The Experts below are selected from a list of 678 Experts worldwide ranked by ideXlab platform
Charles W Emala - One of the best experts on this subject based on the ideXlab platform.
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agonism of the tmem16a calcium activated chloride channel modulates airway smooth muscle tone
American Journal of Physiology-lung Cellular and Molecular Physiology, 2020Co-Authors: Jennifer Danielsson, George Gallos, Aisha S Kuforiji, Gene T Yocum, Yi Zhang, Dingbang Xu, Charles W EmalaAbstract:TMEM16A (anoctamin 1) is an important calcium-activated chloride channel in airway smooth muscle (ASM). We have previously shown that TMEM16A antagonists such as Benzbromarone relax ASM and have pr...
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antagonists of the tmem16a calcium activated chloride channel modulate airway smooth muscle tone and intracellular calcium
Anesthesiology, 2015Co-Authors: Jennifer Danielsson, George Gallos, Yi Zhang, Jose F Perezzoghbi, Kyra Bernstein, Matthew B Barajas, Satish Kumar, Pawan Sharma, Charles W EmalaAbstract:BACKGROUND: Perioperative bronchospasm refractory to β agonists continues to challenge anesthesiologists and intensivists. The TMEM16A calcium-activated chloride channel modulates airway smooth muscle (ASM) contraction. The authors hypothesized that TMEM16A antagonists would relax ASM contraction by modulating membrane potential and calcium flux. METHODS: Human ASM, guinea pig tracheal rings, or mouse peripheral airways were contracted with acetylcholine or leukotriene D4 and then treated with the TMEM16A antagonists: Benzbromarone, T16Ainh-A01, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid, or B25. In separate studies, guinea pig tracheal rings were contracted with acetylcholine and then exposed to increasing concentrations of isoproterenol (0.01 nM to 10 μM) ± Benzbromarone. Plasma membrane potential and intracellular calcium concentrations were measured in human ASM cells. RESULTS: Benzbromarone was the most potent TMEM16A antagonist tested for relaxing an acetylcholine -induced contraction in guinea pig tracheal rings (n = 6). Further studies were carried out to investigate the clinical utility of Benzbromarone. In human ASM, Benzbromarone relaxed either an acetylcholine- or a leukotriene D4-induced contraction (n = 8). Benzbromarone was also effective in relaxing peripheral airways (n = 9) and potentiating relaxation by β agonists (n = 5 to 10). In cellular mechanistic studies, Benzbromarone hyperpolarized human ASM cells (n = 9 to 12) and attenuated intracellular calcium flux from both the plasma membrane and the sarcoplasmic reticulum (n = 6 to 12). CONCLUSION: TMEM16A antagonists work synergistically with β agonists and through a novel pathway of interrupting ion flux at both the plasma membrane and sarcoplasmic reticulum to acutely relax human ASM.
Jennifer Danielsson - One of the best experts on this subject based on the ideXlab platform.
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agonism of the tmem16a calcium activated chloride channel modulates airway smooth muscle tone
American Journal of Physiology-lung Cellular and Molecular Physiology, 2020Co-Authors: Jennifer Danielsson, George Gallos, Aisha S Kuforiji, Gene T Yocum, Yi Zhang, Dingbang Xu, Charles W EmalaAbstract:TMEM16A (anoctamin 1) is an important calcium-activated chloride channel in airway smooth muscle (ASM). We have previously shown that TMEM16A antagonists such as Benzbromarone relax ASM and have pr...
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antagonists of the tmem16a calcium activated chloride channel modulate airway smooth muscle tone and intracellular calcium
Anesthesiology, 2015Co-Authors: Jennifer Danielsson, George Gallos, Yi Zhang, Jose F Perezzoghbi, Kyra Bernstein, Matthew B Barajas, Satish Kumar, Pawan Sharma, Charles W EmalaAbstract:BACKGROUND: Perioperative bronchospasm refractory to β agonists continues to challenge anesthesiologists and intensivists. The TMEM16A calcium-activated chloride channel modulates airway smooth muscle (ASM) contraction. The authors hypothesized that TMEM16A antagonists would relax ASM contraction by modulating membrane potential and calcium flux. METHODS: Human ASM, guinea pig tracheal rings, or mouse peripheral airways were contracted with acetylcholine or leukotriene D4 and then treated with the TMEM16A antagonists: Benzbromarone, T16Ainh-A01, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid, or B25. In separate studies, guinea pig tracheal rings were contracted with acetylcholine and then exposed to increasing concentrations of isoproterenol (0.01 nM to 10 μM) ± Benzbromarone. Plasma membrane potential and intracellular calcium concentrations were measured in human ASM cells. RESULTS: Benzbromarone was the most potent TMEM16A antagonist tested for relaxing an acetylcholine -induced contraction in guinea pig tracheal rings (n = 6). Further studies were carried out to investigate the clinical utility of Benzbromarone. In human ASM, Benzbromarone relaxed either an acetylcholine- or a leukotriene D4-induced contraction (n = 8). Benzbromarone was also effective in relaxing peripheral airways (n = 9) and potentiating relaxation by β agonists (n = 5 to 10). In cellular mechanistic studies, Benzbromarone hyperpolarized human ASM cells (n = 9 to 12) and attenuated intracellular calcium flux from both the plasma membrane and the sarcoplasmic reticulum (n = 6 to 12). CONCLUSION: TMEM16A antagonists work synergistically with β agonists and through a novel pathway of interrupting ion flux at both the plasma membrane and sarcoplasmic reticulum to acutely relax human ASM.
George Gallos - One of the best experts on this subject based on the ideXlab platform.
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agonism of the tmem16a calcium activated chloride channel modulates airway smooth muscle tone
American Journal of Physiology-lung Cellular and Molecular Physiology, 2020Co-Authors: Jennifer Danielsson, George Gallos, Aisha S Kuforiji, Gene T Yocum, Yi Zhang, Dingbang Xu, Charles W EmalaAbstract:TMEM16A (anoctamin 1) is an important calcium-activated chloride channel in airway smooth muscle (ASM). We have previously shown that TMEM16A antagonists such as Benzbromarone relax ASM and have pr...
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antagonists of the tmem16a calcium activated chloride channel modulate airway smooth muscle tone and intracellular calcium
Anesthesiology, 2015Co-Authors: Jennifer Danielsson, George Gallos, Yi Zhang, Jose F Perezzoghbi, Kyra Bernstein, Matthew B Barajas, Satish Kumar, Pawan Sharma, Charles W EmalaAbstract:BACKGROUND: Perioperative bronchospasm refractory to β agonists continues to challenge anesthesiologists and intensivists. The TMEM16A calcium-activated chloride channel modulates airway smooth muscle (ASM) contraction. The authors hypothesized that TMEM16A antagonists would relax ASM contraction by modulating membrane potential and calcium flux. METHODS: Human ASM, guinea pig tracheal rings, or mouse peripheral airways were contracted with acetylcholine or leukotriene D4 and then treated with the TMEM16A antagonists: Benzbromarone, T16Ainh-A01, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid, or B25. In separate studies, guinea pig tracheal rings were contracted with acetylcholine and then exposed to increasing concentrations of isoproterenol (0.01 nM to 10 μM) ± Benzbromarone. Plasma membrane potential and intracellular calcium concentrations were measured in human ASM cells. RESULTS: Benzbromarone was the most potent TMEM16A antagonist tested for relaxing an acetylcholine -induced contraction in guinea pig tracheal rings (n = 6). Further studies were carried out to investigate the clinical utility of Benzbromarone. In human ASM, Benzbromarone relaxed either an acetylcholine- or a leukotriene D4-induced contraction (n = 8). Benzbromarone was also effective in relaxing peripheral airways (n = 9) and potentiating relaxation by β agonists (n = 5 to 10). In cellular mechanistic studies, Benzbromarone hyperpolarized human ASM cells (n = 9 to 12) and attenuated intracellular calcium flux from both the plasma membrane and the sarcoplasmic reticulum (n = 6 to 12). CONCLUSION: TMEM16A antagonists work synergistically with β agonists and through a novel pathway of interrupting ion flux at both the plasma membrane and sarcoplasmic reticulum to acutely relax human ASM.
Yi Zhang - One of the best experts on this subject based on the ideXlab platform.
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agonism of the tmem16a calcium activated chloride channel modulates airway smooth muscle tone
American Journal of Physiology-lung Cellular and Molecular Physiology, 2020Co-Authors: Jennifer Danielsson, George Gallos, Aisha S Kuforiji, Gene T Yocum, Yi Zhang, Dingbang Xu, Charles W EmalaAbstract:TMEM16A (anoctamin 1) is an important calcium-activated chloride channel in airway smooth muscle (ASM). We have previously shown that TMEM16A antagonists such as Benzbromarone relax ASM and have pr...
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antagonists of the tmem16a calcium activated chloride channel modulate airway smooth muscle tone and intracellular calcium
Anesthesiology, 2015Co-Authors: Jennifer Danielsson, George Gallos, Yi Zhang, Jose F Perezzoghbi, Kyra Bernstein, Matthew B Barajas, Satish Kumar, Pawan Sharma, Charles W EmalaAbstract:BACKGROUND: Perioperative bronchospasm refractory to β agonists continues to challenge anesthesiologists and intensivists. The TMEM16A calcium-activated chloride channel modulates airway smooth muscle (ASM) contraction. The authors hypothesized that TMEM16A antagonists would relax ASM contraction by modulating membrane potential and calcium flux. METHODS: Human ASM, guinea pig tracheal rings, or mouse peripheral airways were contracted with acetylcholine or leukotriene D4 and then treated with the TMEM16A antagonists: Benzbromarone, T16Ainh-A01, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid, or B25. In separate studies, guinea pig tracheal rings were contracted with acetylcholine and then exposed to increasing concentrations of isoproterenol (0.01 nM to 10 μM) ± Benzbromarone. Plasma membrane potential and intracellular calcium concentrations were measured in human ASM cells. RESULTS: Benzbromarone was the most potent TMEM16A antagonist tested for relaxing an acetylcholine -induced contraction in guinea pig tracheal rings (n = 6). Further studies were carried out to investigate the clinical utility of Benzbromarone. In human ASM, Benzbromarone relaxed either an acetylcholine- or a leukotriene D4-induced contraction (n = 8). Benzbromarone was also effective in relaxing peripheral airways (n = 9) and potentiating relaxation by β agonists (n = 5 to 10). In cellular mechanistic studies, Benzbromarone hyperpolarized human ASM cells (n = 9 to 12) and attenuated intracellular calcium flux from both the plasma membrane and the sarcoplasmic reticulum (n = 6 to 12). CONCLUSION: TMEM16A antagonists work synergistically with β agonists and through a novel pathway of interrupting ion flux at both the plasma membrane and sarcoplasmic reticulum to acutely relax human ASM.
Ruey-yun Wang - One of the best experts on this subject based on the ideXlab platform.
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Only allopurinol or Benzbromarone use in gout patients.
2019Co-Authors: Hsin-wen Chang, Ya-wen Lin, Ming-hung Lin, Yu-ching Lan, Ruey-yun WangAbstract:Only allopurinol or Benzbromarone use in gout patients.
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Association between allopurinol or Benzbromarone use and risk of developing type 2 diabetes.
2019Co-Authors: Hsin-wen Chang, Ya-wen Lin, Ming-hung Lin, Yu-ching Lan, Ruey-yun WangAbstract:Association between allopurinol or Benzbromarone use and risk of developing type 2 diabetes.
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Associations between urate-lowering therapy and the risk of type 2 diabetes mellitus
2019Co-Authors: Hsin-wen Chang, Ya-wen Lin, Ming-hung Lin, Yu-ching Lan, Ruey-yun WangAbstract:BackgroundGout is independently associated with increased risk of type 2 diabetes mellitus (T2DM). Urate-lowering therapy (ULT) might be beneficial in lowering the risks of T2DM. Therefore, we conducted a nested case-control study to evaluate the associations between ULT and T2DM.MethodsThis study retrieved the data of 29,765 gout patients from the period of 1998–2010 by using data from Taiwan’s National Health Insurance Research Database. Controls (n = 59,530) were matched at a 1:2 ratio by age, sex, and region. Multivariate Cox proportional hazards regression were performed to examine the dose-dependent relationship between ULT and T2DM.ResultsThe adjusted Hazard ratio (HR) for the association of T2DM with allopurinol or Benzbromarone exposure was 1.17 (95% confidence interval (CI) 1.07–1.28) and1.09 (95% CI 1.03–1.15), respectively. The HR for the cumulative allopurinol dose was 0.87 (95% CI 0.71–1.07) for patients with dose ≤1.3 mg/day and was 1.31 (95% CI 1.13–1.52) for those with a dose >15.2 mg/day. Similarly, the HR for the cumulative Benzbromarone dose was 0.85(95% CI 0.75–0.96) for patients with a dose ≤1.3 mg/day and 1.42 (95% CI 1.30–1.55) for patients with a dose>9.4 mg/day, respectively. Moreover, the average exposure dose of >100 mg/day for allopurinol and >100 mg/day for Benzbromarone was associated with a 1.28-fold (95% CI 1.11–1.48) and 1.47-fold (95% CI 1.23–1.76) T2DM risk respectively. The HR for patients in aged >50 years group with cumulative dose ≤1.3 mg/day of allopurinol or Benzbromarone had lower risk of T2DM (HR = 0.74, 95% CI 0.58–0.94 for allopurinol; HR = 0.79, 95% CI 0.69–0.90 for Benzbromarone).ConclusionGout patients with prolonged ULT and a high dose of ULT were associated with a significant increase in T2DM risk. Although gout patients with age greater than 50 years and a lower dose of ULT may be beneficial in lowering T2DM risk, further clinical studies need to be confirmed these associations.
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Association between allopurinol or Benzbromarone use and risk of developing type 2 diabetes stratified by sex.
2019Co-Authors: Hsin-wen Chang, Ya-wen Lin, Ming-hung Lin, Yu-ching Lan, Ruey-yun WangAbstract:Association between allopurinol or Benzbromarone use and risk of developing type 2 diabetes stratified by sex.
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Association between allopurinol or Benzbromarone use and risk of developing type 2 diabetes stratified by age group.
2019Co-Authors: Hsin-wen Chang, Ya-wen Lin, Ming-hung Lin, Yu-ching Lan, Ruey-yun WangAbstract:Association between allopurinol or Benzbromarone use and risk of developing type 2 diabetes stratified by age group.