In vitro, ex vivo and in vivo short-term screening of DHEA nitrate derivatives activity over Trypanosoma cruzi Ninoa and TH strains from Oaxaca State, México.

Chagas disease is a health problem that affects millions of persons, currently Nifurtimox (Nfx) and Benznidazole (Bz) are the unique drugs to treat it. However, these drugs produce adverse effects and high toxicity, which has motivated the search for new candidate drugs. Based on reports about the extensive biological activity of steroidal nitrate esters, in this study three nitrate esters steroids (1b, 2b and 4b) were synthetized and characterized from Dehydroepiandrosterone (DHEA, 1a), 19-hydroxy-DHEA (2a), and Androst-5-en-3ß,17ß-diol (4a), respectively. In addition, compounds 3a and 3b were obtained by introducing an α-ethynyl and a ß-hydroxyl groups at position 17 of 2b and further nitration of the hydroxyl group. The trypanocidal activity of these steroids was evaluated in vitro against the epimastigote stage of two T. cruzi strains, Ninoa and TH, and their cytotoxicity over J774.2 macrophage cell line was assayed. Compounds 3a, 3b, and 4a shown higher trypanocidal activity than Bz and Nfx against epimastigotes of Ninoa strain, whereas DHEA (1a) and its nitrate derivative 1b showed higher activity than the reference drugs against the TH strain epimastigote. None of the compounds showed activity in the ex vivo assays against the blood trypomastigote of both strains. Interestingly, the selectivity index of Androst-5-en-3ß,17ß-diol 4a was almost twice the value of Nfx and 50 times more than Bz, against Ninoa and TH strains, respectively. Therefore, compound 4a could represent a valuable starting point toward the optimization of steroid derivatives as trypanocidal agents.

Copper nanoparticles as nanofillers in an adhesive resin system: An in vitro study.

BACKGROUND: The incorporation of an antibacterial agent into an adhesive could improve its clinical performance. Some nanoparticles (NPs), including copper nanoparticles (Cu NPs), display an antibacterial effect. Therefore, Cu NPs could act as a nanofiller when added to an adhesive. OBJECTIVES: The aim of this study was to evaluate the antibacterial activity, cytotoxicity and shear bond strength (SBS) of an experimental dental adhesive with Cu NPs. MATERIAL AND METHODS: Different concentrations (0.0050 wt%, 0.0075 wt% and 0.0100 wt%) of Cu NPs were added to the adhesive. The distribution of Cu NPs in the polymer matrix was observed based on transmission electron microscope (TEM) images. The antimicrobial activity of the adhesive + Cu NPs was evaluated with the agar disk diffusion test against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Streptococcus mutans (S. mutans). The cytotoxicity assay was performed by means of the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method with human pulp cells (HPC). Additionally, the SBS tests were carried out (n = 31) and the modes of fracture were registered. The vestibular and lingual surfaces of each tooth were randomly assigned to the study groups (group I - control adhesive; group II - adhesive + 0.0100 wt% Cu NPs). The samples were statistically analyzed (p ≤ 0.05). RESULTS: The adhesive + 0.0100 wt% Cu NPs showed inhibition zones against the strains under study that were similar to, or slightly smaller than, the halos produced by chlorhexidine (CHX) and specific drugs for each strain (30 µg of cefotaxime against S. mutans and S. aureus, and 1.25/3.75 µg of sulfamethoxazole/ trimethoprim against E. coli). The control adhesive was moderately cytotoxic (relative cell viability of 36.7 ±0.8%), being more cytotoxic than Cu NPs themselves (58.3 ±0.1%). A significantly higher SBS was obtained for the adhesive + 0.0100 wt% Cu NPs (6.038 ±2.95 MPa) than for the control group (3.278 ±1.75 MPa). The modes of fracture in group I were almost equally distributed between adhesive and cohesive failures whereas in group II, the failure was mainly cohesive. CONCLUSIONS: The results of this study suggest that incorporating Cu NPs into an adhesive improves its SBS and provides it with antibacterial properties, without increasing its inherent cytotoxicity - 2 desirable characteristics for the dental adhesives of composites.