Mutagenicity of hydroxyurea in lymphocytes from patients with sickle cell disease

Hydroxyurea is commonly used in the treatment of myeloproliferative diseases and in patients with sickle cell disease (SCD). The use of this antineoplastic agent in patients with SCD is justified because of the drug's ability to increase fetal hemoglobin levels, thereby decreasing the severity of SCD. However, high doses or prolonged treatment with hydroxyurea can be cytotoxic or genotoxic for these patients, with an increased risk of developing acute leukemia. This danger can be avoided by monitoring the lymphocytes of patients treated with hydroxyurea. Cytogenetic tests are important endpoints for monitoring the physiological effects of physical and chemical agents, including drugs. In this work, we assessed the genotoxicity of hydroxyurea in short-term cultures of lymphocytes from SCD patients. Hydroxyurea was not cytotoxic or genotoxic at the concentrations tested in the G2 phase of the cell cycle. These results support the use of hydroxyurea in the treatment of SCD, although further work is necessary to understand the effects of this drug in vivo

Translation, cultural adaptation to Brazil and validation of the venous leg ulcer quality of life questionnaire (VLU-QoL-Br)

Objetivo:traduzir o instrumento Venous legulcer quality of life questionnaire (VLU-QoL), adaptá-lo culturalmente para o português do Brasil e validá-lo com pacientes do Hospital das Clínicas da Faculdade de Medicina de Botucatu (FMB) da Universidade Estadual Paulista (Unesp). Métodos:o questionário foi traduzido por um tradutor profissional e por dois dermatologistas especialistas na área de úlceras venosas (UV), sendo reformulado em reunião com os três tradutores. O constructo (VLU-QoL-Br) foi submetido a pré-entrevista com 10 portadores de UV para a adaptação da linguagem. Posteriormente, foi aplicado em pacientes do HC-Unesp, e como teste-reteste para verificação de sua reprodutibilidade. Resultados:foram avaliados 82 pacientes, sendo 56 (68%) do sexo feminino. A idade média foi de 67,3 anos. O questionário foi traduzido, adaptado e aplicado aos pacientes. O constructo apresentou alta consistência interna (alfa= 0,94) e adequada correlação item-total. Quando avaliados os 32 retestes, observou-se correlação intraclasse para concordância de 0,78 (p < 0,01), indicando boa reprodutibilidade do constructo. A análise fatorial confirmatória corroborou as dimensões do questionário original: atividades, psicológico e sintomas. Escores do VLU-QoL-Br se associaram, independentemente, à área total das úlceras e a menor escolaridade dos sujeitos (p < 0,01). Conclusão:a tradução, a adaptação e a validação do questionário VLU-Qol-Br demonstrou boa performance psicométrica, permitindo seu uso clínico no Brasil. É importante avaliar seu desempenho em outras regiões e em diferentes amostras de indivíduos.

Quality of life profile and correlated factors in chronic leg ulcer patients in the mid-west of São Paulo State, Brazil

BACKGROUND: Chronic leg ulcer may have an impact on patients' quality of life.OBJECTIVES:This study aimed to identify the impact of leg ulcers on patient's quality of life using the Dermatology Life Quality Index and to define the main factors correlated with this perception.METHOD:Cross-sectional, non-probabilistic sampling study. We included patients with chronic leg ulcers being treated for at least 3 months. A sociodemographic and clinical survey was conducted to assess the profile of the ulcers. We administered a screening for depressive symptoms and the Dermatology Life Quality Index. We performed a descriptive statistical analysis, chi-square test and Mann-Whitney test for categorical data, Pearson for numeric variables, and multiple regression for categorical data.RESULTS:Forty-one patients were assessed. Their mean age was 61.78 years. Venous ulcers (48.8%) were the most prevalent. Seventy-three percent of the sample perceived no impact/low impact on quality of life in the past week, and 26.8% perceived moderate/high impact. A multiple regression analysis identified the causes of lesion, pain related to the ulcers, time of onset, and severity of the depressive symptoms as the variables that had an influence on quality of life.CONCLUSIONS:The majority of the sample perceived low or no impact of the condition on the quality of the life. The variables etiology of the lesion (p<0.001), pain related to the ulcers (p=0.001), time of onset (p=0.006), and severity of the depressive symptoms (p<0.001) had an influence on the quality of life, suggesting the need for further studies with more robust designs to confirm the causal relationship between these characteristics and quality of life.

Genetic and biochemical markers of hydroxyurea therapeutic response in sickle cell anemia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Frequencies of-308G/A (TNFA) and-509C/T (TGFB1) polymorphisms in sickle cell anemia patients from Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of caries-associated virulence of biofilms from Candida albicans isolated from saliva of pediatric patients with sickle-cell anemia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Oral microbial colonization in children with sickle cell anaemia under long-term prophylaxis with penicillin

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Benefits of kinesiotherapy and aquatic rehabilitation on sickle cell anemia. A case report

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The mean corpuscular volume and hydroxyurea in brazilian patients with sickle cell anemia: a surrogate marker of compliance

The suppression of erythropoiesis by Hydroxyurea (HU) therapy is associated with increase in mean corpuscular volume, in addition to the increase in Hb F. Monitoring the mean corpuscular volume values and the presence of macrocytosis are effective tools of adherence to the treatment with HU in patients with sickle cell anemia. The aim of this study is to monitor the mean corpuscular volume values after starting treatment with HU to determine if macrocytosis can be used as a surrogate marker of compliance with therapy. We conducted a prospective cohort study over one year with measurements of blood counts and mean corpuscular volume after starting therapy with HU in 95 patients with sickle cell anemia who were regularly followed in our ambulatory outpatient unit. In one-year of successful use of HU the mean value of the mean corpuscular volume increased significantly. The Andersen and Gill model demonstrated that the increase of one unit of MCV implies a 5% reduction in the risk of visiting the emergency room. Monitoring mean corpuscular volume values after prescribing HU alerts the provider of noncompliance in order to counsel the patient in question for better adherence to the use of HU that could improve the quality of care and to reduce morbidity and the frequency of acute pain crises and associated healthcare costs.

Hydroxyurea in the sickle cell anemia: toxicity and effectiveness

Objective: to evaluate the use of hydroxyurea with regard to effectiveness and toxicity in people with sickle cell anemia. Method: this is a retrospective descriptive study, developed with 57 medical records of patients with sickle cell anemia, treated at the University Hospital Center of Campo Grande (Mato Grosso do Sul, Brazil), from 1993 to 2005. Inclusion criteria: electrophoresis of hemoglobin in medical record; regular use of drugs, for an average of 196 weeks; dosage; and hematological analyses before starting treatment. Exclusion criteria: living with other hemoglobinopathies. The variables evaluated were: neutrophils count; platelets; leukocytes; hemoglobin; time using hydroxyurea; drug response to the optimal dosage; and number and type of episodes of hospitalization. The research protocol was approved by the Ethics Committee of Universidade Federal de Mato Grosso do Sul, under the Protocol 645. Results: of the 57 medical records, 3 cases were evaluated. Comparing the hematological values, according to Portaria 872, enacted on 11/12/2002, it was found that: cases A, B, and C present an use of hydroxyurea (500 mg/day) for four years, with an average of 196 weeks. Case A, female, decreased painful episodes and frequency of hospitalization, keeping hematological values with no toxicity. In Case B, female, there was one hospitalization due to pain crises and important hemolysis. It stood out, in case C, male, neutropenia with hematological values < 2,000/mm3 . Conclusion: in the cases analyzed, we observed a drop in the number of hospitalizations with the decrease in painful crises from three to one a year, and there was no toxicity with regard to the dosage and time using hydroxyurea, in all three cases. For more comprehensive results, one suggests further study on this therapy with significant samples of this clientele.

Potential utility of melatonin as an antioxidant therapy in the management of sickle cell anemia

This study aimed to assess antioxidant effects of melatonintreatment compared to N-acetylcysteine (NAC) and to their combination in asickle cell suspension. Sickle erythrocytes were suspended in phosphate-buffered saline, pH 7.4, composing external control group. They were alsosuspended and incubated at 37°C either in the absence (experimental controlgroup) or in the presence of NAC, melatonin and their combination atconcentrations of 100 pM, 100 nM and 100 lM for 1 hr (treatment groups).The melatonin influences were evaluated by spectrophotometric [hemolysisdegree, catalase (CAT), glutathione S-transferase (GST), glutathioneperoxidase (GPx), glutathione reductase (GR), glucose-6-phosphatedehydrogenase (G6PDH), and superoxide dismutase (SOD) activities] andchromatographic methods [glutathione (GSH) and malondialdehyde (MDA)levels]. Incubation period was able to cause a rise about 64% on hemolysisdegree as well as practically doubled the lipid peroxidation levels (P < 0.01).However, almost all antioxidants tested treatments neutralized this incubationeffect observed in MDA levels. Among the antioxidant biomarkers evaluated,we observed a modulating effect of combined treatment on GPx and SODactivities (P < 0.01), which showed ~25% decrease in their activities. Inaddition, we found an antioxidant dose-dependent effect for melatonin onlipid peroxidation (r = 0.29; P = 0.03) and for combined antioxidanttreatments also on MDA levels (r = 0.37; P = 0.01) and on SOD activity(r = 0.54; P < 0.01). Hence, these findings contribute with important insightthat melatonin individually or in combination with NAC may be useful forsickle cell anemia management.