Rouhos A.,University of Helsinki |
Ekroos H.,Porvoo Hospital |
Karjalainen J.,University of Helsinki |
Karjalainen J.,Institute of Military Medicine |
And 2 more authors.
International Archives of Allergy and Immunology | Year: 2010
Background: Measurement of fractional exhaled nitric oxide (FENO) is useful in assessing eosinophilic airway inflammation. Smoking may modify airway inflammation and reduce FENO levels, compromising the diagnostic value of FENO in smokers. How smoking influences FENO in atopic versus nonatopic asthmatics is unknown. The aim of the present study was to compare FENO in atopic and nonatopic steroid-naive young asthmatic adults and in healthy subjects in terms of smoking. Methods: Forty-six (30 atopic) smoking and 70 (54 atopic) nonsmoking steroid-naive army conscripts (mean age 20 years) with current symptomatic asthma underwent FENO measurement, skin prick tests, spirometry with a bronchodilation test, bronchial histamine challenge, and a standardized exercise test. Ten healthy smokers and 9 healthy nonsmokers underwent FENO measurement, spirometry and bronchial histamine challenge. Results: Smokers with asthma showed significantly higher FENO than did healthy smokers and nonsmokers (p = 0.001, both comparisons). Among atopic asthmatics, FENO was lower in smokers than in nonsmokers (p = 0.002) whereas among nonatopic asthmatics no such difference was detectable (p = 0.89). However, even among nonatopic asthmatic smokers FENO was significantly higher than among healthy controls (p = 0.01). Conclusion: Smoking seems to attenuate the increase in FENO in atopic but not in nonatopic asthmatics. This finding suggests differences in biochemical mechanisms of NO formation in atopic and nonatopic asthma. However, FENO was significantly higher both in atopic and nonatopic asthmatic smokers than in healthy controls. This suggests that FENO can be applied for diagnostic purposes also in young adult smokers. © 2010 S. Karger AG, Basel.
Ye F.,Chinese Institute of Microbiology and Epidemiology |
Ye F.,Institute of Military Medicine |
Mi Q.,China Tobacco Yunnan Industrial Co. |
Zhang N.,Institute of Military Medicine |
And 8 more authors.
Bulletin of the Korean Chemical Society | Year: 2016
Chemical modifications of the nucleotides can improve the stability of aptamers against enzyme degradation in serum, but it is not clear whether these methods are effective in snake venom. In this study, a DNA aptamer, βB-1, which specifically recognize β-bungarotoxin and Bungarus multicinctus venom was chosen, and the key binding sequence of the aptamer was determined. Based on the secondary structure of the truncated aptamer, locked nucleic acids and 2'-O-methyl nucleotides were applied to modify the stem and loop sequences, respectively. In addition, a 3'-3'-thymidine cap was also adopted to block the 3' end. It was shown that these chemical modifications can all enhance the stability of the aptamer in snake venom. Simultaneously, modified aptamer with the above modifications in one sequence exhibited a significantly elevated biostability, with the half-life improved from several minutes to 210 min while maintaining its binding affinity to the target. © 2016 Korean Chemical Society, Seoul and Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim.
Rouhos A.,University of Helsinki |
Kainu A.,University of Helsinki |
Piirila P.,University of Helsinki |
Sarna S.,University of Helsinki |
And 4 more authors.
Clinical Physiology and Functional Imaging | Year: 2011
The assessment of the presence of eosinophilic airway inflammation may help in predicting the steroid response in subjects with respiratory symptoms. Unlike patients with asthma, only a subset of patients with chronic obstructive pulmonary disease (COPD) benefits from steroid treatment. Fractional exhaled nitric oxide (FENO) is a useful surrogate marker for eosinophilic airway inflammation, but data on the repeatability of FENO measurements in COPD needed for the assessment of significant change are insufficient. The aim of this study was to assess the short-term repeatability of FENO measurement in subjects with moderate to very severe chronic airway obstruction compared to that in healthy subjects. We studied 20 patients with stable COPD and 20 healthy subjects, and determined FENO (flow rate 50 ml s-1) three times: at baseline, 10 min and 24 h after baseline. Spirometry was performed on the first study day after the FENO measurements. The median FENO concentration in patients with COPD was 15·6 ppb, and in healthy subjects, 15·2 ppb. The coefficient of variation (CoV) for 24-h measurements was 12·4% in COPD patients, and 15·9% in healthy subjects. Among COPD patients with global initiative for chronic obstructive lung disease stage 2 disease, the CoV was 13·7%, and among those with stage 3-4 disease, 10·5%. The findings indicate that the short-term repeatability of FENO measurement in patients with moderate to very severe COPD is equally good as in healthy subjects. A change in FENO exceeding 24% is likely to reflect a minimum measurable change in COPD. © 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.
Vasilyeva I.N.,Institute of Phthisiopulmonology |
Zinkin V.N.,Institute of Military Medicine
Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry | Year: 2012
The low-molecular-weight DNA appears in blood plasma a few hours after exposure of rats to ionizing radiation, and its content correlates directly with the irradiation dose. Cloning has shown, that the low-molecular-weight DNA is enriched with C + G pairs and features of its primary structure characterize its capacity to form rather stable nucleosomes. DNA isolated after irradiation of rats with principally different doses 8 and 100 Gy differed not only quantitatively, but also by the content of the dinucleotides CpG and CpT; this suggests that they originate from different regions of the genome. It has been shown for the first time that exposure of animals to low-frequency noise results in an increase of the content of blood plasma low-molecular-weight DNA. Strokes are characterized by the increase of this DNA during 3 days after the beginning of the acute period, and dynamics of its excretion differs in patients with ischemic and hemorrhagic forms of this disease. In the case of ischemia low-molecular-weight DNA appears in cerebrospinal fluid. In contrast to patients with non-obstructive chronic bronchitis, patients with the chronic obstructive pulmonary disease in the state of remission are characterized by decreased levels of blood plasma low-molecular-weight DNA. The clear dependence between formation and specific features of the low-molecular-weight DNA fraction in blood plasma suggests that it may serve as a universal quantitative marker of apoptosis, which differentiates basically different conditions of the body. © 2012 Pleiades Publishing, Ltd.
PubMed | Institute of Military Medicine and Chinese Institute of Microbiology and Epidemiology
Type: Journal Article | Journal: PloS one | Year: 2014
Antibody-based technology is the main method for diagnosis and treatment of snake bite envenoming currently. However, the development of an antibody, polyclonal or monoclonal, is a complicated and costly procedure. Aptamers are single stranded oligonucleotides that recognize specific targets such as proteins and have shown great potential over the years as diagnostic and therapeutic agents. In contrast to antibodies, aptamers can be selected in vitro without immunization of animals, and synthesized chemically with extreme accuracy, low cost and high degree of purity. In this study we firstly report on the identification of DNA aptamers that bind to -bungarotoxin (-BuTx), a neurotoxin from the venom of Bungarus multicinctus. A plate-SELEX method was used for the selection of -BuTx specific aptamers. After 10 rounds of selection, four aptamer candidates were obtained, with the dissociation constant ranged from 65.9 nM to 995 nM measured by fluorescence spectroscopy. Competitive binding assays using both the fluorescently labeled and unlabeled aptamers revealed that the four aptamers bound to the same binding site of -BuTx. The best binder, B-1, bound specifically to -BuTx, but not to BSA, casein or -Bungarotoxin. Moreover, electrophoretic mobility shift assay and enzyme-linked aptamer assay demonstrated that B-1 could discriminate B. multicinctus venom from other snake venoms tested. The results suggest that aptamer B-1 can serve as a useful tool for the design and development of drugs and diagnostic tests for -BuTx poisoning and B. multicinctus bites.
Fateev I.V.,Institute of Military Medicine |
Bykov V.N.,Institute of Military Medicine |
Chepur S.V.,Institute of Military Medicine |
Pokrovskaya L.A.,Institute of Military Medicine |
And 3 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2012
A model of brain ischemia induced by staged ligation of the left and right common carotid arteries has been developed in experiments on rats. The use to this model led to reduction of animal mortality. On days 2-5 after the second ligature, the animals lost weight, the level of their CNS vulnerability increased, the volume of perceived information reduced, adaptation to environmental conditions and reproduction of conditioned reflexes were disordered. Focal and diffuse destructive changes in the nerve and glia cells were found in the cerebral cortex, hippocampus, and thalamic nuclei. The severity of disorders in the blood supply to the brain depended on the interval between ligation of the carotid arteries. This recommends this model for evaluation of the efficiency of drugs of various pharmacological groups. © 2012 Springer Science+Business Media, Inc.