Following a brief account of the early history of the discovery of purinergic signalling, a perso... more Following a brief account of the early history of the discovery of purinergic signalling, a personal view of some of the exciting cutting-edge directions being taken by research in the field will be considered. In particular, emphasis will be placed on the pathophysiology of purinergic signalling and its therapeutic potential.
Objective. To identify whether a standardised Echinacea formulation is effective in the preventio... more Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1-5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides) or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P < 0.0005). However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P = 0.05) during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.
Journal of Molecular and Cellular Cardiology, 2006
into three groups of six animals each and treated for 6 weeks with diets as follows: DSS-low salt... more into three groups of six animals each and treated for 6 weeks with diets as follows: DSS-low salt, 0.4% NaCl; DSS-normal salt, 0.7% NaCl, and; DSS-normal salt + vitamin E, 0.7% NaCl + vitamin E 34 mg/Kg feed. At completion, animals in the normal salt group had significantly elevated systolic blood pressure (SBP, mean T SD, 157 T 5) as compared to the low salt group (125 T 2). Normal salt also caused a significant elevation in cytosolic [Ca 2+ ] i and tissue aldehyde conjugates, and smooth muscle cell hyperplasia in small arteries and arterioles of the kidney. Dietary vitamin E supplementation significantly attenuated the increase in SBP (142 T 6) and associated biochemical and histopathological changes.
Intercontinental air travel can be stressful, especially for respiratory health. Elderberries hav... more Intercontinental air travel can be stressful, especially for respiratory health. Elderberries have been used traditionally, and in some observational and clinical studies, as supportive agents against the common cold and influenza. This randomized, double-blind placebo-controlled clinical trial of 312 economy class passengers travelling from Australia to an overseas destination aimed to investigate if a standardised membrane filtered elderberry (Sambucus nigra L.) extract has beneficial effects on physical, especially respiratory, and mental health. Cold episodes, cold duration and symptoms were noted in a daily diary and assessed using the Jackson score. Participants also completed three surveys containing questions regarding upper respiratory symptoms (WURSS-21) and quality of life (SF-12) at baseline, just before travel and at 4-days after travel. Most cold episodes occurred in the placebo group (17 vs. 12), however the difference was not significant (p = 0.4). Placebo group participants had a significantly longer duration of cold episode days (117 vs. 57, p = 0.02) and the average symptom score over these days was also significantly higher (583 vs. 247, p = 0.05). These data suggest a significant reduction of cold duration and severity in air travelers. More research is warranted to confirm this effect and to evaluate elderberry's physical and mental health benefits.
Background Migraine is a chronic disabling neurovascular condition that may in part be caused by ... more Background Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation.
Background.-Migraine is a highly disabling disease affecting a significant proportion of the Aust... more Background.-Migraine is a highly disabling disease affecting a significant proportion of the Australian population. The methylenetetrahydrofolate reductase (MTHFR) C677T variant has been associated with increased levels of homocysteine and risk of migraine with aura (MA). Folic acid (FA), vitamin B6, and B12 supplementation has been previously shown to reduce increased levels of homocysteine and decrease migraine symptoms. However, the influence of dietary folate intake on migraine has been unclear. The aim of the current study was to analyze the association of dietary folate intake in the form of dietary folate equivalent, FA, and total food folate (TFF) on migraine frequency, severity, and disability.
Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatme... more Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatments work with differing efficacies in migraineurs. The opioid system plays an important role in diverse biological functions including analgesia, drug response and pain reduction. The A118G single nucleotide polymorphism (SNP) in exon 1 of the l-opioid receptor gene (OPRM1) has been associated with elevated pain responses and decreased pain threshold in a variety of populations. The aim of the current preliminary study was to test whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. This was a preliminary study to determine whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. A total of 153 chronic migraine with aura sufferers were assessed for migraine head pain using the Migraine Disability Assessment Score instrument and classified into high and low pain severity groups. DNA was extracted and genotypes obtained for the A118G SNP. Logistic regression analysis adjusting for age effects showed the A118G SNP of the OPRM1 gene to be significantly associated with migraine pain severity in the test population (P = 0.0037). In particular, G118 allele carriers were more likely to be high pain sufferers compared to homozygous carriers of the A118 allele (OR = 3.125, 95 % CI = 1.41, 6.93, P = 0.0037). These findings suggest that A118G genotypes of the OPRM1 gene may influence migraineassociated head pain in females. Further investigations are required to fully understand the effect of this gene variant on migraine head pain including studies in males and in different migraine subtypes, as well as in response to head pain medication.
into three groups of six animals each and treated for 6 weeks with diets as follows: DSS-low salt... more into three groups of six animals each and treated for 6 weeks with diets as follows: DSS-low salt, 0.4% NaCl; DSS-normal salt, 0.7% NaCl, and; DSS-normal salt + vitamin E, 0.7% NaCl + vitamin E 34 mg/Kg feed. At completion, animals in the normal salt group had significantly elevated systolic blood pressure (SBP, mean T SD, 157 T 5) as compared to the low salt group (125 T 2). Normal salt also caused a significant elevation in cytosolic [Ca 2+ ] i and tissue aldehyde conjugates, and smooth muscle cell hyperplasia in small arteries and arterioles of the kidney. Dietary vitamin E supplementation significantly attenuated the increase in SBP (142 T 6) and associated biochemical and histopathological changes.
Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatme... more Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatments work with differing efficacies in migraineurs. The opioid system plays an important role in diverse biological functions including analgesia, drug response and pain reduction. The A118G single nucleotide polymorphism (SNP) in exon 1 of the l-opioid receptor gene (OPRM1) has been associated with elevated pain responses and decreased pain threshold in a variety of populations. The aim of the current preliminary study was to test whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. This was a preliminary study to determine whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. A total of 153 chronic migraine with aura sufferers were assessed for migraine head pain using the Migraine Disability Assessment Score instrument and classified into high and low pain severity groups. DNA was extracted and genotypes obtained for the A118G SNP. Logistic regression analysis adjusting for age effects showed the A118G SNP of the OPRM1 gene to be significantly associated with migraine pain severity in the test population (P = 0.0037). In particular, G118 allele carriers were more likely to be high pain sufferers compared to homozygous carriers of the A118 allele (OR = 3.125, 95 % CI = 1.41, 6.93, P = 0.0037). These findings suggest that A118G genotypes of the OPRM1 gene may influence migraineassociated head pain in females. Further investigations are required to fully understand the effect of this gene variant on migraine head pain including studies in males and in different migraine subtypes, as well as in response to head pain medication.
Background Migraine is a chronic disabling neurovascular condition that may in part be caused by ... more Background Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation.
Journal of Pharmacology and Experimental Therapeutics, 2007
P2 purinoceptor modulation of injury during ischemia-reperfusion was studied in murine hearts. Ef... more P2 purinoceptor modulation of injury during ischemia-reperfusion was studied in murine hearts. Effects of P2 agonism or antagonism, and interstitial accumulation of P2 agonists (UTP, ATP, and ADP), were assessed in Langendorff perfused hearts during 20 min of ischemia and 45 min of reperfusion. In control hearts, ventricular pressure development recovered to 68 Ϯ 4 mm Hg (63 Ϯ 3% baseline), diastolic pressure remained elevated (23 Ϯ 2 mm Hg), and 26 Ϯ 4 U/g lactate dehydrogenase (LDH) was released during reperfusion, evidencing necrosis. Treatment with 250 nM UTP improved pressure development (85 Ϯ 5 mm Hg, or 77 Ϯ 2%) and reduced diastolic contracture (by ϳ70%, to 7 Ϯ 1 mm Hg) and LDH loss (by ϳ60%, to 11 Ϯ 2 U/g). In contrast, P2Y 1 agonism with 50 nM 2-methyl-thio-ATP (2-MeSATP) was ineffective. In the presence of the P2Y antagonist suramin (10 or 200 M), UTP no longer improved postisch-
Journal of Molecular and Cellular Cardiology, 2007
573 did not affect body weight, it significantly decreased early atherogenesis lesions confirmed ... more 573 did not affect body weight, it significantly decreased early atherogenesis lesions confirmed by macroscopic, microscopic and biochemical analysis. These results confirm that selective antagonism of TP receptor is effective in reducing atherosclerotic lesion in apo E deficient mice. Consequently, BM-573 could be a potential drug for prevention of atherosclerosis.
Journal of Molecular and Cellular Cardiology, 2007
reperfusion. Postc was elicited by either 3 (PostC-3) or 6 cycles (PostC-6) of 10 s ischemia and ... more reperfusion. Postc was elicited by either 3 (PostC-3) or 6 cycles (PostC-6) of 10 s ischemia and 10 s reperfusion.
Objective. To identify whether a standardised Echinacea formulation is effective in the preventio... more Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1-5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides) or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P < 0.0005). However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P = 0.05) during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.
Following a brief account of the early history of the discovery of purinergic signalling, a perso... more Following a brief account of the early history of the discovery of purinergic signalling, a personal view of some of the exciting cutting-edge directions being taken by research in the field will be considered. In particular, emphasis will be placed on the pathophysiology of purinergic signalling and its therapeutic potential.
Background: The effect of chronic administration of caffeine and/or nifedipine was investigated o... more Background: The effect of chronic administration of caffeine and/or nifedipine was investigated on functional cardiovascular responses and cardiac adenosine receptor and calcium-handling protein gene expression.
Following a brief account of the early history of the discovery of purinergic signalling, a perso... more Following a brief account of the early history of the discovery of purinergic signalling, a personal view of some of the exciting cutting-edge directions being taken by research in the field will be considered. In particular, emphasis will be placed on the pathophysiology of purinergic signalling and its therapeutic potential.
Objective. To identify whether a standardised Echinacea formulation is effective in the preventio... more Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1-5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides) or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P < 0.0005). However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P = 0.05) during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.
Journal of Molecular and Cellular Cardiology, 2006
into three groups of six animals each and treated for 6 weeks with diets as follows: DSS-low salt... more into three groups of six animals each and treated for 6 weeks with diets as follows: DSS-low salt, 0.4% NaCl; DSS-normal salt, 0.7% NaCl, and; DSS-normal salt + vitamin E, 0.7% NaCl + vitamin E 34 mg/Kg feed. At completion, animals in the normal salt group had significantly elevated systolic blood pressure (SBP, mean T SD, 157 T 5) as compared to the low salt group (125 T 2). Normal salt also caused a significant elevation in cytosolic [Ca 2+ ] i and tissue aldehyde conjugates, and smooth muscle cell hyperplasia in small arteries and arterioles of the kidney. Dietary vitamin E supplementation significantly attenuated the increase in SBP (142 T 6) and associated biochemical and histopathological changes.
Intercontinental air travel can be stressful, especially for respiratory health. Elderberries hav... more Intercontinental air travel can be stressful, especially for respiratory health. Elderberries have been used traditionally, and in some observational and clinical studies, as supportive agents against the common cold and influenza. This randomized, double-blind placebo-controlled clinical trial of 312 economy class passengers travelling from Australia to an overseas destination aimed to investigate if a standardised membrane filtered elderberry (Sambucus nigra L.) extract has beneficial effects on physical, especially respiratory, and mental health. Cold episodes, cold duration and symptoms were noted in a daily diary and assessed using the Jackson score. Participants also completed three surveys containing questions regarding upper respiratory symptoms (WURSS-21) and quality of life (SF-12) at baseline, just before travel and at 4-days after travel. Most cold episodes occurred in the placebo group (17 vs. 12), however the difference was not significant (p = 0.4). Placebo group participants had a significantly longer duration of cold episode days (117 vs. 57, p = 0.02) and the average symptom score over these days was also significantly higher (583 vs. 247, p = 0.05). These data suggest a significant reduction of cold duration and severity in air travelers. More research is warranted to confirm this effect and to evaluate elderberry's physical and mental health benefits.
Background Migraine is a chronic disabling neurovascular condition that may in part be caused by ... more Background Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation.
Background.-Migraine is a highly disabling disease affecting a significant proportion of the Aust... more Background.-Migraine is a highly disabling disease affecting a significant proportion of the Australian population. The methylenetetrahydrofolate reductase (MTHFR) C677T variant has been associated with increased levels of homocysteine and risk of migraine with aura (MA). Folic acid (FA), vitamin B6, and B12 supplementation has been previously shown to reduce increased levels of homocysteine and decrease migraine symptoms. However, the influence of dietary folate intake on migraine has been unclear. The aim of the current study was to analyze the association of dietary folate intake in the form of dietary folate equivalent, FA, and total food folate (TFF) on migraine frequency, severity, and disability.
Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatme... more Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatments work with differing efficacies in migraineurs. The opioid system plays an important role in diverse biological functions including analgesia, drug response and pain reduction. The A118G single nucleotide polymorphism (SNP) in exon 1 of the l-opioid receptor gene (OPRM1) has been associated with elevated pain responses and decreased pain threshold in a variety of populations. The aim of the current preliminary study was to test whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. This was a preliminary study to determine whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. A total of 153 chronic migraine with aura sufferers were assessed for migraine head pain using the Migraine Disability Assessment Score instrument and classified into high and low pain severity groups. DNA was extracted and genotypes obtained for the A118G SNP. Logistic regression analysis adjusting for age effects showed the A118G SNP of the OPRM1 gene to be significantly associated with migraine pain severity in the test population (P = 0.0037). In particular, G118 allele carriers were more likely to be high pain sufferers compared to homozygous carriers of the A118 allele (OR = 3.125, 95 % CI = 1.41, 6.93, P = 0.0037). These findings suggest that A118G genotypes of the OPRM1 gene may influence migraineassociated head pain in females. Further investigations are required to fully understand the effect of this gene variant on migraine head pain including studies in males and in different migraine subtypes, as well as in response to head pain medication.
into three groups of six animals each and treated for 6 weeks with diets as follows: DSS-low salt... more into three groups of six animals each and treated for 6 weeks with diets as follows: DSS-low salt, 0.4% NaCl; DSS-normal salt, 0.7% NaCl, and; DSS-normal salt + vitamin E, 0.7% NaCl + vitamin E 34 mg/Kg feed. At completion, animals in the normal salt group had significantly elevated systolic blood pressure (SBP, mean T SD, 157 T 5) as compared to the low salt group (125 T 2). Normal salt also caused a significant elevation in cytosolic [Ca 2+ ] i and tissue aldehyde conjugates, and smooth muscle cell hyperplasia in small arteries and arterioles of the kidney. Dietary vitamin E supplementation significantly attenuated the increase in SBP (142 T 6) and associated biochemical and histopathological changes.
Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatme... more Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatments work with differing efficacies in migraineurs. The opioid system plays an important role in diverse biological functions including analgesia, drug response and pain reduction. The A118G single nucleotide polymorphism (SNP) in exon 1 of the l-opioid receptor gene (OPRM1) has been associated with elevated pain responses and decreased pain threshold in a variety of populations. The aim of the current preliminary study was to test whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. This was a preliminary study to determine whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. A total of 153 chronic migraine with aura sufferers were assessed for migraine head pain using the Migraine Disability Assessment Score instrument and classified into high and low pain severity groups. DNA was extracted and genotypes obtained for the A118G SNP. Logistic regression analysis adjusting for age effects showed the A118G SNP of the OPRM1 gene to be significantly associated with migraine pain severity in the test population (P = 0.0037). In particular, G118 allele carriers were more likely to be high pain sufferers compared to homozygous carriers of the A118 allele (OR = 3.125, 95 % CI = 1.41, 6.93, P = 0.0037). These findings suggest that A118G genotypes of the OPRM1 gene may influence migraineassociated head pain in females. Further investigations are required to fully understand the effect of this gene variant on migraine head pain including studies in males and in different migraine subtypes, as well as in response to head pain medication.
Background Migraine is a chronic disabling neurovascular condition that may in part be caused by ... more Background Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation.
Journal of Pharmacology and Experimental Therapeutics, 2007
P2 purinoceptor modulation of injury during ischemia-reperfusion was studied in murine hearts. Ef... more P2 purinoceptor modulation of injury during ischemia-reperfusion was studied in murine hearts. Effects of P2 agonism or antagonism, and interstitial accumulation of P2 agonists (UTP, ATP, and ADP), were assessed in Langendorff perfused hearts during 20 min of ischemia and 45 min of reperfusion. In control hearts, ventricular pressure development recovered to 68 Ϯ 4 mm Hg (63 Ϯ 3% baseline), diastolic pressure remained elevated (23 Ϯ 2 mm Hg), and 26 Ϯ 4 U/g lactate dehydrogenase (LDH) was released during reperfusion, evidencing necrosis. Treatment with 250 nM UTP improved pressure development (85 Ϯ 5 mm Hg, or 77 Ϯ 2%) and reduced diastolic contracture (by ϳ70%, to 7 Ϯ 1 mm Hg) and LDH loss (by ϳ60%, to 11 Ϯ 2 U/g). In contrast, P2Y 1 agonism with 50 nM 2-methyl-thio-ATP (2-MeSATP) was ineffective. In the presence of the P2Y antagonist suramin (10 or 200 M), UTP no longer improved postisch-
Journal of Molecular and Cellular Cardiology, 2007
573 did not affect body weight, it significantly decreased early atherogenesis lesions confirmed ... more 573 did not affect body weight, it significantly decreased early atherogenesis lesions confirmed by macroscopic, microscopic and biochemical analysis. These results confirm that selective antagonism of TP receptor is effective in reducing atherosclerotic lesion in apo E deficient mice. Consequently, BM-573 could be a potential drug for prevention of atherosclerosis.
Journal of Molecular and Cellular Cardiology, 2007
reperfusion. Postc was elicited by either 3 (PostC-3) or 6 cycles (PostC-6) of 10 s ischemia and ... more reperfusion. Postc was elicited by either 3 (PostC-3) or 6 cycles (PostC-6) of 10 s ischemia and 10 s reperfusion.
Objective. To identify whether a standardised Echinacea formulation is effective in the preventio... more Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1-5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides) or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P < 0.0005). However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P = 0.05) during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.
Following a brief account of the early history of the discovery of purinergic signalling, a perso... more Following a brief account of the early history of the discovery of purinergic signalling, a personal view of some of the exciting cutting-edge directions being taken by research in the field will be considered. In particular, emphasis will be placed on the pathophysiology of purinergic signalling and its therapeutic potential.
Background: The effect of chronic administration of caffeine and/or nifedipine was investigated o... more Background: The effect of chronic administration of caffeine and/or nifedipine was investigated on functional cardiovascular responses and cardiac adenosine receptor and calcium-handling protein gene expression.
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