Extreme Medicine

ISSN Print 2713-2757 ISSN Online 2713-2765

Extreme Medicine

SCIENTIFIC AND PRACTICAL REVIEWED JOURNAL OF FMBA OF RUSSIA

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Many patients with traumatic brain injury develop complications in the postoperative period. The article describes a case of revision surgery in a female patient with cerebrospinal fluid rhinorrhea following a severe car accident. During one surgery, the skull base and the frontal bone defect were repaired and a lumboperitoneal shunt was placed. The skull base was repaired using an autologous musculoaponeurotic graft. For a better cosmetic effect, the implant was designed using CADCAM technologies. The patient had a relapse of the leak in the postoperative period, which required revision surgery (multilayer reconstruction using a fibrin-thrombin sponge). The patient was followed up for 2 years, with no relapse. The desired clinical and cosmetic effects were successfully achieved.

Received: 2021-10-07

Published online: 2021-11-08

DOI: 10.47183/mes.2021.038

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VIEWS 2058

Belyankin AA, Salimova EL, Konon AD, Trukhin VP

The production of vaccines requires constant improvement of methods and tools, revision and modernization of the current technology with the aim to improve quality of the product made for the benefit of public health. The purposяe of this work was to improve the process of production of polysaccharide polyribosyl ribitol phosphate (PRP), which is the active agent of Haemophilus influenzae type b (Hib) vaccines. We investigated how PRP yield depends on the following factors: concentration of dissolved oxygen in the culture liquid, glucose concentration control method applied in cultivation, source of protein for the producer microorganism, stability of the polysaccharide at the culture liquid inactivation stage. As a result, we managed to increase the PRP yield in the culture liquid by 10%, ensured a 25% boost of the biomass accumulation rate during cultivation in the fermenter and reduced the cultivation time by 6.5 hours. The PRP loss rate at the culture liquid inactivation stage was reduced by 80%. Relying on the patented composition, we invented a new composition of the nutrient medium that meets the current regulatory requirements.

Received: 2021-09-15

Published online: 2021-10-17

DOI: 10.47183/mes.2021.037

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VIEWS 2011

Filin KN, Gladkikh VD, Bykov VN

The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 ± 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 ± 0.21 lg PFU/g) and ribavirin group (5.2 ± 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (р < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (р < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (р > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.

Received: 2021-07-21

Published online: 2021-09-30

DOI: 10.47183/mes.2021.036

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VIEWS 2270

Gorodnichev RB, Kornienko MA, Kuptsov NS, Malakhova MV, Bespiatykh DA, Veselovsky VA, Shitikov EA, Ilina EN

The Klebsiella pneumoniae bacterium is capable of causing the broad range of human nosocomial infections associated with antibiotic resistance and high mortality. Virulent bacteriophage therapy is one of the promising alternatives to antibiotic treatment of such infections. The study was aimed to isolate virulent bacteriophages effective against the relevant clinical K. pneumoniae strains, and to perform the molecular genetic characterization of these phages. Bacteriophages were isolated from the river water samples using the enrichment method. The whole-genome sequencing was performed on the MiSeq platform (Illumina). Three novel K. pneumoniae bacteriophages belonging to families Autographiviridae (vB_KpnP_NER40, GenBank MZ602146) and Myoviridae (vB_KpnM_VIK251, GenBank MZ602147; vB_KpnM_FRZ284, GenBank MZ602148) have been isolated and characterized. On the collection of 105 K. pneumoniae clinical strains, it has been found that bacteriophages vB_KpnP_NER40 and vB_KpnM_VIK251 have a narrow lytic spectrum (22% and 11%), which is limited to strains of the capsular types К2 and К20 respectively. In contrast, bacteriophage vB_KpnM_FRZ284 has a broad lytic spectrum (37%), causing the lysis of strains with different types of capsular polysaccharide. The phages are strictly virulent and have no genes encoding integrases, toxins or pathogenicity factors in their genomes. Genes of depolymerases, encoding the potential receptor binding proteins, have been found in the genomes of the capsular-specific bacteriophages vB_KpnP_NER40 and vB_KpnM_VIK251. The cocktail of three bacteriophages has lysed about 65% of the studied collection of K. рneumoniae strain and is potentially applicable for therapeutic purposes.

Received: 2021-07-21

Published online: 2021-09-29

DOI: 10.47183/mes.2021.035

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VIEWS 2270

Dergacheva LI, Derevoyedov AA, Vykhodets IT, Pavlova AA, Parastaev SA

Glycemic control is the biggest challenge for athletes with diabetes mellitus (DM) on insulin therapy. Done well, it can keep glycogen metabolism normal and allow performance improvement through adjustment of the insulin doses to the specifics of nutrition and exercising. In DM Type 1 and Type 2 patients, intense physical activity and resistance exercising, as well as interval training, enable optimal physiological adaptation during the training period and prove to be beneficial when the athlete does one-time exercise sets. But for athletes with DM on insulin therapy, keeping blood glucose at the optimal level is not the only important issue. It is also necessary to factor in the potential body temperature regulation disturbances that increase the risk of heat stress during training/competition, learn the effects the drugs used by athletes may have on the glycemic status, control electrolyte balance and dehydration, know how to execute the application for permission to use insulin for therapeutic purposes submitted to the anti-doping organization. The purpose of this review was to draw attention of sports medicine physicians and coaches to the above problems and to the need for wider use of the new DM control technology; help athletes with DM on insulin therapy continuously perform well and ensure their athletic longevity.

Received: 2021-07-20

Published online: 2021-09-28

DOI: 10.47183/mes.2021.034

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VIEWS 1967

Ershov PV, Makarova AS

Identification of novel low molecular weight compounds with antitumor activity is the first important step towards the development of candidate drugs and a popular trend in in vitro pharmacology. The aim of the study was to assess the key trends and rank the scientific priorities in anticancer drug design using bibliometric analysis. The protocol involved using the panel of bibliographic databases (PubMed, Scopus, Cortellis) and analytical web-based tools PubChem, FACTA +, ClustVis, Reaxys, PathwayStudio and VOSviewer software to review a sample of 1657 papers issued 2020–2021.The work was also focused on 70 new promising basic structures and derivatives targeted at inhibiting both individual pro-tumor proteins and signaling cascades. It was found that serine-threonine protein kinases, receptor tyrosine kinases, DNA topoisomerases and tubulins as well as signaling pathways PI3K, mTOR, AKT1, STAT3, HIF-1a, and p53 account for up to 60% of the total structure of cellular targets for the design of anticancer drugs. The increasing scientific interest in innovative inhibitors of tumor-associated protein complexes, transcription factors and metabolic enzymes has been found. The compounds, which belong to heterocycles, glycosides, quinones and terpenes, were mentioned in 71% of papers as the basic structures for antitumor derivatives design. Papers, published in 2019, in which the compounds, such as lapachone, luteolin, quercetin, monastrol, and crisosplenol D are studied in the context of the design of new drug prototypes, have the highest citation rate. The systematic bibliometric approach involving the use of a panel of analytical resources makes it possible to assess R&D trends and scientific priorities in anticancer drug design, thus organically complementing the classic reviews in periodicals.

Received: 2021-07-21

Published online: 2021-09-27

DOI: 10.47183/mes.2021.033

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VIEWS 2370

Savina NN, Ekimov AA, Trukhin VP, Evtushenko AE, Zhirenkina EN, Sinegubova EO, Slita AV

Inactivation of influenza virus and other potential contaminants like avian adenoviruses coming from embryonated chicken eggs is a critical step in the production of inactivated influenza vaccines. Inactivation must lead to a guaranteed reduction in contaminant titers by at least 4 lg (PFU)/ml. The aim of this study was to identify an optimum cell line for adenovirus propagation and to estimate a reduction in adenovirus titers in vaccine intermediates after inactivation. In a series of experiments, we identified the optimum conditions and the optimum cell line for the propagation of avian adenovirus (strains CELO and Fontes). The most commonly used inactivation methods were analyzed, including inactivation by β-propiolactone and UV light. Viral titers were measured by plaque assays. After 10 h of inactivation with β-propiolactone, CELO titers fell by 4.12 ± 0.06 lg, whereas Fontes titers, by 4.20 ± 0.19 lg, suggesting that β-propiolactone is an effective inactivating agent. Exposure to UV light led to a reduction in CELO titers by 4.69 ± 0.89 lg and a reduction in Fontes titers by 4.44 ± 1.06 lg after 5 min. N-octyl-β-D-glucopyranoside added at the splitting step reduced CELO titers by 0.93 ± 0.15 lg and Fontes titers by 1.04 ± 0.12 lg, whereas tetradecyltrimethylammonium bromide led to a reduction in CELO and Fontes titers by 1.18 ± 0.17 lg and 1.12 ± 0.38 lg, respectively.

Received: 2021-08-18

Published online: 2021-09-26

DOI: 10.47183/mes.2021.032

Comments 0

VIEWS 2164

Vasilyev VV, Grineva AA, Rogozina NV, Ivanova RA, Ushakova GM

Nonspecificity of clinical, laboratory and instrumental manifestations of congenital infectious diseases, including viral infections, and the diversity of methods for etiological verification of pathogens define both the need to choose the optimal approaches to the diagnosis of this pathology, and the feasibility of testing for a broad range of etiologic agents in case of suspected congenital viral infection. The analysis of current guidelines, international consensus documents issued by specialists, and published results of some studies has shown that identification of the genetic material of the pathogen with the use of amniocentesis/ cordocentesis (for cytomegalovirus and parvovirus infections) or in the birth canal (for herpes simplex infection) is the key method for antenatal etiological verification of the widespread viral infections. During the postnatal period, molecular genetic testing is combined with serological diagnosis involving determining specific immunoglobulins M and G, as well as their avidity index.

Received: 2021-08-26

Published online: 2021-09-25

DOI: 10.47183/mes.2021.031

Comments 0

VIEWS 2023