RESUMO
The COVID-19 pandemic has caused an overload on the health care system on a global scale. Because the disease affects the respiratory system, patients may require ventilator equipment for breathing, and consequently, numerous tracheal intubations have been performed. The video laryngoscope is a medical device that aids this procedure. It is used by anesthesiologists to visualize the anatomical structures of the larynx during tube insertion. Unfortunately, many hospitals worldwide are unable to afford sufficient units of this medical device. To satisfy the high demand, low-cost alternatives employing three-dimensional (3D) printing techniques have been developed for health care professional's use. With the intention of ensuring the efficiency, reproducibility, and security of the 3D-printed laryngoscope, this article presents a novel model with versions for pediatric and adult use, which was developed under the supervision of a medical team. The mechanical performance of 3D-printed prototypes (of the proposed models) was evaluated using mechanical assays, and the results indicated a satisfactory safety factor.
RESUMO
Prostate cancer is among the most common cancer diagnoses in men, and the best treatment for patients with metastatic disease in advanced stages is still unclear. Previously, we have demonstrated that the three 1-(3-(aryl-4,5-dihydroisoxazol-5-yl)methyl)-4-trihalomethyl-1H-pyrimidin-2- ones derivatives (8a, 8e and 9c) present important cytotoxicity and selectivity for tumoral cells. Considering that various cytotoxic drugs have been assessed in patients with prostate cancer, but few drugs show survival advantage, we decided to study these three compounds (8a, 8e and 9c) in prostate cancer cells, androgen receptor (AR)-positive 22Rv-1 and AR-negative PC-3 cells. We obtained the half maximal inhibitory concentration (IC50) of 8a, 8e and 9c in prostate cancer cells and based on high selectivity of 9c to PC-3 cells, we determined the mechanism of this compound to induce cell death through different methods. We show here that 9c compound induces cell cycle arrest in G2/M, increasing the levels of reactive oxygen species and DNA damage, and triggers DNA damage response by ataxia-telangiectasia mutated (ATM) and histone H2AX phosphorylation induction. The compound also led PC-3 to lipid peroxidation and mitochondrial depolarization which triggered the activation of intrinsic pathway, confirmed by increase of cleaved caspase-9 and 3. In this work we also show the ability of 9c in reducing vascular endothelial growth factor expression (VEGF) and inhibiting topoisomerase I enzyme, therefore indicating a potential new molecule to be further investigated for prostate cancer management.