BACKGROUND Only benznidazole (Bnz) (1) and nifurtimox (Nfx) (2) are licensed for the treatment of Chagas disease although their safety and efficacy profile are far from ideal. Farmanguinhos from Fiocruz has developed seven nitroimidazole compounds (4-10) analogs of megazol (3). OBJECTIVES To evaluate whether the genotoxic effect of 3 was abolished in the seven nitroimidazoles (4-10) analogs using the in vitro alkaline comet assay (CA) and the in vitro cytokinesis-block micronucleus assay (CBMN) in whole human blood cells (WHBC) and correlate this effect with their trypanocidal activity using bloodstream trypomastigote forms of Trypanosoma cruzi. METHODS The toxicity of 3-10 to WHBC in the in vitro CA was determined using the fluorescein diacetate/ethidium bromide assay. DNA damage in the in vitro CA was evaluated according to tail size in four classes (0-3) and methyl methane-sulfonate (MMS) was used as a positive control. The cytotoxicity of 3-10 to WHBC in the CBMN was measured using the cytokinesis-block proliferation index and the replication index. The number of the micronucleate cells in 2,000 binucleate cells by experimental group was determined. Mitomycin C and N-deacetyl-N-methylcolchicine were used as positive controls. FINDINGS Compound 3 showed a significant DNA strand break effect through the in vitro CA and highly significant clastogenic and/or aneugenic effect in the CBMN. Compounds 5, 6, 8, 9 and 10 showed negative results in the CBMN and positive results in the in vitro CA, while the inverse effect was observed for 4 and 7. MAIN CONCLUSIONS Compound 10 was the most promising to proceed with the development as a drug candidate in the treatment of Chagas disease showing absence of chromosomal cytogenetic damage and high activity against T. cruzi, about two times higher than 3 and the clinical drug 1.

Abstract Background: Several studies have demonstrated that platelet counts in Helicobacter pylori-positive patients with chronic idiopathic thrombocytopenic purpura improved significantly after successful eradication of the infection. However, depending of the geographical region of the study the results have been highly divergent. Objective: The purpose of this study was to evaluate the effect of H. pylori eradication therapy on platelet count in a cohort of chronic idiopathic thrombocytopenic purpura patients from northeastern Brazil. Method: H. pylori status was determined in 28 chronic idiopathic thrombocytopenic purpura patients using the rapid urease test and histology. H. pylori-positive patients received standard triple therapy for one week. The effect of the eradication therapy was evaluated using the 13C-urea breath test two to three months after treatment. Results: The prevalence of H. pylori infection was similar to that found in the general population. Twenty-two patients (78.5%) were H. pylori-positive. Fifteen were treated, 13 (86%) of whom successfully. At six months, 4/13 (30%) displayed increased platelet counts, which remained throughout follow-up (12 months). Platelet response was not associated to mean baseline platelet count, duration of chronic idiopathic thrombocytopenic purpura, gender, age, previous use of medication, or splenectomy. Conclusions: H. pylori eradication therapy showed relatively low platelet recovery rates, comparable with previous studies from southeastern Brazil. The effect of H. pylori eradication on platelet counts remained after one year of follow-up suggesting that treating H. pylori infection might be worthwhile in a subset of chronic idiopathic thrombocytopenic purpura patients.

BACKGROUND: Chronic myeloid leukemia is a neoplasm characterized by clonal expansion of hematopoietic progenitor cells resulting from the (9:22)(q34,11) translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic event in chronic myeloid leukemia, is constitutively activated thus inducing the production of reactive oxygen species. Of particular relevance is the fact that an increase in reactive oxygen species can facilitate genomic instability and may contribute to disease progression. OBJETIVE: To evaluate oxidative stress by determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors monitored at a referral hospital in Fortaleza, Ceará. METHODS: A cross-sectional study was performed of 64 male and female adults. Patients were stratified according to treatment. The levels of malondialdehyde and nitrite were determined by spectrophotometry. Statistical differences between groups were observed using the Student t-test and Fisher's exact test. The results are expressed as mean ± standard error of mean. The significance level was set for a p-value < 0.05 in all analyses. RESULTS: The results show significantly higher mean concentrations of nitrite and malondialdehyde in chronic myeloid leukemia patients using second-generation tyrosine kinase inhibitors compared to patients on imatinib. Conclusion: It follows that chronic myeloid leukemia patients present higher oxidative activity and that the increases in oxidative damage markers can indicate resistance to 1st generation tyrosine kinase inhibitors.

AIM: The objective of this study was to correlate laboratory tests during the evolution of dengue fever, comparing frequencies between the different clinical forms in order to use test results to predict the severity of the disease. METHODS: This is an observational, descriptive and retrospective study of 154 patients with clinical and serological diagnoses of dengue fever who, in the period from January to May 2008, were admitted in a tertiary state hospital in the city of Fortaleza that is a referral center for infectious diseases. The patients were allocated to two groups according to age: under 15 years old (n = 66) and 15 years or older (n = 88). The tests analyzed were blood count, platelet count, and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. RESULTS: Thrombocytopenia and elevated transaminases were observed in patients with classic dengue fever. The main laboratory abnormalities found in dengue hemorrhagic fever were thrombocytopenia, hemoconcentration and elevated transaminases, similar to severe dengue with the exception of hemoconcentration. Most laboratory abnormalities started on the 3rd day but were more evident on the 5th day with restoration of values by the 11th day; this was more prominent in under 15-year-olds and with the more severe clinical forms. CONCLUSIONS: These results are relevant in assessing the disease because they can be used as markers for more severe forms and can help by enabling the adaptation of the therapeutic conduct to the needs of individual patients.

Visceral leishmaniasis (VL) is a severe systemic infectious disease.(1) It has been recognized as an opportunistic disease in patients infected with human immunodeficiency virus (HIV).(2,3) The analysis of the bone marrow of patients co-infected with VL and HIV showed dysplasia of erythroid, granulocytic and megakaryocytic lineages (Figure 1), besides the presence of plasmacytosis, cytoplasmic bodies, hemophagocytosis, granuloma and intracellular and extracellular leishmania amastigotes (Figure 2). These findings are found in the analysis of bone marrow of patients co-infected with HIV and VL; knowledge of these findings may be useful for the diagnosis and prognosis of patients.