RESUMO
Mechanography was used to study contractile reaction of airway smooth muscles in experimental bronchial asthma in intact guinea-pigs and those incubated with IL-5. Development of experimental bronchial asthma (BA) in the animals leads to enhancement of contractile reactions of bronchial smooth muscles in response to histamine action. The exposure to IL-5 of the preparations of bronchial smooth muscles increases histamine-mediated bronchial contractility. This may explain the phenomenon of IL-5-mediated bronchial hyperreactivity in the absence of eosinophilic damage to the tissues. Expression of mRNA of IL-5 receptor alpha-chain suggests that development of IL-5-mediated hypersensitivity of bronchial smooth muscles occurs due to the presence of a relevant IL-5 receptor on their surface.
Assuntos
Brônquios/efeitos dos fármacos , Brônquios/patologia , Hiper-Reatividade Brônquica/patologia , Interleucina-5/farmacologia , Animais , Hiper-Reatividade Brônquica/tratamento farmacológico , Cobaias , Histamina/farmacologia , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores de Interleucina/efeitos dos fármacos , Receptores de Interleucina/genética , Receptores de Interleucina-5RESUMO
We assessed the frequencies of micronucleated lymphocytes in 3,036 individuals living in 16 settlements in the western part of the Altai region. The majority of individuals with significantly high frequencies of micronucleated lymphocytes were detected in settlements adjacent to the Semipalatinsk atomic testing ground (SATG). The most considerable genome instability was found in individuals born in the period of intensive testing at the SATG (1949 to 1962). Moreover, we determined that the residents of the settlements adjacent to the SATG have significantly high levels of antibodies to potentially oncogenic Epstein-Barr virus, in addition to high frequencies of micronucleated lymphocytes. The considerable Epstein-Barr virus contamination among the residents in the radiation-polluted zone around the SATG was supposed to be caused by immunodeficiency disorders in these individuals and was correlated with high frequencies of micronucleated cells.
Assuntos
Herpesvirus Humano 4 , Linfócitos/efeitos da radiação , Micronúcleos com Defeito Cromossômico , Guerra Nuclear , Anticorpos Antivirais/análise , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Linfócitos/ultraestrutura , SibériaRESUMO
We analysed the erythrocytes and lymphocytes with micronuclei of 3902 individuals living in 16 settlements in the west of the Altai region. It was found that the majority of individuals with high frequencies of micronucleated cells were in the settlements located near to the Semipalatinsk atomic proving ground. In particular, considerable cytogenetic alterations were found in individuals born during the period of intensive testing on the Semipalatinsk proving ground (from 1949 to 1962). The data we have obtained allow us to conclude that radiation damage of cytogenetic structures in the prenatal (predelivery) and early postnatal periods leading to the formation of micronuclei can remain in the human organism for decades and, perhaps, throughout life.
Assuntos
Aberrações Cromossômicas , Eritrócitos/efeitos da radiação , Testes para Micronúcleos , Lesões por Radiação/epidemiologia , Cinza Radioativa/efeitos adversos , Linfócitos T/efeitos da radiação , Fatores Etários , Eritrócitos/citologia , Feminino , Humanos , Masculino , Guerra Nuclear , Sibéria/epidemiologia , Linfócitos T/citologiaRESUMO
We have carried out analysis of the number of blood erythrocytes and lymphocytes with micronuclei in the inhabitants of four settlements located near the place of the accident which happened at the atomic power station of the Siberian chemical plant (Tomsk-7) on April 6, 1993. In all cases, the people examined showed a considerable increase in the number of cells with micronuclei as compared with the control. We observed the same people for 2 years and found a gradual decrease in the number of cells with micronuclei. This study shows that people born between 1963-1970 have a much higher level of cells with micronuclei, which we tend to see as a result of the radiation accident at the Siberian chemical plant in 1963. The data we have obtained allow us to conclude that penetration of radionuclides into the human organism in the prenatal and early postnatal periods can lead to the formation of stable clones of erythroid cells with micronuclei and a higher level of erythrocytes with micronuclei which can remain in the blood for a long time.
Assuntos
Poluentes Radioativos do Ar/toxicidade , Eritrócitos/efeitos dos fármacos , Eritrócitos/efeitos da radiação , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Adulto , Criança , Humanos , Testes para Micronúcleos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Grupos Raciais , SibériaRESUMO
We have carried out analysis of the number of blood erythrocytes and lymphocytes with micronuclei in the inhabitants of four settlements located near the place of the accident, which happened at the atomic power station of the Siberian chemical plant (Tomsk-7) on April 6, 1993. In all cases, the people examined showed a considerable increase in the number of cells with micronuclei as compared with the control. We observed the same people for two years and found a gradual decrease in the number of cells with micronuclei. It has been shown in this work, that people born in 1963-1970 have a much higher level of cells with micronuclei, which we tend to regard as a result of the radiation accident at the Siberian chemical plant in 1963. The data we have obtained allow us to conclude that penetration of radionuclides into the human organism in the prenatal and early postnatal periods can lead to the formation of stable clones of erythroid cells with micronuclei and a higher level of erythrocytes with micronuclei, which can remain in the blood for a long time.
Assuntos
Poluentes Radioativos do Ar/toxicidade , Aberrações Cromossômicas , Testes para Micronúcleos , Centrais Elétricas , Liberação Nociva de Radioativos , Radioquímica , Adolescente , Adulto , Criança , Eritrócitos/efeitos da radiação , Humanos , Linfócitos/efeitos da radiação , SibériaRESUMO
Interleukin-5 (IL-5) is an important marker of inflammation in bronchial asthma (BA). The level of IL-5 was investigated by immune-enzyme assay (IEA); the expression degree of IL-5 mRNA was studied, before and after the conducted therapy, by the inhibition reaction-IEA (IR-IEA) in sputum and blood serum of patients. No differences between contents of IL-5 were found in blood plasma of patients with various disease degrees or of patients with different BA etiologies. The IL-5 contents in sputum were reliably different in different groups and depended on a disease severity, exacerbation and remission. An evaluation of an expression degree of the IL-5 RNAm in eosinophiles, derived from patients' blood, provided for clarifying the differences between acute asthma and other disease forms and for defining the therapy influence on the parameter in question. The IL-5 RNAm expression in sputum was reliably different in patients with moderate forms and with acute forms of the disease; it was decreasing due to treatment. Finally, the results of the evaluation of the IL-5 level and the study of mRNA expression of the cytokine mutually supplement one another and make it possible to evaluate the disease degree and therapy efficiency.
Assuntos
Asma/imunologia , Interleucina-5/biossíntese , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Asma/sangue , Asma/tratamento farmacológico , Biomarcadores/análise , Biomarcadores/sangue , Humanos , Técnicas Imunoenzimáticas , Interleucina-5/análise , Interleucina-5/sangue , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Escarro/química , Escarro/metabolismoRESUMO
We studied the effect of selective ligands of cannabinoid (CB) receptors on contractility of isolated Langendorff-perfused rat heart under conditions of 45-min total ischemia and 30-min reperfusion. Perfusion with a solution containing selective CB receptor agonist HU-210 for 10 min before ischemia increased the severity of reperfusion contractile dysfunction. This drug decreased left ventricular developed pressure and maximum rates of contraction and relaxation, but had no effect on heart rate and end-diastolic pressure. The negative inotropic effect of the drug was transitory and disappeared after 5-min reperfusion. Pretreatment with selective CB1 receptor antagonist SR141716A and selective CB2 receptor antagonist SR144528 had no effect on heart rate and myocardial contractility during reperfusion. Our results indicate that stimulation of CB receptors can increase the degree of reperfusion-induced cardiac contractile dysfunction. However, endogenous cannabinoids are not involved in the development of myocardial contractile dysfunction during ischemia/reperfusion of the isolated heart.
Assuntos
Contração Miocárdica/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Receptores de Canabinoides/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Canfanos/farmacologia , Dronabinol/análogos & derivados , Dronabinol/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , Masculino , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptores de Canabinoides/efeitos dos fármacos , RimonabantoRESUMO
Expression of IL-5 mRNA and the content of IL-5 in the sputum of patients with asthma of different severity were studied before and after treatment. The expression of IL-5 mRNA in mild asthma differed from that in severe and moderate asthma before and after treatment. The level of IL-5 before therapy was different in patients with mild and severe disease. In patients with severe asthma the level of IL-5 differed before and after treatment.