In the 1960s Szent-GyBrgyi and his co-workers reported the inhibition of tumor growth with extracts from normal tissues. Characterization using derivatization and spectral analysis demonstrated that the inhibitor was an a.fl dicarbonyl. Methylglyoxal is the lowest class member of the ketoaldehydes. A biological system which catalyses the formation of lactate from methylglyoxal was reported early in this century. The formation of D-lactate (not the L-lactate of glycolysis) is catalyzed by the mammalian enzymes, glyoxalase I (S-lactoyl-glutathione methylglyoxal-lyase, isomenzing; EC 4.4.1.5) and glyoxalase I1 (S-2-hydroxyacylglutathione hydrolase: EC 3.1.2.6).with glutathione (GSH) as a coenzyme. There have been a number of reports on the formation of methylglyoxal in mammalian tissue, and experimental support for the inhibition of tumor growth by inhibition of glyoxalase I has been published. However, the rapid catabolism of analogues of methylglyoxal or glutathione suggests that inhibitors that resemble the transition state may more effectively bind significantly to glyoxalase I. The transition state in the formation of S-lactoylglutathione from the hemimercaptal of methylglyoxal is an enediol. Compounds such as 3,4-dihydroxycyclobutene 1,2dione (squaric acid) (a coplanar compound) significantly inhibit yeast glyoxalase I. Here the inhibition in uitro of human red blood cell glyoxalase I with a number of compounds that resemble the transition state of methylglyoxal hemimercaptal is reported. These include the following with 150 in mM. 3.4-dihydroxy benzoic acid (0.32 m M ) , 3,4-dihydroxy benzohydroxamic acid (0.38 mM). 4-methyl-6,7-dihydroxy coumarin (0.03 mM), and 6.7-dihydroxy coumarin (0.03 mM). Coumarin was not inhibitory. Calculations based on the in uitro data and these structures may be predictive of their growth inhibitory nature in such model animal tumors as L1210 leukemia.
Study Objectives: Emergency medical services (EMS) are an integral component of the health care system. Interaction with EMS and transition of patient care is a daily occurrence in emergency medicine (EM). EM learners present to residency with diverse levels of prior exposure and familiarity with EMS. Though the American College of Graduate Medical Education (ACGME) requires EM residents to have experience with EMS, emergency preparedness, and disaster management, there is significant variability in EMS curricula and training among residency programs. The goal of the exercise was to determine if a novel interdisciplinary education event, with focus on simulation and demonstration, increased EM resident and student knowledge of EMS systems and equipment as well as confidence interacting with EMS.Methods: A four-hour interactive, multidisciplinary simulation event was developed and held in the summer of 2020. EM residents and medical students rotated through multiple interactive stations that focused on EMS equipment and operations, online medical control, tactical EMS, and firefighting operations. Prior to the event, participants completed a survey to assess prior experiences, familiarity, and comfort with topics presented. An additional survey was provided at the completion of the event. Survey data was compared pre-and post-event to assess for change in responses. Items on the surveys were analyzed independently, and similar items were compared in aggregate. The post-event survey also assessed participants' perceptions of the exercise including organization and relevance.Results: 38 participants completed the pre-event survey; 27 completed the postevent survey with 23 participants identified and matched as answering both surveys. Composite scores showed a statistically significant improvement in learner confidence using the demonstrated EMS equipment and performing online medical control. Comfort with use of EMS equipment improved from an average of 3 to 4.33 (on a 1-5 Likert scale) after demonstration and practice with equipment. (p<0.0001). Average confidence providing online medical control improved from 1.33 to 2.67 (p<0.0001). Respondents indicated the event increased their familiarity with EMS, tactical EMS, and fire department operations. Post-survey perception data revealed that 100% of participants overall reviewed the event as well organized and enjoyable. 96% stated the exercise was relevant to emergency medicine. 93% stated they would use the knowledge gained in the experience in their future medical practice.Conclusion: This novel interdisciplinary educational event utilizing hands-on training and simulation was effective in increasing familiarity and confidence with EMS operations, equipment use and online medical control. Participants found the event to be a positive educational experience which increased their knowledge base and relevant to future medical practice. Further investigation comparing hands-on simulation exercises to classroom-based didactics would be instructive.
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