Is chronic use of hydroxyurea safe for patients with sickle cell anemia? An account of genotoxicity and mutagenicity.

Sickle cell anemia (SCA) is a hereditary hematological disease that is characterized by a point mutation in the beta globin S gene and has no specific treatment; hydroxyurea (HU) is the only therapeutic agent used in clinical practice. In the present study, we evaluated the deoxyribonucleic acid (DNA) damage index (DI) and chromosomal damage in leukocytes of adult patients with SCA with and without HU. The DI was assessed by the comet assay and chromosomal damage by the leukocyte micronucleus test of adult patients treated with HU (SCA-HU) and without the use of HU (SCA-NoHU). This is a cross-sectional study with 77 patients with SCA who attended a referral hospital in Fortaleza, Brazil. The control group (CG) consisted of 58 reportedly healthy individuals. The comparisons of means were performed by analysis of variance and Tukey's post-test. Values of P < 0.05 were considered statistically significant. SCA-NoHU patients had statistically higher DI values and a statistically significantly higher frequency of micronuclei compared to the CG. In addition, HU treatment accentuated DNA lesions by significantly increasing both parameters in treated patients (SCA-HU). HU potentiates DNA damage and the occurrence of chromosomal damage, which may promote genomic instability, mutation occurrence, and carcinogenesis. Studies are needed to evaluate the involved pathways, repair mechanisms, and the clinical impact that such damage can cause. Environ. Mol. Mutagen. 60:302-304, 2019. © 2018 Wiley Periodicals, Inc.

In vitro synergistic activity of lidocaine and miconazole against Candida albicans / Atividade sinérgica in vitro de lidocaína e miconazole contra Candida albicans

Candida albicans is the main yeast isolated from vulvovaginal candidiasis(VVC) and a major antifungal used to treat VVC is miconazole (MZ), it shows local toxic effects, such as irritation and burns. The lidocaine (LD) is a local anesthetic. The aim of this study was to evaluate the synergistic activity of LD/MZ against 19 strains of C. albicans isolated from vaginal secretion. 78.9% of the strains were susceptible to the combination LD/MZ, demonstrating synergism of drugs. These drugs can be used to produce vaginal creams to treat VVC, especially drug resistant.

Candida albicans é a principal levedura isolada de candidíase vulvovaginal (CVV) e o principal antifúngico usado para tratar a VVC é miconazol (MZ), que apresenta efeitos tóxicos locais, tais como irritação e queimaduras. A lidocaína (LD) é um anestésico local. O objetivo deste estudo foi avaliar a atividade sinérgica de LD/MZ contra 19 cepas de C. albicans isoladas de secreção vaginal. Foram suscetíveis à combinação LD/MZ, 78.9% das cepas testadas, demonstrando sinergismo de drogas. Estes fármacos podem ser utilizados para a produção de cremes vaginais para tratar VVC, especialmente aquelas resistentes aos fármacos disponíveis.

Association of oxidative stress and DNA damage with grafting time in patients with multiple myeloma and lymphoma submitted to autologous hematopoietic stem cell transplantation.

The aim of the study was to investigate the association between oxidative stress and DNA damage with grafting time in patients submitted to autologous hematopoietic stem-cell transplantation (HSCT). The study included 37 patients submitted to autologous HSCT diagnosed with Multiple Myeloma (MM) and lymphoma (Hodgkin's and non-Hodgkin's). Biomarkers of oxidative stress and DNA damage index (DI) were performed at baseline (pre-CR) of the disease and during the conditioning regimen (CR), one day after the HSCT, ten days after HSCT and twenty days after HSCT, as well as in the control group consisting of 30 healthy individuals. The outcomes showed that both groups of patients had an hyperoxidative state with high DI when compared to baseline and to the control group and that the CR exacerbated this condition. However, after the follow-up period of the study, this picture was re-established to the baseline levels of each pathology. The study patients with MM showed a mean grafting time of 10.75 days (8 to 13 days), with 10.15 days (8 to 15 days) for the lymphoma patients. In patients with MM, there was a negative correlation between the grafting time and the basal levels of GPx (r = -0.54; p = 0.034), indicating that lower levels of this important enzyme are associated with a longer grafting time. For the DI, the correlation was a positive one (r = 0.529; p = 0.030). In the group with lymphoma, it was observed that the basal levels of NOx were positively correlated with grafting time (r = 0.4664, p = 0.032). The data indicate the potential of these biomarkers as predictors of toxicity and grafting time in patients with MM and Lymphomas submitted to autologous HSCT.

Association of oxidative stress and DNA damage with grafting time in patients with multiple myeloma and lymphoma submitted to autologous hematopoietic stem cell transplantation / Associação do estresse oxidativo e dano ao DNA com o tempo de enxertia em pacientes com mieloma múltiplo e linfomas submetidos a transplante autólogo de células-tronco hematopoéticas

ABSTRACT The aim of the study was to investigate the association between oxidative stress and DNA damage with grafting time in patients submitted to autologous hematopoietic stem-cell transplantation (HSCT). The study included 37 patients submitted to autologous HSCT diagnosed with Multiple Myeloma (MM) and lymphoma (Hodgkin’s and non-Hodgkin’s). Biomarkers of oxidative stress and DNA damage index (DI) were performed at baseline (pre-CR) of the disease and during the conditioning regimen (CR), one day after the HSCT, ten days after HSCT and twenty days after HSCT, as well as in the control group consisting of 30 healthy individuals. The outcomes showed that both groups of patients had an hyperoxidative state with high DI when compared to baseline and to the control group and that the CR exacerbated this condition. However, after the follow-up period of the study, this picture was re-established to the baseline levels of each pathology. The study patients with MM showed a mean grafting time of 10.75 days (8 to 13 days), with 10.15 days (8 to 15 days) for the lymphoma patients. In patients with MM, there was a negative correlation between the grafting time and the basal levels of GPx (r = -0.54; p = 0.034), indicating that lower levels of this important enzyme are associated with a longer grafting time. For the DI, the correlation was a positive one (r = 0.529; p = 0.030). In the group with lymphoma, it was observed that the basal levels of NOx were positively correlated with grafting time (r = 0.4664, p = 0.032). The data indicate the potential of these biomarkers as predictors of toxicity and grafting time in patients with MM and Lymphomas submitted to autologous HSCT.

RESUMO O objetivo do estudo foi investigar a associação entre estresse oxidativo e dano ao DNA com o tempo de enxertia em pacientes submetidos ao transplante de células-tronco hematopoéticas autólogo (TCTH). Participaram do estudo 37 pacientes submetidos ao TCTH autólogo com diagnóstico de mieloma múltiplo (MM) e Linfomas (Hodgkin e não Hodgkin). Biomarcadores de estresse oxidativo e índice de dano ao DNA (ID) foram determinados no estado basal (Pré-RC) das doenças e durante o regime de condicionamento (RC), um dia após o TCTH, dez dias após o TCTH e vinte dias após o TCTH e no grupo controle composto por 30 individuos saudáveis. Os resultados demonstraram que os dois grupos de pacientes apresentaram um estado hiperoxidativo com elevado ID quando comparados ao estado basal e ao grupo controle e que o RC exacerbou essa condição. No entanto, após o tempo de acompanhamento do estudo, esse quadro foi reestabelecido ao estado basal de cada patologia. Os pacientes do estudo com MM apresentaram uma média do tempo de enxertia de 10,75 dias (8 a 13 dias), e de 10,15 dias (8 a 15 dias) para o grupo Linfoma. Nos pacientes com MM houve uma correlação negativa entre o tempo de enxertia e os níveis basais de GPx (r=-0,54; p=0,034), indicando que níveis mais baixos de GPx estão relacionados a um maior tempo de enxertia, e para o ID, a correlação foi positiva (r=0,529; p=0,030). No grupo com Linfoma, observou-se que os níveis basais de NOx correlacionaram-se positivamente com o tempo de enxertia (r= 0,4664; p=0,032). Os dados apontam para o potencial desses biomarcadores como preditores da toxicidade e do tempo de enxertia em pacientes com MM e Linfomas submetidos ao TCTH autólogo