Effect of preliminary nanostructuring frictional treatment on the efficiency of nitriding of metastable austenitic steel in electron beam plasma

The paper studies the effect of the temperature of nitriding in electron beam plasma, ranging between 250 and 500 °, on the nitrogen concentration, phase composition and microhardness of the surface of the AISI 321 chromium-nickel austenitic steel in two initial states - quenched undeformed and after nanostructuring frictional treatment. The lowest nitriding temperature (350 °C) for the efficient hardening of the steel has been established. The application of frictional pretreatment with a sliding synthetic diamond indenter in an argon environment is shown to be highly efficient for increasing the depth of the layer nitrided at this temperature. The contribution of the formed S-phase (nitrogen-oversaturated austenite γN) to the intensive hardening of the steel nitrided at low temperatures (300 to 400 °) is noted. © 2017 Author(s).01201354598Russian Foundation for Basic Research, RFBR: 15-08-07947Ural Branch, Russian Academy of Sciences, UB RAS: 15-9-12-45, 01201463331The work was done in the framework of the Complex Program of UB RAS (project No. 15-9-12-45), within the state order on the subject “Structure” (No. 01201463331), the government assignment for IES UB RAS (theme No. 01201354598) and supported by RFBR, project No. 15-08-07947

Клофазимин: история и перспективы

The review analyses 47 publications that follow the pathway of clofazimine from its discovery to recognition as a Group B drug for treatment of multiple drug resistant tuberculosis. It describes its mechanism of action and effects on Mycobacterium tuberculosis, pharmacokinetics, and safety parameters.В обзоре представлен анализ 47 публикаций, прослеживающих путь клофазимина от открытия до признания препаратом группы В для лечения туберкулеза с множественной лекарственной устойчивостью. Приведены сведения о механизмах действия на микобактерии туберкулеза, особенностях фармакокинетики и профиле безопасности

Effect of intraosseous introduction of selenium/arabinogalactan nanoglycoconjugate on the main indicators of primary metabolism in consolidation of bone fracture

The research was carried out on 9 rabbits (males) of Chinchilla breed with modeling of standard perforating fracture of femoral bone. We performed intraosseous introduction of nanocomposite elemental selenium and heteropolysaccharide arabinogalactan 50 mg Se/kg to individuals of experimental group (n = 3) and NaCl 0,9 % to individuals of control group (n = 6). It was established that local intraosseous introduction of the nanocomposite with perforated fracture model did not affect basal metabolic indicators (body temperature, oxygen consumption, carbon dioxide production), but boosted the metabolic processes in the area of the surgical wound from the 9th to 21st days. It proves the bioavailability of the drug and the possibility of creating a local depot of selenium using a nanocomposite

Проблема нейротоксичности лекарственных препаратов при лечении больных туберкулезом

The article presents the analysis of 36 publications about neurotoxic properties of anti-tuberculosis drugs, their clinical manifestations and mechanisms of the neurotoxic action. It specifies predisposing factors for the development of neurotoxicity and risk groups. It highlights the necessity of early detection of neurotoxicity caused by chemotherapy regimens for timely management and adequate treatment of patients.Проанализированы данные 36 источников литературы о нейротоксических свойствах противотуберкулезных препаратов, их клинических проявлениях и механизмах нейротоксического действия. Выделены предрасполагающие факторы к развитию нейротоксичности и группы риска. Обоснована необходимость раннего выявления нейротоксичности схем химиотерапии для своевременной коррекции и полноценного лечения пациентов

IMPACT OF EXPRESS SUSCEPTIBILITY TESTING TO RIFAMPICIN OF M. TUBERCULOSIS ON CHEMOTHERAPY EFFICIENCY IN THOSE SUFFERING FROM MULTIPLE DRUG RESISTANT TUBERCULOSIS

Goal of the study: to compare efficiency of anti-tuberculosis chemotherapy prescribed basing on drug susceptibility testing results obtained by GeneXpertMTB/RIF with relevant correction as per data of culture on liquid media and basing on drug susceptibility testing through culture on liquid media only. Materials and methods. 185 pulmonary tuberculosis patients in the age from 18 to 60 years were included into the study and divided into three groups: Groups 1 and 2 included those susceptible and resistant to rifampicin respectively which was detected by GeneXpert MTB/RIF. Group 3 was formed retrospectively out of patients suffering from multiple drug resistance in whom no test systems had been used.Results. If chemotherapy regimen was appropriately chosen basing on rifampicin susceptibility data obtained only through GeneXpert MTB/RIF, the time of sputum conversion confidently did not differ for those suffering from multiple drug resistance and those without it.Prescription of chemotherapy regimen basing on GeneXpert MTB/RIF results with consequent correction as per culture results obtained by Bactec MGIT 960 confidently enhances treatment outcomes in multiple drug resistant tuberculosis patients both regarding sputum conversion rate and cavity healing compared to the group where treatment regimen was corrected basing on results of culture on liquid media. Using GeneXpert MTB/RIF significantly reduces the number of chemotherapy regimens corrections or transfers to the other regimen. Under-detection of rifampicin resistance when using GeneXpert MTB/RIF compared to Bactec MGIT 960 was fixed on the level of 1.5% (95% CI 0.42-5.44%)

Нефротоксические свойства противотуберкулезных препаратов

The review analyzes publications devoted to the frequency of renal adverse reactions during tuberculosis chemotherapy. The most significant pathophysiological mechanisms causing development of drug-induced nephrotoxicity are presented. The article describes the specific features of nephrotoxic effect of aminoglycosides, capreomycin, rifampicin, pyrazinamide, fluoroquinolones, and linezolid. The authors concluded that it was necessary to perform clinical and laboratory monitoring of kidney function for the timely detection of nephrotoxic reactions.В обзоре представлен анализ данных литературы о частоте нежелательных реакций со стороны почек при химиотерапии больных туберкулезом. Рассмотрены наиболее значимые патофизиологические механизмы развития лекарственной нефротоксичности. Показаны особенности нефротоксического действия аминогликозидов, капреомицина, рифампицина, пиразинамида, фторхинолонов, линезолида. Сделано заключение о необходимости регулярного клинико-лабораторного мониторинга функции почек для своевременного выявления нефротоксических реакций

Особенности проявления нейротоксичности некоторых комбинаций препаратов для лечения лекарственно-устойчивого туберкулеза через призму экспериментальных исследований

The objective: to evaluate comparative neurotoxicity of combinations of anti-tuberculosis and antimicrobial drugs with different and similar toxic potentials assessing behavioral changes in rats.Subjects and Methods: non-linear female rats divided in 3 groups were used in this study. For 14 days, the rats received a daily combinations of drugs: Group 1 – Mxf + Lzd + Cs + Pto, Group 2 – Mxf + Bdq + Cs + Z , and Group 3 – Bdq + Lzd + Cfz + Z. Neurotoxicity was assessed by changes in behavioral responses using Open Field Test. The number of crossed squares and racks was recorded which characterized horizontal and vertical activity, also peeping into burrows (exploratory activity), the number of groomings (washing and scratching) and physiological functions were registered.Results. In rats of Group 1 versus baseline parameters, we observed a significant limitation of horizontal motor activity and a sharp decrease (by 5 times) in exploratory activity, a 2.8-fold decrease in the number of groomings which indicated emotional suppression. In rats of Groups 2 and 3, the decrease in motor and exploratory activity was insignificant but there was a more pronounced emotional depression. The use of the Mxf + Lzd + Cs + Pto combination in which all drugs possessed a neurotoxic potential, led to diverse and profound changes in behavioral responses which indicated a pronounced neurotoxic effect.Цель исследования: оценить сравнительную нейротоксичность сочетаний противотуберкулезных и антимикробных препаратов с различными и сходными токсическими потенциалами по изменению поведенческих реакций у крыс.Материал и методы: исследования проведены на нелинейных крысах-самках, разделенных на 3 группы. В течение 14 дней ежедневно крысы получали комплекс препаратов: в 1-й группе ‒ Mxf + Lzd + Cs + Pto; во 2-й группе ‒ Mxf + Bdq + Cs + Z, в 3-й ‒ Bdq + Lzd + Cfz + Z. Нейротоксичность оценивали по изменению поведенческих реакций в тесте «Открытое поле». Фиксировали количество пересеченных квадратов и стоек, что характеризует горизонтальную и вертикальную активность, заглядываний в норки (исследовательская активность), количество грумингов (умываний, почесываний) и физиологические отправления.Результаты. У крыс 1-й группы по сравнению с исходными показателями наблюдали значительное ограничение горизонтальной двигательной активности и резкое снижение (в 5 раз) исследовательской активности, в 2,8 раза уменьшение количества грумингов, что свидетельствует об эмоциональном угнетении. У крыс 2-й и 3-й групп снижение двигательной и исследовательской активности было незначительным, но было более выраженное эмоциональное угнетение. Применение комбинации Mxf + Lzd + Cs + Pto, в которой все препараты имеют нейротоксический потенциал, привело к разнообразным и глубоким изменениям поведенческих реакций, что свидетельствует о выраженном нейротоксическом эффекте

Distribution of microbial population as a cause and consequence of the anti-bacterial therapy failure of ventilator-associated pneumonia

Goal of the study: to study the specific distribution of microbial population in the lungs in the patients being on artificial pulmonary ventilation for a continuous period of time basing on the results of bacteriological culture of the specimens collected from various parts of the lungs and tracheobronchial system through intravital broncoscopy or post mortem.Materials and methods. Pilot study including intravital and post mortem identification of microbial population in various parts of the lungs and tracheobronchial system in 18 patients with signs of ventilator-associated pneumonia developed after cardiac-vascular and neurosurgical interventions. Intravital microbiological tests of the aspirate collected from all lobar bronchi of both lungs obtained through fiber-optic bronchoscopy were performed in 9 patients. Post mortem collection of pulmonary tissue for culture from all lobes of both lungs, lingulars of the left lung and relevant bronchi (totally 12 specimens from the lungs and bronchi) during 24 hours after death was performed in 9 patients.Results of the study. As per the data of microbiological tests the pulmonary infection was found in all patients from both groups. Intravital tests detected inter-lobar differences of microbial profile in 5 cases, and in 4 cases the differences were detected between the lungs. Post mortem microbiological tests detected differences between lobes and within lobes in 6 cases, of them in 5 cases there were also differences between the lungs. In all cases of nonuniform distribution detected post mortem, differences between lobes were accompanied by the differences within lobes (between tissue of the lungs and draining bronchus). Data analysis of intravital and post mortem microbiological diagnostics detected the similarity in the microbial population distribution in the tracheobronchial system in case of ventilator-associated pneumonia despite the different techniques of specimen collection. The diagnostic test capable to reflect regional distribution of the microbial population has been offered: aspirate culture from 5 lobar bronchi which could be used when managing patients with ventilator-associated pneumonia

Резервуар ВИЧ у больных ВИЧ-инфекцией

An HIV reservoir is a collection of HIV DNA in target cells in an HIV-infected person. HIV reservoir in patients with HIV infection prevents eradication of the pathogen and cure of the disease. The review presents published data on the structure of HIV reservoir, its formation and change of its size at different stages of the disease, depending on the time of treatment initiation. The article demonstrates the results of studies that investigated the effect of antiretroviral therapy on the size of the reservoir and the ability to use the size of HIV reservoir as a clinically significant indicator of the course of the disease. The current strategies for influencing on HIV reservoir are considered, the ultimate goal of which is recovery from HIV infection.Резервуар ВИЧ представляет собой совокупность ДНК ВИЧ в клетках-мишенях в организме больного ВИЧ-инфекцией. Резервуар ВИЧ у больных ВИЧ-инфекцией препятствует эрадикации возбудителя и излечению от заболевания. В обзоре представлены данные литературы о структуре резервуара ВИЧ, его формировании и изменении размера резервуара на разных стадиях заболевания в зависимости от сроков начала лечения. Приведены результаты исследований, в которых изучалось влияние антиретровирусной терапии на размер резервуара и возможность использовать размер резервуара ВИЧ в качестве клинически значимого показателя течения заболевания. Рассмотрены современные стратегии воздействия на резервуар ВИЧ, конечной целью которых является выздоровление от ВИЧ-инфекции