ORCID Profile
0000-0002-6248-2688
Current Organisation
Flinders University
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Publisher: American Physiological Society
Date: 06-2021
Abstract: The COVID-19 pandemic triggered university lockdowns, forcing physiology educators to rapidly pivot laboratories into a remote delivery format. This study documents the experiences of an international group of 10 physiology educators surrounding this transition. They wrote reflective narratives, framed by guiding questions, to answer the research question: “What were the changes to physiology laboratories in response to the COVID-19 pandemic?” These narratives probed educators’ attitudes toward virtual laboratories before, during, and after the transition to remote delivery. Thematic analysis of the reflections found that before COVID-19 only a few respondents had utilized virtual laboratories and most felt that virtual laboratories could not replace the in-person laboratory experience. In response to university lockdowns, most respondents transitioned from traditional labs to remote formats within a week or less. The most common remote delivery formats were commercially available online physiology laboratories, homemade videos, and s le experimental data. The main challenges associated with the rapid remote transition included workload and expertise constraints, disparities in online access and workspaces, issues with academic integrity, educator and student stress, changes in learning outcomes, and reduced engagement. However, the experience generated opportunities including exploration of unfamiliar technologies, new collaborations, and revisiting the physiology laboratory curriculum and structure. Most of the respondents reported planning on retaining some aspects of the remote laboratories postpandemic, particularly with a blended model of remote and on-c us laboratories. This study concludes with recommendations for physiology educators as to how they can successfully develop and deliver remote laboratories.
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/J.BCP.2003.08.025
Abstract: Renal ischaemia is associated with accumulation of fatty acids (FA) and mobilisation of arachidonic acid (AA). Given the capacity of UDP-glucuronosyltransferase (UGT) isoforms to metabolise both drugs and FA, we hypothesised that FA would inhibit renal drug glucuronidation. The effect of FA (C2:0-C20:5) on 4-methylumbelliferone (4-MU) glucuronidation was investigated using human kidney cortical microsomes (HKCM) and recombinant UGT1A9 and UGT2B7 as the enzyme sources. 4-MU glucuronidation exhibited Michaelis-Menten kinetics with HKCM (apparent K(m) (K(m)(app)) 20.3 microM), weak substrate inhibition with UGT1A9 (K(m)(app) 10.2 microM, K(si) 289.6 microM), and sigmoid kinetics with UGT2B7 (S(50)(app)440.6 microM) Similarly, biphasic UDP-glucuronic acid (UDPGA) kinetics were observed with HKCM (S(50) 354.3 microM) and UGT1A9 (S(50) 88.2 microM). In contrast, the Michaelis-Menten kinetics for UDPGA observed with UGT2B7 (K(m)(app) 493.2 microM) suggested that kinetic interactions with UGTs were specific to the xenobiotic substrate and the co-substrate (UDPGA). FA (C16:1-C20:5) significantly inhibited (25-93%) HKCM, UGT1A9 or UGT2B7 catalysed 4-MU glucuronidation. Although linoleic acid (LA) and AA were both competitive inhibitors of 4-MU glucuronidation by HKCM (K(i)(app) 6.34 and 0.15 microM, respectively), only LA was a competitive inhibitor of UGT1A9 (K(i)(app) 4.06 microM). In contrast, inhibition of UGT1A9 by AA exhibited atypical kinetics. These data indicate that LA and AA are potent inhibitors of 4-MU glucuronidation catalysed by human kidney UGTs and recombinant UGT1A9 and UGT2B7. It is conceivable therefore that during periods of renal ischaemia FA may impair renal drug glucuronidation thus compromising the protective capacity of the kidney against drug-induced nephrotoxicity.
Publisher: Wiley
Date: 10-05-2010
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 19-01-2007
Abstract: Studies were performed to elucidate the mechanism responsible for the reduction in Km values of UDP-glucuronosyltransferase 2B7 (UGT2B7) substrates observed for incubations conducted in the presence of albumin. Addition of bovine serum albumin (BSA) and fatty acid-free human serum albumin (HSA-FAF), but not "crude" HSA, resulted in an approximate 90% reduction in the Km values for the glucuronidation of zidovudine (AZT) by human liver microsomes (HLM) and UGT2B7 and a 50 to 75% reduction in the S50 for 4-methylumbelliferone (4MU) glucuronidation by UGT2B7, without affecting Vmax. Oleic, linoleic, and arachidonic acids were shown to be the most abundant unsaturated long-chain fatty acids present in crude HSA and in the membranes of HLM and human embryonic kidney (HEK)293 cells, and it was demonstrated that these and other unsaturated long-chain fatty acids were UGT2B7 substrates. Glucuronides with Rf (retention factor) values corresponding to the glucuronides of linoleic and arachidonic acid were detected when HLM and HEK293 cell lysates were incubated with radiolabeled cofactor, and the intensity of the bands was modulated by the presence of crude HSA (increased) and BSA or HSA-FAF (decreased). Oleic, linoleic, and arachidonic acid inhibited AZT and 4MU glucuronidation by HLM and/or UGT2B7, due to an increase in Km/S50 without a change in Vmax. Addition of BSA and HSA-FAF reversed the inhibition. Likewise, coexpression of UGT2B7 and HSA in HEK293 cells reduced the Km/S50 values of these substrates. It is postulated that BSA and HSA-FAF sequester inhibitory fatty acids released during incubations, and the apparent high Km values observed for UGT2B7 substrates arise from the presence of these endogenous inhibitors.
Publisher: American Physiological Society
Date: 09-2023
Abstract: The homeostasis core concept of physiology was defined and unpacked by an Australian team with the goal of constructing a resource that will improve learning and teaching of this core physiology concept in an Australian Higher Education context.
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 14-08-2007
Abstract: There is currently little information regarding the localization of UDP-glucuronosyltransferases (UGTs) in human renal cortex and medulla, and the functional contribution of renal UGTs to drug glucuronidation remains poorly defined. Using human kidney sections and human kidney cortical microsomes (HKCM) and human kidney medullary microsomes (HKMM), we combined immunohistochemistry to investigate UGT1A and UGT2B7 expression with in vitro microsomal studies to determine the kinetics of S-naproxen acyl glucuronidation. With the exception of the glomerulus, Bowman's capsule, and renal vasculature, UGT1A proteins and UGT2B7 were expressed throughout the proximal and distal convoluted tubules, the loops of Henle, and the collecting ducts. Additionally, UGT1A and UGT2B7 expression was demonstrated in the macula densa, supporting a potential role of UGTs in regulating aldosterone. Consistent with the immunohistochemical data, S-naproxen acyl glucuronidation was catalyzed by HKCM and HKMM. Kinetic data were well described by the two-enzyme Michaelis-Menten equation. K(m) values for the high-affinity components were 34 +/- 14 microM (HKCM) and 45 +/- 14 microM (HKMM). Fluconazole inhibited the high-affinity component establishing UGT2B7 as the enzyme responsible for S-naproxen glucuronidation in cortex and medulla. The low-affinity component was relatively unaffected by fluconazole (<15% inhibition), supporting the presence of other UGTs with S-naproxen glucuronidation capacity (e.g., UGT1A6 and UGT1A9) in cortex and medulla. We postulate that the ubiquitous distribution of UGTs in mammalian kidney may buffer physiological responses to endogenous mediators, but at the same time competitive xenobiotic-endobiotic interactions may provide an explanation for the adverse renal effects of drugs, including nonsteroidal anti-inflammatory drugs.
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.BCP.2007.01.030
Abstract: Mefenamic acid, a non-steroidal anti-inflammatory drug (NSAID), is used commonly to treat menorrhagia. This study investigated the glucuronidation kinetics of flufenamic, mefenamic and niflumic acid using human kidney cortical microsomes (HKCM) and recombinant UGT1A9 and UGT2B7. Using HKCM Michaelis-Menten (MM) kinetics were observed for mefenamic (K(m)(app) 23 microM) and niflumic acid (K(m)(app) 123 microM) glucuronidation, while flufenamic acid exhibited non-hyperbolic (atypical) glucuronidation kinetics. Notably, the intrinsic renal clearance of mefenamic acid (CL(int) 17+/-5.5 microL/minmg protein) was fifteen fold higher than that of niflumic acid (CL(int) 1.1+/-0.8 microL/minmg protein). These data suggest that renal glucuronidation of mefenamic acid may result in high intrarenal exposure to mefenamic acyl-glucuronide and subsequent binding to renal proteins. Diverse kinetics were observed for fenamate glucuronidation by UGT2B7 and UGT1A9. Using UGT2B7 MM kinetics were observed for flufenamic (K(m)(app) 48 microM) and niflumic acid (K(m)(app) 135 microM) glucuronidation and atypical kinetics with mefenamic acid. Similarity in K(m)(app) between HKCM and UGT2B7 suggests that UGT2B7 may be the predominant renal UGT isoform catalysing niflumic acid glucuronidation. In contrast, UGT1A9 glucuronidation kinetics were characterised by negative cooperativity with mefenamic (S(50) 449 microM, h 0.4) and niflumic acid (S(50) 7344 microM, h 0.4) while atypical kinetics were observed with flufenamic acid. Additionally, potent inhibition of the renal glucuronidation of the UGT substrate 'probe' 4-methylumbelliferone by flufenamic, mefenamic and niflumic acid was observed. These data suggest that inhibitory metabolic interactions may occur between fenamates and other substrates metabolised by UGT2B7 and UGT1A9 in human kidney.
Publisher: American Physiological Society
Date: 09-2023
Abstract: This is the first time Australia-wide agreement has been reached on the core concepts of physiology with the Delphi method. Embedding of the core concepts will result in consistency in physiology curricula, improvements to teaching and learning, and benchmarking across Australian universities.
Publisher: Wiley
Date: 05-2021
Publisher: Informa Healthcare
Date: 29-09-2005
Abstract: The exact mechanism(s) of NSAID-induced nephrotoxicity remains unclear, but most theories centre on the initial inhibition of COX and the subsequent perturbation of the numerous actions of COX in the kidney. Since the nineteenth century no NSAIDs have been developed that are devoid of renal adverse effects, including the COX-2 selective inhibitors. Formation of renal eicosanoids from arachidonic acid is significantly increased in the presence of various stimuli, and metabolic degradation of arachidonic acid and its biologically active metabolites is crucial to the maintenance of renal homeostatic mechanisms. An important family of enzymes that function in this capacity are the uridine 5'-diphosphate glucuronosyltransferases (UGTs) that variously metabolise arachidonic acid and its metabolites. This review focuses on arachidonic acid and its biologically active metabolites and their respective fates subsequent to COX inhibition by NSAIDs. The common involvement of UGT in the metabolism of arachidonic acid, eicosanoids and NSAIDs is discussed in the context of novel mechanisms of NSAID-induced nephrotoxicity.
Publisher: American Physiological Society
Date: 12-2021
Abstract: There has been a gradual shift in the delivery of physiology laboratory classes over the last 30 years. For many, wet-lab demonstrations using animal tissues have been reduced or replaced with student-led investigations where students are both subjects and researchers. Despite these changes, expectations remain that physiology courses should include a practical component to encourage deeper and higher-order learning. Wet-lab tissue experiments and student-based group research formats can be expensive to run, associated with various ethical constraints, and, as discovered in these times of COVID-19, difficult to operate while adhering to physical distancing. We address the proposition that online and/or remote delivery of laboratory classes using digital technologies may provide a solution to both financial and ethical constraints of on-c us laboratory classes. Our discussions, as an international group of 10 physiologists from the United States, the United Kingdom, Canada, and Australia, revealed that although some of the financial and ethical constraints of using animal tissues and student-led investigations were addressed by the introduction of online alternatives, the construction and maintenance of online delivery modes could also be expensive and ethical issues, not previously considered, included digital equity and student data security. There was also a collective perception that if face-to-face laboratory classes were changed to an entirely virtual mode there was a risk that some intended learning outcomes would not be met. It was concluded that the “ideal” approach is likely a hybrid model whereby student attendance in face-to-face, on-c us classes is supported with interactive digital content either developed in house or obtained through third-party providers.
Publisher: Wiley
Date: 05-2021
No related grants have been discovered for Voula Gaganis.