The review substantiates the importance of TLRs of female genitals as a necessary and determining factor in the reaction to various changes in the environment, and also responsible for changes in metabolic, structural, or energy, in the maintenance of anti-infective resistance and homeostasis. As universal regulators of vital activity of organism TLRs in conjunction with other receptors of innate immunity provide maintaining the general reactivity and anti-infective resistance at the physiological level. In physiologically developing pregnancy in a background of immunosuppression in response to pregnancy TLRs during contact with infectious and non-infectious pathogens stimulate the production of nonspecific adaptive immunity factors (defensins, cathelicidins, histatines, etc.), which together with the non-specific innate factors lysozyme, complement, properdin, etc. support anti-infective resistance of the female genitals at a high level at the beginning of the infectious process. Possible violations of the development of pregnancy may be accompanied by changes in the response of TLRs to infectious and non-infectious factors until hyper-reaction, excessive inflammation or apoptosis, which requires adequate management of pregnancy. Was established the significance of the influence of pathogens of infectious and noninfectious origin in intrauterine infection indirectly through TLRs in the homeostasis of the organism, on the formation of breaches in anti-infective resistance at the organism and community level the identification of new pathophysiological and immunological pathogenetic mechanisms of development of pathological processes. IUI is a penetration of microorganisms into the tissues of fetus and it's infection. The inhibition of the functional activity of TLRs is accompanied by the direct effect of the pathogen on the tissues, and during hyper-reaction of TLRs to pathogens revealed a pronounced inflammatory response in the fetus. The level of expression of TLRs correlates directly with the severity of the process that can be considered as early markers of infection. Depending on the nature of the pathogen an increased expression of one or the other TLRs is observed. Explained the lack of symptoms, the possibility of atypical manifestations, the asymptomatic course of infection.
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Radiology of postoperative period in patients with orbital trauma
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01.01.2018 |
Pavlova O.
Serova N.
Davydov D.
Shilova M.
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Russian Electronic Journal of Radiology |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: To assess the possibilities of radiology diagnostics in patients with orbital trauma in postoperative period. Materials and methods: From 2015 to 2018 years in the clinic of Sechenov University 72 patients (100%) with traumatic injuries were examined. All patients (n = 72, 100%) were diagnosed with orbital trauma. After the admission all patients (n = 72, 100%) underwent multispiral computed tomography (MSCT) before and after the operation using Toshiba Aquilion One 640 modality, volume mode, slice thickness - 0.5 mm, bone and soft tissue reconstruction. Results: According to MSCT data in postoperative period with orbital volumes were reconstructed and symmetrical compared to the other side in 48 patients (64%). In 24 cases (33%) orbital volumes weren't reconstructed with remaining prolapse of orbital soft tissue structures in the maxillary sinus through the inferior orbital wall defect. Insufficient implantation of the inferior orbital wall prosthesis occurred in 7 patients (10%). Conclusion: MSCT is a method of choice in examining the patients with injuries of the midface. Computed tomography allows detailed determination of performed surgical treatment, to reveal the risk of postoperative complications and assess the dynamic of a patient in late periods.
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Possibilities of using contrast agents in postmortem computed tomography
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01.01.2018 |
Tumanova U.
Serova N.
Bichenko V.
Shchegolev A.
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Russian Electronic Journal of Radiology |
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1 |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. The literature data which demonstrate the possibilities of using computed tomography (CT) with contrast agents for the analysis of the deceased patients' bodies are presented. It is shown that postmortem CT angiography significantly expands the possibility of so-called noninvasive autopsy. The information on the features of the use of different types of con-trast agents as well as the main methods of postmortem CT angiography are presented. The use of targeted postmortem CT angiography allows to study the features of blood supply and to identify pathological changes in blood vessels of certain organs, in particular, coronary heart disease and cerebrovascular lesions. CT angiography of the whole body, especially multiphase postmortem CT angiography, allows to visualization of the cardiovascular system as a whole. The use of CT angiography is most effective for determining the source and volume of internal bleeding, the severity of thrombosis and the degree of stenosis of blood vessels, the type and prevalence of vascular malformations. We noted the complexity of the application and possible artifacts of postmortem CT angiography. It was concluded that postmortem CT angiography can be used to analyze of the bodies and clarify the tanatogenesis of deceased patients. We accented that postmortem CT angiography cannot fully replace the traditional autopsy despite its high specificity and sensitivity with regard to visualization of fatal bleeding.
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Disturbances of cardiovascular system in persons with chronic spinal cord injury during exercise and participation in paralympic sports
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01.01.2018 |
Krassioukov A.
Mashkovskiy E.
Achkasov E.
Kashchenko E.
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Vestnik Rossiiskoi Akademii Meditsinskikh Nauk |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. Spinal cord injury (SCI) is a devastating condition that affects mostly young and active individuals but also impacts their family members and results in significant challenges for medical care and social integration. In addition to obvious motor impairment (tetraplegia/paraplegia), these individuals also suffer from a variety of less obvious but devastating autonomic nervous system dysfunctions that negatively impact their health and affect various aspects of daily living. Physical training and sports are essential components of rehabilitation and leaser activities for people with disabilities. Number of individuals with SCI who run an active lifestyle is increasing. Physical activity puts an additional stress on various organs and body systems. The presented manuscript describes in detail cardiovascular dysfunctions in physically active individuals with a SCI, including those engaged in Paralympic sports: low resting blood pressure, orthostatic hypotension, arrhythmias, and the phenomenon of «autonomic dysreflexia». We also address issues related to self-induced episodes of autonomic dysreflexia in order to improve athletic performance ― a phenomenon known as «boosting». Boosting may improve sports performance in short term but is associated with the risk of serious cardiovascular disorders and even sudden death. This practice is considered as anti-doping rule violation by the International Paralympic Committee and thus prohibited. Understanding of the changes occurring in the body of a physically active individual after SCI is necessary for general practitioners, neurologists, rehabilitation specialists, sports medicine physicians, as well as for specialists of adapted physical education and sports.
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Predictors of hepatic insufficiency in obstructive jaundice
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01.01.2018 |
Vinnik Y.
Pakhomova R.
Kochetova L.
Voronova E.
Kozlov V.
Kirichenko A.
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Khirurgiia |
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AIM: To develop predictive model for hepatic insufficiency in obstructive jaundice.MATERIAL AND METHODS: Obstructive jaundice was modeled by the author's method on 48 mini pigs, while morpho-functional features of erythrocytes were studied by using of INTEGRA Aura atomic force microscope (NT-MDT, Zelenograd, Russia). Histological specimens were stained with hematoxylin and eosin. Discriminant analysis was used to create predictive model for hepatic insufficiency.RESULTS: Mathematical model of hepatic insufficiency prediction has been developed. Sensitivity and specificity of this model were 94.1% and 74.2% respectively. Total percentage of correct predictions was 81.3%.CONCLUSION: Severe obstructive jaundice contributes erythrocyte's transformation from biconcave to dome-shaped followed by changes of its physical properties. Erythrocyte's volume and activity of cytolysis enzymes are the most informative to predict hepatic insufficiency. Our model allows us to diagnose this complication at early stages and to correct pre-, intra- and postoperative therapy.
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The relationship and interaction of menstrual and generative function and depressive disorders in women
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01.01.2018 |
Tyuvina N.
Voronina E.
Balabanova V.
Goncharova E.
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Nevrologiya, Neiropsikhiatriya, Psikhosomatika |
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© 2018 Ima-Press Publishing House. All rights reservbed. Objective: to study of the individual aspects of the relationship and interaction of menstrual and generative function and depressive disorders in women. Patients and methods. 120 women aged 18-65 years with recurrent depressive disorder (RDD) who had experienced at least two depressive episodes (a study group) and 120 mentally healthy women of the same age (a control group) were clinically examined using a specially designed map with subsequent statistical processing of the findings. Results and discussion. In 71.7% of women, depression manifests itself during hormonal rearrangement periods (puberty, postpartum, and menopause). 65.0% of women with RDD have premenstrual syndrome (PMS), the pattern of which shows depressive symptoms. Depression affects menstrual function: the later onset and irregularity of menstruation, the earlier restoration of menstrual function after childbirth, and the earlier onset of premenopause, which has an adverse impact on generative function (a reduction in the number of pregnancies, births, and babies). Depression, the onset of which is observed during puberty, exerts the most malignant effect on menstrual and generative function. Overall, depressive patients are less socially and family-friendly than healthy women. Menstrual and generative function and adaptation minimally suffer in women with postmenopausal depression. Conclusion. The onset of depressive disorders is associated with the hormonal rearrangement periods. The presence of depressive symptoms in the pattern of PMS is a prognostic sign of future depression or indicates partial remission. At the same time, menstrual function is impaired in women suffering from RDD, which along with psychic manifestations of depression (a decrease in sexual drive and contacts, as well as anesthesia of feelings, etc.) leads to infertility.
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Polymixin in oncology clinical practice
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01.01.2018 |
Dmitrieva N.
Petukhova I.
Grigorievskaya Z.
Bagirova N.
Tereshchenko I.
Grigorievsky E.
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Siberian Journal of Oncology |
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© 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved. The purpose of the study was to present data on polymixin-based antibiotics with activity against infections caused by multidrug-resistant Gram-negative bacteria, such as Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Material and methods. The review includes data from clinical as well as in vitro studies for the period 1998–2017. The search for relevant sources was carried out in the Medline, Cochrane Library, Elibrary and other databases. Results. The analysis of the data showed the presence of synergism and additive activity of polymyxin in combination with carbapenems, rifampicin and azithromycin. However, experimental data showed no direct positive correlation between combination of polymyxim and azithromycin/ rifampicin. In clinical studies, in hospital-acquired pneumonia, including ventilator-associated pneumonia, the clinical response rate of polymyxin B combined with other antibiotics ranged from 38 % to 88 %. High nephro- and neurotoxicity of polymyxin observed in previous studies can be explained by a lack of understanding of its toxicodynamics or the use of an incorrect dose. Conclusion. Polymyxin B in combination with other antibiotics is a promising treatment against infectious complications caused by multidrug resistant Gram-negative bacteria.
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Method of quantitative assessment of the severity level of patients with obstructive jaundice
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01.01.2018 |
Scherbuk A.
Dydykin S.
Zhandarov K.
Manuylov V.
Averin A.
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Clinical and Experimental Surgery |
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© 2018 GEOTAR Media. All rights reserved. The purpose of the study is to develop an accessible method of dynamic control of patients with mechanical jaundice for a practical doctor. Data from 258 medical histories of patients with mechanical jaundice were studied. To solve this problem we used a method for calculating the severity level using a universal statistical program StatSoft Statistica for OS Windows. A mathematical relationship between a degree of possibility of a fatal outcome and the nine significant parameters was developed. As a result of the calculations, such factors as disease duration (days), blood bilirubin, body temperature, blood leucocytosis, pulse rate, patient age, blood creatinine, blood lymphocytes, respiratory rate appeared to be significant parameters in calculating the severity of mechanical jaundice of a particular patient. At the second stage, a multivariate regression analysis was performed, used to assess the degree of influence of various factors on the resulting indicator. A statistical dependence was found on the basis of which a formula combining 9 significant parameters was developed to determine the severity level of a patient based on the degree of influence of each of these factors on the resulting parameter: G = 0,002 (d×b) + 1,2 (t - 36,6) + 0,001 (p×v) + 0,322 (L/1000 - 5) + + 0,22 (16 - Lim) + 0,0085 (K - 60) + 0,165 (Di - 20). The formula took into account the stochastic dependence of the resulting parameter on the factors influencing it. When calculating a correlation analysis was conducted aimed at establishing a stochastic relationship between the parameters and estimating the tightness of the connection between the factors and the resulting index. This method of calculating the severity level can be applied by any surgeon and can accurately monitor the minimum changes in the patient's condition, as well as the effect of individual elements of treatment on the state of the disease.
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Effects of artificial tears on ocular surface in glaucomatous patients with long-term instillation of preserved antiglaucoma eye drops
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01.01.2018 |
Makashova N.
Vasilieva A.
Kolosova O.
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Vestnik Oftalmologii |
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© 2018 Media Sfera. All rights reserved. Purpose. To study the effects of long-term instillation of 0.18% sodium hyaluronate artificial tears VISMED multi on ocular surface in glaucomatous patients with long-term instillation of preserved anti-glaucoma drops. Material and methods. The study included 79 patients (40 female and 39 male; 79 eyes in total) with primary open-angle glaucoma (POAG) divided into 3 groups according to disease stage: mild or early (stage I) glaucoma - 15 patients (15 eyes), moderate (stage II) glaucoma - 30 patients (30 eyes), advanced or severe (stage III) glaucoma - 34 patients (34 eyes). Conjunctival and corneal changes were assessed with Norn's test, Schirmer I test and corneal fluorescein staining test. All patients completed Ocular Surface Disease Index (OSDI) questionnaire. Corneal compensated intraocular pressure (IOPcc) was measured using Ocular Response Analyzer (ORA) (Reichert Optics Inc., USA). In addition to hypotensive therapy, all patients received instillations of 0.18% sodium hyaluronate (VISMED multi) three times every day. After 14 days, all examinations were repeated. Results. The condition of eye surface in patients with moderate and advanced (stage II and III) glaucoma depends on the degree of IOPcc compensation. As glaucoma increases in severity, the pathological changes in the ocular surface progress. Instillations of 0.18% sodium hyaluronate solution lead to significant improvement of the test results in all groups, and in early glaucoma patients it restores all objective indicators to normal values. Conclusion. Treatment with 0.18% sodium hyaluronate solution (VISMED multi) leads to statistically significant (p<0.05) improvement of ocular surface condition in glaucoma patients with long-term instillation of preserved antiglaucoma eye drops.
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Trousseau’s syndrome: The forgotten past or actual present?
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01.01.2018 |
Vorobyev A.
Makatsaria A.
Brenner B.
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Akusherstvo i Ginekologiya (Russian Federation) |
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1 |
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© Bionika Media Ltd. Objective. To carry out a systematic analysis of the data available in the current literature on the modern view on Trousseau’s syndrome Material and methods. The review included the data of foreign and Russian articles published in the past 10 years and found in e-Library and PubMed on this topic. Results. This paper provides a pathogenetic explanation for the increased thrombotic potential in cancer patients, which underlies tumor growth and metastasis. In addition to direct thrombotic events, the paper also describes hemorrhagic complications resulting from systemic coagulopathy, including disseminated intravascular coagulation, hemolytic thrombotic microangiopathy, and excessive fibrinolysis. Conclusion. At present, any manifestation of thrombohemorrhagic complications in patients with malignant tumors can be classified as a paraneoplastic syndrome (Trousseau’s syndrome). In addition to Virchow’s classic triad, hyperproduction of tissue factor (TF), the main initiator of the extrinsic coagulation pathway, underlies the pathophysiology of Trousseau’s syndrome. At the same time, the substantial release of microparticles from TF-bearing tumor cells is critical not only for clot formation, but also for the progression of tumor growth.
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Effect of the Content Complexity on Hesitations in Adolescents' Narratives
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01.01.2018 |
Ovchinnikova I.
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Psychology of Language and Communication |
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© by Irina Ovchinnikova 2018. The paper presents analysis of the hesitations in adolescents' narratives. The speech disfluencies in the adolescents differ from those of the adults by frequency of self-corrections and pauses of hesitation. The adolescents rarely turn to repair their narratives but often interrupt the speech flow by pauses while telling a story stimulated by a wordless book. The lack of self-corrections reflects the specific problems with self-control and self-regulation due to immaturity of the executive function. Narrating about a complex multi-propositional event, the adolescents often experienced hesitation that provoked more self-repairs and hesitation pauses compared to the telling the story about a simple event. The description of the relatively simple content was more complicated syntactically than that of the multi-propositional event. Meanwhile, the content complexity significantly influences frequency of the silent hesitation pauses.
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Chemiluminescent activity and cytoarchitectonics of neutrophilic granulocytes in patients with mechanical jaundice
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01.01.2018 |
Vinnik Y.
Pakhomova R.
Kochetova L.
Kozlov V.
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Novosti Khirurgii |
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1 |
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© 2018 Vitebsk State Medical University. All rights reserved. Objective: To study the functional activity and cytoarchitectonics of neutrophilic granulocytes by the atomic force microscopy technique in the patients with mechanical jaundice of benign genesis of varying severity. Methods: The subject of the study were 92 patients aged from 47 to 69 years undergoing the in-patient treatment in the surgical departments of medical institutions in Krasnoyarsk with the diagnosis of mechanical jaundice of benign genesis. The control group consisted of 60 donors, comparable in sex and age with the main group. Depending on the severity of mechanical jaundice, luminol-dependent chemiluminescence of neutrophils was investigated and atomic-force microscopy of neurophilic granulocytes was performed to determine the shape, membrane state, geometric dimensions and adhesion forces of the blood neutrophils. Results: In patients with mechanical jaundice, the intensity of spontaneous chemiluminescence depends on the severity of mechanical jaundice. The kinetics of the chemiluminescent response of the peripheral blood neutrophils indicates an increase in the compensatory functional capacity of this cell population in case of mild degree of mechanical jaundice severity with their depletion in parallel with the increase in the severity of mechanical jaundice. Atomic force microscopy revealed violations of the structural organization of the neutrophil granulocyte. With increasing severity of mechanical jaundice, neutrophil became convex in shape, the number of segments of the nucleus increased, the cell membrane became irregular, the neutrophil volume reached 62.20 + 5.94 m3. The magnitude of the adhesion forces of neutrophils decreased by 25% in patients with class B severity of mechanical jaundice and by 31% with class C severity of mechanical jaundice. Conclusions: Based on the analysis of the chemiluminescent activity of neutrophilic granulocytes and their cytoarchitectonics, we concluded that the functional capabilities of neutrophilic granulocytes in mechanical jaundice are depleted in parallel with the increase in the severity of mechanical jaundice. Dysfunctions of neutrophils in mechanical jaundice are caused by the change in its cytoarchitectonics and by the decrease in adhesion forces.
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The microsurgical tissue autotransplantation in the treatment of late radiation tissue injuries with complicated osteomyelitis of the tibia
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01.01.2018 |
Zelyanin A.
Filippov V.
Dubrov V.
Meskhi K.
Kelban D.
Zelyanin D.
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Clinical and Experimental Surgery |
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© 2018 GEOTAR Media. All rights reserved. Aim. Study of the remote results free flaps usage in treatment of patients with the late radiation injuries complicated by tibial bone osteomyelitis. Material and methods. Our work is based on a retrospective study of treatment of eight patients with late radiation tissue injuries and chronic osteomyelitis of the tibia. In them we performed 9 operations using free, vascularized flaps. According to RTOG/EORTC Late Radiation Morbidity Scoring Scheme, skin lesions corresponded to grade IV, bone damage – grade II–III. In the zone of the late radiation injuries, the lesion of the cortical plate of the tibia was detected in 5 patients, a lesion that occurred more than a third of the tibial circumference – in 3 patients. 6 patients had cicatricial osteomyelitis form, and 2 had osteomyelitis with the inclusion of a chronic draining fistula. Late radiation ulcer was emerged in all patients after previous radiotherapy in a total dose of 40 to 60 Gy for different types of neoplasms. For 7 patients, the timing of the previous radiotherapy ranged from 5 to 19 years before the appearance of a late radiation tissue injury. Three patients received radiotherapy in childhood. In one patient, with posttraumatic osteomyelitis of the tibia, in remission, squamous cell carcinoma was diagnosed. Patients underwent radiation therapy in a total dose of 60 Gy. Later it was associated a radiation ulcer with open defects of the tibia. The objectives of surgical treatment included the preservation of the limb, adequate surgical debridement and the replacement of the tissues defect. The surgical technique included a radical resection of the affected areas of the bone tissue. To fill dead space, a musculo-fasciocutaneous thoracodorsal flap was used in all paients. In 2 out of 3 patients with localized form of osteomyelitis, the autograft complex, supplementary to the thoracodorsal component, included additionally a fragment of the anterior serratus muscle for tamponade of the osteomyelitis cavity. For one patient with localized osteomyelitis, a tamponade method of the post osteomyelitis bone defects included use of the distal part of the fragment of the latissimus muscle flap. 1 patient originally addressed concerning a late radiation ulcer on the back surface of a crus without involvement of bone structures. Two years after elimination of cicatricial and ulcer defect the torakodorsal skin and muscular flap, created a late radiation ulcer on the forward surface of a shin with defeat of a cortical plate of a tibial bone. Discussion. Fundamental difference of patients with local radiation injury from patients with traumatic osteomyelitis and investing tissue extensive defects is the feature of a course of wound process against the background of the progressing depression of a reparation both in the focus, and in surrounding tissues with lack of a clear boundary defeat. Morphological basis of local late radiation defeat are permanent damages of blood and lymphatic vessels with tissue fibrosis progressing. In the conditions of local reserve opportunities decrease, free revascularised flaps application, with one's own axial blood supply, allows to save an extremity, to receive the best immediate and long-term results of tissues defects elimination in the irradiated zone. It can be confirmed with the fact that directly under the replaced skin and muscular revascularised flap the covered functional structures purulent defeat stopped and patients achieved osteomyelitic process permanent remission. Results. In all observations the full flap engraftment has received. All patients have achieved osteomiyelitic process remission. Conclusions. The radical debridement of the affected zones, followed by the filling of the bone defect with muscle tissue and the defect elimination of the tissues by the skin portion of the vascularized musculocutaneous autograft is the method of choice in the treatment of patients with local post radiation injuries, complicated by osteomyelitis of the tibia.
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Study of the biological activity of liposomal sanguinarine on cultures of tumor cells and protozoa
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01.01.2018 |
Lutsenko S.
Cheremnykh E.
Sedyakina N.
Moldogazieva N.
Gromovykh T.
Feldman N.
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Vestnik Tomskogo Gosudarstvennogo Universiteta, Biologiya |
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© 2018 Tomsk State University. All Rights Reserved. Sanguinarine is a benzophenanthridine alkaloid with antimicrobial, antiviral, antiparasitic, anti-inflammatory, antiplatelet, antiangiogenic, and antitumor activity. One of the important properties of sanguinarine is a pronounced ability to suppress thrombogenesis, tumor growth and metastasis. However, the low solubility of sanguinarine in biological fluids limits its medical use. The present research was devoted to the development of the liposomal form of sanguinarine and the study of its biological activity. We obtained liposomes with sanguinarine on the basis of lecithin and cholesterol by the method of hydration of a thin film with buffer, followed by sonication and extrusion through a polycarbonate membrane with a pore size of 100 nm. Purification of liposomal dispersion from a drug that was not included in the vesicles was performed by gel filtration chromatography. We studied the morphology of the obtained liposomal particles by scanning electron microscopy; particle size and zeta potential were determined by dynamic light scattering. The study of the dynamics of sanguinarine release was conducted using the method of dialysis; quantitative analysis of the released sanguinarine from liposomes was performed using reverse-phase HPLC. The cytotoxic activity (CTA) of liposomal preparation against tumor cells of human breast carcinoma MCF-7 line was determined by the MTT assay. The toxicity and biological effects of liposomal sanguinarine on the cultures of Paramecium caudatum Ehrenberg and Tetrahymena pyriformis WH1, as well as the study of the effect of the drug on the complement system, were evaluated using the automated video registration system “BioLaT” (Russia). According to electron microscopy data, the obtained liposomes were spherical nanosized particles (See Fig. 1). The mean size of the obtained liposomal particles with sanguinarine included in their composition, determined using the method of the dynamic light scattering, was 108.5±2.2 nm, and the zeta potential was –34.7±1.4 mV. The effectiveness of sanguinarine inclusion in liposomes was quite high and amounted to 72.8±4.8%. The study of the dynamics of sanguinarine release from liposomes in conditions close to physiological (pH 7.4; 37°C) showed that this process occurs at the highest rate in the first 2 h of incubation. Then, the process is prolonged (release of about 50% sanguinarine after 6 h of incubation, and about 93% after 70 h) (See Fig. 2). Liposomal sanguinarine showed dose-dependent cytotoxic activity against tumor cells of human carcinoma MCF-7 in the micromolar concentration range (Seе Fig. 3). The CTA of liposomal sanguinarine (IC 50 14.5 mM) was slightly lower than the activity of free sanguinarine (IC 50 9.4 mM), which can be explained by the prolonged release of sanguinarine from liposomes into the cell medium, as well as by the specificity of compartmentalization and intracellular release of the drug when it is absorbed by tumor cells by endocytosis. The prolonged release and the property of preferential accumulation of liposomes in tumor tissue can have a positive effect on therapeutic efficacy in the application of liposomal sanguinarine in vivo. The effect of liposomal sanguinarine on the survival of P. caudatum ciliates was dose-dependent (See Fig. 4). The minimum inhibitory concentration of liposomal sanguinarine was 0.49 mM. At concentrations from 0.245 mM and below, the drug did not cause cell death for 2 h; over the next 24 h, the death of the ciliates was neither observed. Thus, liposomal sanguinarine has a pronounced cytotoxic effect on P. caudatum, a representative of the protozoa, which can serve as the basis for the development of antiprotozoal drugs. To identify pathogenic Protozoa species spectrum vulnerable to the action of liposomal sanguinarine, additional research is required. We also assessed the influence of liposomal sanguinarine on the protective blood systems - coagulation and the complement system. The effect of liposomal sanguinarine on thrombus formation in vitro was evaluated in citrate plasma after its recalcification according to the time of the onset of thrombus formation and the resulting clot density (See Fig. 5). The clot size in plasma solutions with the addition of the drug was significantly smaller compared with the control. At the same time, liposomal sanguinarine induces the formation of a clot after 7 min of incubation, whereas in the control the formation of a clot begins only after 14 min of incubation. Thus, under the conditions of this experiment, liposomal sanguinarine had a pronounced stimulating effect on thrombus formation. Stimulation of thrombosis by liposomal sanguinarine can be caused both by direct activation of coagulation enzymes and by the induction of enzymatic reactions of the coagulation system, which can efficiently proceed on the surface of liposomal nanoparticles. The study of the effect of liposomal sanguinarine in a non-toxic concentration of 60 ng/ml on the functional activity of the complement system against T. pyriformis ciliates showed that the half-life of the ciliates as a target of the complement system in the medium containing serum and liposomal sanguinarine (T 50 21.7 min) reduced approximately twice compared with the control (T 50 41.6 min) (See Fig. 6). In the absence of serum in the samples, liposomal sanguinarine at a concentration of 60 ng/ml, on the contrary, had a stimulating effect on T. pyriformis growth - the value of the proliferation coefficient for native cells was 2.1±0.2, and for the treated cells it was 6.4±0.8. The obtained data may indicate the activating effect of liposomal sanguinarine with respect to the assembly of the membrane attack complex of the complement system on the surface of T. pyriformis cells, causing their death. This effect allows to envisage the prospect of using liposomal sanguinarine as an immunostimulating agent. Thus, the pronounced cytotoxic antitumor and antiprotozoal activity, demonstrated in experiments in vitro, makes it possible to consider liposomal sanguinarine as a promising antitumor and antiprotozoal agent. The detected effect of thrombosis stimulation by liposomal sanguinarine seems to be important when selecting the dose of the drug introduced into the bloodstream.
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Immunological effects of a rituximab biosimilar (acelbia, biocad) in patients with rheumatoid arthritis
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01.01.2018 |
Avdeeva A.
Cherkasova M.
Kusevich D.
Rybakova V.
Nasonov E.
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Nauchno-Prakticheskaya Revmatologiya |
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© 2018 Ima-Press Publishing House.All right reserved. Objective: to study changes of acute-phase reactants (erythrocyte sedimentation rate – ESR, C-reactive protein – CRP), autoantibodies (IgM/IgA rheumatoid factors – RF, anti-citrullinated protein antibodies), immunoglobulin classes G, M, and A, and CD19+ B-lymphocytes in patients with rheumatoid arthritis (RA) 12 and 24 weeks after initiation of therapy with a rituximab (RTM) biosimilar at a total dose of 1200 mg. Subjects and methods. Examinations were made in 20 patients with a reliable diagnosis of RA (including 18 women; median age, 61.5 [54; 66.5] years; disease duration, 39.5 [20; 84] years; DAS28, 5.6 [4.9; 6.8]). All the patients received two intravenous infusions of RTM (Acellbia®) 600 mg at a 2-week interval during therapy with methotrexate, nonsteroidal anti-inflammatory drugs, and glucocorticoids. Clinical and laboratory parameters were analyzed immediately before therapy and then 12 and 24 weeks after the first infusion of the drug. Results and discussion. DAS28, ESR, and CRP level in respondents significantly decreased 12 and 24 weeks after RTM administration. The serum IgM RF concentration in the respondents was found to be significantly reduced at weeks 12 and 24 and amounted to 79.7 and 87.1% of baseline, respectively. The IgA RF level significantly decreased by 72 and 85% of baseline at weeks 12 and 24 of RTM therapy, respectively, in patients with a good response, and by 59.7 and 67.5% at weeks 12 and 24 in patients with a satisfactory response. The serum concentration of anti-cyclic citrullinated peptide antibodies in the respondents remained high throughout the follow-up. All the patients achieved CD19+ B-cell depletion at week 12 of therapy (absolute levels, 0); there was an increase in the level of CD19+ B-lymphocytes at week 24 (0.0030 [0.0003; 0.0270] 109/l). In both in the good and satisfactory response groups, the mean immunoglobulin levels remained within normal limits. Conclusion. The analysis of the efficiency of two infusions of the RTM biosimilar at a total dose of 1200 mg following 24 weeks of therapy initiation suggests that the drug is able to cause reductions in disease activity, laboratory signs of inflammatory activity, autoantibody concentrations, and complete B-lymphocyte depletion.
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Prospects for anti-B-cell therapy in rheumatology
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01.01.2018 |
Nasonov E.
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Nauchno-Prakticheskaya Revmatologiya |
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© 2018 Ima-Press Publishing House.All right reserved. Impaired B-cell immunological tolerance plays a central role in the pathogenesis of autoimmune rheumatic diseases and autoimmune diseases of another nature. B-cells link innate and acquired immunity: they express Toll-like receptors that respond to danger signals; act as antigen-presenting cells; induce an antigen-specific immune response; determine the development of immunological memory; and synthesize a wide range of cytokines that regulate (stimulate or suppress) an immune response and inflammation. In autoimmune diseases, there are metabolic and B-cellular signaling disturbances that lead to defects in B-regulatory, T-regulatory, follicular T-helper, and dendritic cells. B-cells synthesize organ-nonspecific and organ-specific autoantibodies that are biomarkers for autoimmune diseases and play an important role in their immunopathogenesis. Anti-B-cell therapy that causes B-cell depletion in blood and target organs is effective in a wide range of autoimmune diseases. Its efficiency is determined by various mechanisms, such as suppression of pathogenic autoantibody synthesis; modulation of the function of B-cells (antigen presentation, cytokine synthesis, and costimulation), T-lymphocytes and dendritic cells. Further study of a strategy for targeted anti-B-cell therapy, mechanisms of action, and new targets is important for the progress of modern rheumatology to improve the treatment strategy of autoimmune rheumatic diseases.
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Features of diagnostics and "whole body" multispiral computed tomography in patients with severe combined trauma
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01.01.2018 |
Dushin D.
Ternovoy S.
Burenchev D.
Karaseva E.
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Russian Electronic Journal of Radiology |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: This scientific review of the literature presents the most relevant discussions in the world community, aimed at improving the implementation of the diagnostic algorithm in patients with severe combined trauma. Materials and methods: The work deals with the main traumatic injuries of various anatomical zones, the criteria of the Advanced Trauma Life Support (ATLS) protocol and diagnostic methods aimed at detecting acute traumatic pathology. Conclusion: The authors consider unsolved issues, as well as the improvement of the multislice computed tomography (MSCT) algorithm in the "whole body" mode, to optimize diagnostic activities aimed at managing patients with severe combined trauma.
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Autoimmune/inflammatory syndrome induced by adjuvants
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01.01.2018 |
Radenska-Lopovok S.
Volkova P.
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Arkhiv Patologii |
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© 2018, Media Sphera Publishing Group. All rights reserved. The development of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is associated with the hyperergic reaction of the human immune system. The development of autoimmune inflammation is preceded by contact with internal or external trigger factors (adjuvants) of immune disorders. ASIA is associated with an individual genetic predisposition that is probably associated with the carriage of HLA-DRB1*01 or HLA-DRB4. The paper presents five possible options for the impact of adjuvants in the pathogenesis of autoimmune disorders. It gives diagnostic criteria for the syndrome, as well as its clinical, laboratory and morphological manifestations. Emphasis is laid on the importance of morphological changes in the diagnosis of autoimmune disorders. The spectrum of morphological changes in ASIA is extensive. The tissues show signs of immune inflammation, such as lymphohistiocytic infiltration, granulomatous inflammation, and scleroderma-like changes. The characteristic feature is the regression of clinical, laboratory, and morphological manifestations after adjuvant removal.
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Genetic factors of the development of chronic pancreatitis
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01.01.2018 |
Litvinova М.
Khafizov K.
Shipulin G.
Аyginin А.
Vinokurova L.
Nikolskaya K.
Dubtsova E.
Bordin D.
Asanov A.
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Voprosy Prakticheskoi Pediatrii |
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© 2018, Dynasty Publishing House. All rights reserved. Chronic pancreatitis, being a complex multifactor clinico-genetic phenomenon, is a significant medical, social and economic problem. Study of pancreatitis remains a topical theme also for the paediatric cohort, especially taking into account practically similar morbidity rates in adults and children. The review presents information and analyzes main genetic risk factors of the development of pancreatitis. Mutations and polymorphisms of the CFTR, CTRC, SPINK1, CPA1, PRSS1, PRSS2 genes that are significant for functioning of the pancreas are discussed in detail. Examples of genetic variants associated with increased or decreased risks of developing disease are given. Special attention is paid to difficulties of interpreting the results of molecular-genetic testing associated with certain gene homology, presence of pseudogenes and disease cases conditioned by spontaneous mutation. Detection of genetic risk factors of chronic pancreatitis allows to early prevent the development of disease in the proband’s relatives, and also to take a more personalized approach to the patient’s treatment.
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The joint scientific research projects carried out by the department of forensic medicine of the sechenovsky university and the bureau of forensic medical expertise of the Moscow health department
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01.01.2018 |
Nagornov M.
Shigeev S.
Lomakin Y.
Leonova E.
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Sudebno-Meditsinskaya Ekspertiza |
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© 2018, Media Sphera Publishing Group. All rights reserved. This article was designed to report the results of scientific research and practical forensic medical work carried out jointly by the personnel of Department of Forensic Medicine of the Sechenovsky University and the Bureau of Forensic Medical Expertise of the Moscow Health Department during the last 5 years.
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