7 research outputs found
Breaking the Binary:Conceptions of Sex and Gender in Undergraduate Science
The need to make higher education curricula gender-inclusive is increasingly pressing as student cohorts diversify. We adopted a student-staff partnership approach to design, integrate, and evaluate a module that taught first-year science students the difference between biological sex, gender identity, gender expression, and sexual orientation in the context of genetics concepts at an Australian university. This module aimed to break the binary in misconceptions of both sex and gender, emphasising that both exist on separate spectra. Data triangulation was used to evaluate studentsâ attitudes towards the module and their learning of module concepts. Studentsâ attitudes were positive overall, and evaluation of studentsâ learning indicated that the majority of students understood and retained key concepts, while also identifying common misconceptions. Perhaps the most important finding was that students who identified as belonging to a minority group had significantly more positive attitudes towards the module than non-minority students. This finding supports previous research that has found inclusive curricula have greater benefit for students from minority backgrounds, indicating the importance of making such curriculum enhancements. Our results speak to both the co-creation process and studentsâ learning outcomes, providing valuable insights for practitioners both within science and beyond
TRPM2 channels mediate acetaminophen-induced liver damage
Acetaminophen (paracetamol) is the most frequently used analgesic and antipyretic drug available over the counter. At the same time, acetaminophen overdose is the most common cause of acute liver failure and the leading cause of chronic liver damage requiring liver transplantation in developed countries. Acetaminophen overdose causes a multitude of interrelated biochemical reactions in hepatocytes including the formation of reactive oxygen species, deregulation of Ca2+ homeostasis, covalent modification and oxidation of proteins, lipid peroxidation, and DNA fragmentation. Although an increase in intracellular Ca2+ concentration in hepatocytes is a known consequence of acetaminophen overdose, its importance in acetaminophen-induced liver toxicity is not well understood, primarily due to lack of knowledge about the source of the Ca2+ rise. Here we report that the channel responsible for Ca2+ entry in hepatocytes in acetaminophen overdose is the Transient Receptor Potential Melanostatine 2 (TRPM2) cation channel. We show by whole-cell patch clamping that treatment of hepatocytes with acetaminophen results in activation of a cation current similar to that activated by H2O2 or the intracellular application of ADP ribose. siRNA-mediated knockdown of TRPM2 in hepatocytes inhibits activation of the current by either acetaminophen or H2O2. In TRPM2 knockout mice, acetaminophen-induced liver damage, assessed by the blood concentration of liver enzymes and liver histology, is significantly diminished compared with wildtype mice. The presented data strongly suggest that TRPM2 channels are essential in the mechanism of acetaminophen-induced hepatocellular death
Intermittent Ischemia but Not Ischemic Preconditioning Is Effective in Restoring Bile Flow After Ischemia Reperfusion Injury in the Livers of Aged Rats
BackgroundlAims. Ischemic preconditioning (IPC) and intermittent ischemia (INT) reduce liver injury following ischemia reperfusion in liver resections. Aged livers are at higher risk for ischemia reperfusion injury, but little is known of the effectiveness of IPC and INT in aged livers. The aim of this study was to investigate the effects of IPC and INT on ischemia reperfusion injury in aged livers. Methods. A rat model of segmental hepatic ischemia (45 min) and reperfusion (60 min) was used. Bile flow, as an indicator of early hepatocyte damage and dynamic liver function, plasma concentrations of bilirubin, liver marker enzymes, and liver histology were assessed. Results. In young rats (8-13 weeks), IPC regimes of 10 min clamping and 10 min reperfusion, and 5 min clamping and 30 min reperfusion, restored bile flow to 23 and 42%, respectively, of the initial value, compared to 14 and 88% for continuous clamping and controls, respectively. An M regime of three cycles of alternating 15 min perfusion and 15 min clamping gave a substantially greater (70%) restoration of bile flow. In aged rats (20-24 months), the IPC regimes did not give any restoration of bile flow. By contrast, the INT regime restored bile flow to 68%. Plasma bilirubin concentrations were lowest in the INT groups, whereas alanine transaminase concentrations for the IPC and INT groups compared with the continuous clamping groups showed no significant differences. Conclusions. In young rats, INT is more effective than IPC in restoring the immediate consequences of IP-induced damage to hepatocytes and liver function after ischemia-reperfusion. In aged rats INT, but not IPC, reverses hepatocyte damage and restores liver function. INT may promote better hepatocyte and liver function than IPC following the surgical resection of aged livers. (c) 2009 Elsevier Inc. All rights reserved
Increasing cycles of intermittent ischemia can effectively maintain liver function during the acute phase of ischemia reperfusion injury by promotion of bile flow and reduction in bile salt toxicity
Background/Aims: Intermittent ischemia (INT) can improve liver function following inflow occlusion. The aim was to test whether the number of cycles of INT can be increased without impairing liver function. Methods: Liver function in the acute phase of ischemia reperfusion injury was assessed by measuring bile flow in rat livers. Phospholipid and bile salts in bile, liver marker enzymes in blood, and liver histology were measured. Aged livers were compared with young livers. Results: Clamping for 45 min reduced postperfusion bile flow to 13% of the initial value compared with 88 +/- 5% for control livers (means +/- SEM, n = 5-8), and substantially reduced the phospholipid: bile salt ratio in bile. Application of 3, 4, 5 and 6 cycles of INT (15 min) restored bile flow to 70 +/- 11, 61 +/- 4, 48 +/- 2 and 35 +/- 3% (p <0.01) of the initial value, respectively, and restored the phospholipid: bile salt ratio. Multiple cycles of INT were less effective in aged rats. Conclusion: Several cycles of INT, through promotion of bile flow recovery and reduction in the cytotoxic actions of bile salts, may provide an effective clinical strategy for increasing clamping time in liver resections. Copyright (C) 2010 S. Karger AG, Base
Ischemic Preconditioning and Intermittent Ischemia Preserve Bile Flow in a Rat Model of Ischemia Reperfusion Injury
Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury
Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question. Material and methods. A rat model of segmental hepatic ischemia was employed. Rats were pre-treated with the estrogen receptor antagonist ICI182,780 and/or the estrogen receptor agonist 17 beta-estradiol. Bile flow, blood concentrations of bilirubin and liver enzymes were measured, and liver histology was assessed. Results. Bile flow recovery immediately after the initiation of reperfusion was faster in females than in males. ICI182,780 reduced the rate of bile flow recovery in females but this reduction was not reversed by co-administration of 17 beta-estradiol. In males, 17 beta-estradiol alone did not enhance bile flow recovery. The changes in bile flow recovery observed under a given condition were correlated with small changes in blood liver enzymes and liver histology. Conclusions. Sex has a significant influence on the early recovery of liver function in the acute phase of IR injury. However, in female rats estrogen receptors play only a limited role in mediating enhanced recovery of liver function
Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury
Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question. Material and methods. A rat model of segmental hepatic ischemia was employed. Rats were pre-treated with the estrogen receptor antagonist ICI182,780 and/or the estrogen receptor agonist 17 beta-estradiol. Bile flow, blood concentrations of bilirubin and liver enzymes were measured, and liver histology was assessed. Results. Bile flow recovery immediately after the initiation of reperfusion was faster in females than in males. ICI182,780 reduced the rate of bile flow recovery in females but this reduction was not reversed by co-administration of 17 beta-estradiol. In males, 17 beta-estradiol alone did not enhance bile flow recovery. The changes in bile flow recovery observed under a given condition were correlated with small changes in blood liver enzymes and liver histology. Conclusions. Sex has a significant influence on the early recovery of liver function in the acute phase of IR injury. However, in female rats estrogen receptors play only a limited role in mediating enhanced recovery of liver function.</p