22 research outputs found

    Agricultural Development in Kuzbass in 1981–1985

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    The article describes the agricultural sector of the Kemerovo Region (Kuzbass). The author used it as an example to identify the main stages of agricultural development of Western Siberia in 1981–1985. The study relied on the theory of modernization, which links economic and political changes with agricultural reforms. According to archival documents and regional statistics, the new tools of economic development and the favorable investment climate allowed the industry to overcome the agrarian crisis in the early 1980s, improve the state of affairs on collective and state farms, and increase the agricultural production. The new measures included producing for profit, labor contracts, and elements of land lease as the economic independence of agricultural enterprises continued to grow. The regional agricultural sector developed much faster in the 1980s than in the late 1970s. However, non-production costs, crop waste, and cattle mortality remained high while irrational utilization of state resources was quite common. In general, Kuzbass showed average agricultural indicators for the West Siberian economic region

    Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance?

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    Rapidly growing resistance of pathogenic bacteria to conventional antibiotics leads to inefficiency of traditional approaches of countering infections and determines the urgent need for a search of fundamentally new anti-infective drugs. Antimicrobial peptides (AMPs) of the innate immune system are promising candidates for a role of such novel antibiotics. However, some cytotoxicity of AMPs toward host cells limits their active implementation in medicine and forces attempts to design numerous structural analogs of the peptides with optimized properties. An alternative route for the successful AMPs introduction may be their usage in combination with conventional antibiotics. Synergistic antibacterial effects have been reported for a number of such combinations, however, the molecular mechanisms of the synergy remain poorly understood and little is known whether AMPs cytotoxicy for the host cells increases upon their application with antibiotics. Our study is directed to examination of a combined action of natural AMPs with different structure and mode of action (porcine protegrin 1, caprine bactenecin ChBac3.4, human alpha- and beta-defensins (HNP-1, HNP-4, hBD-2, hBD-3), human cathelicidin LL-37), and egg white lysozyme with varied antibiotic agents (gentamicin, ofloxacin, oxacillin, rifampicin, polymyxin B, silver nanoparticles) toward selected bacteria, including drug-sensitive and drug-resistant strains, as well as toward some mammalian cells (human erythrocytes, PBMC, neutrophils, murine peritoneal macrophages and Ehrlich ascites carcinoma cells). Using “checkerboard titrations” for fractional inhibitory concentration indexes evaluation, it was found that synergy in antibacterial action mainly occurs between highly membrane-active AMPs (e.g., protegrin 1, hBD-3) and antibiotics with intracellular targets (e.g., gentamicin, rifampcin), suggesting bioavailability increase as the main model of such interaction. In some combinations modulation of dynamics of AMP-bacterial membrane interaction in presence of the antibiotic was also shown. Cytotoxic effects of the same combinations toward normal eukaryotic cells were rarely synergistic. The obtained data approve that combined application of antimicrobial peptides with antibiotics or other antimicrobials is a promising strategy for further development of new approach for combating antibiotic-resistant bacteria by usage of AMP-based therapeutics. Revealing the conventional antibiotics that increase the activity of human endogenous AMPs against particular pathogens is also important for cure strategies elaboration

    Клинико-экономический анализ применения препарата Гиотриф® (афатиниб) в первой линии терапии местнораспространённого или метастатического немелкоклеточного рака лёгкого с мутацией Del19 рецептора эпидермального фактора роста (EGFR)

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    Purpose of the analysis is to assess the cost-effectiveness and cost-utility of Giotrif® (afatinib) as first line treatment for metastatic non-small cell lung cancer NSCLC with Del 19 mutation of EGFR gene in comparison with erlotinib, gefitinib and combination cisplatin/ pemetrexed. Markov modeling was implemented to simulate clinical and economical outcomes of different strategies in treatment of na ve patients based on randomized clinical trial results. Direct medical costs were considered. Afatinib used as first line treatment in patients with NSCLC with Del 19 gene mutation increased quality-adjusted life years (QALY) by 0,354, 0,665 and 0,670 QALY in comparison with erlotinib, gefitinib and combination cisplatin/ pemetrexed respectively. The ICERs were 1 052 934, 1 067 116 и 1 064 708 rubles in comparison with erlotinib, gefitinib and combination cisplatin/ pemetrexed respectively per QALY. Afatinib was shown to be the cost-effective strategy in first line treatment of metastatic NSCLC with Del 19 gene mutation as willingness to pay threshold (1 455 741,77 rubles) was not exceeded.Целью данного исследования является анализ клинико- экономической эффективности и полезности применения препарата афатиниб у больных немелкоклеточным раком лёгкого (НМРЛ) с мутацией Del19 гена EGFR в 1-й линии терапии в сравнении с эрлотинибом, гефитинибом и комбинацией цисплатин/ пеметрексед. Использовано моделирование на основе результатов клинических исследований. Учитывались только прямые медицинские затраты: стоимость медикаментозного лечения НМРЛ в первой и второй линиях терапии; затраты на коррекцию нежелательных явлений, затраты на госпитализации и амбулаторное лечение пациентов. Анализ показал, что афатиниб увеличивает продолжительность жизни с учётом качества по сравнению с эрлотинибом на 0,354 QALY, по сравнению с гефитинибом на 0,665 QALY, по сравнению с комбинацией цисплатин/пеметрексед на 0,670 QALY у пациентов с мутацией Del19 рецептора EGFR. Значение коэффициента эффективности дополнительных затрат ICER для афатиниба, в сравнении с альтернативными режимами терапии 1-й линии эрлотинибом, гефитинибом и комбинацией цисплатин/пеметрексед составляет 1 052 934, 1 067 116 и 1 064 708 руб. соответственно и не превышает порог готовности общества платить (1 455 741,77 руб.). Таким образом, терапия препаратом Гиотриф® (афатиниб) больных НМРЛ с мутацией Del19 рецептора EGFR в 1-й линии терапии в условиях российского здравоохранения является максимально клинически эффективной и экономически целесообразной

    Hydrogen-Induced Microstructure Changes in Zr/Nb Nanoscale Multilayer Structures

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    Zr/Nb nanoscale multilayer coatings (NMCs) were studied after hydrogenation in a gaseous environment at 400 °C. The hydrogen distribution and content were determined by pressure and hydrogenation time. Increasing the pressure from 0.2 to 2 MPa resulted in different hydrogen distribution within the Zr/Nb NMCs, while the concentration remained constant at 0.0150 ± 0.0015 wt. %. The hydrogen concentration increased from 0.0165 ± 0.001 to 0.0370 ± 0.0015 wt. % when the hydrogenation time was extended from 1 to 7 h. The δ-ZrH hydride phase was formed in the Zr layers with Zr crystals reorienting towards the [100] direction. The Nb(110) diffraction reflex shifted towards smaller angles and the interplanar distance in the niobium layers increased, indicating significant lateral compressive stresses. Despite an increase in pressure, the nanohardness and Young’s modulus of the Zr/Nb NMCs remained stable. Increasing the hydrogen concentration to 0.0370 ± 0.0015 wt. % resulted in a 40% increase in nanohardness. At this concentration, the relative values of the Doppler broadening variable energy positron annihilation spectroscopy (S/S0) increased above the initial level, indicating an increase in excess free volume due to hydrogen-induced defects and changes. However, the predominant positron capture center remained intact. The Zr/Nb NMCs with hydrogen content ranging from 0.0150 ± 0.0015 to 0.0180 ± 0.001 wt. % exhibited a decrease in the free volume probed by positrons, as demonstrated by the Doppler broadening variable energy positron annihilation spectroscopy. This was evidenced by opposite changes in S and W (S↓W↑). The microstructural changes are attributed to defect annihilation during hydrogen accumulation near interfaces with the formation of hydrogen–vacancy clusters and hydrides

    Peculiarities of Oxidative Polymerization of Diarylaminodichlorobenzoquinones

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    New oxidative polymerization monomers—diarylaminodichlorobenzoquinones were synthesised by alkylating aniline, m-phenylenediamine and methanilic acid with chloranil. Oxidative polymerization of diarylaminodichlorobenzoquinones was studied for the first time in relation to the concentration of the monomer, acid, and oxidant/monomer ratio. It was found that the synthesized monomers are highly active in the polymerization reaction, and the oxidation rate grows with the increase in the acid concentration. Only one arylamine group is involved in the polymerization reaction. The optimal oxidant/monomer ratio is stoichiometric for one arylamine group, despite the bifunctionality of the monomers. It was shown that the type of the substituent in the aniline ring (electron donor or electron acceptor) determines the growth of the polymer chain and the structure of the resulting conjugated polymers. A mechanism for the formation of active polymerization centers for diarylaminodichlorobenzoquinones was proposed. FTIR-, NMR-, X-ray photoelectron spectroscopy, and SEM were used to identify the structure of the synthesized monomers and polymers. The obtained polymers have an amorphous structure and a loose globular morphology. The frequency dependence of the electrical conductivity was studied

    New geographical and host records of bat fleas (Siphonaptera: Ischnopsyllidae) in Russia

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    To better understand the distribution and host-parasite relationships, we explored 12 large regions of Russia and recorded new bat fleas (Insecta: Siphonaptera: Ischnopsyllidae) for Dagestan, Bashkiria, Mordovia, Khakassia and Buryatia Republics. Also we curate previously known data and registered new host-parasite associations for species belonging to genus Ischnopsyllus (Ischnopsyllus octactenus and I. variabilis ex Pipistrellus pygmaeus, I. intermedius ex Hypsugo savii, I. variabilis ex Myotis dasycneme, I. hexactenus ex Murina hilgendorfi) and species Myodopsylla trisellis. One of the associations we recorded in Altai republic is particularly interesting (Myodopsylla trisellis – Myotis blythii). Further investigation is required to study vector role of bat fleas and the effects of flea parasitism on their natural hosts

    Arterial-ventricular coupling and tolerance to physical exertion in patients with primary hypothyroidism

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    Aim. To study the influence of medicamentous compensation of primary hypothyroidism on tolerance to physical exertion and arterial-ventricular coupling. Material and methods. Thirty-one women with primary hypothyroidism underwent stress-echocardiography before and after medicamentous achievement of euthyroid state. Subclinical hypothyroidism was diagnosed in 15 patients. Overt hypothyroidism was diagnosed in 16 patients. Results are presented with 95% confidence interval. Results. In patients with subclinical hypothyroidism reaching of euthyroid state was associated with an increase of physical capacity from 72.2 (55.9–88.5) to 95.5 (82.1–108.9) Wt (p  0.001), a decrease in arterial stiffness index from 4.80 (4.45–5.15) to 3.87 (3.56–4.18) mm Hg × ml-1 × m-2 (p  0.001), a decrease in left ventricular stiffness index from 6.67 (6.03–7.31) to 5.87 (5.30–6.44) mm Hg × ml-1× m-2 (p  0.005). In patients with overt hypothyroidism reaching of euthyroid state was associated with an increase of physical capacity from 75.4 (64.1–86.6) to 98.2 (88.6–107.7) Wt (p  0.001), a decrease in arterial stiffness index from 4.56 (4.18–4.94) to 4.00 (3.73–4.27) mm Hg × ml-1 × m-2 (p  0.001), a decrease in left ventricular stiffness index from 6.47 (5.86–7.08) to 6.13 (5.69–6.57) mm Hg × ml-1 × m-2 (p  0.05). In patients with subclinical hypothyroidism cardiovascular arterial-ventricular coupling index decreased from 0.72 (0.69–0.75) to 0.66 (0.62–0.71) units. In patients with overt hypothyroidism cardiovascular arterial-ventricular coupling index decreased from 0.71 (0.67–0.74) to 0.66 (0.63–0.69) units. In the whole group gain of left ventricular stiffness index after physical exertion increased from 4.13 (3.67–4.59) to 6.05 (5.60–6.50) mm Hg × ml-1 × m-2 (p  0.01), cardiovascular arterial-ventricular coupling index increased from 0.07 (0.03–0.10) to 0.14 (0.11–0.17) units (p 0.01)
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