The use of apolipoprotein A-I as a component of serum-free nutrient medium for bone marrow cell culture

An important step in preparation of cells for cell therapy and tissue engineering is the cultivation of cells in vitro. The aim of this work is to study the effect of human apolipoprotein A-I (apoA-I) on the functional activity of cultured bone marrow cells and to show the possibility of using this protein instead of animal fetal serum. Material and methods. Bone marrow cells were cultured in 24-well plates in RPMI-1640 medium in a CO2 incubator at a temperature of 37 °C. The rate of incorporation of [14C]-leucine into the total cell protein and [3H]-thymidine into the DNA was used as an integral indicator of cell viability during cultivation. Results and discussion. It was found that the rate of DNA synthesis in bone marrow cells in the presence of apo A-I increased compared with the control group (without apo A-I) by 55 % after 8 hours, by 523 % after 24 hours and by 219 % after 48 hours. Under these conditions the rate of protein synthesis was also increased. The results indicate that the presence of apo A-I in serum-free culture medium preserves the functional activity of cultured bone marrow cells. Considering that the regulatory effect of apo A-I is achieved at a low protein concentration in the medium (15 μg/ml), isolation of apo A-I from the patient’s own blood serum will provide a practically safe nutrient medium for culturing autologous bone marrow cells with applications in personalized cell therapy and tissue engineering

Evaluation of the Efficacy and Safety of Initial Empirical Antibiotic Therapy for Community-Acquired Pneumonia in Middle-Aged People

β-lactam antibiotics, including cephalosporins, are the drugs of choice for empirical antibiotic therapy (ABT) in patients with community-acquired pneumonia. Unreasonable and irrational use of antibiotics leads to an increased risk of adverse reactions, contributes to the growth of antibiotic resistance.The aim of the study was to analyse data on the efficacy and safety of initial empirical ABT using cephalosporins for community-acquired pneumonia in middle-aged patients of multidisciplinary hospitals in Moscow.Materials and methods: the authors analysed 177 archived medical records of the patients admitted to three multidisciplinary hospitals (I.V. Davydovsky City Clinical Hospital, City Clinical Hospital 52 and City Clinical Hospital 4) in Moscow from 2017 to 2019 and prescribed mono- and/or combination therapy including a cephalosporin antibiotic as a starting therapy for community-acquired pneumonia. The initial ABT was considered effective if a patient’s body temperature normalised within 48–72 h following initiation of treatment and safe if no adverse reactions developed during the period of inpatient treatment.Results: the combination of ceftriaxone and azithromycin was the most frequently prescribed ABT regimen; its effectiveness was 71.9%. Ceftriaxone monotherapy was the second in frequency of prescription; its effectiveness amounted to 77.2%. The third regimen included cefotaxime and azithromycin and was effective in 70% of cases. The patients who needed a change in initial ABT had a significantly higher incidence of developing severe community-acquired pneumonia and complications. The study results indicate that the structure of comorbidity did not affect the effectiveness of initial empirical ABT. Streptococcus pneumoniae was found to be the most common causative agent of community-acquired pneumonia in the studied population (44.8% of cases). Only 13% of the patients faced adverse reactions associated with the use of antibiotics as part of the initial empirical ABT; the most common were leukopenia and diarrhoea.Сonclusions: the results of the study indicate the feasibility of mono- and/or combination ABT including a cephalosporin antibiotic as a starting empirical therapy for community-acquired pneumonia due to its effectiveness and favourable safety profile

Retrospective Analysis of the Safety of Antibacterial Medicinal Products for Elderly Patients with Community-Acquired Lower Respiratory Tract Infections

Cephalosporins are the empirical antibiotic therapy (ABT) of choice for patients with community-acquired pneumonia (CAP). When treated with antibiotics, elderly patients, especially those with comorbidities, are at higher risk of developing adverse drug reactions (ADRs).The aim of the study was to analyse data on the safety and efficacy of initial empirical ABT with cephalosporins in elderly patients over 75 years old with CAP admitted to multidisciplinary hospitals in Moscow.Materials and methods. The retrospective study included 305 medical records of patients with CAP admitted to three multidisciplinary hospitals in Moscow in 2017–2019 and prescribed initial mono- and/or combination ABT including a cephalosporin. Initial ABT was considered effective if the body temperature normalised within 48–72 h from the start of treatment. It was considered safe if there were no ADRs during hospital stay.Results. Mostly, patients were prescribed ceftriaxone monotherapy or ceftriaxone and azithromycin combination therapy. These ABT regimens were effective in 69.07% and 78.10% of the cases, respectively. Patients with severe CAP needed their initial ABT adjusted significantly more often than those with non-severe CAP. The initial ABT was changed for a number of reasons, including ineffectiveness, ADRs, abscesses formed as a complication of CAP, sputum culture results enabling causal ABT, secondary hospital-acquired infections, and exacerbated chronic infections. All patients had comorbidities, and the most prevalent were arterial hypertension (83.9%), coronary heart disease (45.6%), chronic heart failure (44.9%), cerebrovascular disease (40.9%), atrial fibrillation (26.9%), diabetes mellitus (21.3%), and chronic obstructive pulmonary disease (19.0%). Initial ABT was significantly more often considered ineffective in patients with chronic heart failure and cerebrovascular disease. The most common causative agent of CAP in the study population was Streptococcus pneumoniae (31.9%). In 16% of patients, the authors identified ADRs associated with the antibiotics used as initial therapy. The most common were diarrhoea, anaemia, leucopenia, and hepatopathy. Ceftriaxone was associated with ADRs in 11% of patients.Conclusions. The study results suggest that initial mono- and/or combination ABT including a cephalosporin is effective and relatively safe; therefore, this treatment option is expedient for elderly patients with CAP. For this population, the safety of ABT may be improved through the wider use of existing markers of ADRs and the identification of new ones

Features of Toxic Nephropathy Development during Antibiotic Therapy

Antibacterials can have nephrotoxic effects because medicinal products of this class are primarily excreted by the kidneys. The aim of the study was to analyse literature data on the mechanisms, risk factors and specific features of toxic nephropathy development during antibiotic therapy. The article considers mechanisms of development of acute interstitial nephritis, acute tubular necrosis, crystal deposits in the tubules, proximal or distal tubulopathy with electrolyte abnormalities during the use of antibiotics. Nephrotoxicity was shown to be most often associated with the use of aminoglycosides, beta-lactams, and vancomycin. The authors analysed the dependence of nephrotoxicity on antibacterial agent lipophilicity and drug-drug interactions. The main risk factors for developing nephropathy are older age; male sex; black race; hypovolemia; arterial hypotension; angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, non-steroidal anti-inflammatory drugs or their combinations; and individual genetic characteristics. Nephrotoxicity is associated with genetic characteristics of the systems responsible for metabolism and excretion of antibacterial products: cytochrome P450 isoenzymes, P-glycoprotein, multidrug resistance protein (MRP), multidrug and toxin extrusion (MATE), breast cancer resistance protein (BCRP), and organic anion transporters. Severe generalised infections change pharmacokinetic parameters of antibacterial products. This should be taken into account when prescribing the hydrophilic antibiotics that are excreted by tubular secretion and reabsorbed in the renal tubules. The study demonstrated the effectiveness of the method comprising a combination of dose adjustment based on therapeutic drug monitoring results and renal function monitoring for improving the safety of antibiotic therapy

FORMATION OF NANOCRYSTALLINE COMPOSITIONS TiC–Co AND TiN–Co IN THE PRESENCE OF MOLYBDENUM AND ITS REFRACTORY COMPOUNDS DURING PLASMA RECONDENSATION

Методом плазменной переконденсации в низкотемпературной азотной плазме были переработаны механические смеси микрокристаллических порошков TiC–Co и TiN–Co. В ходе рентгенографических и электронно-микроскопических исследований, в том числе с использованием методик EDX-анализа, было установлено, что нанокристаллические композиции имеют радиально-слоевую структуру, состоящую из тугоплавкого ядра и металлической оболочки, содержащей кобальт, молибден или их взаимные твердые растворы.Mechanical mixtures of microcrystalline TiC–Co and TiN–Co powders were processed by plasma recondensation in a low-temperature nitrogen plasma. It was found that during radiographic and electron microscopic studies, including using EDX analysis techniques, nanocrystalline compositions have a radial layer structure consisting of a refractory core and a metallic shell containing cobalt, molybdenum or their mutual solid solutions.Авторы выражают благодарность канд. техн. наук Э. К. Добринскому (ФГУП ГНИИХТЭОС) за помощь в проведении экспериментов по плазменной переконденсации механической смеси TiN–Co и TiC–Co

Особенности развития токсической нефропатии при проведении антибиотикотерапии

Antibacterials can have nephrotoxic effects because medicinal products of this class are primarily excreted by the kidneys. The aim of the study was to analyse literature data on the mechanisms, risk factors and specific features of toxic nephropathy development during antibiotic therapy. The article considers mechanisms of development of acute interstitial nephritis, acute tubular necrosis, crystal deposits in the tubules, proximal or distal tubulopathy with electrolyte abnormalities during the use of antibiotics. Nephrotoxicity was shown to be most often associated with the use of aminoglycosides, beta-lactams, and vancomycin. The authors analysed the dependence of nephrotoxicity on antibacterial agent lipophilicity and drug-drug interactions. The main risk factors for developing nephropathy are older age; male sex; black race; hypovolemia; arterial hypotension; angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, non-steroidal anti-inflammatory drugs or their combinations; and individual genetic characteristics. Nephrotoxicity is associated with genetic characteristics of the systems responsible for metabolism and excretion of antibacterial products: cytochrome P450 isoenzymes, P-glycoprotein, multidrug resistance protein (MRP), multidrug and toxin extrusion (MATE), breast cancer resistance protein (BCRP), and organic anion transporters. Severe generalised infections change pharmacokinetic parameters of antibacterial products. This should be taken into account when prescribing the hydrophilic antibiotics that are excreted by tubular secretion and reabsorbed in the renal tubules. The study demonstrated the effectiveness of the method comprising a combination of dose adjustment based on therapeutic drug monitoring results and renal function monitoring for improving the safety of antibiotic therapy.Антибактериальные препараты могут оказывать нефротоксическое действие, поскольку препараты этой группы преимущественно элиминируются почками. Цель работы — анализ данных литературы о механизмах, факторах риска и особенностях развития токсической нефропатии при проведении антибиотикотерапии. Рассмотрены механизмы развития острого интерстициального нефрита, острого некроза канальцев, отложения кристаллов внутри канальцев, проксимальной или дистальной тубулопатии с аномалиями расходования электролитов на фоне применения антибиотиков. Показано, что нефротоксичность наиболее часто ассоциирована с применением аминогликозидных, бета-лактамных антибактериальных средств, ванкомицина. Проанализирована зависимость нефротоксичности от липофильности антибактериальных препаратов и межлекарственного взаимодействия. Определено, что основными факторами риска развития нефропатии являются пожилой возраст, мужской пол, негроидная раса, гиповолемия, артериальная гипотензия, прием ингибиторов ангиотензинпревращающего фермента, блокаторов рецепторов ангиотензина II, нестероидных противовоспалительных препаратов или их комбинации, индивидуальные генетические особенности. Отмечена связь нефротоксичности и генетических особенностей систем метаболизма и выведения антибактериальных средств: изоферментов цитохрома P450, Р-гликопротеина, белков семейства множественной лекарственной резистентности MRP (multidrug resistance-associated protein) и MATE (multidrug and toxin extrusion protein), белка резистентности рака молочной железы BCRP (breast cancer resistance protein). Тяжелая генерализованная инфекция изменяет фармакокинетические параметры антибактериальных лекарственных средств, что следует учитывать при назначении гидрофильных антибиотиков, которые выводятся путем канальцевой секреции и реабсорбируются в почечных канальцах. Показано, что коррекция дозирования антибактериальных лекарственных препаратов на основе результатов терапевтического лекарственного мониторинга в совокупности с контролем функции почек является эффективным методом повышения безопасности антибиотикотерапии

Vasoproliferative retinal tumors. Current approach to treatment Relevance. Vasoproliferative retinal tumor is a rare acquired disease.

The exact pathogenesis of vasoproliferative tumors remains completely unknown, and it has long been assumed that their development is a reactive process with the proliferation of glial cells and blood vessels. Despite the widespread use of this term, vasoproliferative tumor cannot be fully attributed to true tumors and it cannot be reliably established that it is vascular in its pathogenesis. The clinical signs of vasoproliferative retinal tumor manifests itself as a yellowish-red, often loose mass with vessels of normal or slightly enlarged caliber, usually small, single and located in the lower-outer or lower part of the fundus. Due to their rarity, there are currently no uniform recommendations for the diagnosis and treatment of this pathology. Most of the available methods have limited effectiveness, causing a temporary regression of the process, which makes it necessary to repeatedly re-treat or combine several treatments. In some cases, the use of several therapeutic options leads to complications that can be caused by both therapy and the natural progression of the disease, which together prevents reconvalescence and improvement of visual func tions.Purpose. This article presents for the first time a detailed review of the literature, including generalized data on the epidemiology, pathogenesis, histological features, differential diagnosis and modern approaches to the treatment of this pathology.Material and methods. The article uses literary materials of domestic and foreign authors published in the period from 1982 to the present.Conclusion. It is necessary to further study the mechanisms of development of vasoproliferative tumors and related complications

Adaptive techniques of the wavefield formation in random-inhomogeneous multimode propagation channels by the use of large arrays

We address the source array synthesis problem in a random propagation channel under the different optimization criteria specified for the remote receiving array, namely, the criteria of (i) the output SNR and (ii) the array gain. For the first step, we discuss the optimal schemes for the source excitation and array beamforming by using a general technique of the eigenvalue-eigenvector expansion associated with the normal-mode model of long-range signal propagation in a channel. Then, we develop an adaptive approach to the source array synthesis which is shown to be an iterative correction of the sources excitation coefficients depending on the signal coherence, the receiving array arrangement in a channel, and also on the modal spectrum of the ambient noise interference. Computer simulation is performed for the vertical source and receiving arrays in random-inhomogeneous environments typical for sound propagation in shallow-water channels from the Barents Sea. The results exhibit distinctly a rather high efficiency of the adaptive synthesis algorithms for various sets of the source and environmental parameters including the signal frequency, distance, vertical locations of the sources and receivers

Major Aspects of Detection and Monitoring of Adverse Reactions Associated with Cephalosporin Antibiotic Treatment

Widespread use of cephalosporin antibiotics in clinical practice calls for greater attention to the risk of adverse drug reactions. Information on serious or unexpected adverse events reported during post-marketing experience is submitted to national and international pharmacovigilance databases. Analysis of these reports helps to identify new adverse drug reactions.The aim of the study was to analyse the safety profile of cephalosporin antibiotics based on spontaneous reports in the international VigiBase database.Materials and methods: the analysis of the adverse reaction profile of cephalosporin antibiotics was based on MedDRA system organ classes and included spontaneous reports submitted to VigiBase from the moment of its creation until August 2020.Results: the authors identified the most clinically significant adverse reactions for different cephalosporin generations. They compared and analysed information on adverse events in VigiBase and in patient information leaflets of medicinal products authorised in the Russian Federation. It was demonstrated that some serious events described in VigiBase spontaneous reports for V-generation cephalosporins are not included in the “Side effects” section of the patient information leaflets. According to VigiBase, the use of ceftaroline was associated with the development of generalised exfoliative dermatitis, Stevens–Johnson syndrome, tubulointerstitial nephritis, while the use of ceftolozane was associated with acute kidney injury, renal insufficiency, sepsis, pneumonia, and respiratory insufficiency.Conclusion: reporting of unexpected and serious adverse drug reactions to cephalosporin antibiotics is an important task of healthcare practitioners. Availability of information on class-specific and generation-specific serious adverse reactions will help predict and prevent their development