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Piotr Kuna Yavor Ivanov Vasily Ivanovich Trofimov Takefumi Saito Ola Beckman Thomas Bengtsson Carin Jorup Fran?ois Maltais 《Respiratory research》2013,14(1):64
Background
We investigated the efficacy and safety of AZD3199, a novel inhaled ultra-LABA, with the main aim of establishing a dose that would maintain 24-hour bronchodilation in patients with COPD.Methods
Patients (n = 329) were randomized to AZD3199 (200, 400 or 800 μg o.d.), formoterol (9 μg b.i.d.) or placebo via Turbuhaler® in a parallel group study. The primary objective of the study was to compare the clinical efficacy of three doses of AZD3199 inhaled once daily with 9 μg formoterol twice daily and placebo, over a 4-week treatment period in adults with moderate-to-severe COPD. After 4 weeks, peak (0–4 h) and trough (24–26 h) forced expiratory volume in 1 second (FEV1) were assessed as the primary efficacy outcome variables.Results
All AZD3199 doses significantly increased mean peak and trough FEV1 versus placebo (106–171 ml and 97–110 ml increases, respectively), but with no clear dose–response; the level of bronchodilation was comparable to or greater than that achieved with formoterol. Forced vital capacity (FVC) at peak bronchodilation also significantly increased with AZD3199 versus placebo (153–204 ml). COPD symptom scores and reliever use were reduced with AZD3199, while FEV1 reversibility was unaltered. Adverse events were mild-to-moderate, with no safety concerns identified. Drug exposure was dose-proportional, but lower than predicted from healthy volunteers.Conclusions
All three doses of AZD3199 produced 24-hour bronchodilation, but with no clear dose–response, suggesting that doses of 200 μg or less may be sufficient to maintain bronchodilation over 24 hours in patients with COPD. No safety concerns were identified. Further studies are required to determine the once-daily AZD3199 dose for COPD.Trial registration
Clinicaltrials.gov, NCT00929708相似文献64.
Homeostasis as an ability to maintain structural-functional parameters of the system at the required level is a basic characteristic for providing the stability of any biological system (from biosphere and separate ecosystems to communities, populations, and individuals). The study of homeostatic mechanisms that provide the stability of biological systems is the main task for solving many theoretical and practical questions. The search for criteria of homeostasis estimation and study of homeostatic mechanism ratio at different levels are principally important in this direction. Estimation of the role of homeostatic mechanisms of the organism and population for providing the stability of biological systems of different levels when using the approach based on estimation of the population state from ontogenetic positions (population developmental biology) seems promising. 相似文献
65.
A. V. Maerle D. Yu. Ryazantsev O. A. Dmitrenko E. E. Petrova R. L. Komaleva I. V. Sergeev D. Yu. Trofimov S. K. Zavriev 《Russian Journal of Bioorganic Chemistry》2014,40(5):526-531
A highly sensitive test system, based on the immuno-PCR method, was developed for the detection of two staphylococcal toxins: enterotoxin A (SEA) and toxic shock syndrome toxin (TSST). A key element of the developed systems was to obtain supramolecular complexes of bisbiotinylated oligodeoxynucleotides and streptavidin, which were to be used as DNA-tags. Specificity studies showed no cross-reactivity when determining SEA and TSST. The sensitivity of detection of these toxins in the culture supernatants S. aureus was not lower than 10 pg/mL. 相似文献
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N I Riabchenko S Ia Proskuriakov K M Petrova V I Riabchenko F A Trofimov 《Radiobiologiia》1985,25(6):795-798
Among three substances under study, only o-nitroanilide of maleic acid (oNAM) possessed a radiosensitizing activity. Radiosensitivity of E. coli B/r cells irradiated in the presence of Ar and oNAM was higher by 4.8 times than that of irradiated controls. The survival rate of E. coli B/r cells irradiated in the presence of oxygen was changed by 1.4 times by the effect of oNAM. 相似文献
69.
Alexander V. Trofimov Alexey V. Sokolov Alexandra Y. Rak Alexander M. Ischenko Tatiana V. Kudling Andrey V. Vakhrushev Alexei A. Gorbunov 《Journal of molecular recognition : JMR》2020,33(9)
Monoclonal antibodies (mAbs) against morphine are important in the development of immunotherapeutic and diagnostic methods for the treatment and prevention of drug addiction. By the surface plasmon resonance (SPR) and enzyme immunoassay techniques, we characterized two previously obtained mAbs 3K11 and 6G1 and showed their ability to recognize free morphine and morphine‐containing antigens in different ways because of the epitope specificity thereof. Using the defined amino acid sequences, we obtained three‐dimensional models of the variable regions of Fab fragments of these antibodies and compared them with the known sequence and spatial structure of the anti‐morphine antibody 9B1. Docking simulations are performed to obtain models of the antibodies complexes with morphine. Differences in the models of 3K11 and 6G1 complexes with morphine correlate with their experimentally detected epitope specificity. The results, in particular, can be used for the structure‐based design of the corresponding humanized antibodies. According to our modeling and docking results, the very different modes of morphine binding to mAbs 3K11 and 6G1 are qualitatively similar to those previously reported for cocaine and two anti‐cocaine antibodies. Thus, the obtained structural information brings more insight into the hapten recognition diversity. 相似文献
70.
I. E. Trofimov 《Entomological Review》2008,88(6):651-657
The population phenetic structure was studied in the burying beetle Nicroforus vespillo (Linnaeus, 1761) from Kaluga city pine forest. Some possible phenes of N. vespillo were distinguished and frequencies of their occurrence studied. As a result, all the samples belonged to the same population. The phene pool of the population was characterized by indices of intrapopulation diversity and a share of rare morphs. Based on these characteristics, logarithmic trends were elaborated showing graphically the annual dynamics of the beetle population. 相似文献