红霉素对狗消化间期和餐后胃肠运动的影响及机制探讨

目的观察静脉注射红霉素对狗消化间期胃肠移行性复合运动（ＭＭＣ）和餐后运动的作用并探讨可能机制。方法应用低顺应性毛细管水灌注消化道腔内测压系统记录清醒狗胃肠收缩活动。在ＭＭＣＩ相和餐后静脉注射红霉素记录胃肠运动变化并抽血测定血浆胃动素浓度。结果①血浆胃动素随ＭＭＣ不同时相呈周期性波动,血浆胃动素浓度在 ＭＭＣⅢ相时最高,ＭＭＣＩ相时最低。②在 ＭＭＣＩ相时从静脉注射红霉素可以激发胃和十二指肠ＭＭＣⅢ相收缩,但不伴有血浆胃动素升高。引起狗ＭＭＣⅢ相收缩的最适红霉素浓度为０,５ｍｇ·ｋｇ－１体重;红霉素１０ｍｇ·ｋｇ－１引起胃肠持续收缩并出现十二指肠－胃逆蠕动,导致恶心呕吐。③阿托品明显抑制红霉素所致的胃和十二指肠ＭＭＣⅢ相收缩。④红霉素增强狗餐后胃窦和十二指肠的收缩活动。结论红霉素有促进胃肠动力作用,作用机制与胃动素释放无关,可能部分通过胆碱能神经介导。     

红霉素对消化间期胃和十二指肠动力的影响

采用连续水灌注导管法记录了8例NOD病人消化间期胃及十二指肠的压力,每例记录3.5小时,均未出现MMC3期,仅MMC1期和2期交替出现,提示NUD存在消化间期胃和十二指肠动力障碍;此后在MMC1期匀速静滴红霉素200mg,滴莲为每分钟6.6mg,在静滴红霉素期间,胃窦和十二指肠的收缩频率、平均收缩强度、平均收缩面积,每次收缩的持续时间和运动指数均显著增加,在5例诱发了MMC3期,6例腹胀症状减轻,提示静滴红霉素对NUD消化间期胃和十二指肠动力有促进作用,动力障碍可能与NUD的部分症状产生有关。     

胃动素受体的研究进展

胃动素主要在胃肠道表达，促进消化间期Ⅲ相收缩。而胃动素系统具体的作用机制尚未阐明，主要是因为缺乏对胃动素受体的了解。1999年Feighner等成功地鉴定和研究了胃动素受体的基因序列和生物学特笥。这一重大发现促进了人们对胃动素系统的认识，并对开发更加有效的胃肠动力药物提供了广阔的前景，为治疗临床大量胃肠动力性疾病将提供更有效的手段。本文就胃动素受体的研究进展作一综述。     

复合凝乳酶胶囊联合多潘立酮治疗儿童功能性消化不良的临床研究

目的探讨复合凝乳酶胶囊联合多潘立酮治疗儿童功能性消化不良的临床效果。方法选取2016年7月—2017年7月河南科技大学第一附属医院收治的功能性消化不良患儿80例,随机分成对照组(40例)和治疗组(40例)。对照组餐前30 min口服多潘立酮混悬液,4～6岁5 mL/次,7～9岁7 mL/次,10～14岁9 mL/次,3次/d。治疗组在对照组基础上餐后30 min口服复合凝乳酶胶囊,4～6岁1粒/次,7～14岁2粒/次,3次/d。两组均连续治疗2周。观察两组患者临床疗效,同时比较治疗前后两组患者主要症状情况、胃动力学参数水平、胃电节律异常情况和胃肠激素水平。结果治疗后,对照组和治疗组临床总有效率分别为85.0%和97.5%,两组比较差异具有统计学意义(P0.05)。治疗后,两组餐后饱胀、早饱、嗳气发生率均显著降低(P0.05),且治疗组比对照组下降更显著(P0.05)。治疗后,两组胃排空时间均显著缩短(P0.05),胃窦收缩幅度(CA)、收缩次数(CF)值均显著增大(P0.05),且治疗组胃动力学参数比对照组改善更显著(P0.05)。治疗后,两组餐前和餐后胃电节律异常率均显著下降(P0.05),且治疗组患者胃电节律异常率比对照组降低更明显(P0.05)。治疗后,两组患者血浆胃动素(MLT)、胃泌素(GAS)浓度均显著升高(P0.05),且治疗组患者血浆MLT和GAS浓度明显高于对照组(P0.05)。结论复合凝乳酶胶囊联合多潘立酮治疗儿童功能性消化不良,可明显消除消化不良症状,改善胃肠动力,调节胃肠激素分泌。     

功能性消化不良患者胃排空时间和血浆胃动素的相关性与临床研究

目的研究分析功能性消化不良患者胃排空时间和血浆胃动素的相关性与临床意义。方法对40名健康者和80例FD患者应用实时超声显像法进行胃排空时间测定。受试者空腹饮水后0、10、20、30、40、50 min测定胃窦面积和胃体-底交界区前后壁切面内径,测定胃起始收缩时间和2 min收缩次数;并空腹测其血浆胃动素水平。结果 80例FD中有70%存在胃液体排空延迟,且与胃起始收缩时间和2 min收缩次数相关。FD患者血浆胃动素水平明显低于正常组。结论 FD发病确与胃动力障碍有关,胃肠激素中胃动素在FD发病中也起一定作用。     

西沙必利的临床药物配伍

西沙必利(商品名普瑞博思)为一种胃肠动力药,可加强并协调胃肠运动,防止食物滞留与反流.其作用机制主要是选择性地促进肠肌层神经丛节后处乙酰胆碱的释放(在时间和数量上),增强胃肠的运动;但不影响粘膜下神经丛,因此不改变粘膜的分泌.本品可增强人的食管、胃和十二指肠的收缩与蠕动,改善胃窦-十二指肠部的协调功能,防止胃-食管和十二指肠-胃反流,加强胃和十二指肠的排空,并可促进小肠和大肠的蠕动[1].临床主要用于治疗反流性食管炎、功能性消化不良、消化性溃疡、慢性特发性假性肠梗阻、胃轻瘫、Roux-en-Y综合征、胆囊收缩不良及便秘等[2],疗效确切,颇受临床医师欢迎.本文就如何充分发挥药物的疗效,做到药物合理配伍谈几点看法.     

胃癌全胃切除术后Roux肠袢运动变化的研究

目的通过对胃癌全胃切除、食管空肠Roux-Y吻合术后患者进行Roux空肠袢动力测定，探讨RouxY综合征的发病机制。方法全胃切除、Roux-Y食管空肠重建术后6～12个月，通过7通道测压导管监测Roux空肠袢在消化间期及消化期的压力变化。结果Roux肠袢消化间期缺乏移行性复合运动波（MMC）Ⅲ相活动，呈逆行传播或出现非传播性压力活动暴发群等，多数患者消化间期向消化期运动转换障碍。结论Roux肠袢运动紊乱，可能与患者术后发生Roux～Y综合征有关。     

疏肝和胃汤治疗功能性消化不良

功能性消化不良(FD)是一组以上腹胀痛不适、餐后腹胀、恶心呕吐等消化不良症状为主要表现的临床综合征.已经证实本病存在对固体食物和不消化固体的排空延迟,提示胃肠动力减慢是FD的主要发病因素.现代医学多以多潘立酮(吗丁林)、西沙比利等胃肠动力药治疗.笔者十余载来,每以自拟疏肝和胃汤施治,兹报告如下.     

胃电振幅与胃运动间相关性的研究

在28例功能性消化不良(FD)患者和13例健康人,进行了胃电描记和胃窦测压,探讨体表胃电图(EGG)的振幅与胃动力间的相关性。记录空腹胃动力3.5小时,餐后胃动力1.5小时,于移行运动复合波(MMC)的每一期及餐后记录EGG。在8例FD患者,于MMC的Ⅰ期静滴红霉素200mg,滴速为6.6mg/min,滴注期间记录EGG。结果表明;空腹胃电振幅在MMC的Ⅲ期最高,Ⅰ期最低(P<0.01);在静滴红霉素期间,胃窦收缩的频率、强度、动力指数(MI)和胃电振幅均较静滴前显著增加(P<0.01);在7例FD,餐后胃窦MI低于正常;在9例FD,餐后MI正常;餐后胃电振幅在动力减低的FD患者显著低于动力正常的FD(P<0.01)。结论:胃电振幅与胃平滑肌机械收缩有关,高电振幅伴随强收缩活动,胃电振幅有可能成为反映胃动力的指标。     

诺为(马来酸曲美布汀)治疗功能性消化不良的临床观察(附65例分析)

功能性消化不良 (Functional dyspepsia,FD)是一种上胃肠动力功能紊乱的疾病 ,其发病机理尚未完全清楚 ,目前认为有多种因素参与 ,包括胃的舒张与收缩功能失常、幽门阻力增加、胃窦十二指肠运动不协调、胃肠激素、心理和环境等 ,占消化专科门诊的 2 0 %～ 4 0 %。诺为 (马来酸曲美布汀 )于2 0世纪 70年代中期在日本上市 ,作为胃肠动力紊乱调节剂主治胃肠道功能紊乱疾病 ,如各型肠易激综合症、腹部术后不适、慢性胃炎等所致胃肠功能紊乱 ,能显著改善各种腹部不适症状 [1 ]。本文对 6 5例 FD患者进行随机对照研究 ,以观察诺为治疗 FD的疗效…     

Stimulating action of KW-5139 (Leu13-motilin) on gastrointestinal motility in the rabbit.

1. The gastrointestinal motor stimulating action of the motilin analogue, KW-5139 (Leu13-motilin), was investigated both in the anaesthetized rabbit and in rabbit isolated smooth muscle tissues. 2. KW-5139 (0.3-10 micrograms kg-1, i.v.) produced motor stimulating actions in the gastric antrum, ileum and descending colon, the excitatory responses of which were initiated at the same time but declined with different time courses. The rank order of the excitatory response was: descending colon > or = gastric antrum >> ileum. 3. Atropine (1-3 mg kg-1, i.v.) or naloxone (1 mg kg-1, i.v.) completely suppressed the excitatory response to KW-5139 in the gastric antrum, but only partially attenuated that in the descending colon. This suggests that the mechanism of the excitatory response is different in the gastric antrum and the descending colon, and that cholinergic neural pathway is involved in the response of the gastric antrum. 4. KW-5139 (0.1 nM-1 microM) caused concentration-dependent contractions of the gastric antrum, duodenum, jejunum, ileum and the descending colon in vitro. In the rabbit intestine, the contractile response to KW-5139 was strongest in the duodenum and weakest in the ileum. 5. The contractile response to KW-5139 in the intestinal segments were not affected by tetrodotoxin, but were decreased by verapamil, or pretreatment with a high concentration of porcine motilin, confirming the involvement of motilin receptors in the response to KW-5139. 6. The present results suggest that the rabbit is a suitable species for the investigation of motilin on gut motility, because of the high responsiveness of the descending colon as well as the upper gastrointestinal tract.     

Dose-related effects of motilin on proximal gastrointestinal motility

AIM: To assess non-invasively the dose-response relations for the effects of exogenous motilin on antrum contraction frequency, gall-bladder volume and gastric myoelectrical activity. METHODS: In a double-blind, randomized, placebo-controlled, five-way crossover study, 10 fasted healthy volunteers were infused intravenously with synthetic human motilin (0.5, 1, 2 and 4 pmol x min/kg) or placebo for 60 min. Gall-bladder volume and antrum contractions were assessed by ultrasonography and gastric myoelectrical activity by electrogastrography. Motilin concentrations were measured using a radioimmunoassay. RESULTS: Baseline plasma motilin levels (60 pmol/L) were similar for all treatments. Motilin levels increased upon the start of infusion and rapidly returned to baseline after cessation of the infusion. At motilin doses of 2 and 4 pmol.min/kg, the antrum contraction frequency was significantly augmented, with maximum differences of two contractions per 2-min interval compared to placebo, while no changes in gastric myoelectrical activity were observed. Changes in gall-bladder volume were not significantly different for any of the motilin doses compared to placebo. CONCLUSIONS: Motilin increased antrum contraction frequency, whereas no effect on gastric myoelectrical activity was observed. Antrum contraction frequency appears to be a useful biomarker for motilin efficacy, and motilin doses of 2 and 4 pmol x min/kg were equally effective.     

Effect of midecamycin acetate on gastrointestinal motility in humans.

The effect was studied on gastrointestinal motor activity of three different macrolides (erythromycin, roxithromycin and midecamycin acetate), administered by mouth in therapeutic doses. This placebo-controlled study was performed in 12 normal human subjects by means of intraluminal pressure measurements in the gastric antrum, duodenum and upper jejunum. In each subject, three manometries were done for 5 h in the interdigestive period and for 3 h postprandially. In the interdigestive period, midecamycin acetate did not affect the characteristics of the gastric migrating motor complex (MMC) and did not increase the number of antral contractions or the gastric motility index as compared to the placebo. Erythromycin and roxithromycin increased the number of antral contractions (24.5 +/- 11 versus 15.2 +/- 7 and 28.4 +/- 12 versus 14.9 +/- 5.9 respectively) and the motility index (4.05 +/- 0.5 versus 3.17 +/- 0.6 and 4.38 +/- 0.2. versus 3.64 +/- 0.7 respectively) as compared to the placebo. In the postprandial period, the number of antral contractions was not significantly increased by any of the three antibiotics. The postprandial antral motility index was not significantly increased by midecamycin acetate. In contrast, the postprandial antral motility indexes after erythromycin (4.4 +/- 0.5) and after roxithromycin (4.3 +/- 0.2) were significantly greater than after the placebo. In the upper small intestine, erythromycin elicited an increased number of phase-III-like activity events and roxithromycin shortened the MMC cycle length. Midecamycin acetate had no effect on interdigestive upper jejunal motility. The postprandial jejunal motor activity was not altered by any of the three antibiotics neither during the interdigestive nor the postprandial periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects

AIMS: Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release. METHODS: Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day(-1) s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured. RESULTS: After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment. CONCLUSIONS: The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function.     

The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action

Background and purpose:

The underlying mechanisms of gastric dysfunction during or after an episode of intestinal inflammation are poorly understood. This study investigated the effects of colitis on the contractile effects of motilin, an important endocrine regulator of gastric motility, in the antrum.

Experimental approach:

Myeloperoxidase (MPO) activity, NF-κB activity and motilin receptor density were determined in the antrum of rabbits 5 days after the induction of 2,4,6-trinitrobenzenesulphonic acid colitis. Smooth muscle and neural responses to motilin were studied in antral smooth muscle strips in vitro.

Key results:

Colitis did not affect MPO activity, but increased NF-κB activity in the antrum. Motilin receptor density in the antrum was not affected. Under control conditions, motilin induced a slowly developing tonic smooth muscle contraction. Five days post-inflammation, tonic contractions to motilin were reduced and preceded by a rapid initial contraction. Other kinases were recruited for the phosphorylation of myosin light chain (MLC) (a multi-functional MLC kinase), and for the inhibition of MLC phosphatase (Rho kinase in addition to protein kinase C) to mediate the motilin-induced contractions during inflammation. Colitis potentiated the cholinergic neural on-contractions in the antrum. This was associated with a hyper-reactivity to motilin and an increased muscle response to ACh.

Conclusions and implications:

Colitis altered the course of the motilin-induced smooth muscle contraction in the antrum. This involved changes in the kinases phosphorylating MLC. Increased cholinergic excitability to motilin in the antrum may play a role in the pathogenesis of inflammation-associated gastric motility disorders.     

In vitro pharmacological profile of SK-896, a new human motilin analogue

SK-896 ([Leu(13)]motilin-Hse) is a new human motilin analogue synthesized by Escherichia coli using a biotechnological method. We investigated the binding of SK-896 to motilin receptors and the contractile effect of SK-896 on smooth muscle preparations isolated from the gastrointestinal tract and various regional organs in order to clarify its in vitro pharmacological profile. SK-896 inhibited the binding of (125)I-human motilin to rabbit gastroduodenal motilin receptors with the same potency as unlabeled human motilin. The IC(50) values of SK-896 and human motilin were 3.5 +/- 1.5 and 3.1 +/- 1.8 nmol/l, respectively. The K(d) of human motilin was 3.0 +/- 1.5 nmol/l, and the Ki of SK-896 was 3.4 +/- 1.5 nmol/l. SK-896 induced contraction of smooth muscle preparations isolated from rabbit duodenum in a concentration-dependent manner. However, there was no effect of SK-896 on duodenal preparations isolated from the dog and the rat. SK-896 thus exhibited species specificity in its contractile effect. We next investigated the effect of SK-896 on various smooth muscle preparations isolated from rabbit gastrointestinal tract, trachea, bladder, gallbladder, uterus, vas deferens and artery. Results showed that SK-896 induced contraction of smooth muscle preparations isolated from gastrointestinal tract, with potencies in the order duodenum > gastric pylorus = jejunum = descending colon > ascending colon >/= ileum. However, there was no effect of SK-896 on smooth muscle preparations from gastric fundus and other regional organs. SK-896 thus exhibited regional specificity in its contractile effect. Moreover, the effects of SK-896 on smooth muscle preparations from rabbit duodenum were the same as those of human motilin, and were not inhibited by pretreatment with tetrodotoxin and atropine but were inhibited by verapamil. These findings indicate that SK-896 has the same pharmacological profile as human motilin. They suggest that SK-896 acts on gastrointestinal smooth muscle isolated from rabbit directly and specifically.     

Effect of rokitamycin on upper gastrointestinal contractile activity. Analysis of side-effects on gastrointestinal tract

In order to determine whether rokitamycin (RKM), one of the macrolide antibiotics, has any side effects on the gastrointestinal tract, the effect of intraduodenal administration of RKM (1.0, 3.0 and 9.0 mg/kg) on gastrointestinal contractile activity was studied by means of force transducers implanted chronically on the gastric body, gastric antrum, duodenum and upper jejunum in conscious dogs. Erythromycin (EM 0.3, 1.0 and 3.0 mg/kg) and kitasamycin (LM 1.0, 3.0 and 9.0 mg/kg), both macrolide antibiotics, were used as control drugs. RKM, when given at 3.0 mg/kg and 9.0 mg/kg doses, induced segmentation contractions only in the duodenum where it was administered. The duration of the RKM-induced contractions was 7.5 +/- 2.5 minutes for 3.0 mg/kg and 15.8 +/- 3.0 minutes for 9.0 mg/kg, and the contractile force of the contractions was 43 to 82% of the maximum contractile force of the interdigestive contractions in the duodenum. EM, at 0.3 mg/kg, evoked a series of strong contractions quite different from those induced by RKM but similar to the natural interdigestive contractions, and with large doses, dose-dependent long-lasting interdigestive contractions were induced. On the other hand, LM did not stimulate notable gastrointestinal contractile activity even at a 9.0 mg/kg dose. In order to eliminate the possibilities of the contraction being caused by the effect of RKM on the duodenum through the general circulation upon absorption, 3.0 mg/kg RKM was given intravenously. It was found that intravenous injection of RKM did not evoke any contractions attributable to the direct action of RKM in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Digestive tract endoluminal perfusion of cisapride (R 51619) and effects on gastrointestinal hormone levels in anaesthetized pigs

The authors evaluated the in vivo effects of the new drug Cisapride on gastrointestinal hormone release in the mini-pig. Cisapride has been reported to stimulate and coordinate peristalsis of the GI tract. Selective endoluminal perfusion with Cisapride solution of the isolated but not denervated gastric antrum, duodenum and distal ileum demonstrated a significant increase of gastrin levels following perfusion of the gastric antrum and a decrease in vasoactive intestinal peptide following perfusion of the duodenum, only at very high doses.