Diffuse cutaneous leishmaniasis (DCL) is a rare type of leishmaniasis characterized by diffuse skin lesions. In Brazil, Leishmania (L.) amazonensis is the main etiological agent of this clinical form. The state of Maranhão has the highest prevalence of this disease in the country, as well as a high rate of HIV infection. Here, we report the first case of DCL/HIV of Brazil. A 46-year-old man from the Amazonian area of Maranhão state presented atypical lesion in the left upper limb and dissemination of diffuse erythematous nodules over his entire body. Histopathological examination confirmed the presence of intracellular amastigotes of Leishmania, and a polymerase chain reaction and molecular identification by restriction fragment profile identified L. (L.) amazonensis as the causative agent of the disease. The patient was also diagnosed with HIV virus after the leishmaniasis diagnosis. The initial treatments for leishmaniasis were liposomal amphotericin B (AmB-L) (4 mg/kg) for 10 days and prophylactic use of Glucantime® (10 mg/Sb+5/kg) for 2 months. After unsuccessful initial treatments, he was treated with a combination of AmB-L (4 mg/kg) alternated with pentamidine (4 mg/kg) for 10 days but failed in the first therapeutic cycle. Subsequently, he had a good response to treatment with pentamidine (4 mg/kg).

Meglumine antimoniate (Glucantime) is an antimonial pentavalent used to treat leishmaniasis, despite its acknowledged toxic effects, such as its ability to cause oxidative damage to lipids and proteins. Recently, our group demonstrated that meglumine antimoniate causes oxidative stress-derived DNA damage. Acknowledging that antioxidants modulate reactive oxygen species, we evaluated the capacity of genistein and ascorbic acid for preventing genotoxicity caused by meglumine antimoniate. For that, mice (n=5/group) received genistein (via gavage) in doses of 5, 10 and 20mg/kg for three consecutive days. After this period, they were treated with 810mg/kg meglumine antimoniate via intraperitoneal (i.p.). Furthermore, mice (n=5/group) received, simultaneously, ascorbic acid (i.p.) in doses of 30, 60 and 120mg/kg and 810mg/kg meglumine antimoniate. We also conducted post- and pre-treatment assays, in which animals received ascorbic acid (60mg/kg) 24 hours prior to or after receiving meglumine antimoniate. Genomic instability and mutagenicity were analyzed through conventional Comet assay and enzymatic assay using Formamidepyrimidine-DNA-glycosylase (Fpg) enzyme, as well as the Micronucleus Test, respectively. Meglumine antimoniate induced an increase in the DNA damage after digestion with Fpg, reinforcing its mutagenic potential by oxidizing DNA bases, which was prevented by genistein. Similarly, ascorbic acid proved itself capable of reducing mutagenic effects in simultaneous treatment, as well as in post-treatment. Therefore, our results demonstrate that both compounds are efficient in preventing mutations in mammalian cells treated with meglumine antimoniate.

Notwithstanding the advances in molecular target-based drugs, chemotherapy remains the most common cancer treatment, despite its high toxicity. Consequently, effective anticancer therapies with fewer adverse effects are needed. Therefore, this study aimed to determine the anticancer activity of the dichloromethane fraction (DCMF) isolated from Arrabidae brachypoda roots, whose components are three unusual dimeric flavonoids. The toxicity of DCMF was investigated in breast (MCF-7), prostate (DU145), and cervical (HeLa) tumor cells, as well as non-tumor cells (PNT2), using sulforhodamine B (cell viability), Comet (genotoxicity), clonogenicity (reproductive capacity) and wound healing (cell migration) assays, and atomic force microscopy (AFM) for ultrastructural cell membrane alterations. Molecular docking revealed affinity between albumin and each rare flavonoid, supporting the impact of fetal bovine serum in DCMF antitumor activity. The IC₅₀ values for MCF7, HeLa, and DU145 were 2.77, 2.46, and 2.51 µg/mL, respectively, and 4.08 µg/mL for PNT2. DCFM was not genotoxic to tumor or normal cells when exposed to twice the IC₅₀ for up to 24 h, but it inhibited tumor cell migration and reproduction compared to normal cells. Additionally, AFM revealed alterations in the ultrastructure of tumor nuclear membrane surfaces, with a positive correlation between DCMF concentration and tumor cell roughness. Finally, we found a negative correlation between roughness and the ability of DCMF-treated tumor cells to migrate and form colonies with more than 50 cells. These findings suggest that DCFM acts by causing ultrastructural changes in tumor cell membranes while having fewer toxicological effects on normal cells.

To investigate the association between the FTO gene polymorphism with obesity in Brazilian adolescents from the Northeast region. This was a case-control study with adolescents aged 18 to 19 years. The case group consisted of 378 obese individuals and the control group of 378 non-obese individuals. Obesity was measured by percentage of body fat using the air displacement plethysmography technique. The study variables included data on socioeconomics, demographics, lifestyle, physical activity, waist circumference, waist-to-height ratio, and body mass index. To identify the rs9939609 polymorphism of the FTO gene, blood samples were obtained for genomic DNA extraction by the real-time PCR (Polymerase Chain Reaction) technique. Categorical variables were compared between the groups by the chi-squared test. The normality of the anthropometric measurements body mass index, waist circumference, waist-to-height ratio, and percentage of body fat was evaluated by the Shapiro-Wilk test. Comparison of the anthropometric measurements, stratified by the polymorphism genotypes, was performed by the Kruskal-Wallis test. The Hardy-Weinberg equilibrium was calculated. The significance level was set at 5%. The variables gender, age, and physical activity showed significant differences between the groups (p<0.001). The samples of obese and non-obese adolescents were in Hardy-Weinberg equilibrium (p=0.0515). There was no significant difference between the genotypic (p=0.719) and allelic frequencies (p=0.812) regarding the case and control groups. When comparing the anthropometric measurements according to the genotypes (AA, AT, and TT), no significant difference was observed for body mass index (p=0.337), waist circumference (p=0.3473), percentage of body fat (p=0.7096), and waist-to-height ratio (p=0.2584). The excess adiposity of the study adolescents was not influenced by their genotype.