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1.
Heliyon ; 9(11): e21451, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027802

RESUMO

Since previous few decays the consideration of non-Newtonian liquids motion due to its immense usages in medicine, biology, industrial procedures, chemistry of catalysts and in environment. Various studies examine the significance of bio-materials flow in physiological procedures to explore the cure of diagnosed symptoms of disease appearing during movement in a human physiological system. To illustrate the characteristics of physiological liquids various non-Newtonian models have been proposed, but yet no such single liquid model is exploited which describes all the properties of nonlinear behaving liquids. Among these several non-Newtonian models, Jeffery liquid model should be reduced to its base fluid case (i.e. viscous liquid) by choosing λ1 = λ2 = 0. Various physiological materials which represents both linear and nonlinear characteristics respectively blood is one of these. Jeffery fluid and peristaltic motion have some common properties such as radii, relaxation time and retardation time. Moreover heat and mass transfer is also an important phenomenon which is suitable for various physiological processes such as hemodialysis and oxygenation etc. Thus due to such motivating facts this research is conducted to investigate the peristaltic motion of electrically conducting Jeffery liquid. The peristaltic propagating channel walls are asymmetric and inclined. Joule heating and magnetic field effects are considered by applying magnetic field in transverse direction to the flow. Further conservation laws modelled the flow situation via considering quadric mix convection, thermos diffusion and diffusion-thermos, heat generation and absorption, chemical reaction with activation energy features. Moreover, creeping flow and long wavelength assumptions are used to simplify the mathematical modelling. The reduced system of equation is solved numerically through built-in technique in Mathematica software. This built-in technique is working through ND Solve command and shooting and RK-Felburg numerical schemes are behind this technique. These numerical results are used to discuss the flow quantities i.e., velocity, temperature and concentration against the sundry dimensionless quantities. Examining the results it comes to know that both thermal and concentration nonlinear mix convection have oppositely affecting the axial velocity. Both heat and mass transfer are escalating function of thermo-diffusion/diffusion-thermo aspects.

2.
Urologiia ; (5): 127-134, 2022 Nov.
Artigo em Russo | MEDLINE | ID: mdl-36382831

RESUMO

Since the end of 2019, the world has been overwhelmed by a pandemic of a new coronavirus infection (COVID-19), a disease that damages various organs and systems. Because of the extensive coverage of the population by the infection, the long-term effects of the disease are not well understood, which is of considerable scientific and practical interest. We performed an in-depth analysis and systematization of data from foreign and domestic publications in the Scopus, Web of Science, eLIBRARY, PubMed, Wiley Online Library, and Google Scholar databases were performed. Information searches included original articles, reviews, guidelines, manual comments, and editorials related to the effects of SARS-CoV-2 virus on the male reproductive system. Accumulated clinical evidence suggests that the SARS-CoV-2 virus and the COVID-19 disease it causes have a negative impact on male reproductive health.. Drugs with a negative effect on spermatogenesis are used in the therapy of patients with COVID-19. These include lopinavir, chloroquine and its derivatives, and widely used glucocorticosteroids. Lopinavir and chloroquine have subsequently been excluded from potential COVID-19 therapy. Although available data on the fertility of men with COVID-19 are scarce and the results of published studies are from a limited sample, it is clear that maintaining male reproductive health during the COVID-19 pandemic is a pressing issue in modern medicine and requires further in-depth study. Preconceptional screening should be recommended for men who have undergone COVID-19.


Assuntos
COVID-19 , Infertilidade , Humanos , Masculino , SARS-CoV-2 , Pandemias , Lopinavir , Cloroquina
3.
Ter Arkh ; 94(5): 610-615, 2022 Jun 17.
Artigo em Russo | MEDLINE | ID: mdl-36286958

RESUMO

AIM: To evaluate the possible association of CYP2C8 gene polymorphisms with the clinical efficacy and safety of ketorolac in relation to postoperative pain. MATERIALS AND METHODS: The study included 107 patients after video laparoscopic cholecystectomy, who received ketorolac (30 mg 2.0 w/m 3 r/d) as postoperative pain relief. All patients were genotyped for CYP2C8. The pain syndrome was assessed using the visual analog scale, the McGill pain questionnaire. The profile of adverse reactions was assessed by the dynamics of red blood counts, as a possible trigger for the development of gastrointestinal bleeding according to the method of global assessment of triggers (Global Trigger Tool GTT). RESULTS: According to visual analog scale data: in carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080) after 12, 24, 36, 48 hours the intensity of pain syndrome is lower than in carriers of the wild type (p0.05). According to the McGill pain questionnaire, there were no statistically significant differences in pain intensity between the two groups. CONCLUSION: In carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080), the effectiveness of anesthesia with ketorolac is higher than in carriers of the wild type. Carriage of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs10509681) does not affect the risk of developing adverse reactions after ketorolac anesthesia.


Assuntos
Cetorolaco , Dor Pós-Operatória , Humanos , Cetorolaco/efeitos adversos , Citocromo P-450 CYP2C8/genética , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/genética , Medição da Dor , Polimorfismo Genético , Método Duplo-Cego , Anti-Inflamatórios não Esteroides/efeitos adversos
4.
Ann Oncol ; 33(10): 1052-1060, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35764271

RESUMO

BACKGROUND: In the phase II multicohort CheckMate 142 study, nivolumab plus low-dose (1 mg/kg) ipilimumab provided robust and durable clinical benefit with a manageable safety profile in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) at 13.4- and 25.4-month median follow-up (Overman MJ, Lonardi S, Wong KYM et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36:773-779. Overman MJ, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: long-term follow-up. J Clin Oncol. 2019;37:635). Here, we present results from the 4-year follow-up of these patients. PATIENTS AND METHODS: Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression. Primary endpoint was investigator-assessed objective response rate (ORR; as per RECIST version 1.1). RESULTS: A total of 119 patients were treated; 76% had ≥2 prior lines of therapy. Median follow-up was 50.9 months (range 46.9-62.7 months). Median duration of therapy was 24.9 months [95% confidence interval (CI) 15.8-33.2 months]. Investigator-assessed ORR increased from 55% (95% CI 45% to 64%) at 13.4 months to 65% (95% CI 55% to 73%) at 50.9 months with a disease control rate of 81% (95% CI 72% to 87%). The complete response rate increased from 3% at 13.4 months to 13% at 50.9 months. Partial responses were observed in 52% of patients; 21% had stable disease, and 12% had progressive disease. Median time to response was 2.8 months (range 1.1-37.1 months), and median duration of response was not reached (range 1.4+ to 58.0+ months). At data cut-off, 37 (48%) patients had ongoing responses. Median progression-free survival was not reached [95% CI 38.4 months-not estimable (NE)], and median overall survival was not reached (95% CI NE). Grade 3-4 treatment-related adverse events (TRAEs) were observed in 32% of patients; 13% of patients had any-grade TRAEs leading to discontinuation. CONCLUSIONS: The results confirm long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC. The safety profile was manageable with no new safety signals.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA/genética , Seguimentos , Humanos , Ipilimumab , Instabilidade de Microssatélites , Nivolumabe/uso terapêutico
5.
Urologiia ; (6): 122-126, 2022 Dec.
Artigo em Russo | MEDLINE | ID: mdl-36625625

RESUMO

Individual differences in efficacy and safety of drugs between patients are a significant problem in modern pharmacotherapy. The bodys pharmacological response to the administration of a particular drug is determined by multiple factors, where up to 50% of the variability of the pharmacological response may be determined by the genetic variability of the body. The article presents an up-to-date review of the data on genetic polymorphisms influencing the efficacy and safety of tamsulosin therapy in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Tansulosina/uso terapêutico , Sulfonamidas/efeitos adversos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/genética , Quimioterapia Combinada , Biologia Molecular , Resultado do Tratamento , Sintomas do Trato Urinário Inferior/tratamento farmacológico
6.
Environ Monit Assess ; 193(3): 127, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33587193

RESUMO

According to several reports, the presence of transition metal elements in the atmosphere was associated with adverse health effects. The purpose of this investigation was to analyze the presence of transition metal particles with atomic numbers 22-29 on some medicinal plants (n = 22) from various regions of the Republic of Tajikistan and their content in the atmosphere. Samples (n = 43) of individual plant organs, such as seeds, flowers, leaves, trunks, and plant roots, were examined for their elemental composition using X-ray fluorescence analysis. Selection of particles contained in the atmosphere was carried out for 24 h/3 days by the aspiration method using fiberglass filters GF 10 in an apparatus installed at an altitude of 864 m on the periphery of the capital. For the analysis of plant samples, measurements were carried out on a SPECTROSCAN MAX-G wave-dispersive X-ray fluorescence spectrometer. For samples containing filtered atmosphere elements, a high-resolution PANanalytical Epsilon 5 high-resolution energy-dispersive spectrometer was used. Eight transition elements from the 1st main series of metals with atomic numbers 22-29, such as titanium, vanadium, chromium, manganese, iron, cobalt nickel, and copper, were found in plant organs, as well as in the atmosphere samples. Our results showed that the distribution of metals on plants varied depending on plants and their organs. We did not find any correlation between the region of plant collection and their absorption of metal elements. The distribution of metals varied in various plant organs. In the atmosphere samples, we found all the metals that were found in plants. In conclusion, medicinal plants can adsorb and accumulate some harmful chemical elements in their organs, are involved in the recirculation of these metals, and contribute air pollution.


Assuntos
Poluição do Ar , Metais Pesados , Cobre/análise , Monitoramento Ambiental , Metais/análise , Metais Pesados/análise , Tadjiquistão
7.
Ter Arkh ; 93(11): 1334-1339, 2021 Nov 15.
Artigo em Russo | MEDLINE | ID: mdl-36286656

RESUMO

AIM: Find the prevalence of CYP2C8*3 (rs10509681; rs11572080), PTGS-1 (rs10306135; rs12353214) and PTGS-2 (rs20417) alleles and genotypes in four ethnic groups among Laks, Avars, Dargins and Kumyks. MATERIALS AND METHODS: The study involved 400 volunteers from four ethnic groups living in Republic of Dagestan: 100 participants from each group. Carriage of polymorphic markers was determined by reverse transcription polymerase chain reaction. RESULTS: Minor allele frequency of the CYP2C8 (rs10509681) was 5.5% in Avars, 10% in Dargins, Laks and Kumyks 6.5% both; CYP2C8 (rs11572080) was 5.5% in Avars, 9.5% in Dargins, 6.5% in Laks, 8.5% in Kumyks; PTGS-1 (rs10306135) in Avars 10.5%, in Dargins 13.0%, in Laks 9.5% and Kumyks 7.5%; PTGS-1 (rs12353214) in Avars 9.0%, in Dargins 4.5%, in Laks 7.5%, in Kumyks 8.0%; PTGS-2 (rs20417) in Avars 1.0%, in Dargins 2.5%, in Laks 3.5%, in Kumyks 5.0%. There were no significant differences between groups. CONCLUSION: The study of CYP2C8 and PTGS-1 and 2 gene polymorphisms is promising for predicting the effectiveness and safety of non-steroidal anti-inflammatory drug therapy, due to the high prevalence of these polymorphisms in ethnic groups in the North Caucasus.


Assuntos
Etnicidade , Polimorfismo Genético , Humanos , Alelos , Anti-Inflamatórios não Esteroides/efeitos adversos , Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP2C9/genética , Etnicidade/genética , Frequência do Gene , Genótipo , Prevalência
8.
Ter Arkh ; 92(8): 43-51, 2020 Sep 03.
Artigo em Russo | MEDLINE | ID: mdl-33346461

RESUMO

AIM: To study the peculiarities of carrying clinically significant allelic variants of TPMT and DPYD genes associated with the response to drug therapy in cancer practice among 9 ethnic groups of the Russian Federation. MATERIALS AND METHODS: The study included 1446 conditionally healthy volunteers from 9 ethnic groups. Carriage of polymorphic TPMT and DPYD gene markers was detected by the Real-Time PCR (polymerase chain reaction) method. RESULTS: In all ethnic groups, the distribution of genotypes and alleles matched the equilibrium of Hardy-Weinberg. TPMT*3A (rs1800460) and TPMT*3C (rs1142345) were observed in heterozygous state in all investigated ethnic groups. In the Kabardinian group (n=204) the frequency of the TPMT*3A minor allele (MAF, %) was 2.94%; Balkars (n=200) 1.25%; Ossetians (n=239) 1.67%; Chuvashes (n=238) 1.89%: Mari (n=206) 1.21%; Tatars (n=141) 1.77%; Russians (n=134) 4.85%. The frequency of the TPMT*3C minor allele (MAF, %) in the Kabardinian group (n=204) MAF was 4.90%; Balkars (n=200) 1. 75%; Buryats (n=114) 0.44%; Ossetians (n=239) 1.88%; Chuvashes (n=238) 1.68%: Mari (n=206) 1.21%; Tatars (n=141) 1.42%; Russians (n=134) 4.48%. The results of the analysis of DPYD*2A polymorphism (rs3918290) demonstrated ethnic peculiarities of distribution. In the heterozygous state it was found only in the groups of Kabardins (n=204, MAF 1.22%), Balkars (n=200, MAF 2.00%), and Ossetians (n=239, MAF 0.63%). CONCLUSION: The results obtained in the study will be useful for developing personalized algorithms of antitumor therapy in cancer practice, including those aimed at increasing the safety of chemotherapy.


Assuntos
Etnicidade , Neoplasias , Alelos , Frequência do Gene , Genótipo , Humanos , Metiltransferases/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Federação Russa
9.
Ter Arkh ; 91(8): 22-27, 2019 Aug 15.
Artigo em Russo | MEDLINE | ID: mdl-32598750

RESUMO

AIM: To evaluate the clinical and economic feasibility of pharmacogenetic testing (PGT) for dabigataran etexilate administration in the treatment of atrial fibrillation (AF) without valve in comparison with tactics without pharmacogenetic testing. MATERIALS AND METHODS: The pharmacoeconomic model was done using generalized data from published clinical, epidemiological and clinical - economic studies. RESULTS AND DISCUSSION: Application of PGT on the carrier of allelic variant rs2244613 of CES1 gene for adjustment of dabigatrane etexilate dosage in patients with non - valve AF may be more cost - effective strategy for prevention of thromboembolic complications in patients with non - valve AF. Thus, due to the decrease in the number of undesirable drug reactions in the form of minor and major bleedings, the difference in treatment costs in the group with PGT compared to the group with standard pharmacotherapy tactics per 100 patients was 11 827.65 rubles. The expected cost per patient per year for standard treatment was 36 051.35 rubles, while in the group with PGT it was 35 933.07 rubles. The difference was 1182.76 rubles in favor of the pharmacogenetic approach Conclusion. A PGT approach to correct dabigatrane dosage can reduce the cost of pharmacotherapy by reducing the risk of adverse reactions of minor and major bleeding.


Assuntos
Antitrombinas , Fibrilação Atrial , Dabigatrana , Acidente Vascular Cerebral , Anticoagulantes , Antitrombinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Benzimidazóis , Análise Custo-Benefício , Dabigatrana/economia , Dabigatrana/uso terapêutico , Humanos , Testes Farmacogenômicos , Acidente Vascular Cerebral/prevenção & controle
10.
Radiats Biol Radioecol ; 54(4): 341-9, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25775822

RESUMO

The present work was aimed at studying the molecular and cellular levels of the response of the hematopoietic system in mice and their progeny to the action of low-LET and high-LET radiation at different times after exposure. The damage to the genome at the molecular level was assessed by the comet assay in peripheral blood leucocytes, whereas at the cellular level it was estimated by means of the micronuclear test in the marrow cells, after exposure of mice to X-radiation of 1, 3 and 5 Gy and to a high-LET low-intensity radiation at thedoses of 0.14 and 0.35 Gy, as well as to a combined effect of these types of radiation. When accessing the level of the DNA damage to individual cells by the comet assay, we also used, apart from a commonly accepted parameter %TDNA, additional characteristics: the proportions of leucocytes with an intact and highly fragmented DNA. Using these parameters, we detected the changes characterizing the dynamics of the leukocyte population in mouse blood at different times after the action of X-ray and high-LET radiation. It was found that: (1) the DNA damage increases with the dose of high-LET radiation; (2) the level of damage in the progeny of the animals exposed to high-LET radiation does not differ from that in unirradiated animals both at the molecular and cytogenetic levels; and (3) a decrease in the radiosensitivity of the progeny of the mice exposed to high-LET radiation at a dose of 0.35 Gy makes itself evident only at the molecular level, which may point to the possible transgeneration transmission of genomic lesions.


Assuntos
Medula Óssea/efeitos da radiação , Dano ao DNA , Raios gama/efeitos adversos , Leucócitos/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Efeitos Tardios da Exposição Pré-Natal/genética , Lesões Experimentais por Radiação/genética , Animais , Medula Óssea/patologia , Ensaio Cometa , Relação Dose-Resposta à Radiação , Feminino , Leucócitos/ultraestrutura , Masculino , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/patologia , Doses de Radiação , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/patologia , Fatores de Tempo
11.
Radiats Biol Radioecol ; 53(4): 380-8, 2013.
Artigo em Russo | MEDLINE | ID: mdl-25427370

RESUMO

Transfer of mtDNA in the nuclear genome is usually regarded as a continued and dynamic process of forming numt-pseudogenes or numt-insertions. They can be regarded not only as a neutral polymorphism, but may be involved in oncogenesis, aging and genetic diseases. Experimental identification of numt-insertions arising de novo is limited due to the presence of numerous homology mtDNA constitutively existing in the nuclear genomes of eukaryotes. It is known that the chick nuclear DNA (nDNA) constitutively contains 12 numt-pseudogenes. We attempted to experimentally detect the formation of numt-insertions de novo in the nDNA of chick embryos (Gallus gallus) from the eggs exposed to X-rays. Free mtDNAs were removed from preparations of nDNA of liver embryos through double gel electrophoresis. Numt-inserts in nDNA of control and survival embryos (from irradiated eggs) were revealed by PCR using 11 pairs of primers flanking the region of mtDNA of about 300-400 bp. PCR analysis with nDNA of control group showed no presence of homology mtDNA amplified with selected primers. PCR assays of nDNA of eight embryos from irradiated eggs showed that nDNA of two embryos contained new sites of mtDNA. PCR amplification of 3 loci of mtDNA is stably detected in nDNA from one embryo and 4 loci of mtDNA in nDNA from another embryo. Sequencing of PCR amplicons synthesized on templates of these nDNA showed that their sequences are identical to mtDNA and accurately cover the sites of several genes and the site of mtDNA D-loop. Thus, the experimental results indicate that ionizing radiation can induce integration of mtDNA fragments in the nuclear genome, apparently, through the mechanism of nonhomologous end-joining repair of double-strand breaks of nDNA.


Assuntos
Núcleo Celular/genética , Galinhas/genética , DNA Mitocondrial/genética , Pseudogenes/genética , Envelhecimento/genética , Animais , Núcleo Celular/efeitos da radiação , Transformação Celular Neoplásica/genética , Genoma , Mitocôndrias/efeitos da radiação , Dados de Sequência Molecular , Radiação Ionizante
12.
Phys Rev E Stat Nonlin Soft Matter Phys ; 84(2 Pt 2): 026204, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21929078

RESUMO

Chaotic transport in a hamiltonian system perturbed by a weak turbulent wave field is studied. It is assumed that a turbulent wave field has a wide spectrum containing up to thousands of modes whose phases are fluctuating in time with a finite correlation time. To integrate the hamiltonian equations a fast symplectic mapping is derived. It has a large time-step equal to one full turn in angle variable. It is found that the chaotic transport across tori caused by the interactions of small-scale resonances have a fractal-like structure with the reduced or zero values of diffusion coefficients near low-order rational tori thereby forming transport barriers there. The density of rational tori is numerically calculated and its properties are investigated. It is shown that the transport barriers are formed in the gaps of the density of rational tori near the low-order rational tori. The dependencies of the depth and width of transport barriers on the wave field spectrum and the correlation time of fluctuating turbulent field (or the Kubo number) are studied. These numerical findings may have importance in understanding the mechanisms of transport barrier formation in fusion plasmas.

13.
Biomed Khim ; 56(4): 517-25, 2010.
Artigo em Russo | MEDLINE | ID: mdl-21032903

RESUMO

Quantitative and qualitative changes in circulating extracellular DNA (ec-DNA) of blood plasma are considered as markers for diagnosis and prognostic of tumor pathology. We investigated the content of mutant copies of the circulating extracellular mitochondrial DNA (ec-mtDNA) in blood plasma (using the enzymatic method, based on the cleavage of DNA with unpaired bases by CEL-I endonuclease) in 8 patients with lung cancer before and after radiotherapy, as well as in healthy young and elderly donors. It was found that in the plasma of healthy elderly donors share of ec-mtDNA with mutations (consisting of total circulating DNA) is much greater, than that of young donors. On the other hand, in the plasma of lung cancer patients (aged 70-76 years) before radiotherapy a substantial increase in the share of ec-mtDNA with mutations, compared with that of healthy elderly donors. Following radiotherapy, patients with lung cancer found a twofold increase of the proportion of ec-mtDNA with mutations in the total circulating plasma DNA. This increase is largely, perhaps due to the release of ec-mtDNA with mutations from dying tumor cells and cells damaged by normal tissues.


Assuntos
DNA Mitocondrial/sangue , Neoplasias Pulmonares/sangue , DNA Mitocondrial/genética , Espaço Extracelular/metabolismo , Humanos , Neoplasias Pulmonares/radioterapia , Mutação
14.
Radiats Biol Radioecol ; 50(3): 318-28, 2010.
Artigo em Russo | MEDLINE | ID: mdl-20734805

RESUMO

With violations of the mitochondrial genome associated wide range of degenerative diseases, the development of tumor pathology, aging and the processes of cell death. We investigated the levels of mitochondrial DNA (mtDNA) with mutations and their total content in the tissues of the brain, and spleen of mice exposed to X-rays at doses of 1-5 Gy, and depending on the post-radiation time (8-28 days). These same mice were analyzed for the level of mutant copies of the extra cellular mtDNA (ec-mtDNA) and its total content in blood plasma. Mutations were determined by means of CEL-I endonuclease (mismatch-specific enzyme) cleavage of heteroduplexes, obtained by hybridization of PCR amplicons of mtDNA (D-loop region) of irradiated and control mice. The changes of total amount of mtDNA (ND4 gene) copies vs. nuclear DNA (GAPDH gene) measured by real-time PCR method. The results showed that in the tissues of the brain, and of the spleen of irradiated mice (with a maximum at 8 days after exposure) the level of mutant mtDNA copies, with a subsequent decline to a 28-day post-radiation time dramatically increased. Was shown that mutagenesis of mtDNA in the brain and spleen tissues of irradiated mice, well as mutagenesis of nuclear genes, has a linear dependence on the dose X-rays. In contrast, mutant nuclear genes, the majority of mutant mtDNA copies is eliminated from the tissues of the brain and of the spleen, while maintaining them at the same level of total content of mtDNA within 28 days after irradiation in mice. The results show that during this post-radiation time in the plasma of irradiated mice high levels of ec-mtDNA with mutations, with a maximum at the 14th day in the total circulating DNA maintained. These data suggest that the mutant copies of mtDNA eliminated from tissues cells of irradiated animals in the post-radiation period. Elevated levels of ec-mtDNA with mutations in the plasma can be considered as a potential marker for the assessment of radiation injury of organism.


Assuntos
DNA Mitocondrial/análise , DNA Mitocondrial/efeitos da radiação , Mutação/efeitos da radiação , Lesões Experimentais por Radiação/genética , Animais , Biomarcadores/sangue , Encéfalo/efeitos da radiação , DNA Mitocondrial/sangue , Relação Dose-Resposta à Radiação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Baço/efeitos da radiação , Fatores de Tempo , Raios X/efeitos adversos
15.
Genetika ; 45(7): 949-56, 2009 Jul.
Artigo em Russo | MEDLINE | ID: mdl-19705747

RESUMO

Changes in the number of mutant copies of mitochondrial DNA (mtDNA) were studied in the brain and spleen tissues of mice after their X-irradiation at a dose of 5 Gy. For this purpose, heteroduplexes obtained via hybridization of the products of PCR amplification of mtDNA (ND3 gene and two D-loop regions) from irradiated and control mice were digested with the CelI nuclease capable of specific mismatch cleavage. Heteroduplexes obtained via hybridization of the products of PCR amplification of mtDNA from irradiated and control mice were digested by the CelI nuclease to a greater degree than heteroduplexes of the PCR products of mtDNA of mice from the control group. This suggests the presence of mutations in mtDNA regions in irradiated mice. Digestion by the CelI nuclease of heteroduplexes obtained via hybridization of the PCR products of mtDNA (ND3 gene and D-loop regions) on day 8 after irradiation is essentially more efficient than digestion of heteroduplexes obtained via hybridization of the PCR products of mtDNA isolated from mouse tissues on days 14 and 28 of the postradiation period. These results indicate a reduction in the number of mtDNA copies with mutations in tissues of irradiated mice by day 28 of the postradiation period. The reduction in the level of mutant mtDNA copies by this term is especially significant in the spleen. The total number of mtDNA copies in the mouse brain and spleen tissues estimated by real-time PCR, relative to the nuclear beta-actin gene, is also decreased by 30-50% as compared to the control on days 8 to 28 after irradiation. The results of the study suggest that mutant mtDNA copies are eliminated from tissues of irradiated animals in the postradiation period. This elimination can be regarded either as a result of selective degradation of mitochondria carrying mutant DNA copies or as a result of cell death being continued in tissues of irradiated animals.


Assuntos
Encéfalo/efeitos da radiação , Dano ao DNA , DNA Mitocondrial/efeitos da radiação , Baço/efeitos da radiação , Animais , Encéfalo/metabolismo , DNA Mitocondrial/genética , Desoxirribonucleases/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Mutação , Ácidos Nucleicos Heteroduplexes/química , Ácidos Nucleicos Heteroduplexes/genética , Baço/metabolismo , Raios X
16.
Radiats Biol Radioecol ; 49(1): 21-8, 2009.
Artigo em Russo | MEDLINE | ID: mdl-19368317

RESUMO

We defined the mutations in mtDNA of X-irradiated mice brair using mismatch-specific endonuclease (CEL I-nuclease method) and by temporal temperature gradient gel electrophoresis (TTGE-technique). The comparison of the received by both methods, allows to conclude, that CEL I-nuclease method gives more qualitative results, than TTGE-technique. Moreover, CEL I-nuclease method is more sensitive, in contrast with TTGE-technique. The CEL I-nuclease method allows simultaneously to conduct the analysis of big amount of sample DNA, to get the reproducible results. It does not require complex equipment and economical. The analysis of mutations in mtDNA of brain of X-irradiated mice by CEL I-nuclease method has shown, that the amount of mutant copies mtDNA is essentially reduced (in 2-3 times) with 8 up to 28 days of the post-radiation period. However the amount mtDNA copies in brain tissue of the irradiated animals is remains during all post radiation time without change though lower, concerning given control group. The results permit the suggestion that mutant mtDNA copies are eliminated from the tissues of irradiated animals in the post-radiation period.


Assuntos
Encéfalo/metabolismo , Análise Mutacional de DNA/métodos , DNA Mitocondrial/genética , DNA Mitocondrial/efeitos da radiação , Eletroforese em Gel de Poliacrilamida/métodos , Endonucleases/química , Animais , Pareamento Incorreto de Bases , Encéfalo/efeitos da radiação , Genes p53/genética , Genes p53/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ácidos Nucleicos Heteroduplexes/análise , Reação em Cadeia da Polimerase/métodos , Temperatura
17.
Mol Biol (Mosk) ; 43(6): 1063-9, 2009.
Artigo em Russo | MEDLINE | ID: mdl-20088383

RESUMO

Nucleic acids circulating in blood plasma and other biological fluids may be of interest as potential markers for diagnosis of various pathologies and monitoring of stress influences. For many genotoxic agents, mitochondrial DNA (mtDNA) is a more vulnerable target than nuclear DNA, and mutations of mitochondrial genome may be markers of many diseases. In the present study extracellular mtDNA with mutations was determined in the blood plasma of mice exposed to X-radiation at a dose of 5 Gy. Mutations were assessed from cleavage by CEL-endonuclease (mismatch specific cleavage enzyme) of heteroduplexes obtained by hybridization of mtDNA PCR amplikons (gene ND3 and D-loop region) from the blood plasma of irradiated and control mice. The total number of copies of mtDNA (gene ND4) against nuclear DNA (gene GAPDH) was measured by the Real-Time PCR method. A content of mtDNA with mutations in the blood plasma of mice was elevated during one month of the post-radiation period, however, the levels were not the same at different time periods (1, 4, 8, 14, 28 days), the highest one being detected on the 14 day after irradiation. The increased content of extracellular mutant mtDNA in blood plasma of X-irradiated mice can be considered as a sensitive biomarker for assessing radiation injury and effects of other genotoxic agents.


Assuntos
DNA Mitocondrial/sangue , Genoma Mitocondrial , Mutação , Lesões Experimentais por Radiação/sangue , Raios X/efeitos adversos , Animais , Biomarcadores/sangue , DNA Mitocondrial/genética , Relação Dose-Resposta à Radiação , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Tempo
18.
Phys Rev Lett ; 100(25): 255003, 2008 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-18643669

RESUMO

The generation of runaway electrons in the international fusion experiment ITER disruptions can lead to severe damage at plasma facing components. Massive gas injection might inhibit the generation process, but the amount of gas needed can affect, e.g., vacuum systems. Alternatively, magnetic perturbations can suppress runaway generation by increasing the loss rate. In TEXTOR disruptions runaway losses were enhanced by the application of resonant magnetic perturbations with toroidal mode number n=1 and n=2. The disruptions are initiated by fast injection of about 3x10{21} argon atoms, which leads to a reliable generation of runaway electrons. At sufficiently high perturbation levels a reduction of the runaway current, a shortening of the current plateau, and the suppression of high energetic runaways are observed. These findings indicate the suppression of the runaway avalanche during disruptions.

19.
Phys Rev E Stat Nonlin Soft Matter Phys ; 76(2 Pt 2): 026216, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17930130

RESUMO

In many Hamiltonian systems subjected to a time (or space) -periodic perturbation with a broad spectrum an approach is widely used of replacing the system by periodically delta -kicked dynamical systems, which allows us to reduce them to symplectic mappings. In this paper it is shown that this approach has a fundamental failure, and the corresponding mapping does not correctly describe the continuous original system. It is demonstrated on the example of the stochastic web map obtained by this approach to describe a periodically driven harmonic oscillator which exhibits non-Kolmogorov-Arnold-Moser chaos, particularly, the formation of stochastic webs. A correct canonical map corresponding to this system is obtained using a recently developed method based on the canonical transformation of variables [S. S. Abdullaev, J. Phys. A 35, 2811 (2002)]. Using a direct numerical integration of the system it is shown that the canonical map correctly describes the periodically driven harmonic oscillator with a finite number of spectrum modes.

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