SCD increases, slightly but significantly, DNA damage in lymphocytes from patients with SCD. Patients with SCD treated with HU do not present more nucleoid damage than patients with SCD not treated with HU. Good responders to the HU treatment have significantly less nucleoid damage than poor responders. HU treatment at ≤30 mg/kg/day does not expose patients to a genotoxic plasma concentration.

Hydroxyurea is the unique drug having demonstrated a significant efficacy in sickle cell disease treatment. We developed a liquid chromatography method with electrochemical detection for hydroxyurea analysis in plasma and aqueous solutions. Analytical goals included an analytical range from 2 to 50 mg/L, a total imprecision lower than 15% and a total error lower than 30%. After protein precipitation with acetonitrile, the separation was performed on a C18 Atlantis T3 column and eluted with sodium acetate 25 mM, acetonitrile 2.5%, pH 6.5. Thioacetamide was used as internal standard. The method was linear for drug concentrations ranging from 0.5 to 50 mg/L and recovery was comprised between 100 and 120%. The intra-day precision was lower than 6.0% and between-day precision was lower than 11%. The detection limit was 0.18 and 0.63 mg/L for aqueous solution and plasma, respectively and the quantification limit was 1.0 and 1.2 mg/L for aqueous solution and plasma, respectively. No interference from urea was observed. The liquid chromatography method developed can be used for pharmacokinetic studies in plasma and other biological samples such as saliva or urine. It requires low sample volumes and a simple pre-treatment and it allows a direct measure of non-derivatized hydroxyurea.

Hydroxycarbamide, well known in clinical settings as hydroxyurea (HU), is an antineoplastic agent inhibiting the ribonucleotide reductase enzyme, and thus, the conversion of ribonucleotides into deoxyribonucleotides. A concern about long term side effects of HU treatment in sickle cell disease patients, particularly genotoxicity, has often been evoked. The present study assessed two suitable methods to evaluate oxidative DNA damage associated with HU: the comet assay on blood lymphocytes and the quantification of urinary excretion of 8-oxodeoxyguanosine (8-oxodG). Both methods were applied in a preliminary study including seven sickle cell disease patients treated with HU, seven untreated sickle cell disease patients and five healthy volunteers. Concerning DNA damage, the comet assay and the 8-oxodG assay did not reveal any significant differences among the three groups. Methodologies used in this pilot study could be suitable to carry out further research in this area including a larger size sample setting.

Malrotación intestinal en adulto y apendicitis agudaPalabras clave: Malrotación intestinal. Apendicitis.