Pyrazoline derivatives as promising novel antischistosomal agents.

Praziquantel is the only available drug to treat schistosomiasis, a parasitic disease that currently infects more than 240 million people globally. Due to increasing concerns about resistance and inadequate efficacy there is a need for new therapeutics. In this study, a series of 17 pyrazolines (15-31) and three pyrazoles (32-34) were synthesized and evaluated for their antiparasitic properties against ex vivo adult Schistosoma mansoni worms. Of the 20 compounds tested, six had a 50% effective concentration (EC50) below 30 µM. Our best hit, pyrazoline 22, showed promising activity against adult schistosomes, with an EC50 < 10 µM. Additionally, compound 22 had low cytotoxicity, with selectivity index of 21.6 and 32.2 for monkey and human cell lines, respectively. All active pyrazolines demonstrated a negative effect on schistosome fecundity, with a marked reduction in the number of eggs. Structure-activity relationship analysis showed that the presence of the non-aromatic heterocycle and N-substitution are fundamental to the antischistosomal properties. Pharmacokinetics, drug-likeness and medicinal chemistry friendliness studies were performed, and predicted values demonstrated an excellent drug-likeness profile for pyrazolines as well as an adherence to major pharmaceutical companies' filters. Collectively, this study demonstrates that pyrazoline derivatives are promising scaffolds in the discovery of novel antischistosomal agents.

The complications associated with Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA).

Non-compressible torso hemorrhage (NCTH) remains a significant cause of morbidity and mortality in the field of trauma and emergency medicine. In recent times, there has been a resurgence in the adoption of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for patients who present with NCTH. Like all medical procedures, there are benefits and risks associated with the REBOA technique. However, in the case of REBOA, these complications are not unanimously agreed upon with varying viewpoints and studies. This article aims to review the current knowledge surrounding the complications of the REBOA technique at each step of its application.

Resuscitative endovascular balloon occlusion of the aorta (REBOA): an updated review / Oclusão ressuscitativa por meio de balão endovascular da aorta (REBOA): revisão atualizada

ABSTRACT In a current scenario where trauma injury and its consequences account for 9% of the worlds causes of death, the management of non-compressible torso hemorrhage can be problematic. With the improvement of medicine, the approach of these patients must be accurate and immediate so that the consequences may be minimal. Therefore, aiming the ideal method, studies have led to the development of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). This procedure has been used at select trauma centers as a resuscitative adjunct for trauma patients with non-compressible torso hemorrhage. Although the use of this technique is increasing, its effectiveness is still not clear. This article aims, through a detailed review, to inform an updated view about this procedure, its technique, variations, benefits, limitations and future.

RESUMO Em um cenário atual onde a lesão traumática e suas consequências representam 9% das causas de morte no mundo, o manejo da hemorragia não compressível do tronco pode ser problemático. Com a melhoria da medicina, a abordagem desses pacientes deve ser precisa e imediata, para que as consequências possam ser mínimas. Portanto, visando o método ideal de manejo, estudos levaram ao desenvolvimento da técnica de oclusão ressuscitativa por balão endovascular da aorta (Resuscitative Endovascular Balloon Occlusion of the Aorta - REBOA). Este procedimento foi utilizado em centros de trauma selecionados como um complemento durante a reanimação para pacientes vítimas de trauma com hemorragia não compressível do tronco. Embora o uso dessa técnica esteja aumentando, sua eficácia ainda não é clara. Este artigo objetiva, por meio de uma revisão detalhada, trazer uma visão atualizada sobre este procedimento, sua técnica, variações, benefícios, limitações e futuro.