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1.
J Appl Toxicol ; 41(1): 175-189, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32969520

RESUMEN

Heterocycles have long been the focus of intensive study in attempts to develop novel therapeutic compounds, and acridine, a polynuclear nitrogen molecule containing a heterocycle, has attracted a considerable amount of scientific attention. Acridine derivatives have been studied in detail and have been found to possess multitarget properties, which inhibit topoisomerase enzymes that regulate topological changes in DNA and interfere with the essential biological function of DNA. This article describes some recent advancements in the field of new 9-substituted acridine heterocyclic agents and describes both the structure and the structure-activity relationship of the most promising molecules. The article will also present the IC50 values of the novel derivatives against various human cancer cell lines. The mini review also investigates the topoisomerase inhibition and antibacterial and antimalarial activity of these polycyclic aromatic derivatives.


Asunto(s)
Acridinas/química , Acridinas/farmacología , Acridinas/toxicidad , Inhibidores de Topoisomerasa II/química , Inhibidores de Topoisomerasa II/farmacología , Inhibidores de Topoisomerasa II/toxicidad , Células Tumorales Cultivadas/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/toxicidad , Antimaláricos/química , Antimaláricos/farmacología , Antimaláricos/toxicidad , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/toxicidad , Humanos , Relación Estructura-Actividad
2.
J Appl Toxicol ; 40(1): 64-71, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31222780

RESUMEN

Proflavine derivatives are extremely interesting chemotherapeutic agents, which have shown promising pharmaceutical potential due to their wide range of biological activities. This review summarizes the current state of research into the anticancer, antimicrobial, antimalarial and antileishmanial properties of these attractive compounds. Our attention has focused on new classes of proflavine conjugates, which display significant levels of anticancer activity. Highly promising cytotoxic properties have been identified in proflavine conjugates with imidazolidinones, ureas and thioureas. In particular, proflavine-dialkyldithioureas displayed substantial cytotoxic effect against the human leukemia HL-60 cells with IC50 values from 7.2 to 34.0 µm. As well, palladium complexes with proflavine ligand have important biologic activity. The LC50 values of these complexes were significantly lower than that of cisplatin against the SK-BR-3 cell line.


Asunto(s)
Acriflavina/farmacología , Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Proflavina/farmacología , Acriflavina/análogos & derivados , Acriflavina/toxicidad , Animales , Antiinfecciosos/toxicidad , Antineoplásicos/toxicidad , Relación Dosis-Respuesta a Droga , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Proflavina/análogos & derivados , Proflavina/toxicidad , Relación Estructura-Actividad
3.
Cent Eur J Public Health ; 28(1): 70-73, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32228821

RESUMEN

OBJECTIVE: Hepatitis E infection is one of the most frequent acute hepatitis in the world. Currently five human genotypes with different geographical distributions and distinct epidemiologic patterns are identified. In Slovakia, only rare cases of hepatitis E have been reported in recent years. Therefore, the aim of the study was to evaluate the prevalence of anti-HEV total antibodies and the main risk factors for HEV in the general population in Eastern Slovakia. METHODS: Detection of anti-HEV total antibodies samples was done by a commercial enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Of 175 hospitalized patients included in the study, 76 (43.5%) showed positivity for anti-HEV total antibodies. No statistically significant differences were found in anti-HEV positivity between men and women or in the groups of different living areas (town/village - urban/rural). CONCLUSION: Prevalence of anti-HEV total antibodies of hospitalised patients was high. The risk factor significantly associated with antibody positivity was eating raw meat. Other factors, such as sex, age, living area and contact with animals were not associated with antibody positivity.


Asunto(s)
Hepatitis E/epidemiología , Hospitalización/estadística & datos numéricos , Ensayo de Inmunoadsorción Enzimática , Femenino , Anticuerpos Antihepatitis/aislamiento & purificación , Virus de la Hepatitis E/inmunología , Humanos , Masculino , Factores de Riesgo , Estudios Seroepidemiológicos , Eslovaquia/epidemiología
4.
J Appl Toxicol ; 38(11): 1377-1387, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29624715

RESUMEN

This review describes the synthesis of a wide range of novel tetrahydroacridine derivatives (tiocyanates, selenocyanates, ureas, selenoureas, thioureas, isothioureas, disulfides, diselenides and several tacrine homo- and hetro-hybrids). These tacrine congeners exhibit significant anticholinesterase and cytotoxic properties and may therefore be of considerable potential for the development of new drugs for the treatment of Alzheimer's disease.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores de la Colinesterasa/farmacología , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/enzimología , Antineoplásicos/química , Antineoplásicos/toxicidad , Butirilcolinesterasa/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/toxicidad , Descubrimiento de Drogas , Humanos , Relación Estructura-Actividad , Tacrina
5.
J Appl Toxicol ; 37(10): 1132-1139, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28370171

RESUMEN

Acridines possess two characteristics that have led many researchers to consider the agents interesting targets for future development as potential farmacophores: the planar acridine skeleton, which is able to intercalate into DNA, and the intense fluorescence of the agents. This review offers a study of the multifunctional character of acridines and the synthesis of novel acridine derivatives, with particular focus being placed on isothiocyanates and their congeners, e.g. thioureas, isothioureas, quaternary ammonium salts and platinum/gold conjugates. The review provides an overview of the structure, spectral properties, DNA binding and biological activity of acridinylthiourea congeners. These acridinylthiourea derivatives display significant cytotoxic activities against different types of cancer cell lines at micromolar concentrations. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Acridinas/síntesis química , Acridinas/farmacología , Daño del ADN/efectos de los fármacos , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Isotiocianatos/síntesis química , Isotiocianatos/farmacología , Proflavina/síntesis química , Proflavina/farmacología , Relación Estructura-Actividad , Tiourea/síntesis química , Tiourea/farmacología
6.
Bioorg Chem ; 57: 13-29, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25171773

RESUMEN

A novel series of trisubstituted acridines were synthesized with the aim of mimicking the effects of BRACO19. These compounds were synthesized by modifying the molecular structure of BRACO19 at positions 3 and 6 with heteroacyclic moieties. All of the derivatives presented in the study exhibited stabilizing effects on the human telomeric DNA quadruplex. UV-vis spectroscopy, circular dichroism, linear dichroism and viscosimetry were used in order to study the nature of the DNA binding in more detail. The results show that all of the novel derivatives were able to fold the single-stranded DNA sequences into antiparallel G-quadruplex structures, with derivative 15 exhibiting the highest stabilizing capability. Cell cycle analysis revealed that a primary trend of the "braco"-like derivatives was to arrest the cells in the S- and G2M-phases of the cell cycle within the first 72h, with derivative 13 and BRACO19 proving particularly effective in suppressing cell proliferation. All studies derivatives were less toxic to human fibroblast cell line in comparison with HT 29 cancer cell line.


Asunto(s)
Acridinas/química , Acridinas/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , ADN/metabolismo , G-Cuádruplex/efectos de los fármacos , Animales , Bovinos , Ciclo Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , ADN/química , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo
7.
Cent Eur J Public Health ; 22 Suppl: S37-42, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24847613

RESUMEN

BACKGROUND: The simultaneous presence of chronic hepatitis B (CHB) and metabolic syndrome (MS) in the high-risk Roma community constitutes a high risk for liver cirrhosis and potentially hepatocellular carcinoma. This study aims to explore the relationship between MS and CHB. METHODS: Data from the cross-sectional HepaMeta Study conducted in Slovakia in 2011 among Roma living in rural communities were used. Participants were tested for the presence of MS, and lipid levels--total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides (TG), apolipoprotein B100, and CHB HBsAg and anti-HBc IgG were also monitored. Viral load was measured in HBsAg-positive patients. RESULTS: A total of 452 patients were screened; MS was diagnosed in 29.6% of patients, and 12.5% had CHB. Anti-HBc IgG antibodies were present in 52.8% of patients. CHB patients had lower levels of total cholesterol (5.45 +/-1.21 vs. 4.71 +/- 1.23 mmol/l; p = 0.035), LDL cholesterol (median 2.2 mmol/l, interquartile range 0.88 mmol/l vs. 2.5 mmol/l, interquartile range 0.9 mmol/l; p = 0.01) and apolipoprotein B100 (median 0.66 mmol/l, interquartile range 0.26 mmol/l vs. 0.74 mmol/l, interquartile range 0.29 mmol/l; p = 0.025). Patients diagnosed with MS had a higher HBV DNA load than patients without MS (1,728.2 +/- 14.33 IU/ml vs. 12,779.1 +/- 20.9 IU/ml; p = 0.037). CHB patients with TC and apolipoprotein B100 within the reference range had a lower hepatitis B DNA (HBV DNA) load than patients with high or low values of TC or apolipoprotein B100. CONCLUSION: The prevalence of chronic hepatitis B and simultaneous presence of MS was high among Roma. HBsAg-positive patients had lower levels of total and LDL cholesterol along with decreased apolipoprotein B100. The viral load of chronic hepatitis B patients with MS was higher than in patients without MS.


Asunto(s)
Hepatitis B/etnología , Síndrome Metabólico/etnología , Romaní/estadística & datos numéricos , Adolescente , Adulto , Apolipoproteína B-100/sangre , Biomarcadores/sangre , Colesterol/sangre , Comorbilidad , Estudios Transversales , Femenino , Encuestas Epidemiológicas/métodos , Encuestas Epidemiológicas/estadística & datos numéricos , Hepatitis B/sangre , Humanos , Lípidos/sangre , Masculino , Síndrome Metabólico/sangre , Persona de Mediana Edad , Romaní/etnología , Población Rural/estadística & datos numéricos , Eslovaquia/epidemiología , Triglicéridos/sangre
8.
Cent Eur J Public Health ; 22 Suppl: S43-50, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24847614

RESUMEN

BACKGROUND: Elevated gamma-glutamyl transpeptidase (GGT) is present approximately in half of all patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is the liver manifestation of metabolic syndrome (MS). This study aimed to explore the relationship between GGT and MS or proinflammatory parameters. METHODS: Data from the cross-sectional HepaMeta study conducted in Slovakia in 2011 among Roma living in rural communities were used. Participants (n = 446) were divided into 2 groups; those with elevated GGT and those with normal GGT levels. MS was diagnosed according to the International Diabetes Federation criteria; presence of central obesity and low density lipoproteins (LDL) or high density lipoproteins (HDL), high triglycerides, hypertension, glucose intolerance or type 2 diabetes. Participants were tested for the presence of MS and its components, and biochemical tests for lipid levels (total cholesterol, HDL, LDL, TG) and inflammatory parameters (high sensitivity C-reactive protein--hs-CRP and ferritin) were performed. RESULTS: Of 446 Roma participants, only 29 (6.5%) had GGT levels above the normal value. After exclusion of patients with viral hepatitis and alcohol abuse, patients with elevated GGT suffered from MS more often (p < 0.001), and patients with more MS components had a higher risk of elevated GGT. We found a significant association between GGT and the individual MS components, except HDL (waist circumference > or = 94 cm in men or 80 cm in women: p < 0.01; BMI > 30: p < 0.001; fasting glucose > or = 5.6 mmol/l: p < 0.001; arterial hypertension: p < 0.05, and TAG > or = 1.7 mmol/l: p < 0.001). Patients with elevated GGT levels had also significantly higher hs-CRP (hs-CRP > 2 mg/l: p < 0.001; hs-CRP > 3 mg/l: p < 0.001) and ferritin (ferritin > 300 mg/l: p < 0.01) levels. CONCLUSION: Patients with MS have more significantly elevated levels of GGT. There is a significant association of GGT with individual MS components, except HDL and inflammatory parameters (hs-CRP, ferritin).


Asunto(s)
Inflamación/sangre , Inflamación/epidemiología , Síndrome Metabólico/etnología , Síndrome Metabólico/enzimología , Romaní/estadística & datos numéricos , gamma-Glutamiltransferasa/sangre , Adolescente , Adulto , Proteína C-Reactiva , Comorbilidad , Estudios Transversales , Dieta/etnología , Dieta/métodos , Dieta/estadística & datos numéricos , Hígado Graso/sangre , Hígado Graso/etnología , Femenino , Ferritinas/sangre , Encuestas Epidemiológicas/métodos , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Inflamación/etnología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Actividad Motora/fisiología , Enfermedad del Hígado Graso no Alcohólico , Factores de Riesgo , Romaní/etnología , Población Rural/estadística & datos numéricos , Eslovaquia/epidemiología , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto Joven
9.
Cent Eur J Public Health ; 22 Suppl: S51-6, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24847615

RESUMEN

BACKGROUND: Viral hepatitis B and C prevalence in the Roma population of eastern Slovakia is largely unknown. This study aimed to explore the prevalence and associated risk factors of chronic viral hepatitis B and C among Roma living in segregated communities in eastern Slovakia. METHODS: Data from the cross-sectional HepaMeta study conducted in Slovakia in 2011 among Roma living in rural communities were used. Participants were tested for the presence of HBsAg, anti-HBc IgG and anti-HCV. The risk factors were assessed mainly via a structured questionnaire/interview. RESULTS: Altogether 452 Roma were screened, and 11 were excluded due to missing data. A total of 441 patients were included (mean age 34.7 +/- 9.14 years; 35.2% men). 12.5% of participants were HBsAg positive, 40.4% anti-HBc IgG positive while negative for HBsAg and 47.2% of participants were negative for all serological markers of hepatitis B. Hepatitis C prevalence was very low (0.7%), while 2 out of 3 anti-HCV positive participants were coinfected with hepatitis B. Risk factors for hepatitis B infection were male sex, higher age, tattoo, and previous imprisonment. No difference was found in intravenous drug use, blood transfusions and sexual behaviour. CONCLUSION: More than half of the Roma residing in eastern Slovakia have been infected at one point in life with the hepatitis B virus, and 12.5% are HBsAg positive. Hepatitis C prevalence is very low, which is probably due to very low intravenous drug use.


Asunto(s)
Hepatitis B/etnología , Hepatitis C/etnología , Romaní/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Enfermedad Crónica , Comorbilidad , Estudios Transversales , Femenino , Encuestas Epidemiológicas/métodos , Encuestas Epidemiológicas/estadística & datos numéricos , Hepatitis B/sangre , Hepatitis C/sangre , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Romaní/etnología , Población Rural/estadística & datos numéricos , Eslovaquia/epidemiología , Encuestas y Cuestionarios , Adulto Joven
10.
Cent Eur J Public Health ; 21(1): 22-5, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23741894

RESUMEN

OBJECTIVES: The aim of this study was to determine the prevalence of HBV infection among pregnant women in districts of Eastern Slovakia with a diverse prevalence of Roma population. METHODS: Overall 59,279 serum samples from 9 regional departments of clinical microbiology from Eastern Slovakia were collected in the period from January 2008 till December 2009 and analysed. RESULTS: The number of HBsAg positive samples overall and during pregnancy was 1.74% and 2.12%, respectively. Comparing districts with higher (> 5%) and lower (< 5%) Roma population, there was no significant difference in the prevalence of HBsAg positive samples overall (1.95% vs.1.62%). However, in the subgroup of pregnant women the prevalence of HBsAg positive samples (2.72% vs. 0.95%) differs significantly (p < 0.01). CONCLUSIONS: The prevalence of HBV infection among pregnant women in Eastern Slovakia did not rapidly exceed the estimated nationwide prevalence. However, in districts with higher Roma population the expected higher prevalence of HBV infection was confirmed. This indicates the need to pay special attention to the prevention of hepatitis B in these districts.


Asunto(s)
Hepatitis B/etnología , Hepatitis B/epidemiología , Complicaciones Infecciosas del Embarazo/etnología , Complicaciones Infecciosas del Embarazo/virología , Femenino , Hepatitis B/virología , Antígenos de la Hepatitis B/aislamiento & purificación , Humanos , Vigilancia de la Población , Embarazo , Eslovaquia/epidemiología
11.
Viruses ; 15(8)2023 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-37632037

RESUMEN

BACKGROUND: It is assumed that the prevalence of hepatitis D in HBsAg-positive individuals reaches 4.5-13% in the world and on average about 3% in Europe. Data from several European countries, including Slovakia, are missing or are from an older period. METHODS: We analyzed all available data on hepatitis D from Slovakia, including reports from the Slovak Public Health Authority and the results of one prospective study, and three smaller surveys. The determination of anti-HDV IgG and IgM antibodies and/or HDV RNA was used to detect hepatitis D. RESULTS: In the years 2005-2022, no confirmed case of acute or chronic HDV infection was reported in Slovakia. The presented survey includes a total of 343 patients, of which 126 were asymptomatic HBsAg carriers, 33 acute hepatitis B, and 184 chronic hepatitis B cases. In a recent prospective study of 206 HBsAg-positive patients who were completely serologically and virologically examined for hepatitis B and D, only 1 anti-HDV IgG-positive and no anti-HDV IgM or HDV RNA-positive cases were detected. In other smaller surveys, two anti-HDV IgG-positive patients were found without the possibility of HDV RNA confirmation. In total, only 3 of 329 HBsAg-positive patients (0.91%) tested positive for anti-HDV IgG antibodies, and none of 220 tested positive for HDV RNA. CONCLUSION: The available data show that Slovakia is one of the countries with a very low prevalence of HDV infection, reaching less than 1% in HBsAg-positive patients. Routine testing for hepatitis D is lacking in Slovakia, and therefore it is necessary to implement testing of all HBsAg-positive individuals according to international recommendations.


Asunto(s)
Hepatitis B , Hepatitis D , Humanos , Eslovaquia/epidemiología , Antígenos de Superficie de la Hepatitis B , Estudios Prospectivos , Hepatitis D/diagnóstico , Hepatitis D/epidemiología , Inmunoglobulina M , Infección Persistente , Inmunoglobulina G
12.
Biochim Biophys Acta ; 1810(4): 465-74, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21276838

RESUMEN

BACKGROUND: Amyloid-related diseases (such as Alzheimer's disease or diabetes type II) are associated with self-assembly of protein into amyloid aggregates. METHODS: Spectroscopic and atomic force microscopy were used to determine the ability of acridines to affect amyloid aggregation of lysozyme. RESULTS: We have studied the effect of acridine derivatives on the amyloid aggregation of lysozyme to investigate the acridine structure-activity relationship. The activity of the effective planar acridines was characterized by the half-maximum depolymerization concentration DC(50) and half-maximal inhibition concentration IC(50). For the most effective acridine derivatives we examined their interaction with DNA and their effect on cell viability in order to investigate their eventual influence on cells. We thus identified planar acridine derivatives with intensive anti-amyloid activity (IC(50) and DC(50) values in micromolar range), low cytotoxicity and weak ability to interfere with the processes in the cell. CONCLUSIONS: Our findings indicate that both the planarity and the tautomerism of the 9-aminoacridine core together with the reactive nucleophilic thiosemicarbazide substitution play an important role in the anti-amyloid activities of studied derivatives. GENERAL SIGNIFICANCE: The present findings favor the application of the selected active planar acridines in the treatment of amyloid-related diseases.


Asunto(s)
Acridinas/química , Acridinas/farmacología , Amiloide/antagonistas & inhibidores , Amiloide/metabolismo , Muramidasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Pollos , ADN/metabolismo , Humanos , Concentración 50 Inhibidora , Relación Estructura-Actividad
13.
Mol Cell Probes ; 26(4): 159-63, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22521237

RESUMEN

BACKGROUND & AIM: Hepatitis C is a liver disease caused by the hepatitis C virus. Interferon and ribavirin combination therapy has been a standard treatment of chronic hepatitis C. But only about 50% of patients have positive response to treatment and achieve so called sustained virological response. Recent studies indicate association of several single nucleotide polymorphisms near IL28B gene and response of hepatitis C patients to combined interferon/ribavirin treatment. In this study, rapid, specific and cost-effective small amplicon genotyping method for the two clinically important polymorphisms, rs12979860 C > T and rs8099917 T > G, near the IL28B gene is described. METHODS: The distribution of genotypes of 181 HCV-uninfected Slovak Caucasians was analyzed using this novel method, based on a real-time melting analysis of the small amplicon. RESULTS AND CONCLUSIONS: The frequency of wild-type (TT) homozygotes for rs8099917 was 66.30%, frequency of heterozygotes (TG) was 30.94% and we found only 2.76% subjects homozygous for risk G allele (allelic frequencies: T = 81.77%, G = 18.23%) were found. The frequency of wild-type genotype (CC) for rs12979860 was 49.72%, frequencies of heterozygous (CT) and risk-allele homozygous genotypes (TT) were 39.78% and 10.50%, respectively (allele frequencies: C = 69.61%, T = 30.39%). Statistically significant differences in the distribution of the alleles between the men and the women were not found. The novel method developed in our laboratory proved to be simple and highly customizable.


Asunto(s)
Hepatitis C/tratamiento farmacológico , Hepatitis C/genética , Interleucinas/genética , Adulto , Anciano , Alelos , Femenino , Pruebas Genéticas , Genotipo , Hepatitis C/metabolismo , Heterocigoto , Homocigoto , Humanos , Interferones , Interleucinas/metabolismo , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple
14.
Bioorg Med Chem ; 20(24): 7139-48, 2012 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-23122936

RESUMEN

Three new acridine-thiazolidinone derivatives (2a-2c) have been synthesized and their interactions with calf thymus DNA and a number of cell lines (leukemic cells HL-60 and L1210 and human epithelial ovarian cancer cell lines A2780) were studied. The compounds 2a-2c possessed high affinity to calf thymus DNA and their binding constants determined by spectrofluorimetry were in the range of 1.37 × 10(6)-5.89 × 10(6) M(-1). All of the tested derivatives displayed strong cytotoxic activity in vitro, the highest activity in cytotoxic tests was found for 2c with IC(50) = 1.3 ± 0.2 µM (HL-60), 3.1 ± 0.4 µM (L1210), and 7.7 ± 0.5 µM (A2780) after 72 h incubation. The cancer cells accumulated acridine derivatives very fast and the changes of the glutathione level were confirmed. The compounds inhibited proliferation of the cells and induced an arrest of the cell cycle and cell death. Their influence upon cells was associated with their reactivity towards thiols and DNA binding activity.


Asunto(s)
Acridinas/síntesis química , Acridinas/farmacología , ADN/metabolismo , Glutatión/metabolismo , Tiazolidinas/síntesis química , Tiazolidinas/farmacología , Acridinas/química , Células HL-60 , Humanos , Sustancias Intercalantes/síntesis química , Sustancias Intercalantes/química , Sustancias Intercalantes/farmacología , Modelos Moleculares , Tiazolidinas/química
15.
Klin Mikrobiol Infekc Lek ; 17(6): 190-3, 2011 Dec.
Artículo en Sk | MEDLINE | ID: mdl-22247028

RESUMEN

Currently, the gold standard for the treatment of chronic hepatitis C is combination therapy with pegylated interferon alpha and ribavirin. Despite advances in treatment modalities, only 50 % of patients achieve sustained virological response. Therefore, determination of predictive factors related to response to therapy is very important. In 2009, three independent studies concerning genome-wide association identified several single nucleotide polymorphisms near the IL-28 gene, associated with virological response. Hence, it appears that genetic polymorphism may become important predictive factors. All patients beginning therapy, will probably be tested for the presence of these polymorphisms, allowing individualized treatment options for every patient.


Asunto(s)
Antivirales/administración & dosificación , Estudio de Asociación del Genoma Completo , Hepatitis C Crónica/genética , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Quimioterapia Combinada , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Humanos , Interferón-alfa/administración & dosificación , Interferones , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Ribavirina/administración & dosificación , Resultado del Tratamiento
16.
Pathogens ; 11(1)2021 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-35055968

RESUMEN

The hepatitis B virus (HBV), belonging to the Hepadnaviridae family, is responsible for a global health concern still in the 21st century. The virus is divided into 10 genotypes, which differ in geographical distribution and in their effect on disease progression and transmission, susceptibility to mutations, and response to treatment. There are many methods for diagnostics of HBV and differentiating its genotypes. Various commercial kits based on real-time polymerase chain reaction (RT PCR) and hybridization available, as well as whole genome sequencing or the sequencing of only individual parts of the genomes. We compared a commercial kit AmpliSens HBV-genotype-FRT, based on RT PCR, with an adapted method of amplification of the surface genomic region combined with Sanger sequencing. In the examined samples we identified the A, B, C, D, and E genotypes. By PCR with Sanger sequencing, the genotypes were determined in all 103 samples, while by using the commercial kit we successfully genotyped only 95 samples, including combined genotypes, which we could not detect by sequencing.

17.
Klin Mikrobiol Infekc Lek ; 16(4): 139-44, 2010 Aug.
Artículo en Sk | MEDLINE | ID: mdl-20809465

RESUMEN

OBJECTIVE: The study aimed at evaluating antiviral therapy and the impact of selected factors on its efficacy in patients with chronic hepatitis C treated at the Department of Infectology and Travel Medicine in Kosice, Slovakia, between 2003 and 2007. MATERIAL AND METHODS: A retrospective analysis of a group of 213 patients treated for chronic hepatitis C and of prognostic factors for treatment efficacy in a subgroup of 159 patients who completed therapy with pegylated interferon alpha and ribavirin. RESULTS: From the entire group, 193 patients were treated with a combination of pegylated interferon and ribavirin, 5 received pegylated interferon monotherapy and in 15 cases, conventional interferon was used. A total of 179 patients (84 %) were treated for the first time, the remaining 34 patients were treated repeatedly. Genotype 1 was detected in 91.5 % of 189 studied patients. Liver biopsy was performed in 143 patients, with mild, moderate and severe histological changes or liver cirrhosis being detected in 46.9 %, 38.5 % and 14.7 % of them, respectively. In 12.2 % of cases, treatment was discontinued due to adverse effects. In the group of 159 patients who completed therapy, sustained viral response (SVR) was found in 35.8 %; another 12.6 % had viral response at the end of therapy (SVR has not been assessed as yet). Viral relapse or breakthrough were observed in 26.4 % and 25.2 % showed no response. Patients who achieved SVR were more frequently infected with genotypes 2 and 3, had lower degrees of liver fibrosis, lower mean age and more frequently achieved complete early viral response. By contrast, the group of non-responders was characterized by a higher proportion of patients with reduced therapy below 80 %. The other observed differences such as male/female ratio, weight, proportion of patients with normal ALT activity or proportion of previously untreated patients were not significant. CONCLUSION: The efficacy of treatment in our group adjusted for the adverse proportion of genotypes and proportion of patients with repeated therapy was comparable with the literature data. The favorable prognostic factors observed in the group included infection with genotypes 2 or 3, lower degree of liver fibrosis and lower age.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Adulto , Femenino , Hepatitis C Crónica/virología , Humanos , Masculino , Pronóstico
18.
Artículo en Inglés | MEDLINE | ID: mdl-32365672

RESUMEN

Background: The Roma population is one of the largest marginalized population groups in Europe. The aim of our work was to summarize the morbidity of lifestyle-related diseases and infectious diseases in the Roma population living in segregated settlements. Methods: We used data from the cross-sectional study HepaMeta, in which we examined 452 Roma subjects with an average age of 34.7 ± 9.1 years, 35.2% of which were men, and 403 non-Roma subjects with an average age of 33.5 ± 7.4 years, 45.9% of which were men. We collected data by means of a questionnaire, anthropometric measures, and we analyzed blood and urine samples. Results: Roma subjects had a higher incidence of metabolic syndrome (RR: 1.478 (1.159-1.885), p < 0.0001), obesity or waist circumference >94 cm in men/80 cm in women (RR: 1.287 (1.127-1.470), p < 0.0001), and HDL-C < 1.03 mmol/L in men or <1.29 in women (RR: 2.004 (1.730-2.321), p < 0.0001) than their non-Roma counterparts. Subjects of the Roma population were more frequently diagnosed with kidney disease (RR: 1.216 (1.096-1.349), p < 0.0001), HBsAg positivity (RR: 4.468 (2.373-8.415), p < 0.0001), anti HBc IgG positivity (RR: 3.13 (2.598-4.224), p < 0.0001), and anti HEV positivity (RR: 2.972 (1.226-7.287), p < 0.0001). Serological markers of Toxoplasma gondii infection and Toxocara spp. were observed much more frequently among Roma than non-Roma subjects (RR: 1.868 (1.520-2.296), p < 0.0001, for Toxoplasma gondii; and RR: 21.812 (8.097-58.761), p < 0.0001, for Toxocara spp.). Conclusions: Poor socio-economic conditions, an unhealthy lifestyle, and barriers precluding access to healthcare are factors that affect the Roma population in settlements and lead to an increased prevalence of metabolic syndrome and its components, kidney disease, viral hepatitis B and E, and some parasitic diseases.


Asunto(s)
Hepatitis B/etnología , Enfermedades Renales/etnología , Síndrome Metabólico/etnología , Enfermedades Parasitarias/etnología , Romaní/etnología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Prevalencia , Factores de Riesgo , Población Rural , Eslovaquia/epidemiología
19.
Artículo en Inglés | MEDLINE | ID: mdl-32397342

RESUMEN

Background: The aim of our work is to objectify the manner of transmission of HBV infection in young adult and middle-aged Roma people who live in the settlements. Methods: We used data from the cross-sectional study HepaMeta. We analyzed Roma people living in the settlements in East Slovakia, who have had HBsAg and anti HBc IgG antibodies examined. Results: We analyzed a cohort of 452 Roma participants with a mean of age 34.67 ± 9.14 years-159 (35.2%) were males. HBsAg positivity was diagnosed in 12.4% and the presence of anti HBc IgG antibodies was confirmed in 52% of participants. Prevalence of HBsAg positivity increases significantly with higher age, (p = 0.026), as well as the presence of anti HBc IgG antibodies (p < 0.0001). The prevalence of HBsAg positivity has doubled and anti HBc IgG positivity has tripled within two decades (<25 years vs. 35-45 years) in Roma settlements in East Slovakia. Conclusions: These findings allow us to express an opinion that horizontal transmission in adulthood may play an important role in the spreading of HBV infection.


Asunto(s)
Virus de la Hepatitis B , Hepatitis B , Romaní , Abuso de Sustancias por Vía Intravenosa , Adulto , Anciano , Estudios Transversales , Hepatitis B/epidemiología , Hepatitis B/transmisión , Anticuerpos contra la Hepatitis B , Virus de la Hepatitis B/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Población Rural , Eslovaquia/epidemiología , Adulto Joven
20.
Int J Public Health ; 65(9): 1723-1735, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33040165

RESUMEN

OBJECTIVES: The MOSAIC study gathered data on chronic hepatitis C virus (HCV) infection and its treatment in various countries worldwide. Here we summarise patient and HCV characteristics in the Czech Republic and Slovakia. METHODS: MOSAIC was an observational study that included patients with chronic HCV infection untreated at the time of enrolment. Study collected and descriptively analysed patient demographics, disease stage and viral characteristics. Data were collected between February 2014 to October 2014. RESULTS: Among 220 patients enrolled, 51.4% were treatment-naïve. The most prevalent HCV genotype was G1 (78.4%), followed by G3 (19.7%). Higher prevalence of G1 was found in treatment-experienced patients (94.3%) compared to treatment-naïve (63.4%). Most participants (67.7%) presented viral RNA load of ≥ 800,000 IU/mL. Liver cirrhosis was reported in 24.5% of patients. Higher HCV RNA load and duration of HCV infection correlated with the degree of liver fibrosis. Anti-HCV interferon-based treatments were initiated in 88.2% of participants. CONCLUSIONS: The study confirmed significant changes in the HCV genotypes partition with G3 genotype rapidly increasing in both countries, with possible impact on the WHO eradication initiative and treatment selection.


Asunto(s)
Hepatitis C Crónica/epidemiología , Adulto , Anciano , República Checa/epidemiología , Femenino , Genotipo , Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Prevalencia , ARN Viral , Índice de Severidad de la Enfermedad , Eslovaquia/epidemiología , Factores Socioeconómicos , Carga Viral , Adulto Joven
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