The use of radio-opaque markers and abdominal X-ray is the standard method for determining colonic transit time(CTT). However, when there are deviations in the intake of these markers by participants in clinical trial...The use of radio-opaque markers and abdominal X-ray is the standard method for determining colonic transit time(CTT). However, when there are deviations in the intake of these markers by participants in clinical trials it is desirable to improve observations by introducingcorrections, where possible. To date, there is no standard procedure to adjust for such deviations. This report proposes a series of alternatives based on possible scenarios for deviations from the intended intake of radio-opaque markers. The proposed method to correct for missed or delayed consumption of radioopaque markers can help to increase the accuracy of the CTT measurements in clinical trials.展开更多
AIM: To evaluate the effect of thienorphine on small intestinal transit in vivo and on guinea-pig ileum (GPI) contraction in vitro . METHODS: The effects of thienorphine on intestinal transit were examined in mice and...AIM: To evaluate the effect of thienorphine on small intestinal transit in vivo and on guinea-pig ileum (GPI) contraction in vitro . METHODS: The effects of thienorphine on intestinal transit were examined in mice and in isolated GPI. Buprenorphine and morphine served as controls. The distance traveled by the head of the charchol and the total length of the intestine were measured in vivo . Gastrointestinal transit was expressed as a percentage of the distance traveled by the head of the marker relative to the total length of the small intestine. The isolated GPI preparations were connected to an isotonic force transducer and equilibrated for at least 1 h before exposure to drugs. Acetylcholine was used for muscle stimulation. RESULTS: Thienorphine (0.005-1.0 mg/kg, ig ) or bu-prenorphine (0.005-1.0 mg/kg, sc ) dose-dependently significantly inhibited gut transit compared with saline. Thienorphine inhibited gut transit less than buprenorphine. The maximum inhibition by thienorphine on the intestinal transit was 50%-60%, whereas the maximum inhibition by morphine on gut transit was about 100%. Thienorphine also exhibited less inhibition on acetylcholine-induced contraction of GPI, with a maximum inhibition of 65%, compared with 93% inhibition by buprenorphine and 100% inhibition by morphine. Thienorphine induced a concentration-dependent decrease in the basal tonus of spontaneous movement of the GPI, the effect of which was weaker than that with buprenorphine. The duration of the effect of thienorphine on the GPI was longer than that with buprenorphine. CONCLUSION: Thienorphine had less influence, but a longer duration of action on GPI contraction and moderately inhibited intestinal transit.展开更多
AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period...AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.展开更多
目的:从不同角度探讨大鼠肠缺血再灌注对小肠屏障、吸收、通透和传输等功能的影响,为更深入地研究肠道损伤及其保护提供防治依据。方法:以 Wistar 大鼠肠缺血再灌注(I/R)作模型,将动物随机分为健康对照(C)、肠系膜上动脉夹闭1h(Ⅰ)、夹...目的:从不同角度探讨大鼠肠缺血再灌注对小肠屏障、吸收、通透和传输等功能的影响,为更深入地研究肠道损伤及其保护提供防治依据。方法:以 Wistar 大鼠肠缺血再灌注(I/R)作模型,将动物随机分为健康对照(C)、肠系膜上动脉夹闭1h(Ⅰ)、夹闭后再灌1h(R 1h)、2h(R 2h)和4h(R 4h)共5个组。分别测血或小肠组织的二胺氧化酶(DAO)、D-乳酸、D-木糖、肠传输、脂质过氧化物(MDA)和髓过氧化物酶(MPO),并作小肠普通光镜检查。结果:R1h 和R 4h 组的血浆 DAO 显著升高(P<0.05),小肠 DAO 各组有不同程度的降低,R 2h 组降低显著,血浆和小肠 DAO 的变化呈负相关(r=-0.648,P<0.05)。缺血和再灌注后各时相点血 D-乳酸浓度升高,其中 R 1h和 R 2h升高显著(P<0.05)。缺血再灌后肠道 D-木糖的吸收增加,小肠的传输显著加快。结论:肠缺血和再灌注后小肠的屏障、吸收、通透和传输功能均显示不同程度的改变。展开更多
文摘The use of radio-opaque markers and abdominal X-ray is the standard method for determining colonic transit time(CTT). However, when there are deviations in the intake of these markers by participants in clinical trials it is desirable to improve observations by introducingcorrections, where possible. To date, there is no standard procedure to adjust for such deviations. This report proposes a series of alternatives based on possible scenarios for deviations from the intended intake of radio-opaque markers. The proposed method to correct for missed or delayed consumption of radioopaque markers can help to increase the accuracy of the CTT measurements in clinical trials.
基金Supported by National New Drugs Foundation of China, No.2011ZX09101-005-01"Integrated Drug Discovery Technology Plat form" of National Science and Technology Major Projects for "Major New Drugs Innovation and Development", No.2012ZX09301003-001
文摘AIM: To evaluate the effect of thienorphine on small intestinal transit in vivo and on guinea-pig ileum (GPI) contraction in vitro . METHODS: The effects of thienorphine on intestinal transit were examined in mice and in isolated GPI. Buprenorphine and morphine served as controls. The distance traveled by the head of the charchol and the total length of the intestine were measured in vivo . Gastrointestinal transit was expressed as a percentage of the distance traveled by the head of the marker relative to the total length of the small intestine. The isolated GPI preparations were connected to an isotonic force transducer and equilibrated for at least 1 h before exposure to drugs. Acetylcholine was used for muscle stimulation. RESULTS: Thienorphine (0.005-1.0 mg/kg, ig ) or bu-prenorphine (0.005-1.0 mg/kg, sc ) dose-dependently significantly inhibited gut transit compared with saline. Thienorphine inhibited gut transit less than buprenorphine. The maximum inhibition by thienorphine on the intestinal transit was 50%-60%, whereas the maximum inhibition by morphine on gut transit was about 100%. Thienorphine also exhibited less inhibition on acetylcholine-induced contraction of GPI, with a maximum inhibition of 65%, compared with 93% inhibition by buprenorphine and 100% inhibition by morphine. Thienorphine induced a concentration-dependent decrease in the basal tonus of spontaneous movement of the GPI, the effect of which was weaker than that with buprenorphine. The duration of the effect of thienorphine on the GPI was longer than that with buprenorphine. CONCLUSION: Thienorphine had less influence, but a longer duration of action on GPI contraction and moderately inhibited intestinal transit.
文摘AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.
文摘目的:从不同角度探讨大鼠肠缺血再灌注对小肠屏障、吸收、通透和传输等功能的影响,为更深入地研究肠道损伤及其保护提供防治依据。方法:以 Wistar 大鼠肠缺血再灌注(I/R)作模型,将动物随机分为健康对照(C)、肠系膜上动脉夹闭1h(Ⅰ)、夹闭后再灌1h(R 1h)、2h(R 2h)和4h(R 4h)共5个组。分别测血或小肠组织的二胺氧化酶(DAO)、D-乳酸、D-木糖、肠传输、脂质过氧化物(MDA)和髓过氧化物酶(MPO),并作小肠普通光镜检查。结果:R1h 和R 4h 组的血浆 DAO 显著升高(P<0.05),小肠 DAO 各组有不同程度的降低,R 2h 组降低显著,血浆和小肠 DAO 的变化呈负相关(r=-0.648,P<0.05)。缺血和再灌注后各时相点血 D-乳酸浓度升高,其中 R 1h和 R 2h升高显著(P<0.05)。缺血再灌后肠道 D-木糖的吸收增加,小肠的传输显著加快。结论:肠缺血和再灌注后小肠的屏障、吸收、通透和传输功能均显示不同程度的改变。
