Asbestos remains ubiquitous in the Australian built environment. Of the 13 million tonnes of asbe... more Asbestos remains ubiquitous in the Australian built environment. Of the 13 million tonnes of asbestos products installed in earlier decades, an estimated 50% remain in situ today. Because of the extensive past use of asbestos, and the increasing age of these products, the potential for exposure to asbestos fibres in both indoor and outdoor environments remains high, even while the actual asbestos exposure levels are mostly very low. Sources of these exposures include disturbance of in situ asbestos-containing materials (ACMs), for example during renovations or following disaster events such as fires, cyclones and floods. Our understanding of the risk of asbestos-related disease arising from long-term low-level or background exposure, however, is poor. We provide the most up-to-date review of asbestos exposure risks currently affecting different groups of the Australian population and the settings in which this can manifest. From this, a need for low-level asbestos monitoring has eme...
Artificial Intelligence (AI) is providing the technology for large-scale, cost-effective and curr... more Artificial Intelligence (AI) is providing the technology for large-scale, cost-effective and current asbestos-containing material (ACM) roofing detection. AI models can provide additional data to monitor, manage and plan for ACM in situ and its safe removal and disposal, compared with traditional approaches alone. Advances are being made in AI algorithms and imagery applied to ACM detection. This study applies mask region-based convolution neural networks (Mask R-CNN) to multi-spectral satellite imagery (MSSI) and high-resolution aerial imagery (HRAI) to detect the presence of ACM roofing on residential buildings across an Australian case study area. The results provide insights into the challenges and benefits of using AI and different imageries for ACM detection, providing future directions for its practical application. The study found model 1, using HRAI and 460 training samples, was the more reliable model of the three with a precision of 94%. These findings confirm the efficac...
Given Australia’s significant and aged asbestos legacy, the long-term sustainability of effective... more Given Australia’s significant and aged asbestos legacy, the long-term sustainability of effective and accessible asbestos waste management is a national priority of Australia’s Asbestos National Strategic Plan. The current policy for managing hazardous asbestos waste is via deep burial in landfill. Technological alternatives to approved deep burial landfill methods exist and could be considered innovative and sustainable additional options for managing asbestos waste, where these are proven viable, and where appropriate policy and regulatory changes are implemented. We present a summary of alternative asbestos waste management technologies and discuss issues influencing their potential application in the Australian context. Increasing the options for asbestos waste management in Australia may additionally facilitate the safe, planned removal of asbestos-containing materials (ACMs) from the built environment. Altogether, this will reduce the potential for exposure to asbestos fibres ...
Journal of Pharmacological and Toxicological Methods, Mar 1, 2008
Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is dimi... more Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is diminished early in the evolution of beta-cell dysfunction, ultimately contributing to the development of Type 2 diabetes. We sought to standardise and validate the intravenous glucose tolerance test (IVGTT), a commonly used technique to assess GSIS, in anaesthetised and conscious cannulated male Han Wistar rats. Male Han Wistar rats were cannulated via the right jugular vein and left carotid artery. Anaesthetised and chronically cannulated conscious models underwent IVGTT using increasing doses of glucose (0.2, 0.5 and 1.0 g glucose/kg LBM) or following pre-treatment with Exendin-4 (EX-4) before receiving a 0.5 g glucose/kg LBM bolus dose. Blood glucose, plasma insulin and plasma C-peptide were measured at time-points throughout the experiments. Dose-dependent increases in blood glucose, insulin and C-peptide (where measured) were observed following administration of increasing doses of an intravenous glucose bolus in both the anaesthetised and conscious cannulated rats. The 0.5 g glucose/kg LBM bolus resulted in an intermediate response and was used in the second part of the study. EX-4 pre-treatment in combination with glucose resulted in GSIS potentiation, as assessed by plasma insulin measurement alone (anaesthetised model) or insulin and C-peptide measurements (conscious model). The IVGTT was standardised in anaesthetised and conscious cannulated male Han Wistar rats by performing a glucose dose response study and validated by examining GSIS potentiation using EX-4. Based on these results, the 0.5 g glucose/kg LBM bolus dose is recommended as the dose to use to assess GSIS in any standardised screening phase of new compounds with the potential to enhance glucose-sensitive pancreatic function. The experimental conditions described in these studies could be transferred to disease models for more detailed assessment of novel compound efficacy.
Medium chain fatty acids and insulin action Enhancement of muscle mitochondrial oxidative capacit... more Medium chain fatty acids and insulin action Enhancement of muscle mitochondrial oxidative capacity and alterations in insulin action are lipid species-dependent: Potent tissue-specific effects of medium chain fatty acids
Journal of Pharmacological and Toxicological Methods, 2008
Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is dimi... more Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is diminished early in the evolution of beta-cell dysfunction, ultimately contributing to the development of Type 2 diabetes. We sought to standardise and validate the intravenous glucose tolerance test (IVGTT), a commonly used technique to assess GSIS, in anaesthetised and conscious cannulated male Han Wistar rats. Male Han Wistar rats were cannulated via the right jugular vein and left carotid artery. Anaesthetised and chronically cannulated conscious models underwent IVGTT using increasing doses of glucose (0.2, 0.5 and 1.0 g glucose/kg LBM) or following pre-treatment with Exendin-4 (EX-4) before receiving a 0.5 g glucose/kg LBM bolus dose. Blood glucose, plasma insulin and plasma C-peptide were measured at time-points throughout the experiments. Dose-dependent increases in blood glucose, insulin and C-peptide (where measured) were observed following administration of increasing doses of an intravenous glucose bolus in both the anaesthetised and conscious cannulated rats. The 0.5 g glucose/kg LBM bolus resulted in an intermediate response and was used in the second part of the study. EX-4 pre-treatment in combination with glucose resulted in GSIS potentiation, as assessed by plasma insulin measurement alone (anaesthetised model) or insulin and C-peptide measurements (conscious model). The IVGTT was standardised in anaesthetised and conscious cannulated male Han Wistar rats by performing a glucose dose response study and validated by examining GSIS potentiation using EX-4. Based on these results, the 0.5 g glucose/kg LBM bolus dose is recommended as the dose to use to assess GSIS in any standardised screening phase of new compounds with the potential to enhance glucose-sensitive pancreatic function. The experimental conditions described in these studies could be transferred to disease models for more detailed assessment of novel compound efficacy.
The aim of this study was to examine the effect of an acute, physiological increase in plasma fre... more The aim of this study was to examine the effect of an acute, physiological increase in plasma free fatty acid (FFA) on initial signalling events in rat red quadriceps muscle (RQ). Male Wistar rats received a 7% glycerol (GLYC) or 7% Intralipid/heparin (LIP) infusion for 3 h, after which they were either killed or infused with insulin at a rate of 0.5 U/kg per h for 5 min, before RQ collection. Plasma FFAs were elevated to ∼2 mM in the LIP rats only. Insulin-stimulated insulin receptor (IR) Tyr1162/Tyr1163 phosphorylation and IR substrate (IRS)-1 Tyr612 phosphorylation were increased at least twofold over basal in GLYC rats with insulin and this increase was not significantly impaired in the LIP rats. However, there was no insulin-stimulated protein kinase B (PKB) Ser473 or glycogen synthase kinase (GSK)-3β Ser9 phosphorylation in the LIP rats, compared with at least a twofold increase over basal in GLYC rats for both proteins. c-Jun N-terminal kinase, inhibitor of κ kinase β and inh...
Our aim was to determine the importance of changes in phosphorylation of key insulin signaling in... more Our aim was to determine the importance of changes in phosphorylation of key insulin signaling intermediates in the insulin resistance observed in skeletal muscle of rats fed diets high in saturated or n-6 polyunsaturated fat. We used phospho-specific antibodies to measure the time course of phosphorylation of key components of the insulin signaling pathway by immunoblotting during the initial stages of a physiological elevation in the circulating insulin concentration. The phosphorylation of insulin receptor at Tyr1162/1163 (IR Tyr1162/1163) increased over 20 min of insulin infusion, whereas the downstream phosphorylation of insulin receptor substrate-1 Tyr612 (IRS-1 Tyr612) peaked at 5 min and declined thereafter. Interestingly, phosphorylation of IRS-1 at Tyr895 continued to increase over the 20-min period, and protein kinase B (PKB) phosphorylation at Ser473 reached a plateau by 5 min, demonstrating that different profiles of phosphorylation are involved in transmission of the i...
Exercise improves insulin sensitivity. As AMP-activated protein kinase (AMPK) plays an important ... more Exercise improves insulin sensitivity. As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) on insulin action in insulin-resistant high-fat-fed (HF) rats. Rats received a subcutaneous injection of 250 mg/kg AICAR (HF-AIC) or saline (HF-Con). The next day, euglycemic-hyperinsulinemic clamp studies were performed. Glucose infusion rate during the clamp was enhanced (50%) in HF-AIC compared with HF-Con rats. Insulin-stimulated glucose uptake was improved in white but not in red quadriceps, whereas glycogen synthesis was improved in both red and white quadriceps of HF-AIC rats. HF-AIC rats also showed increased insulin suppressibility of hepatic glucose output (HGO). AICAR-induced responses in both liver and muscle were accompanied by reduced malonyl-CoA content. Clamp HGO correlated closely with hepatic triglyceride content (r = 0...
OBJECTIVE Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-cha... more OBJECTIVE Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-chain fatty acids (LCFAs); however, relatively little is known regarding their effect on insulin action. Here, we examined the tissue-specific effects of MCFAs on lipid metabolism and insulin action. RESEARCH DESIGN AND METHODS C57BL6/J mice and Wistar rats were fed either a low-fat control diet or high-fat diets rich in MCFAs or LCFAs for 4–5 weeks, and markers of mitochondrial oxidative capacity, lipid levels, and insulin action were measured. RESULTS Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%, P < 0.01) but remained at low-fat diet control levels in the MCFA-fed animals. The LCFA diet increased (20–50%, P < 0.05) markers of mitochondrial metabolism in muscle compared with low-fat diet–fed controls; however; the increase in oxidative capacity was s...
Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory inte... more Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg · d), or MYR (0.3 mg/kg · d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated...
Asbestos remains ubiquitous in the Australian built environment. Of the 13 million tonnes of asbe... more Asbestos remains ubiquitous in the Australian built environment. Of the 13 million tonnes of asbestos products installed in earlier decades, an estimated 50% remain in situ today. Because of the extensive past use of asbestos, and the increasing age of these products, the potential for exposure to asbestos fibres in both indoor and outdoor environments remains high, even while the actual asbestos exposure levels are mostly very low. Sources of these exposures include disturbance of in situ asbestos-containing materials (ACMs), for example during renovations or following disaster events such as fires, cyclones and floods. Our understanding of the risk of asbestos-related disease arising from long-term low-level or background exposure, however, is poor. We provide the most up-to-date review of asbestos exposure risks currently affecting different groups of the Australian population and the settings in which this can manifest. From this, a need for low-level asbestos monitoring has eme...
Artificial Intelligence (AI) is providing the technology for large-scale, cost-effective and curr... more Artificial Intelligence (AI) is providing the technology for large-scale, cost-effective and current asbestos-containing material (ACM) roofing detection. AI models can provide additional data to monitor, manage and plan for ACM in situ and its safe removal and disposal, compared with traditional approaches alone. Advances are being made in AI algorithms and imagery applied to ACM detection. This study applies mask region-based convolution neural networks (Mask R-CNN) to multi-spectral satellite imagery (MSSI) and high-resolution aerial imagery (HRAI) to detect the presence of ACM roofing on residential buildings across an Australian case study area. The results provide insights into the challenges and benefits of using AI and different imageries for ACM detection, providing future directions for its practical application. The study found model 1, using HRAI and 460 training samples, was the more reliable model of the three with a precision of 94%. These findings confirm the efficac...
Given Australia’s significant and aged asbestos legacy, the long-term sustainability of effective... more Given Australia’s significant and aged asbestos legacy, the long-term sustainability of effective and accessible asbestos waste management is a national priority of Australia’s Asbestos National Strategic Plan. The current policy for managing hazardous asbestos waste is via deep burial in landfill. Technological alternatives to approved deep burial landfill methods exist and could be considered innovative and sustainable additional options for managing asbestos waste, where these are proven viable, and where appropriate policy and regulatory changes are implemented. We present a summary of alternative asbestos waste management technologies and discuss issues influencing their potential application in the Australian context. Increasing the options for asbestos waste management in Australia may additionally facilitate the safe, planned removal of asbestos-containing materials (ACMs) from the built environment. Altogether, this will reduce the potential for exposure to asbestos fibres ...
Journal of Pharmacological and Toxicological Methods, Mar 1, 2008
Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is dimi... more Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is diminished early in the evolution of beta-cell dysfunction, ultimately contributing to the development of Type 2 diabetes. We sought to standardise and validate the intravenous glucose tolerance test (IVGTT), a commonly used technique to assess GSIS, in anaesthetised and conscious cannulated male Han Wistar rats. Male Han Wistar rats were cannulated via the right jugular vein and left carotid artery. Anaesthetised and chronically cannulated conscious models underwent IVGTT using increasing doses of glucose (0.2, 0.5 and 1.0 g glucose/kg LBM) or following pre-treatment with Exendin-4 (EX-4) before receiving a 0.5 g glucose/kg LBM bolus dose. Blood glucose, plasma insulin and plasma C-peptide were measured at time-points throughout the experiments. Dose-dependent increases in blood glucose, insulin and C-peptide (where measured) were observed following administration of increasing doses of an intravenous glucose bolus in both the anaesthetised and conscious cannulated rats. The 0.5 g glucose/kg LBM bolus resulted in an intermediate response and was used in the second part of the study. EX-4 pre-treatment in combination with glucose resulted in GSIS potentiation, as assessed by plasma insulin measurement alone (anaesthetised model) or insulin and C-peptide measurements (conscious model). The IVGTT was standardised in anaesthetised and conscious cannulated male Han Wistar rats by performing a glucose dose response study and validated by examining GSIS potentiation using EX-4. Based on these results, the 0.5 g glucose/kg LBM bolus dose is recommended as the dose to use to assess GSIS in any standardised screening phase of new compounds with the potential to enhance glucose-sensitive pancreatic function. The experimental conditions described in these studies could be transferred to disease models for more detailed assessment of novel compound efficacy.
Medium chain fatty acids and insulin action Enhancement of muscle mitochondrial oxidative capacit... more Medium chain fatty acids and insulin action Enhancement of muscle mitochondrial oxidative capacity and alterations in insulin action are lipid species-dependent: Potent tissue-specific effects of medium chain fatty acids
Journal of Pharmacological and Toxicological Methods, 2008
Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is dimi... more Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is diminished early in the evolution of beta-cell dysfunction, ultimately contributing to the development of Type 2 diabetes. We sought to standardise and validate the intravenous glucose tolerance test (IVGTT), a commonly used technique to assess GSIS, in anaesthetised and conscious cannulated male Han Wistar rats. Male Han Wistar rats were cannulated via the right jugular vein and left carotid artery. Anaesthetised and chronically cannulated conscious models underwent IVGTT using increasing doses of glucose (0.2, 0.5 and 1.0 g glucose/kg LBM) or following pre-treatment with Exendin-4 (EX-4) before receiving a 0.5 g glucose/kg LBM bolus dose. Blood glucose, plasma insulin and plasma C-peptide were measured at time-points throughout the experiments. Dose-dependent increases in blood glucose, insulin and C-peptide (where measured) were observed following administration of increasing doses of an intravenous glucose bolus in both the anaesthetised and conscious cannulated rats. The 0.5 g glucose/kg LBM bolus resulted in an intermediate response and was used in the second part of the study. EX-4 pre-treatment in combination with glucose resulted in GSIS potentiation, as assessed by plasma insulin measurement alone (anaesthetised model) or insulin and C-peptide measurements (conscious model). The IVGTT was standardised in anaesthetised and conscious cannulated male Han Wistar rats by performing a glucose dose response study and validated by examining GSIS potentiation using EX-4. Based on these results, the 0.5 g glucose/kg LBM bolus dose is recommended as the dose to use to assess GSIS in any standardised screening phase of new compounds with the potential to enhance glucose-sensitive pancreatic function. The experimental conditions described in these studies could be transferred to disease models for more detailed assessment of novel compound efficacy.
The aim of this study was to examine the effect of an acute, physiological increase in plasma fre... more The aim of this study was to examine the effect of an acute, physiological increase in plasma free fatty acid (FFA) on initial signalling events in rat red quadriceps muscle (RQ). Male Wistar rats received a 7% glycerol (GLYC) or 7% Intralipid/heparin (LIP) infusion for 3 h, after which they were either killed or infused with insulin at a rate of 0.5 U/kg per h for 5 min, before RQ collection. Plasma FFAs were elevated to ∼2 mM in the LIP rats only. Insulin-stimulated insulin receptor (IR) Tyr1162/Tyr1163 phosphorylation and IR substrate (IRS)-1 Tyr612 phosphorylation were increased at least twofold over basal in GLYC rats with insulin and this increase was not significantly impaired in the LIP rats. However, there was no insulin-stimulated protein kinase B (PKB) Ser473 or glycogen synthase kinase (GSK)-3β Ser9 phosphorylation in the LIP rats, compared with at least a twofold increase over basal in GLYC rats for both proteins. c-Jun N-terminal kinase, inhibitor of κ kinase β and inh...
Our aim was to determine the importance of changes in phosphorylation of key insulin signaling in... more Our aim was to determine the importance of changes in phosphorylation of key insulin signaling intermediates in the insulin resistance observed in skeletal muscle of rats fed diets high in saturated or n-6 polyunsaturated fat. We used phospho-specific antibodies to measure the time course of phosphorylation of key components of the insulin signaling pathway by immunoblotting during the initial stages of a physiological elevation in the circulating insulin concentration. The phosphorylation of insulin receptor at Tyr1162/1163 (IR Tyr1162/1163) increased over 20 min of insulin infusion, whereas the downstream phosphorylation of insulin receptor substrate-1 Tyr612 (IRS-1 Tyr612) peaked at 5 min and declined thereafter. Interestingly, phosphorylation of IRS-1 at Tyr895 continued to increase over the 20-min period, and protein kinase B (PKB) phosphorylation at Ser473 reached a plateau by 5 min, demonstrating that different profiles of phosphorylation are involved in transmission of the i...
Exercise improves insulin sensitivity. As AMP-activated protein kinase (AMPK) plays an important ... more Exercise improves insulin sensitivity. As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) on insulin action in insulin-resistant high-fat-fed (HF) rats. Rats received a subcutaneous injection of 250 mg/kg AICAR (HF-AIC) or saline (HF-Con). The next day, euglycemic-hyperinsulinemic clamp studies were performed. Glucose infusion rate during the clamp was enhanced (50%) in HF-AIC compared with HF-Con rats. Insulin-stimulated glucose uptake was improved in white but not in red quadriceps, whereas glycogen synthesis was improved in both red and white quadriceps of HF-AIC rats. HF-AIC rats also showed increased insulin suppressibility of hepatic glucose output (HGO). AICAR-induced responses in both liver and muscle were accompanied by reduced malonyl-CoA content. Clamp HGO correlated closely with hepatic triglyceride content (r = 0...
OBJECTIVE Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-cha... more OBJECTIVE Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-chain fatty acids (LCFAs); however, relatively little is known regarding their effect on insulin action. Here, we examined the tissue-specific effects of MCFAs on lipid metabolism and insulin action. RESEARCH DESIGN AND METHODS C57BL6/J mice and Wistar rats were fed either a low-fat control diet or high-fat diets rich in MCFAs or LCFAs for 4–5 weeks, and markers of mitochondrial oxidative capacity, lipid levels, and insulin action were measured. RESULTS Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%, P < 0.01) but remained at low-fat diet control levels in the MCFA-fed animals. The LCFA diet increased (20–50%, P < 0.05) markers of mitochondrial metabolism in muscle compared with low-fat diet–fed controls; however; the increase in oxidative capacity was s...
Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory inte... more Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg · d), or MYR (0.3 mg/kg · d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated...
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