Antimyotoxic Activity of Synthetic Peptides Derived from Bothrops atrox Snake Gamma Phospholipase A2 Inhibitor Selected by Virtual Screening.

BACKGROUND: Several studies have aimed to identify molecules that inhibit the toxic actions of snake venom phospholipases A2 (PLA2s). Studies carried out with PLA2 inhibitors (PLIs) have been shown to be efficient in this assignment. OBJECTIVE: This work aimed to analyze the interaction of peptides derived from Bothrops atrox PLIγ (atPLIγ) with a PLA2 and to evaluate the ability of these peptides to reduce phospholipase and myotoxic activities. METHODS: Peptides were subjected to molecular docking with a homologous Lys49 PLA2 from B. atrox venom modeled by homology. Phospholipase activity neutralization assay was performed with BthTX-II and different ratios of the peptides. A catalytically active and an inactive PLA2 were purified from the B. atrox venom and used together in the in vitro myotoxic activity neutralization experiments with the peptides. RESULTS: The peptides interacted with amino acids near the PLA2 hydrophobic channel and the loop that would be bound to calcium in Asp49 PLA2. They were able to reduce phospholipase activity and peptides DFCHNV and ATHEE reached the highest reduction levels, being these two peptides the best that also interacted in the in silico experiments. The peptides reduced the myotubes cell damage with a highlight for the DFCHNV peptide, which reduced by about 65%. It has been suggested that myotoxic activity reduction is related to the sites occupied in the PLA2 structure, which could corroborate the results observed in molecular docking. CONCLUSION: This study should contribute to the investigation of the potential of PLIs to inhibit the toxic effects of PLA2s.

Conceptualizing and measuring potentially inappropriate drug therapy.

WHAT IS KNOWN AND OBJECTIVE: Elderly people are the principal consumers of prescription drugs. The more the medication used by the patient, the greater the likelihood there is of the patient being subjected to potentially inappropriate drug therapy (PIDT). PIDT has been measured in the literature with both implicit and explicit tools. The purpose of this review was to assess the use of tools to detect PIDT in various studies and to determine which terms are used to refer to PIDT in practice. METHODS: A systematic review was conducted according to the following steps: the first was identification. In this step, studies were selected from different combinations of the descriptors 'aged', 'elderly', 'inappropriate prescribing' and 'drug utilization' in three different languages, using the Embase, Medline, Scielo, Scopus and Web of Science databases. Second, the papers that satisfied the inclusion criteria for data extraction were carefully examined by three evaluators to determine the tools used and terms that referred to PIDT. RESULTS AND DISCUSSION: From the combinations of keywords, 8610 articles were found. At the end of the selection process, 119 of the articles complied with the specified criteria. The degree of agreement among evaluators was moderate for the study titles (κ1  = 0·479) and substantial for abstracts (κ2  = 0·647). With respect to the PIDT evaluation criteria used by the studies, 27·7% used two criteria. Of the 27 evaluation criteria identified, the Beers criteria were used by 82·3% of the studies. More than 50 different terms to identify PIDT were found in the literature. WHAT IS NEW AND CONCLUSION: This review is the first study to conceptualize and discuss terms that refer to PIDT. At present, there is no consensus regarding terms used to refer to PIDT, with over 50 different terms currently in use. This review shows an increase in the number of articles aimed at evaluating PIDT using implicit and explicit tools.