Modern Means of Personal Protection of People from Bloodsucking Arthropods

The review focuses on the means of personal protection of people from blood-sucking arthropods, mainly from Ixodidae ticks. Individual (personal) protection of humans is an important component of nonspecific prevention of natural-focal vector-borne diseases. The paper considers statistical data describing the level of significance and relevance of the information about the infections transmitted by ticks, for instance, tick-borne viral encephalitis, tick-borne borreliosis etc. Presented are the characteristics of different groups of personal protection means: insectoacaricidal, repellent, and insectoacaricidal-repellent ones. Indicators of their effectiveness are assessed; their practical use, as well as the features of special protective clothing and the necessity of its application is described. The toxicity of protective clothing is reduced through a lining fabric, local inserts of fabric with insectoacaricidal impregnation and the use of underwear. Different interpretation of the term “repellent” in the domestic and foreign literature, and also two different approaches (“Eastern” and “Western”) to the design and manufacture of personal protection means for people against attacks of blood-sucking arthropods, including Ixodidae ticks, in Russia and Western Europe countries and the USA is discussed. The paper highlights the effect of different pyrethroid groups on the behavioral reactions of ticks. It is shown that in the Russian Federation the use of permethrin is prohibited for the treatment of protective clothing against blood-sucking arthropods, in particular against the taiga tick Ixodes persulcatus, which is the main vector of dangerous infections across the major part of the country (in the east of the European part, the Urals, Siberia and the Far East)

Successful long-term prophylaxis of hereditary pregnancy-associated angioedema with plasma-derived C1-inhibitor concentrate: a case report

Hereditary angioedema (HAE) is a rare autosomal dominant disease caused by quantitative (type I) or functional (type II) deficiency in C1 esterase inhibitor (C1-INH). It may be caused by new mutations in up to 20% of patients. Prevalence of HAE is uncertain but is estimated to be approximately 1 case per 50,000 persons, without known differences among ethnic groups. C1-INH protein is a serine protease inhibitor that is important in controlling vascular permeability by acting on the initial phase of the complement activation, blood clotting, and fibrinolysis. Deficiency in functional C1-INH protein permits release of bradykinin, a key mediator of vascular permeability. Symptoms typically begin since childhood, worsening at puberty, and persist throughout the life, with unpredictable clinical course. The patients with HAE suffer from recurrent, acute attacks of edema that can affect any body sites, causing potentially life-threatening disorders (laryngeal edema). Results of clinical studies show that minor traumas, stress and medical interventions may be frequent precipitants of swelling episodes, but many attacks occur without an apparent cause. Pregnancy-associated hormonal changes may affect the course of C1-INH angioedema attacks by worsening, improving, or having no impact at all, but a higher percentage of pregnant women experienced an increase in C1-INH-HAE attack rates. Therapeutic options for patients with HAE are limited during pregnancy. C1-INH concentrate is recommended as the first-line therapy for pregnant women with HAE for on-demand treatment, shortterm and long-term prophylaxis, due to its safety and efficiency. Other therapies, e.g., treatment with fresh frozen plasma, androgens, icatibant, antifibrinolytics, may show variable efficacy, or cause undesirable side effects. The case below illustrates the successful treatment of HAE in a pregnant woman with C1 esterase inhibitor (C1-INH) concentrate. This patient had a very mild course of HAE during her lifetime and didn’t get any treatment. During pregnancy, she experienced a significant increase in the frequency of attacks, and the decision was made to start replacement therapy with a plasma-derived, double virus-inactivated C1-INH concentrate as a long-term prophylaxis throughout the full term of her pregnancy, before, during and after the cesarean section delivery

Modern Trends in Psychological and Pedagogical Education Under the Influence of Technical Progress

The article considers the impact of technological progress on the educational environment. In particular, the main problems of interaction between different generations are shown. The features of learning and understanding of the growing "children" are generalized. After all, it is important to build a model of communication in which the process of learning and development will not be inhibited.В статье рассмотрено влияние технического прогресса на образовательную среду. В частности, показаны основные проблемы взаимодействия между разными поколениями. Обобщаются особенности обучения и понимания подрастающих «детей». Ведь важно выстроить такую модель общения, при которой не будет тормозится процесс обучения и становления

Hyperexpression of TLR2 and TLR4 in patients with ischemic stroke in acute period of the disease

Pathogenesis of ischemic stroke  is actively  involved  in the  system  of innate immunity. Under conditions of cerebral  ischemia, a number of biologically  active  substances are  released  that  interact with innate immunity receptors, in particular TLR2  and  TLR4, which  exacerbate inflammation in brain  tissue. Identification of predictor markers  at the level of the innate immunity system may foresee the clinical course of ischemic stroke and ensure timely treatment. Our objective was to study expression of TLR2 and TLR4 receptors in peripheral blood leukocytes  in patients with ischemic stroke in the dynamics of the disease. 27 people  were included in the study. The main  group consisted of patients with ischemic stroke of varying severity (n = 19). Patients of the main  group were divided into two subgroups:  with an NIHSS index value of < 10 (n = 10) and > 10 (n = 9). The control group included healthy  donors  with no history  of acute  and chronic inflammatory diseases (n = 8). Peripheral blood  leukocytes  were used as the  test material. To determine expression  of the TLR2  and TLR4  genes, RT-PCR in real time was used. Surface  expression  of TLRs was determined by flow cytometry. A study of the TLR2 and TLR4 gene expression showed that on the 1st, 3rd  and 7th  day post-stroke, the TLR4 gene expression  in patients was significantly  increased, when compared to the control group (p < 0.01), whereas TLR2 gene expression on the 3rd  day of the disease was not statistically different from the control group. A study of surface expression  of receptors showed that the average TLR2 fluorescence intensity on the patients’ peripheral blood monocytes was significantly  increased on the 1st  and 3rd  day of disease when compared to the control group.  The  surface  expression  of TLR4  on monocytes has a statistically significant  increase  only on day 7. Assessment  of surface expression  of TLRs in subgroups  with different  severity values by NIHSS showed that  patients with a NIHSS index > 10 had a significantly  higher  level of surface of TLR2  expression  over the observation period, while the largest difference in TLR4  expression  in the subgroups  was observed  on the 1st day of the disease (p < 0.05). Patients with ischemic stroke showed an increase  in TLR2 and TLR4 expression at the gene and protein level, compared to healthy  donors. These indices can be considered possible predictors for clinical  prognosis  of ischemic stroke

Development of Composition and Technologies of Dental Gel of Meloxicam

BACKGROUND: Dental gels have several advantages over other oral dosage forms. Being a viscoplastic dosage form, the gel, when applied to the damaged area of the gum or mucous membrane, creates a protective film, preventing mechanical irritation, and providing a localized effect of the drug components. AIM: The aim of this work was to develop the composition and technology of the dental gel of meloxicam, the study of the main technological and consumer characteristics, as well as the local irritating effect of the dosage form. METHODS: Dental gels were prepared using purified water, alcohol, glycerol, and buckthorn oil as solvents, gelling agents used were: Hydroxyethylcellulose Natrosol® 250 HHX Pharm, Carbopol® 974P NF Polymer, and solubilizer Poloxamer 407 (Lutrol® F 127). The bioadhesive component and Noveon® Polycarbophil component were used for dental gel preparation. Aspartame was used as sweetener. Menthol and ascorbic acid were used to correct the organoleptic properties of the pharmaceutical composition. The formulated dental gel of meloxicam at a concentration of 7.5% was evaluated for organoleptic properties, pH, rheological characteristics, bioadhesive properties, and stability under the accelerated aging period. The in vivo local irritant effect was evaluated using ten rabbits by cutaneous, subcutaneous, subconjunctival administration, as well as application to the upper palate. RESULTS: Based on the results of studying technological and organoleptic properties, the optimal composition based on the Natrosol® 250 HHX hydroxyethylcellulose gelling agent, glycerol solvent, and purified water in the ratio 1/5 was selected, the composition contains Noveon® bioadhesive in an amount of 2%. The composition has good taste, pH close to pH of saliva has high bioadhesive properties, satisfactory rheological characteristics. The shelf life of the experimental series by accelerated aging was 2 years. The selected composition does not have a local irritant effect. CONCLUSION: A new dosage form of meloxicam was developed – a gel for use in dental practice

Применение ингибиторов фактора некроза опухоли α у женщин с анкилозирующим спондилитом во время беременности

Objective: to present our own experience of tumor necrosis factor α (TNFα) inhibitors (iTNFα) usage during pregnancy in women with ankylosing spondylitis (AS), to assess AS activity and outcomes of gestation.Patients and methods. A prospective observation of 55 pregnant women with AS who met the modified New York criteria of 1984. Fifty-six pregnancies were followed. The average age of the patients was 31.7±4.7 years, the duration of the disease was 132.2±85.4 months. The median BASDAI for pregnancy trimesters was 2.4 [1.2; 4.4], 2.7 [1.4; 4.2] and 2.2 [1.5; 4.0], respectively. 14 women received iTNFα 3 months before pregnancy.Results and discussion. In the first trimester, TNFα was used in 9 (16.1%) patients, in the second – in 9 (16.1%) and in the third – in 5 (9.3%); the median BASDAI for trimesters was 2.3 [1.0; 3.7], 3.4 [1.2; 3.5], 3.0 [0.8; 3.4], respectively. All patients who discontinued iTNFα just before or in early pregnancy had indications for resuming therapy in the second half of gestation. Cancellation of iTNFα at the end of the second trimester was not a risk factor for high activity in the third trimester. There was 1 adverse pregnancy outcome. In other cases, childbirth occurred at 38.9±1.4 weeks, newborns' body weight was 3273.1±435.6 g.Conclusion. Women with AS who plan a pregnancy should be prescribed drugs with the maximum allowed duration of use during gestation. Cancellation of iTNFα before and in early pregnancy is a risk factor for high AS activity, while renewal of iTNFα therapy during pregnancy is not always effective.Цель исследования – представить собственный опыт применения ингибиторов фактора некроза опухоли (иФНОα) во время беременности у женщин с анкилозирующим спондилитом (АС), оценить активность АС и исходы гестации.Пациенты и методы. Проведено проспективное наблюдение 55 беременных с АС, соответствовавших модифицированным Нью-Йоркским критериям 1984 г. Прослежено 56 беременностей. Средний возраст пациенток составлял 31,7±4,7 года, продолжительность болезни – 132,2±85,4 мес. Медиана BASDAI по триместрам беременности – 2,4 [1,2; 4,4], 2,7 [1,4; 4,2] и 2,2 [1,5; 4,0] соответственно. ИФНОα за 3 мес до наступления беременности получали 14 женщин.Результаты и обсуждение. В I триместре иФНОα применяли 9 (16,1%) пациенток, во II – 9 (16,1%) и в III – 5 (9,3%); медиана BASDAI по триместрам составляла 2,3 [1,0; 3,7], 3,4 [1,2; 3,5], 3,0 [0,8; 3,4] соответственно. Все пациентки, отменившие иФНОα накануне или на ранних сроках беременности, имели показания к возобновлению терапии во второй половине гестации. Отмена иФНОα в конце II триместра не являлась фактором риска высокой активности в III триместре. Имел место 1 неблагоприятный исход беременности. В остальных случаях роды произошли на сроке 38,9±1,4 нед, масса тела новорожденных – 3273,1±435,6 г.Заключение. Женщинам с АС, планирующим беременность, необходимо назначать препараты с максимально разрешенным сроком применения во время гестации. Отмена иФНОα перед беременностью и на ее ранних сроках – фактор риска высокой активности АС, при этом возобновление терапии иФНОα во время беременности не всегда эффективно

Zika virus has an oncolytic activity against human glioblastoma U87 cells

Glioblastoma is a highly lethal brain cancer. Virotherapy with the use of oncolytic viruses has since recently been regarded as a promising approach for the clinic treatment of human glioblastomas. The purpose of this work was to perform a primary evaluation of the Zika virus as a potential oncolytic agent against glioblastomas. In vitro experiments showed that the Zika virus strain MR 766 is able to selectively infect and lyse neoplastic cells of the human glioblastoma cell line U87 MG. The selectivity index (SI, the ratio of infectious titer for tumor cells to titer on normal untransformed cells) was 2·102. The selectivity of the replicative activity of Zika virus in relation to U87 MG glioblastoma cells was additionally confrmed by indirect immunofluorescence. Using the model of immunodefcient SCID mice with subcutaneous xenografts of human glioblastoma U87 MG, a strong antitumor activity of the Zika virus under a course (daily for 4 days) of intratumoral administration of 5·105 TCID50 of Zika virus was shown. Treatment with Zika virus resulted in more than a 10­fold reduction in mean volumes of tumors. The tumor growth inhibition index was 92.63 %. Recurrences (metastases) of tumor re­growth were not registered within 64 days of observation. This result demonstrated the prospect of further in­depth studies of the Zika virus as a potential oncolytic agent against human glioblastomas

Finding of the Low Molecular Weight Inhibitors of Resuscitation Promoting Factor Enzymatic and Resuscitation Activity

Background: Resuscitation promoting factors (RPF) are secreted proteins involved in reactivation of dormant actinobacteria, including Mycobacterium tuberculosis. They have been considered as prospective targets for the development of new antituberculosis drugs preventing reactivation of dormant tubercle bacilli, generally associated with latent tuberculosis. However, no inhibitors of Rpf activity have been reported so far. The goal of this study was to find low molecular weight compounds inhibiting the enzymatic and biological activities of Rpfs. Methodology/Principal Findings: Here we describe a novel class of 2-nitrophenylthiocyanates (NPT) compounds that inhibit muralytic activity of Rpfs with IC50 1–7 mg/ml. Fluorescence studies revealed interaction of active NPTs with the internal regions of the Rpf molecule. Candidate inhibitors of Rpf enzymatic activity showed a bacteriostatic effect on growth of Micrococcus luteus (in which Rpf is essential for growth protein) at concentrations close to IC50. The candidate compounds suppressed resuscitation of dormant (‘‘non-culturable’’) cells of M. smegmatis at 1 mg/ml or delayed resuscitation of dormant M. tuberculosis obtained in laboratory conditions at 10 mg/ml. However, they did not inhibit growth of active mycobacteria under these concentrations. Conclusions/Significance: NPT are the first example of low molecular weight compounds that inhibit the enzymatic an

Block Copolymers of Ethylene Oxide and Propylene Oxide: Prospects for Medical and Pharmaceutical Application in Russia

Block copolymers of ethylene oxide and propylene oxide (EO/PO block copolymers) are polymeric non-ionic surfactants with a high hydrophilic–lipophilic balance also referred to as pluronics, poloxamers, or proxanols. These compounds are among the most demanded modern excipients for the production of medicines. EO/PO block copolymers are used both in the production of traditional (liquid, semi-solid, and solid) dosage forms and as part of targeted delivery systems. The extensive application of EO/PO block copolymers is due to the diverse array of their properties, including not only solubilising, emulsifying, gelling, and other effects but also thermoreversibility, which is essential for developing in situ delivery systems and 3D printing technologies.The aim of the study was to evaluate the potential of EO/PO block copolymers for medicinal use and to assess the range of medicinal products approved in the Russian Federation that contain EO/PO block copolymers.This review presents an analysis of the register of poloxamer-containing medicines approved in the Russian Federation, a list of the largest manufacturers of EO/PO block copolymers in the world, and a study of the possibility to use copolymers for medical purposes. Currently, there are more than 10 chemical manufacturers producing EO/PO block copolymers for the pharmaceutical, biotechnology, and other industries around the world. EO/PO block copolymers are included in more than 60 medicinal products present in the Russian pharmaceutical market; this observation indicates the need to phase out the import of poloxamers