Browsing by Author "Nguyen, Julian"
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Item Does Intermittent Hypoxia Training Augment Antioxidant and Anti-Glycation Enzymes in Rat Brain?(2017-03-14) Cherry, Brandon; Williams, Arthur Jr.; Marianna, Jung; Myoung-Gwi, Ryou; Mallet, Robert T.; Nguyen, JulianHypothesis: Intermittent hypoxia training (IHT) has been found to minimize damage in the brain of rats subjected to ischemic stroke and alcohol intoxication-withdrawal, but the neuroprotective mechanisms are unclear. The finding that antioxidant treatments during IHT blunt the protection identifies a pivotal role of reactive oxygen species (ROS). Because ROS activate expression of antioxidant and anti-glycation enzymes, this study addressed the hypothesis that IHT augments these enzymes in rat brain. Specifically, the cerebral activities of anti-glycation (glyoxalase-1, i.e. GLO1), anti-oxidant (glucose 6-phosphate dehydrogenase, i.e. G6PDH) and hypoxia-inert (lactate dehydrogenase, i.e. LDH) enzymes were analyzed in IHT and non-hypoxic rats. Material and Methods: Ten rats (5 males) completed a 20 day IHT program (5-8 daily cycles of 5-10 min exposures to 9.5-10% O2 followed by 4 min room air exposures), and another 10 rats (5 males) were sham-conditioned by cyclic exposures to 21% O2. One day after completing the IHT or sham programs, the rats were isoflurane-anesthetized and decapitated. The cerebra were harvested, flash-frozen in liquid N2, pulverized in a mortar under liquid N2, homogenized in phosphate buffer, and centrifuged. Enzyme activities in supernatants were analyzed by spectrophotometry, and total protein content by colorimetric Bradford assay. Results: Activities of GLO1 were 78 ± 8 and 62 ± 7 mU/mg protein in the IHT and sham groups, respectively (P = 0.23). G6PDH activities were 21 ± 2 and 24 ± 2 mU/mg protein in the IHT and sham groups (P = 0.32). As expected, LDH activities were similar in the two groups: 899 ± 49 mU/mg protein in the IHT rats, and 940 ± 58 mU/mg protein in the sham rats (P = 0.60). Thus, IHT did not produce a statistically significant treatment effect on these enzymes. Conclusions: The 20 day IHT program, which exerts robust cerebroprotection against ischemia-reperfusion and ethanol intoxication-withdrawal, did not augment activities of selective antioxidant and anti-glycation enzymes. The impact of IHT on other antioxidant (e.g. glutathione peroxidase, superoxide dismutase, catalase) and anti-glycation (e.g. glyoxalase-2) enzymes remains to be evaluated. It also is possible that IHT activates other cytoprotective mechanisms, including signaling cascades that ameliorate mitochondrial permeability transition, oxidative stress and other mechanisms of neural injury. Such alternative mechanisms merit investigation.Item Evaluation of the Sepsis Screening Tool’s Efficacy in Assessing Organ Dysfunction(2017-03-14) Nguyen, Julian; Gelvez, Javier; Williams, Lorrainea; Darnell, Charity; Hamby, Tyler; Issa, TesneemBackground: Sepsis is a life threatening condition caused by the dysregulation of the immune system due to multiple organ dysfunction. It is usually caused by an infection that can affect the respiratory, neurological, circulatory, and metabolic systems. The best way to help these patients is to give them the appropriate care as quickly as possible. In order to help make this possible, a sepsis screening tool was developed for patients at Cook Children’s Medical Center (CCMC). Purpose: The purpose of this project was to see if patients screened for sepsis were less likely to develop organ dysfunction. A new adult definition of sepsis was developed in February 2016 by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine; this definition, modified to apply pediatric norms, was applied at CCMC in order to assess the level of organ dysfunction in children. Methods: The level of organ dysfunction was based on the first set of vitals at admission to the pediatric intensive care unit (PICU) at CCMC. To be included in this study, patients had to have had an initial PICU visit between the dates of 10/12-5/16, and the providers’ diagnoses had to have included billing codes related to sepsis. There were 520 patients meeting these criteria. Patients were screened for respiratory, neurological, circulatory, or metabolic dysfunction, and then were given an organ dysfunction score. Results: The results showed that 82% of the patients who were not screened had organ dysfunction compared to only 69% of those for which the sepsis screening tool was utilized. Thus, those who were not screened were more likely to have organ dysfunction than those who were screened, P=.001, OR=2.08. Among those screened, patients with positive screens (73%) were more likely to have organ dysfunction than those with negative screens (60%), P=.03, OR=1.78. Conclusions: In conclusion, patients who were screened were significantly less likely to have organ dysfunction than those who were not screened, and among those screened, those with positive screens were significantly more likely to have organ dysfunction. The tool successfully assessed the risk of sepsis and septic shock at CCMC and could be used to increase sepsis awareness if it was to be used at other hospitals.