Duodenal acidification inhibits sphincter of Oddi motility in the prairie dog

Recent studies have explored the influence of various hormones, peptides, and neural innervation on the sphincter of Oddi (SO). However, only older and conflicting data are available on the effect of intraduodenal (ID) perfusion of acid on SO activity. Therefore, we tested the hypothesis that acidification of the proximal small bowel would alter SO motility. In acute terminal experiments, 19 adult male prairie dogs underwent cannulation of the gallbladder (GB) with a pressure-monitored perfusion catheter. The common bile duct was cannulated proximally with a drainage catheter and distally with a triple-lumen, side-hole, closed-tip catheter with one port positioned in the SO. The duodenum was cannulated distal to the SO to allow perfusion of the proximal 30 cm of intestine with saline. SO phasic wave frequency (F), amplitude (A), and baseline pressure as well as GB pressure were measured for 40 min prior to and during ID perfusion of saline at pH 8.8, pH 6.0, or pH 2.0. A SO motility index (MI = F X A) was calculated for each 10-min period of the experiment. Infusion of saline at pH 8.8 had no effect on SO function. ID perfusion of saline at pH 6.0 reduced SO MI to 39% (P less than 0.05) and 34% (P less than 0.05) of control values at 20-30 and 30-40 min, respectively. ID saline at pH 2.0 reduced the SO MI to 51% (P less than 0.01) and 53% of control values during the same periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

犬Oddi括约肌肌电的研究

目的探索能准确稳定记录犬Oddi括约肌(sphincter of Oddi,SO)肌电活动的新方法,并对记录到的肌电波形进行初步分析。方法用自行研制的黏膜接触式电极记录30只犬SO肌电活动,同时记录十二指肠和胃的肌电活动,分析SO肌电波形的规律以及和胃十二指肠肌电的关系。结果用我们的方法可以记录到犬SO的快波和慢波,同步记录以及切离实验证实记录到的波形是犬的SO肌电而不是来自十二指肠和胃。结论犬的SO肌电记录是可行的,犬SO快波和慢波的发现将对SO功能研究提供一个新的平台。     

Multimodal contractile activity of the canine sphincter of Oddi

Using a high-fidelity recording system, simultaneous manometric measurements of the sphincter of Oddi and duodenum were performed in 6 dogs. The sphincter of Oddi was a high-pressure zone with superimposed phasic activity. The tracings were analyzed according to the distribution of the peak-to-peak contraction intervals (PPI), and a multimodal distribution was consistently found with a basal mode of 3.5 s. If not occurring at this interval, the PPI would be a multiple of this value. These findings suggest that slow-wave control activity is present in the canine sphincter of Oddi. The origin of this control is still unknown.     

Peptide YY inhibits the growth of Barrett's esophageal adenocarcinoma in vitro

BACKGROUND: Peptide YY (PYY) is an endogenous gut hormone that inhibits the growth of certain cancers. Adenocarcinoma of the esophagus usually arises from Barrett's esophagus. We hypothesized that treatment of Barrett's adenocarcinoma with PYY would result in decreased proliferation. METHODS: Barrett's cancer cell lines (BIC and SEG-1) were treated with PYY (3-36) at 500 pmol/mL. Viability was measured by MTT at 24 and 72 hours. Apoptosis and necrosis was evaluated by flow cytometry. RESULTS: PYY reduced proliferation in SEG-1 cells at 24 hours (21.2% +/- 3.4%, P <0.001) and 72 hours (14.2% +/- 6.2%, P <0.001). In the BIC cells, growth was inhibited by 7.9% +/- 7.0%, P = 0.021 after 72 hours. PYY increased late apoptotic activity in SEG-1 cells by 31%, P = 0.014. CONCLUSIONS: This is the first report of antiproliferative effects of PYY against Barrett's carcinoma in vitro. Reductions in cell growth appear to be mediated by proapoptotic mechanisms. Further investigation of PYY in the treatment of Barrett's adenocarcinoma is warranted.     

Lovastatin inhibits gallstone formation in the cholesterol-fed prairie dog.

The efficacy of lovastatin, an inhibitor of hepatic cholesterol synthesis in the prevention of cholesterol gallstone formation, was evaluated in the prairie dog model. Two groups of animals were maintained on either nonlithogenic or 1.2% cholesterol-enriched chow for 21 days. Seven of the animals in each group received lovastatin, and the remaining six received only distilled water. All of the cholesterol-fed/water-treated animals had crystals and 83% had gallstones, but none of the cholesterol-fed/lovastatin-treated animals had gallstones and only three had microscopic crystals. These data indicate that lovastatin inhibits cholesterol gallstone formation in a diet-induced model of gallstone disease.     

Duodenal but not gastric transection disturbs motility of the sphincter of Oddi in the dog

The aim of the present study was to elucidate the effect of gastric and duodenal transection on biliary manometry in anesthetized dogs. The basal biliary pressure and increase in pressure during saline perfusion at rates of 1.0 and 1.5 ml/min were studied in intact controls, during infusion of cholecystokinin (CCK) alone, and after gastric and duodenal transection. CCK dose-dependently lowered the basal pressure and the increase in pressure during perfusion. Gastric transection 1.5 cm proximal to the pylorus did not affect these parameters. In contrast, duodenal transection 1.0 cm distal to the pylorus significantly increased these parameters compared to all other groups. These observations suggest that the proximal duodenal transection, as performed during conventional distal gastrectomy, may contribute to the pathogenesis of postgastrectomy gallstone formation by altering motor function of the sphincter of Oddi.     

Postprandial sphincter of Oddi myoelectric activity and gallbladder emptying

Feeding initiates gallbladder emptying and bile delivery into the duodenum. It is not yet defined how the sphincter of Oddi regulates flow of bile into the duodenum during gallbladder emptying. The aim of this study was to assess postprandial spike burst activity in the sphincter of Oddi, while quantitating gallbladder emptying with noninvasive radioisotope imaging. Six adult opossums were prepared with bipolar electrodes in the sphincter of Oddi. After 2 weeks of recovery the animals were fasted overnight and positioned under a gamma camera, and myoelectric recordings were begun. After two cycles of the migrating motor complex (MMC), 2 mCi 99Tc-HIDA was infused intravenously and permitted to concentrate in the gallbladder for a period of 30 min. Subsequently, a 30-ml liquid meal, containing 0.9 g protein, 3.5 g carbohydrate, and 3.3 g fat, was instilled into the stomach. Sphincter of Oddi myoelectric activity (spike bursts/min) and gallbladder emptying (expressed as percentage of original 99Tc counts in the gallbladder) were measured at intervals for 120 min following feeding. Feeding resulted in prompt gallbladder emptying. Sphincter of Oddi spike burst activity was not altered significantly in the first 30 min after feeding, suggesting that motor activity in the sphincter of Oddi does not initially influence bile flow. Subsequently, spike burst activity increased progressively, suggesting that sphincter of Oddi motor activity may accelerate bile delivery into the duodenum during later phases of gallbladder emptying.     

Cholescintigraphic observation of the sphincter of Oddi motor activity in patients with gallstone

In 36 cases with gallstones, biliary scintigraphy was performed before and after operation to prepare the time-activity curve in the juxta-papillary duodenum. This curve showed different patterns depending on the conditions of disease, and seemed to represent on aspect of the sphincter of Oddi phasic activity, in view of the exerted effect of caerulein administration. This method is useful as a non-invasive one for the diagnosis of dynamic function of the sphincter of Oddi.     

Peptide YY inhibits growth of human breast cancer in vitro and in vivo

BACKGROUND. Hormonal manipulation is important in the treatment of breast cancer. Gastrointestinal hormones may have antiproliferative effects on malignancies arising outside the gastrointestinal tract. Peptide YY (PYY) suppresses growth of, and levels of, intracellular cyclic adenosine monophosphate (cAMP) in pancreatic adenocarcinoma. We hypothesized that PYY would inhibit growth of breast cancer. MATERIALS AND METHODS. MCF-7 human breast infiltrative ductal carcinoma cells in 96-well plates were treated with PYY at 1.25 pmol/mcl. Control wells received an equal volume of bovine serum albumin to mimic experimental conditions. In vitro survival was determined by MTT assays, which reflect cell viability by measuring mitochondrial NADH-dependent dehydrogenase activity. MCF-7 cells in six-well plates were treated with PYY or albumin as described above. Intracellular cAMP levels in cell lysates were determined with a tritiated cAMP assay. One million MCF-7 cells were injected into mammary fat pads of 20 female athymic nude mice. Pellets releasing PYY at 400 pmol/kg/h were placed subcutaneously in 10 mice 24 h prior to cell inoculation. Tumors were harvested after 21 days, weighed, and measured with vernier calipers. RESULTS. PYY reduced in vitro growth by 40% (P < 0.001). Intracellular cAMP levels in PYY-treated cells were 62.4% less than those of controls (P < 0.001). Tumors from control mice weighed twice as much as those from PYY-treated mice (P < 0.006); volume of PYY-exposed tumors was one-third that of controls (P < 0.005). CONCLUSIONS. PYY inhibits growth of breast cancer in vitro and in vivo and may be of benefit in the treatment of this malignancy. The reduction in intracellular cAMP levels may contribute to the observed suppression of cell proliferation.     

犬Oddi括约肌狭窄模型的建立及其胆道动力学的变化

目的建立犬Oddi括约肌（sphincter of Oddi,SO）狭窄模型,探讨其胆道动力学的变化。方法禁食16～18h成年杂种犬麻醉后,超声测量胆总管管径。实验组行经腹切开十二指肠,机械性损伤SO致其狭窄;对照组仅行经腹切开十二指肠,术毕饲养。定期检查肝功能,4周后再次麻醉下行超声测量胆总管管径及开腹行SO测压。最后切取SO及周围组织行病理检查。结果实验组术后4周肝功能TBIL、DBIL、GGT、ALP明显高于术前,超声测量胆总管管径大于术前,病理检查发现括约肌组织纤维化,而对照组均无明显变化。与对照组相比,实验组胆总管及SO基础压明显升高,SO收缩幅度降低,收缩频率升高,收缩时间缩短。结论SO狭窄模型成功建立;Oddi括约肌狭窄后其胆道动力学发生明显改变。     

Characterization of substance P effects on sphincter of Oddi myoelectric activity

We examined the effects of substance P (SP) on the myoelectric activity of the opossum sphincter of Oddi (SO). Myoelectric data from the SO in five adult opossums were recorded using thin stainless steel electrodes and computer-assisted analog-to-digital conversion. In fully awake and conscious animals, baseline spikeburst activity during phase I of the MMC occurred at a frequency of 28.6 +/- 3.1 spikebursts (SB) per 20-min period. Intravenous infusion of graded doses of substance P (from 0.5 to 8.0 micrograms/kg) stimulated SO myoelectric activity in a dose-related manner (from 80 +/- 8 to 235 +/- 11 SB/20 min, respectively, P less than 0.05 when compared to baseline). The effect of substance P on SO myoelectric activity was antagonized by administration of the H2-blocker, cimetidine (92.0 +/- 6.1 vs 48.2 +/- 7.0, n = 5, P less than 0.05). Administration of the antimuscarinic drug atropine only slightly affected the SO spikeburst frequency when infused prior to SP (73.0 +/- 10.4 vs 70.8 +/- 8.2, P greater than 0.05). We conclude that SP stimulated the SO spikeburst frequency in a dose-dependent fashion. Cimetidine markedly inhibited the response of the SO to SP but atropine did not. The excitatory effect of substance P on the opossum SO is mediated at least in part by a histaminergic, noncholinergic pathway.     

Cyclic motility of the sphincter of Oddi

The sphincter of Oddi has a cyclic motility that is closely associated with the duodenal migrating motor complex during fasting. This close association affects the bile flow mechanism and may play several roles in keeping the intestine clean and maintaining the migrating motor complex. The cyclic motility of the sphincter of Oddi changes after surgery and abnormal motility causes biliary dyskinesia. In this article, the gastrointestinal migrating motor complex and cyclic motility of the sphincter of Oddi are reviewed for better understanding of biliary and gastrointestinal physiology and the relationship between the two phenomena. Received for publication on May 17, 1999; accepted on Aug 16, 1999     

The anatomy of the sphincter of Oddi

A three-dimensional reconstruction of the intrinsic musculature surrounding the end of the common bile duct in man, generally referred to as the sphincter of Oddi, is presented. Here is visualized grossly for the first time the structure of the muscles in this important region in the adult human. A separate circular sheath of muscle is seen which by contraction can cause the clinical picture known as biliary dyssynergia. The model substantiates in the main and visualizes in three dimensions the findings reported by Hendrickson, Nuboer, Schwegler and Boyden, and Kreilkamp and Boyden.