Impact of direct-acting antiviral treatment of hepatitis C on the quality of life of adults in Ukraine.

BACKGROUND: Direct-acting antivirals (DAAs) are highly effective in achieving sustained virologic response among those with chronic hepatitis C virus (HCV) infection. Quality of life (QOL) benefits for an HCV-infected population with high numbers of people who inject drugs and people living with HIV (PLHIV) in Eastern Europe have not been explored. We estimated such benefits for Ukraine. METHODS: Using data from a demonstration study of 12-week DAA conducted in Kyiv, we compared self-reported QOL as captured with the MOS-SF20 at study entry and 12 weeks after treatment completion (week 24). We calculated domain scores for health perception, physical, role and social functioning, mental health and pain to at entry and week 24, stratified by HIV status. RESULTS: Among the 857 patients included in the final analysis, health perception was the domain that showed the largest change, with an improvement of 85.7% between entry and week 24. The improvement was larger among those who were HIV negative (104.4%) than among those living with HIV (69.9%). Other domains that showed significant and meaningful improvements were physical functioning, which improved from 80.5 (95% CI 78.9-82.1) at study entry to 89.4 (88.1-90.7) at 24 weeks, role functioning (64.5 [62.3-66.8] to 86.5 [84.9-88.2]), social functioning (74.2 [72.1-76.2] to 84.8 [83.2-86.5]) and bodily pain (70.1 [68.2-72.0] to 89.8 [88.5-91.1]). Across all domains, QOL improvements among PLHIV were more modest than among HIV-negative participants. CONCLUSION: QOL improved substantially across all domains between study entry and week 24. Changes over the study period were smaller among PLHIV.

Role of cannabinoid receptors in the regulation of cardiac contractility during ischemia/reperfusion.

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.

[The role of interleukin-5 in manifestation of bronchial hyperreactivity (an experimental study)].

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.

[Comparative assessment of various methods of determination of interleukin-5 production and their clinical significance in bronchial asthma]. / Sravnitel'naia otsenka razlichnykh metodov opredeleniia produktsii interleikina-5 i ikh klinicheskoe znachenie pri bronkhial'noi astme.

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.

IL-5 expression in the sputum of patients with bronchial asthma.

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.

[Use of the micronucleus test in the evaluation of cytogenetic state of persons living in the polluted area of the Siberian chemical plant]. / Ispol'zovanie mikroiadernogo testa dlia otsenki sostoianiia tsitogeneticheskogo apparata u liudei, prozhivaiushchikh v zone vliianiia Sibirskogo khimicheskogo kombinata.

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.

Frequencies of micronucleated lymphocytes and Epstein-Barr virus contamination in Altai region residents living near the Semipalatinsk atomic testing ground.

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.

Micronucleus test of erythrocytes and lymphocytes in the blood of the Altai region residents living near the Semipalatinsk atomic proving ground.

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.

Micronucleus test of erythrocytes and lymphocytes in the blood of the people living in the radiation pollution zone as a result of the accident at the Siberian chemical plant on April 6, 1993.

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.