Bile acids are not only important for the absorption of dietary lipids and fat soluble vitamins but are signalling molecules with diverse endocrine and paracrine functions. Bile acids regulate bile acid, lipid and glu...Bile acids are not only important for the absorption of dietary lipids and fat soluble vitamins but are signalling molecules with diverse endocrine and paracrine functions. Bile acids regulate bile acid, lipid and glucose metabolism and modulate temperature and energy homeostasis. Furthermore, bile acids can not only promote cell proliferation and liver regeneration but can also induce programmed cell death. Bile acid functions are mediated through different pathways which comprise the activation of nuclear hormone receptors, of intracefular kinases and of the plasma membranebound, G-protein coupled bile acid receptor TGRS/Gpbar-1.展开更多
AIM: To study the stereoselectivity of phase Ⅱ glucuronidation metabolism of side-chain propranolol in Chinese Han population. METHODS: Sixteen adult Chinese Han volunteers with an average age of 20 years were given ...AIM: To study the stereoselectivity of phase Ⅱ glucuronidation metabolism of side-chain propranolol in Chinese Han population. METHODS: Sixteen adult Chinese Han volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC. RESULTS: The mean values of k were 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of closes were 14.7±2.46% and 7.68±1.60% for S-(-)-and R-(+)-propranolol glucuronide, respectively. The results showed the elimination rate constant k of S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide. CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.展开更多
Hormone-stimulated pancreatic function tests (PFTs) are considered the gold standard for measuring pancreatic exocrine function. PFTs involve the administration of intravenous secretin or cholecystokinin, followed by ...Hormone-stimulated pancreatic function tests (PFTs) are considered the gold standard for measuring pancreatic exocrine function. PFTs involve the administration of intravenous secretin or cholecystokinin, followed by collection and analysis of pancreatic secretions. Because exocrine function may decline in the earliest phase of pancreatic fibrosis, PFTs are considered accurate for diagnosing chronic pancreatitis. Unfortunately, these potentially valuable tests are infrequently performed except at specialized centers, because they are time consuming and complicated. To overcome these limitations, endoscopic PFT methods have been developed which include aspiration of pancreatic secretions through the suction channel of the endoscope. The secretin endoscopic pancreatic function test (ePFT) involves collection of duodenal aspirates at 15, 30, 45 and 60 min after secretin stimulation. A bicarbonate concentration greater than 80 mmol/L in any of the samples is considered a normal result. The secretin ePFT has demonstrated good sensitivity and specificity compared with various reference standards, including the "Dreiling tube" secretin PFT, endoscopic ultrasound, and surgical histology. Furthermore, a standard autoanalyzer can be used for bicarbonate analysis, which allows the secretin ePFT to be performed at any hospital. The secretin ePFT may complement imaging tests like endoscopic ultrasound (EUS) in the diagnosis of early chronic pancreatitis.This paper will review the literature validating the use of ePFT in the diagnosis of exocrine insufficiency and chronic pancreatitis. Newer developments will also be discussed, including the feasibility of combined EUS/ ePFT, the use of cholecystokinin alone or in combination with secretin, and the discovery of new protein and lipid pancreatic juice biomarkers which may complement traditional fluid analysis.展开更多
AIM:To investigate the effects and mechanisms of action of glycine on phagocytosis and tumor necrosis factor(TNF)-α secretion by Kupffer cells in vitro. METHODS:Kupffer cells were isolated from normal rats by collage...AIM:To investigate the effects and mechanisms of action of glycine on phagocytosis and tumor necrosis factor(TNF)-α secretion by Kupffer cells in vitro. METHODS:Kupffer cells were isolated from normal rats by collagenase digestion and Percoll density gradient differential centrifugation.After culture for 24 h,Kupffer cells were incubated in fresh Dulbecco's Modification of Eagle's Medium containing glycine (G1:1 mmol/L,G2:10 mmol/L,G3:100 mmol/L and G4:300 mmol/L)for 3 h,then used to measure phagocytosis by a bead test,TNF-α secretion after lipopolysaccharide stimulation by radioactive immunoassay,and microfilament and microtubule expression by staining with phalloidin-fluorescein isothiocyanate (FITC)or a monoclonal anti-α tubulin-FITC antibody, respectively,and evaluated under a ultraviolet fluorescence microscope. RESULTS:Glycine decreased the phagocytosis of Kupffer cells at both 30 min and 60 min(P<0.01,P< 0.05).The numbers of beads phagocytosed by Kupffer cells in 30 min were 16.9±4.0(control),9.6±4.1(G1), 12.1±5.7(G2),8.1±3.2(G3)and 7.5±2.0(G4),and were 22.5±7.9(control),20.1±5.8(G1),19.3±4.8 (G2),13.5±4.7(G3)and 9.2±3.1(G4)after 60 min. TNF-α secretion by Kupffer cells in G1(0.19±0.03),G2 (0.16±0.04),G3(0.14±0.03)and G4(0.13±0.05) was significantly less than that in controls(0.26±0.03, P<0.01),and the decrease in secretion was dose-dependent(P<0.05).Microfilaments of Kupffer cells in G2, G3 and G4 groups were arranged in a disorderly manner. The fluorescence densities of microtubules in G1(53.4± 10.5),G2(54.1±14.6),G3(64.9±12.1)and G4(52.1 ±14.2)were all lower than those in the controls(102.2 ±23.7,P<0.01),but the decrease in microtubule fluorescence density was not dose-dependant. CONCLUSION:Glycine can decrease the phagocytosis and secretion by Kupffer cells in vitro,which may be related to the changes in the expression of microfilaments and microtubules induced by Kupffer cells.展开更多
文摘Bile acids are not only important for the absorption of dietary lipids and fat soluble vitamins but are signalling molecules with diverse endocrine and paracrine functions. Bile acids regulate bile acid, lipid and glucose metabolism and modulate temperature and energy homeostasis. Furthermore, bile acids can not only promote cell proliferation and liver regeneration but can also induce programmed cell death. Bile acid functions are mediated through different pathways which comprise the activation of nuclear hormone receptors, of intracefular kinases and of the plasma membranebound, G-protein coupled bile acid receptor TGRS/Gpbar-1.
基金Supported by the National Natural Science Foundation of China, No. 30225047
文摘AIM: To study the stereoselectivity of phase Ⅱ glucuronidation metabolism of side-chain propranolol in Chinese Han population. METHODS: Sixteen adult Chinese Han volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC. RESULTS: The mean values of k were 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of closes were 14.7±2.46% and 7.68±1.60% for S-(-)-and R-(+)-propranolol glucuronide, respectively. The results showed the elimination rate constant k of S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide. CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.
文摘Hormone-stimulated pancreatic function tests (PFTs) are considered the gold standard for measuring pancreatic exocrine function. PFTs involve the administration of intravenous secretin or cholecystokinin, followed by collection and analysis of pancreatic secretions. Because exocrine function may decline in the earliest phase of pancreatic fibrosis, PFTs are considered accurate for diagnosing chronic pancreatitis. Unfortunately, these potentially valuable tests are infrequently performed except at specialized centers, because they are time consuming and complicated. To overcome these limitations, endoscopic PFT methods have been developed which include aspiration of pancreatic secretions through the suction channel of the endoscope. The secretin endoscopic pancreatic function test (ePFT) involves collection of duodenal aspirates at 15, 30, 45 and 60 min after secretin stimulation. A bicarbonate concentration greater than 80 mmol/L in any of the samples is considered a normal result. The secretin ePFT has demonstrated good sensitivity and specificity compared with various reference standards, including the "Dreiling tube" secretin PFT, endoscopic ultrasound, and surgical histology. Furthermore, a standard autoanalyzer can be used for bicarbonate analysis, which allows the secretin ePFT to be performed at any hospital. The secretin ePFT may complement imaging tests like endoscopic ultrasound (EUS) in the diagnosis of early chronic pancreatitis.This paper will review the literature validating the use of ePFT in the diagnosis of exocrine insufficiency and chronic pancreatitis. Newer developments will also be discussed, including the feasibility of combined EUS/ ePFT, the use of cholecystokinin alone or in combination with secretin, and the discovery of new protein and lipid pancreatic juice biomarkers which may complement traditional fluid analysis.
基金Supported by The Natural Science Foundation of Taiyuan City,China, No. 09121014
文摘AIM:To investigate the effects and mechanisms of action of glycine on phagocytosis and tumor necrosis factor(TNF)-α secretion by Kupffer cells in vitro. METHODS:Kupffer cells were isolated from normal rats by collagenase digestion and Percoll density gradient differential centrifugation.After culture for 24 h,Kupffer cells were incubated in fresh Dulbecco's Modification of Eagle's Medium containing glycine (G1:1 mmol/L,G2:10 mmol/L,G3:100 mmol/L and G4:300 mmol/L)for 3 h,then used to measure phagocytosis by a bead test,TNF-α secretion after lipopolysaccharide stimulation by radioactive immunoassay,and microfilament and microtubule expression by staining with phalloidin-fluorescein isothiocyanate (FITC)or a monoclonal anti-α tubulin-FITC antibody, respectively,and evaluated under a ultraviolet fluorescence microscope. RESULTS:Glycine decreased the phagocytosis of Kupffer cells at both 30 min and 60 min(P<0.01,P< 0.05).The numbers of beads phagocytosed by Kupffer cells in 30 min were 16.9±4.0(control),9.6±4.1(G1), 12.1±5.7(G2),8.1±3.2(G3)and 7.5±2.0(G4),and were 22.5±7.9(control),20.1±5.8(G1),19.3±4.8 (G2),13.5±4.7(G3)and 9.2±3.1(G4)after 60 min. TNF-α secretion by Kupffer cells in G1(0.19±0.03),G2 (0.16±0.04),G3(0.14±0.03)and G4(0.13±0.05) was significantly less than that in controls(0.26±0.03, P<0.01),and the decrease in secretion was dose-dependent(P<0.05).Microfilaments of Kupffer cells in G2, G3 and G4 groups were arranged in a disorderly manner. The fluorescence densities of microtubules in G1(53.4± 10.5),G2(54.1±14.6),G3(64.9±12.1)and G4(52.1 ±14.2)were all lower than those in the controls(102.2 ±23.7,P<0.01),but the decrease in microtubule fluorescence density was not dose-dependant. CONCLUSION:Glycine can decrease the phagocytosis and secretion by Kupffer cells in vitro,which may be related to the changes in the expression of microfilaments and microtubules induced by Kupffer cells.
