Effect of Endoscopic Sphincterotomy on Gallbladder Motility

In experimental animals, sphincterotomyfacilitates passage of solids from the gallbladder andinhibits gallstone formation apparently by improvementin gallbladder emptying. In humans, however, gallbladder emptying has not been studied followingendoscopic sphincterotomy (ES) in patients withgallstones. We therefore prospectively studied restingand cerulinstimulated gallbladder volumes by real timeultrasonography in 15 patients of choledocholithiasis withgallbladder in situ (eight with and seven withoutgallbladder calculi) before and after (after bile ductclearance) ES. ES significantly lowered restinggallbladder volume (21.2 ± 10.6 vs 11.1 ±5.0; P < 0.0001) and cerulin-stimulated residualgallbladder volume (10.8 ± 5.6 vs 4.4 ±2.1; P < 0.0001). ES also significantly increased thegallbladder ejection fraction (47.3 ± 12.1% vs 58.8 ± 11.1%; P < 0.0001). Therate constant for gallbladder emptying after cerulininfusion also increased significantly after ES(–0.022/min vs –0.031/ min; P < 0.0001).Significant improvement in gallbladder motility was observed in both groups ofpatients with and without gallbladder calculi. ESsignificantly improves gallbladder motility inhumans.     

慢性胃炎中医证侯与胃窦十二指肠运动及胃炎程度的相 …

研究慢性胃炎中医辩证分型与幽门螺杆菌（Ｈｐ）感染、胃粘膜炎症程度以及胃窦十二指肠消化间期移行性运动复合波之间的关系。将慢性胃炎１１７例,按中医辩证分为实证和虚证,实施包括脾胃湿热型３７例和肝胃不和型３４例,虚证包括脾胃虚型２６例和胃阴不足型２０例。均进行内镜、Ｈｐ及病理检查,分型统计并进行显著性检验。其中３８例用腔内测压法分别测定其消化间期移行性运动复合波（ＭＭＣ）。实证组Ｈｐ阳性率高于虚证组,依     

The CINOD, AZD3582, exhibits an improved gastrointestinal safety profile compared with naproxen in healthy volunteers

COX-inhibiting nitric oxide donators (CINODs) are a new class of drugs in development for the treatment of acute and chronic pain. They comprise a COX-inhibiting moiety linked to a nitric-oxide-donating component and are designed to provide an innovative mechanism of action of balanced COX inhibition and controlled nitric oxide donation. Through these pathways, CINODs should provide analgesic and anti-inflammatory efficacy, while offering gastrointestinal safety through the tissue-protective effects of nitric oxide donation. AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is the first agent in the CINOD class to enter extensive clinical development. Pre-clinical studies demonstrate that AZD3582 has a superior gastrointestinal safety profile to naproxen, while demonstrating analgesic and anti-inflammatory efficacy. In healthy human volunteers, AZD3582 caused little gastrointestinal damage compared with equimolar doses of naproxen. Studies to evaluate the longer-term gastrointestinal safety of AZD3582, alongside its efficacy in alleviating chronic and acute pain, are ongoing.     

COX-inhibiting nitric oxide donators (CINODs) -- a new paradigm in the treatment of pain and inflammation

The clinical utility of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief is tempered by their propensity to cause gastrointestinal toxicity. Cyclooxygenase (COX)-inhibiting nitric oxide donators (CINODs) are a new class of drugs designed to provide analgesic efficacy through COX inhibition and gastrointestinal safety through the protective effects of controlled nitric oxide donation. Pre-clinical studies assessing the pharmacology, efficacy and gastrointestinal safety of AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] support this concept. Based on these studies, AZD3582 was the first CINOD to enter clinical development for the treatment of acute and chronic pain. The potential clinical utility of this new class is illustrated by a study of AZD3582 in healthy volunteers in which it caused significantly less acute gastrointestinal toxicity than an equimolar dose of naproxen. The results of the animal studies and the initial clinical study warrant long-term tolerability studies of AZD3582 along with evaluation of its anti-inflammatory and analgesic effects in humans.     

豚鼠、大鼠、猫离体肠道运动及推进行为的比较生理学特点

应用“离体肠道流体推进检测系统”发现:(1)大鼠十二指肠的腔内压较高,并循空肠—回肠—结肠逐渐降低。(2)豚鼠、大鼠、猫十二指肠、空肠的推进活动不活跃,回肠自发明显而规律的推进复合波,结肠的袋状壁运动及推进复合波强劲,并有显著的肛向纯输出。(3)三种不同食性动物离体小肠的推进复合波频率在大鼠最快,豚鼠次之,猫最慢;但大鼠和豚鼠的推进波频率曲线在结肠交叉倒置,转变为豚鼠(草食)—大鼠(杂食)—猫(肉食)的频率高低次序。(4)豚鼠空肠、回肠推进复合波幅值高于大鼠;在豚鼠结肠,推进波的肛向幅值更明显升高,致使肛向纯输出远超过大鼠。(5)实验动物肠管的紧张性及腔内压高低循远口方向形成梯度,且不同食性动物肠道的壁运动和推进行为各具特点,以适应不同类型食物消化吸收、残渣传送、粪团形成和排出的功能需要;这是肠平滑肌和壁内神经调控机制适应性发展的结果。     

Functional Changes in Nonadrenergic, Noncholinergic Inhibitory Neurons in Ileal Circular Smooth Muscle After Small Bowel Transplantation in Rats

This experiment was designed to determinemechanisms of change in nonadrenergic, noncholinergic(NANC) inhibitory neurons in the ileum after small boweltransplantation (SBT) in the rat and whether nitric oxide (NO) serves as an important NANCinhibitory neurotransmitter in the rat ileum. Eightgroups of rats (N 8 rats/group) were studied:neurally intact unoperated controls; rats one week afteranesthesia and sham celiotomy; and separate groups one andeight weeks after either 40 min of cold ischemia of thejejunoileum, combined jejunal and ileal intestinaltransection/reanastomosis, or orthotopic SBT of the entire jejunoileum. Contractile activitywas evaluated in full-thickness ileal circular musclestrips under isometric conditions. Spontaneous activitydid not differ among groups. In all groups, exogenous NO, N^G-monomethyl-L-arginine(L-NMMA, an NO synthase inhibitor), and methylene blue(soluble guanylate cyclase inhibitor) had no effect onspontaneous activity, while 8-bromocyclic guanosinemonophosphate (8Br-cGMP) inhibited contractile activity inall groups. Low frequency (2-10 Hz) electrical fieldstimulation (EFS) inhibited contractile activity only incontrol and SBT groups; L-NMMA and methylene blue did not alter the response to EFS in any group.These results suggest that each aspect of the SBTprocedure, ischemia/reperfusion injury, disruption ofenteric neural continuity by intestinal transection, and extrinsic denervation, alter function ofenteric ileal inhibitory neurons separately early (oneweek) after operation. NO, a known inhibitoryneurotransmitter in other gut regions, does not affectileal circular muscle in neurally intact tissue normediate functional changes in inhibitory nerve functionnor smooth muscle contractility after SBT.     

Change in Colonic Motility After Extrinsic Autonomic Denervation in Dogs

Changes in colonic motility were compared indogs undergoing autonomic denervation of the paraaorticand presacral (group A), paraaortic (group B), ormesocolonic region (group C), and sham operation (group D). Five bipolar recording electrodes wereplaced into the seromuscular layer of the colon andrectum. The numbers of continuous electrical responseactivity and contractile electrical complex after an intragastric olive oil injection were smallerin group A than in the other groups (P < 0.05) fromthree weeks through six months after denervation. Thisdifference was significant even in the proximal colon. These data suggest that the pelvic plexus mayplay an important role in colonic motility including theproximal colon. The damage to the plexus did not recoverfor at least six months after denevation. Pelvic plexus injury may thus be one ofpossible explanations for the prolonged change in bowelhabit after anterior resection of the rectum.     

Plasma Cholecystokinin and Gallbladder Responses to Increasing Doses of Bombesin in Celiac Disease

Impaired postprandial gallbladder emptying inceliac disease has been attributed to an absence ofappropriate cholecystokinin release. To determine if aflat jejunal mucosa in celiac patients is related to a reduced cholecystokinin-secretingcapacity, increasing doses of bombesin were infused intosix patients with celiac disease and a flat jejunalmucosa (group A), in seven celiac patients with a normal jejunal mucosa while on a gluten-free diet(group B), and in seven healthy controls (group C).Bombesin induced significant (P < 0.05) increments ofplasma CCK to a maximum value of 1.0 ± 0.3 pM in group A, to 1.5 ± 0.3 pM in group B, andto 1.2 ± 0.3 pM in group C (NS between groups),that were accompanied by significant (P < 0.05)gallbladder emptying responses of 70 ± 4% ingroup A, 47 ± 10% in group B and 65 5% in group C.Dose-response relationships were not different betweengroups. We conclude that there is no major impairment ofgallbladder responsiveness to bombesin or ofcholecystokinin-secreting capacity in patients with a flat jejunal mucosadue to celiac disease.     

Adrenoceptors and Colocolonic Inhibitory Reflex

The colocolonic inhibitory reflex ischaracterized by inhibition of proximal colonic motilityinduced by distal colonic distension. The aim of thisstudy was to investigate the underlying neuralmechanisms of this reflex, in vivo , using an isolatedloop of canine colon. In five beagle dogs, motility wasrecorded from an exteriorized colonic loop via a serosalstrain gauge connected to a digital data logger and chart recorder. Inflation of a balloon inthe distal colon resulted in inhibition of motility inthe isolated loop. Inhibition of motor activitypersisted following injection of propranolol (100g/kg intravenously), a -adrenoceptorantagonist, but was abolished following administrationof the ₂-adrenoceptor antagonistyohimbine (200 g/kg intravenously). This studyconfirms that the colocolonic inhibitory reflex is mediatedvia the extrinsic nerves to the colon. As the reflex wasabolished by ₂-, but not-adrenoceptor blockade, this indicates that thereflex pathway involves₂-adrenoceptors.