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1.
J Infect Dev Ctries ; 15(9.1): 7S-16S, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34609955

RESUMO

INTRODUCTION: Approximately 3% of all pediatric TB cases develop MDR-TB, with only 3-4% of such children receiving MDR-TB treatment. In Tajikistan, children as a proportion of all DR-TB in the country increased from 4.3 to 7.5% during 2013-2018. Despite limited evidence on the use of new anti-TB drugs in children, WHO has updated its guidelines for DR-TB treatment for children, and Tajikistan did so in 2013 and 2017. Novel and adapted regimens included individual regimens for RR/MDR, XDR (with and without Bedaquiline and Delamanid) and short treatment regimens with and without injectables. It is important to document the outcomes of the treatment regimens. Therefore, the aim of this study was to describe characteristics of children receiving different treatment regimens for DR-TB, the culture conversion and treatment outcomes. METHODOLOGY: Cohort study of children enrolled in DR-TB treatment by the National Tuberculosis Program in Dushanbe, Tajikistan, January 2013 to July 2019. RESULTS: The study included 60 DR-TB children. The male to female ratio was 1:2 and mean age 13.6 years. Median time to culture conversion was 66 days [IQR:31-103; Range:2-232]. In children with treatment outcomes (N = 58), 93% had favorable outcomes. There were four children (7%) with unfavorable treatment outcomes, all of whom were female 15-17 years, on standard (RR/MDR) treatment during 2013-2015. Favorable outcomes by DR-TB type were 91%, 90%, and 100% in RR/MDR, PreXDR, and XDR-TB patients, respectively. CONCLUSIONS: All children enrolled after the introduction of modified guidelines for novel and adapted regimens for DR-TB showed positive TB treatment outcomes.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Guias de Prática Clínica como Assunto , Tadjiquistão , Resultado do Tratamento
2.
J Infect Dev Ctries ; 15(9.1): 43S-50S, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34609959

RESUMO

INTRODUCTION: Poor human immunodeficiency virus (HIV) testing practices and underreporting of HIV-related data in TB information systems remain barriers to effective care for TB-HIV co-infected patients. HIV testing and recording practices in national TB program have not been formally evaluated in Armenia. This study aimed to assess the recording completeness of HIV testing and HIV status in the national TB program electronic database, and to determine trend in HIV testing and the association between HIV testing and treatment outcomes for all TB patients registered in Armenia (2015-2019). METHODOLOGY: A cohort study of TB patients using routine programmatic data from the national TB program of Armenia. RESULTS: From 2015 to 2019, the electronic database was completed for HIV testing and HIV status by 48.1% and 97.5%, respectively. Of all registered TB patients 93.6% were tested for HIV. Of a total 4,674 patients, 1,085 (23.2%) had unsuccessful outcomes. Patients with HIV status "not tested" and "not recorded" compared to HIV "negatives" had 1.76 (95%CI 1.42-2.11) and 1.6 (95%CI 1.20-2.06) times higher risk of unsuccessful outcomes, respectively. Lost to follow-up was the most frequent unsuccessful outcome in HIV status "not tested" group. CONCLUSIONS: An analysis of nationwide data revealed incompleteness of the national TB electronic database for HIV data. Patients with HIV status "not tested" and "not recorded" had higher risk of unsuccessful TB treatment outcomes. Upgrade of the electronic database with information on key indicators of TB-HIV services will facilitate improved monitoring and reporting.


Assuntos
Infecções por HIV/epidemiologia , Teste de HIV/estatística & dados numéricos , Tuberculose/epidemiologia , Adulto , Armênia/epidemiologia , Estudos de Coortes , Bases de Dados Factuais/normas , Feminino , Infecções por HIV/diagnóstico , Soroprevalência de HIV , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Artigo em Inglês | MEDLINE | ID: mdl-34071899

RESUMO

People living with the human immunodeficiency virus (PLHIV) have a higher risk of developing active tuberculosis (TB) disease, and TB remains a major cause of death in PLHIV. Uzbekistan is facing a substantial TB epidemic, which increases the risk of PLHIV developing active TB. Our retrospective cohort study aimed to evaluate the incidence rate and assess the risk factors for developing active TB among PLHIV. We collected secondary data extracted from medical charts of all patients, newly diagnosed at the AIDS Center in Tashkent, during the period of 2015-2017. The incidence rate of TB among PLHIV was 5.1 (95% CI: 4.5-6.0) per 1000 person/month. Adjusted regression analysis showed three major risk factors for TB, namely, being less than 15 years old (hazard ratio (HR) 5.83; 95% CI: 3.24-10.50, p value = 0.001),low CD4 count (adjusted hazard ratio(aHR) 21.0; 95% CI: 9.25-47.7, p value < 0.001), and antiretroviral therapy (ART) interruption/not receiving ART (aHR 5.57; 95% CI: 3.46-8.97 and aHR 6.2; 95% CI: 3.75-10.24, p value < 0.001, respectively) were significantly associated with developing active TB among PLHIV. Our findings indicate that taking prescribed ART without interruptions and maintaining CD4cell counts higher than 320 cells/µL are essential to prevent the development of active TB among PLHIV.


Assuntos
Infecções por HIV , Tuberculose , Adolescente , Contagem de Linfócito CD4 , Estudos de Coortes , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Tuberculose/epidemiologia , Uzbequistão/epidemiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-34072161

RESUMO

Tuberculosis (TB) pleural effusion (TPE) is the second most common manifestation of extrapulmonary TB (EPTB), which remains a great diagnostic challenge worldwide. In Uzbekistan, there has been no formal evaluation of the actual practices of diagnosing and treating TPE. Our cohort study therefore aimed to describe the frequency and types of different diagnostic procedures of TPE during 2017-2018 and assess the association of baseline characteristics and establish diagnostic methods with TB treatment outcomes. In total, 187 patients with presumptive TPE were assessed, and 149 had a confirmed diagnosis of TPE (other diagnoses included cancer n = 8, pneumonia n = 17, and 13 cases were unspecified). TB was bacteriologically confirmed in 22 (14.8%), cytologically confirmed in 64 (43.0%), and histologically confirmed in 16 (10.7%) patients. Hepatitis was the only co-morbidity significantly associated with unsuccessful treatment outcomes (RR 4.8; 95%CI: 1.44-15.98, p value 0.011). Multivariable regression analysis showed that drug-resistant TB was independently associated with unsuccessful TB treatment outcome. (RR 3.83; 95%CI: 1.05-14.02, p value 0.04). Multidisciplinary approaches are required to maximize the diagnostic accuracy of TPE and minimize the chances of misdiagnosis. TPE patients with co-infections and those with drug resistance should be more closely monitored to try and ensure successful TB treatment outcomes.


Assuntos
Derrame Pleural , Tuberculose Pleural , Estudos de Coortes , Humanos , Derrame Pleural/diagnóstico , Derrame Pleural/epidemiologia , Sensibilidade e Especificidade , Resultado do Tratamento , Uzbequistão/epidemiologia
5.
Trop Med Infect Dis ; 6(2)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073360

RESUMO

BACKGROUND: High compliance to infection prevention and control (IPC) is vital to prevent health care-associated infections. In the worst 2014-2015 Ebola-affected district in Sierra Leone (Kenema), we assessed (a) average yearly IPC compliance (2016-2018) using a National IPC assessment tool in the district hospital and peripheral health units (PHUs), and (b) gaps in IPC activities, infrastructure and consumables in 2018. METHODS: This was a cross-sectional study using secondary program data. RESULTS: At the district hospital, compliance increased from 69% in 2016 to 73% in 2018 (expected minimal threshold = 70%; desired threshold ≥ 85%). Compliance for screening/isolation facilities and decontamination of medical equipment reached 100% in 2018. The two thematic areas with the lowest compliance were sanitation (44%) and sharps safety (56%). In PHUs (2018), the minimal 70% compliance threshold was not achieved in two (of 10 thematic areas) for Community Health Centers, four for Community Health Posts, and five for Maternal and Child Health Units. The lowest compliance was for screening and isolation facilities (range: 33-53%). CONCLUSION: This baseline assessment is an eye opener of what is working and what is not, and can be used to galvanize political, financial, and material resources to bridge the existing gaps.

6.
Trop Med Infect Dis ; 6(2)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068850

RESUMO

Wastewater treatment plants receive sewage containing high concentrations of bacteria and antibiotics. We assessed bacterial counts and their antibiotic resistance patterns in water from (a) influents and effluents of the Legon sewage treatment plant (STP) in Accra, Ghana and (b) upstream, outfall, and downstream in the recipient Onyasia stream. We conducted a cross-sectional study of quality-controlled water testing (January-June 2018). In STP effluents, mean bacterial counts (colony-forming units/100 mL) had reduced E. coli (99.9% reduction; 102,266,667 to 710), A. hydrophila (98.8%; 376,333 to 9603), and P. aeruginosa (99.5%; 5,666,667 to 1550). Antibiotic resistance was significantly reduced for tetracycline, ciprofloxacin, cefuroxime, and ceftazidime and increased for gentamicin, amoxicillin/clavulanate, and imipenem. The highest levels were for amoxicillin/clavulanate (50-97%) and aztreonam (33%). Bacterial counts increased by 98.8% downstream compared to the sewage outfall and were predominated by E. coli, implying intense fecal contamination from other sources. There was a progressive increase in antibiotic resistance from upstream, to outfall, to downstream. The highest resistance was for amoxicillin/clavulanate (80-83%), cefuroxime (47-73%), aztreonam (53%), and ciprofloxacin (40%). The STP is efficient in reducing bacterial counts and thus reducing environmental contamination. The recipient stream is contaminated with antibiotic-resistant bacteria listed as critically important for human use, which needs addressing.

7.
Trop Med Infect Dis ; 6(1)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33800026

RESUMO

Antimicrobial resistance (AMR) is the acquired ability of pathogens to withstand antimicrobial treatment. To bridge the gap in knowledge for implementing effective and targeted interventions in relation to the AMR in Armenia, we designed this study to explore the performance of AMR diagnostics and the profile of AMR in the Nork Infection Clinical Hospital (NICH) for the period of 2016-2019, particularly to (i) determine the proportions of antimicrobial resistance among all samples tested at the hospital laboratory, (ii) determine the proportion of resistance against specific antimicrobials, and (iii) identify factors associated with AMR. A cross-sectional study was conducted with a secondary data analysis that included all the patients tested for AMR in the laboratory of the NICH for the period of 2016-2019. For this period, only 107 (0.3%) patients out of 36,528 had their AMR test results available and of them, 87 (81%) had resistance at least to one tested antimicrobial. This study has provided some valuable information on the AMR situation in Armenia. The results call for immediate actions to control the access to and the use of antimicrobials, strengthen AMR surveillance, and improve laboratory capacity for the proper and fast identification of drug resistance through a comprehensive system.

8.
Monaldi Arch Chest Dis ; 91(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33470082

RESUMO

To evaluate factors associated with tuberculosis (TB) treatment outcomes in human Immunodeficiency Virus-Associated (HIV) TB patients in Armenia, we conducted a nation-wide cohort study using routine programmatic data of all HIV-associated TB patients receiving TB treatment with first- or second-line drugs from 2015 to 2019. Data were obtained from the TB and HIV electronic databases. We analysed occurrence of the combined unfavourable outcome (failure, lost to follow-up, death and not evaluated) and death separately, and factors associated with both outcomes using Cox regression. There were 320 HIV-associated TB patients who contributed a total of 351 episodes of TB treatment. An unfavourable TB treatment outcome was registered in 155 (44.2%) episodes, including 85 (24.2%) due to death, 38 (10.8%) lost to follow up, 13 (3.7%) failure and 19 (5.4%) not evaluated. Multivariable analysis showed that receipt of Antiretroviral Treatment (ART) [ART start before TB treatment: adjusted hazard ratio (aHR)=0.3, 95% confidence interval (CI): 0.2-0.5, aHR=, 95% CI:, 95% CI:, 95% CI:TB meningitis (aHR=4.4, 95% CI: 1.6-11.9) increased the risk. The risk of death was affected by the same factors as above in addition to the low BMI (aHR=2.5, 95% CI: 1.3-4.5) and drug resistance (aHR=2.3, 95% CI: 1.0-5.4). In the subsample of episodes receiving ART, history of interruption of ART during TB treatment increased the risk of unfavourable outcome (aHR=2.1 95% CI: 1.2-3.9), while ART start during TB treatment was associated with lower risk of both unfavourable outcome (within first 8 weeks: aHR: 0.5, 95% CI: 0.3-0.9; after 8 weeks: aHR: 0.4, 95% CI: 0.2-1.0) and death (within first 8 weeks: aHR: 0.2, 95% CI: 0.1-0.4; after 8 weeks: aHR: 0.1, 95% CI: 0.01-0.3). The rates of unfavourable TB treatment outcomes, and death in particular, among HIV-associated TB patients in Armenia are high. Our findings emphasize the protective effect of ART and the importance of proper management of cases complicated by drug resistance or meningitis.


Assuntos
Infecções por HIV , Tuberculose , Armênia/epidemiologia , Estudos de Coortes , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia
9.
Monaldi Arch Chest Dis ; 91(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33470086

RESUMO

Rifampicin-Resistant/Multidrug-Resistant Tuberculosis (RR/MDR-TB) is recognized as a major public health concern globally. In Armenia, the proportion of RR/MDR-TB is increasing among all people affected with TB. We conducted a nationwide cohort study involving analysis of programmatic data to investigate the rates of and factors associated with unfavourable treatment outcomes among patients with RR/MDR-TB registered by the national TB programme from 2014 to 2017 in Armenia. We used Cox regression to identify factors associated with the outcome. Among 451 RR/MDR-TB patients, 80% were men and median age was 46 years. Of them, 53 (11.8%) had Extensively Drug-Resistant Tuberculosis (XDR-TB) and 132 (29.3%) had pre-XDR-TB. Almost half (224, 49.7%) of the patients had unfavourable treatment outcome, which included 26.8% Loss To Follow-Up (LTFU), 13.3% failures and 9.5% deaths. In multivariable analysis, people with pre-XDR-TB [adjusted Hazard Ratio [aHR] 3.13, 95% confidence intervals [CI] 2.16-4.55] and XDR-TB (aHR 4.08, 95% CI 2.45-6.79) had a higher risk of unfavourable outcomes. Patients receiving home-based treatment (71/451, 15.7%) and treatment with new drugs (172/451, 38.1%) had significantly lower risk (aHR 0.45, 95% CI 0.28-0.72 and aHR 0.26, 95% CI 0.18-0.39) of unfavourable treatment outcome.  The proportion of MDR-TB patients reaching favourable treatment outcome in Armenia was substantially lower than the recommended level (75%). The most common treatment outcome was LTFU indicating the need for further assessment of underlying determinants. Home-based treatment looks promising and future studies are required to see if expanding it to all RR/MDR-TB patients is feasible and cost-effective.


Assuntos
Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/uso terapêutico , Armênia/epidemiologia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Rifampina/uso terapêutico , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
10.
Exp Gerontol ; 146: 111244, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33454353

RESUMO

Accounting for increasingly developed population aging and dramatic elevation of aging-related severe disorders worldwide, search of the efficient antiaging agents is becoming one of the urgent problems of contemporary biomedical science. The aim of current study was to reveal the potential protective effects of water-soluble proteins extracted from albumen gland of snails against aging processes. We evaluated the antioxidant effect of the extract in 20 older adult rats in vivo and on 60 human blood samples ex vivo at the cellular level under physiological and oxidative stress conditions using the methods of spectrophotometric analysis, two-photon imaging and cell viability assay. The in vivo animal experiments showed significant increase in the levels of catalase and superoxide dismutase in treated older adult rats, compared to non-treated group. The ex vivo studies involving three human groups (young, middle aged and older adult), demonstrated that the extract has no effect on the cell viability, moreover significantly increases the number of erythrocytes, decreases age-related oxidative stress and the percentage of hemolysis of erythrocytes by aging. Thus, the snails albumen gland protein extract can be considered as effective natural antioxidative antiaging agent in prevention of aging-related pathological processes associated with oxidative stress.


Assuntos
Antioxidantes , Água , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Estresse Oxidativo , Ratos , Superóxido Dismutase/metabolismo
11.
J Infect Dev Ctries ; 14(11.1): 88S-93S, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33226965

RESUMO

INTRODUCTION: Odesa province has the highest TB/HIV prevalence in Ukraine, exceeding the total prevalence in the country by 3 times. The objective of this study was to investigate the unfavorable treatment outcomes and associated factors in patient with drug-resistant (DR) TB in people living with HIV (PLH) in Odesa. METHODOLOGY: A cohort study with secondary data analysis was conducted among 373 PLH with confirmed pulmonary DR TB for 2014-2016. RESULTS: About 2/3rd of the cohort were males from urban areas. Mean age and CD4 counts were 39 and 203, respectively. The overall treatment success was 44.2% with the most unfavorable treatment outcomes being observed in extensively and pre-extensively drug resistant (XDR and PreXDR) TB. The mean time between the results of GeneXpert (manufactured by Cepehid) and DR TB treatment based on GeneXpert was 1.3 days. However, the mean time between DR TB treatment based on GeneXpert and results of drug susceptibility test (DST) was 37.0 days referring to a late reporting of DST and to a late adjustment of previously prescribed treatment. The factors associated with the treatment unfavorable outcome included XDR and Pre-XDR TB, lack of antiretroviral treatment (ART), contrimoxazole preventive therapy (CPT) and CD4 test. CONCLUSIONS: The rate of successful DR TB treatment in PLH in Odesa remains low. The delayed reporting of DST contributes to lack of timely adjusted treatments. XDR and Pre-XDR TB, lack of ART and CPT are associated with unfavorable treatment outcomes. Additional studies would help to understand the temporal relationship between CD4 test and treatment outcomes.


Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Análise de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/virologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/virologia , Ucrânia/epidemiologia
12.
J Infect Dev Ctries ; 14(11.1): 122S-127S, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33226970

RESUMO

INTRODUCTION: Men who have sex with men (MSM) are one of the key populations driving HIV/AIDS epidemic globally. To date, MSM is the only population in Ukraine where the prevalence and incidence of HIV is increasing. As HIV-positive MSM might feel uncomfortable to report homosexual intercourses as a possible mode of transmission (MoT) of HIV, they prefer being registered as patients with heterosexual or non-defined MoT. This study aimed to calculate the proportion of misclassified MoT among HIV-positive MSM registered in Lviv oblast, Ukraine, during 2014-2018. METHODOLOGY: Cross-sectional study with 127 HIV-positive MSM patients from Lviv region for the period of 2014-2018. RESULTS: Out of 127 HIV-positive MSM included in the study, 110 (86.6%) were from urban areas. In addition, 52 patients (40.9%) were diagnosed with stage 1 HIV, 16 (12.6%) - stage 2, 19 (15%) - stage 3, and 36 (28.3%) - stage 4. CD4 count < 200 cells/µL was found in 35 (27.6%) patients. Mean time from registration to antiretroviral therapy initiation was 80 days. During the first visit to medical doctor out of those 48 patients who had previously reported "other modes" of HIV transmission, 33 patients (68.7%) disclosed homosexual MoT of HIV. The remaining 15 (31.3%) patients disclosed their homosexual MoT of HIV later - during their regular follow-up visits to the doctor. CONCLUSION: Special measures are needed to improve the reporting of homosexual MoT which can potentially strengthen the HIV care among MSM.


Assuntos
Infecções por HIV/transmissão , Homossexualidade Masculina/psicologia , Homossexualidade Masculina/estatística & dados numéricos , Estigma Social , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Transmissão de Doença Infecciosa , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sexual , Ucrânia/epidemiologia , Adulto Jovem
13.
Biomed Opt Express ; 11(7): 3444-3454, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33014543

RESUMO

According to the "oxidative stress theory" of aging, this process is accompanied by a progressive and irreversible accumulation of oxidative damage caused by reactive oxygen species (ROS). This, in turn, has a deleterious impact on molecular mechanisms in aging thereby altering the physiological function of the organism, increasing the risk of different aging-related diseases, as well as impacting the life span. The aim of the current study was to investigate oxidative stress in living red blood cells (RBCs) in human aging as an oxidative stress-related pathological condition. Two-photon laser scanning and light microscopy techniques were applied to analyze the oxidative stress in RBCs and the cell viability. Spectrophotometric analyzes were performed to determine the percentage of RBC hemolysis, activities of superoxide dismutase and catalase in RBCs, as well as the ferroxidase activities of ceruloplasmin in blood plasma samples. The studies included three human aging groups, young, middle-aged, and elderly. According to the results, the two-photon fluorescence of carboxy-DCFDA, indicating the intensity of oxidative stress, significantly increase in RBCs by the increase of age (P < 0.05), and these intensities are in statistically significant positive correlation with age (P < 0.001) and a strong negative correlation (P < 0.05) with the activity of catalase in RBCs and ferroxidase activity of ceruloplasmin in plasma. In conclusion, two-photon fluorescent imaging of oxidative stress in human living RBCs is a valuable and accurate method for the determination of aging processes in humans and can be suggested as a novel indicator for human aging processes in individual aging.

14.
Mycotoxin Res ; 36(1): 73-81, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31441013

RESUMO

Recently, it was reported that ochratoxin A (OTA) mycotoxin, produced by a number of Aspergillus and Penicillium fungal species, may cause neuropsychological impairment or mental and emotional disorders but the mechanism of neurotoxicity remains unknown. Adverse effects of OTA in human (SHSY5Y) and mouse (HT22) neuronal cell lines were studied in vitro. OTA was found to be non-cytotoxic in both cell lines at concentrations 2.5-30 µmol/l, which are above the levels reported for human and animal plasma. OTA led to slightly elevated chromosomal instability in HT22 cells at concentrations of 15-30 µmol/l after 48 h, while in SHSY5Y cells, no evidence for genotoxic effects was observed at concentrations of 2.5-30 µmol/l. OTA treatment at 10 µmol/l resulted in elevated levels of unmethylated cytosines in CpG dinucleotides (up to 1.4-fold), elevated levels of intracellular reactive oxygen species (up to 1.6-fold), and in elevated levels of oxidized DNA purines (up to 2.2-fold) in both cell lines. Detected global DNA hypomethylation and oxidative stress were found to be reversible in 96 h and 24-72 h, respectively. In general, the observed pattern of OTA-induced effects in both cell lines was similar, but HT22 cells exhibited higher sensitivity, as well as better repair capacity in response to OTA toxicity. In conclusion, the results suggest that oxidative stress and epigenetic changes are directly involved in OTA-induced neurotoxicity, while cytotoxicity and genotoxicity cannot be considered as primary cause of toxicity in neuronal cells in vitro.


Assuntos
Metilação de DNA/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Ocratoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Cromossomos/efeitos dos fármacos , Humanos , Camundongos , Micotoxinas/toxicidade , Neurônios/patologia , Síndromes Neurotóxicas
15.
Int J Mol Sci ; 20(20)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31627284

RESUMO

Rapidly evolving laser technologies have led to the development of laser-generated particle accelerators as an alternative to conventional facilities. However, the radiobiological characteristics need to be determined to enhance their applications in biology and medicine. In this study, the radiobiological effects of ultrashort pulsed electron beam (UPEB) and X-ray radiation in human lung fibroblasts (MRC-5 cell line) exposed to doses of 0.1, 0.5, and 1 Gy are compared. The changes of γH2AX foci number as a marker of DNA double-strand breaks (DSBs) were analyzed. In addition, the micronuclei induction and cell death via apoptosis were studied. We found that the biological action of UPEB-radiation compared to X-rays was characterized by significantly slower γH2AX foci elimination (with a dose of 1 Gy) and strong apoptosis induction (with doses of 0.5 and 1.0 Gy), accompanied by a slight increase in micronuclei formation (dose of 1 Gy). Our data suggest that UPEB radiation produces more complex DNA damage than X-ray radiation, leading to cell death rather than cytogenetic disturbance.


Assuntos
Apoptose/efeitos da radiação , Fibroblastos/efeitos da radiação , Terapia a Laser , Lasers , Pulmão/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Quebras de DNA de Cadeia Dupla , Histonas/genética , Humanos , Testes para Micronúcleos
16.
J Radiat Res ; 58(6): 894-897, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28992052

RESUMO

Laser-generated electron beams are distinguished from conventional accelerated particles by ultrashort beam pulses in the femtoseconds to picoseconds duration range, and their application may elucidate primary radiobiological effects. The aim of the present study was to determine the dose-rate effect of laser-generated ultrashort pulses of 4 MeV electron beam radiation on DNA damage and repair in human cells. The dose rate was increased via changing the pulse repetition frequency, without increasing the electron energy. The human chronic myeloid leukemia K-562 cell line was used to estimate the DNA damage and repair after irradiation, via the comet assay. A distribution analysis of the DNA damage was performed. The same mean level of initial DNA damages was observed at low (3.6 Gy/min) and high (36 Gy/min) dose-rate irradiation. In the case of low-dose-rate irradiation, the detected DNA damages were completely repairable, whereas the high-dose-rate irradiation demonstrated a lower level of reparability. The distribution analysis of initial DNA damages after high-dose-rate irradiation revealed a shift towards higher amounts of damage and a broadening in distribution. Thus, increasing the dose rate via changing the pulse frequency of ultrafast electrons leads to an increase in the complexity of DNA damages, with a consequent decrease in their reparability. Since the application of an ultrashort pulsed electron beam permits us to describe the primary radiobiological effects, it can be assumed that the observed dose-rate effect on DNA damage/repair is mainly caused by primary lesions appearing at the moment of irradiation.


Assuntos
Dano ao DNA , Reparo do DNA/efeitos da radiação , Elétrons , Ensaio Cometa , Relação Dose-Resposta à Radiação , Humanos , Células K562 , Probabilidade
17.
BMC Public Health ; 16: 945, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27604802

RESUMO

BACKGROUND: Children's exposure to lead poses a significant risk for neurobehavioral consequences. Existing studies documented lead contamination in residential soil in mining and smelting communities in Armenia. This study aimed to assess blood lead levels (BLL) in children living in three communities in Armenia adjacent to metal mining and smelting industries, and related risk factors. METHODS: This cross-sectional study included 159 children born from 2007 to 2009 and living in Alaverdi and Akhtala communities and Erebuni district in Yerevan - the capital city. The BLL was measured with a portable LeadCare II Blood Lead Analyzer; a survey was conducted with primary caregivers. RESULTS: Overall Geometric Mean (GM) of BLL was 6.0 µg/dl: 6.8 for Akhtala, 6.4 for Alaverdi and 5.1 for Yerevan. In the sample 68.6 % of children had BLL above CDC defined reference level of 5 µg/dl: 83.8 % in Akhtala, 72.5 % in Alaverdi, and 52.8 % in Yerevan. Caregiver's lower education, dusting furniture less than daily, and housing distance from toxic source(s) were risk factors for higher BLL. Additional analysis for separate communities demonstrated interaction between housing distance from toxic source(s) and type of window in Erebuni district of Yerevan. CONCLUSIONS: The study demonstrated that children in three communities adjacent to metal mining and smelting industries were exposed to lead. Investigation of the risk factors suggested that in addition to promoting safe industrial practices at the national level, community-specific interventions could be implemented in low- and middle-income countries to reduce BLL among children.


Assuntos
Exposição Ambiental/análise , Chumbo/sangue , Metalurgia , Mineração , Adulto , Armênia , Cuidadores , Pré-Escolar , Estudos Transversais , Feminino , Geografia , Habitação/estatística & dados numéricos , Humanos , Masculino , Metais , Fatores de Risco , Solo
18.
F1000Res ; 5: 1921, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28344771

RESUMO

Schiff bases and their metal-complexes are versatile compounds exhibiting a broad range of biological activities and thus actively used in the drug development process. The aim of the present study was the synthesis and characterization of new Schiff bases and their copper (II) complexes, derived from L-tryptophan and isomeric (2-; 3-; 4-) pyridinecarboxaldehydes, as well as the assessment of their toxicity in vitro. The optimal conditions of the Schiff base synthesis resulting in up to 75-85% yield of target products were identified. The structure-activity relationship analysis indicated that the location of the carboxaldehyde group at 2-, 3- or 4-position with regard to nitrogen of the pyridine ring in aldehyde component of the L-tryptophan derivative Schiff bases and corresponding copper complexes essentially change the biological activity of the compounds. The carboxaldehyde group at 2- and 4-positions leads to the higher cytotoxic activity, than that of at 3-position, and the presence of the copper in the complexes increases the cytotoxicity. Based on toxicity classification data, the compounds with non-toxic profile were identified, which can be used as new entities in the drug development process using Schiff base scaffold.

19.
Emerg Infect Dis ; 21(3): 474-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25695488

RESUMO

To understand use of tuberculosis (TB) services for migrant workers, we conducted a cross-sectional census of 95 migrant workers with TB from Armenia by using medical record reviews and face-to-face interviews. Prolonged time between diagnosis and treatment, treatment interruption, and treatment defaults caused by migrant work might increase the risk for multidrug-resistant TB.


Assuntos
Migrantes , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Idoso , Antituberculosos/uso terapêutico , Armênia/epidemiologia , Humanos , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Razão de Chances , Vigilância da População , Prevalência , Risco , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
20.
Health Care Women Int ; 36(1): 121-34, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25126825

RESUMO

Despite documented low-quality care in Armenia, surveys document high ratings of patient satisfaction with health care services. We explored reasons for high satisfaction in Armenia despite poor quality. Twenty-five women who recently delivered participated in this qualitative study through in-depth interviews. Patients avoided critiquing health care services because of personal relationships with and respect for providers and fear of losing services. Although they shared an understanding of what quality care should be, many were satisfied because their low expectations were met. Further mixed methods research may explain this dissonance. Until then, patient satisfaction measures need careful, contextual interpretations.


Assuntos
Serviços de Saúde Materna/organização & administração , Parto , Satisfação Pessoal , Qualidade da Assistência à Saúde/normas , Adulto , Armênia , Atitude Frente a Saúde , Estudos Transversais , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Entrevistas como Assunto , Parto/etnologia , Satisfação do Paciente , Gravidez , Pesquisa Qualitativa , Apoio Social , Fatores Socioeconômicos , Inquéritos e Questionários
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