Transcription Factor MafB Promotes Hepatocellular Carcinoma Cell Proliferation through Up-Regulation of Cyclin D1.

BACKGROUND/AIMS: MafB, a member of the Maf transcription factor family, plays a key role in the regulation of pancreatic alpha and beta cell differentiation. However, its function in the control of cancer cell proliferation remains unknown. METHODS: The mRNA and protein expression levels of MafB in hepatocellular carcinoma tissues and adjacent non-tumor normal specimens were determined by real-time RT-PCR and Western blot, respectively. Report assay was performed to determine whether the regulation of Cyclin D1 by MafB is at the transcriptional level. The binding of MafB to the Cyclin D1 promoter was determined by Chromatin Immunoprecipitation (ChIP) assays. To determine the potential oncogenic effects of MafB in vivo, HepG2 cells transfected with adenovirus containing empty vector or MafB were injected subcutaneously to the skin under the front legs of the nude mice. RESULTS: In the current study, we showed that MafB was markedly up-regulated in hepatocellular carcinoma (HCC) tissues and cells. Enforced overexpression of MafB enhanced, while its deficiency inhibited HCC cell proliferation. Mechanistically, Cyclin D1, an important regulator of cell cycle progression, was identified as a direct transcriptional target of MafB. Consistently, knockdown of Cyclin D1 largely attenuated the proliferative roles of MafB in HCC cells. Importantly, MafB overexpression significantly promoted cancer cell growth in mice. CONCLUSIONS: Collectively, our results identified a novel HCC regulatory pathway involving MafB and Cyclin D1, the dysfunction of which drives proliferative character in HCC.

DAX-1 inhibits hepatocellular carcinoma proliferation by inhibiting ß-catenin transcriptional activity.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) represents the most common type of liver cancer. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1), an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains, has been known for its fundamental roles in the development, especially in the sex determination and steroidogenesis. Previous studies also showed that DAX-1 played a critical role in endocrine and sex steroid-dependent neoplasms such as adrenocortical, pituitary, endometrial, and ovarian tumors. However, its biological roles in the development of HCC remain largely unexplored. METHODS: Real-time PCR and Western blot were used to detect the expression of DAX-1 in HCC tissues and cell lines. Immunoprecipitation (IP) assay was used to show the interaction between DAX-1 and ß-Catenin. Small interfering RNA (siRNA) was used to silence the expression of DAX-1. BrdU incorporation and Cell-cycle assays were used to detect the role of DAX-1 in HCC cells proliferation. Migration and invasion assays were carried out to test the metastasis ability of DAX-1 in HCC cells. RESULTS: In the present study, we found that mRNA and protein levels of DAX-1 were down-regulated in HCC tissues and cell lines. Furthermore, overexpression of DAX-1 could inhibit while its knockdown using small interfering RNA promoted cell proliferation in several HCC cell lines. At the molecular level, we demonstrated that DAX-1 could interact with ß-Catenin and attenuate its transcriptional activity. CONCLUSION: Therefore, our results suggest a previously unknown DAX-1/ß-Catenin molecular network controlling HCC development.

MicroRNA-195 regulates steroid receptor coactivator-3 protein expression in hepatocellular carcinoma cells.

Multiple studies have shown that steroid receptor coactivator-3 (SRC-3) is upregulated and promotes cell proliferation in several human cancers, including breast, lung, and prostate carcinoma. However, its molecular determinants remain largely unexplored. In the current study, by way of informatics software, we found that MicroRNA-195 (miR-195) could negatively regulate protein levels of SRC-3 through targeting its 3'-untranslated region (3'-UTR) in hepatocellular carcinoma (HCC) cells. As a result, miR-195 mimics inhibited while its antisense enhanced SRC-3 protein levels. Furthermore, miR-195 could modulate cell proliferation and tumor growth in vivo and in vitro. Therefore, our results demonstrate a novel molecular mechanism for the dysregulated expression of SRC-3 in hepatocellular carcinoma.

Celastrol exerts synergistic effects with PHA-665752 and inhibits tumor growth of c-Met-deficient hepatocellular carcinoma in vivo.

PHA665752 (PHA), a selective small molecule c-Met Inhibitor, potently inhibited HGF-stimulated and constitutive c-Met phosphorylation, as well as HGF and c-Met-driven phenotypes of a variety of tumor cells including hepatocellular carcinoma cells. However, these effects were impaired in c-Met-deficient cancer cells. In the present study, we investigated the potential anti-human c-Met-deficient hepatocellular carcinoma effects of Celastrol, a novel triterpene, and its combination with PHA. Human hepatocellular carcinoma cells BEL-7402 (c-Met-positive) and Huh7 (c-Met-deficient) were treated with different dose of PHA with or without equal dose of Celastrol, and cell growth, cell cycle and apoptosis were evaluated, respectively, by MTT assay, flow cytometry and Caspase3/7 activity. Nude mice bearing Huh7 xenografts were used to assess the in vivo anti-tumor activity. Our results showed that Celastrol at high concentration (>1.0 µM) induced G2/M arrest and apoptosis with the activation of Caspase3/7 in Huh7 cells whereas at low concentration (<1.0 µM) had no obvious effects. Low concentration Celastrol presented significant combined effects with PHA on Huh7 cells and Huh7 xenografts in terms of growth inhibition, migration inhibition and apoptosis induction. These results suggest that Celastrol and its combination with PHA present the therapeutic potential on c-Met-deficient hepatocellular carcinoma, and deserve further preclinical and clinical studies.

[Relationship between pigment gallstone and intestinal barrier function: experiment with guinea pigs and clinical observations].

OBJECTIVE: To investigate the relationship between the intestinal barrier function and pigment gallstone formation. METHODS: Ninety Guinea pigs were divided randomly into 3 groups: normal control (CON) group receiving normal forage, pigment gallstone (PS) group receiving pigment gallstone-forming forage, and intestinal mucosa protection group receiving pigment gallstone-forming forage with supplemental glutamine intestinal (GLN), a mucosa protector. The guinea pigs were observed for 8 weeks, the gallstone-forming rate, plasma diamine oxidase ( DAO), serum endotoxin, proportionality of urine lactulose/mannitol, and biliary beta-glucuronidase were detected. PCR was used to detect the bacteria in abdominal lymph node taking 16SrRNA as the target gene common in most bacteria. 32 gallstone patients, 16 with cholesterol gallstone and 16 with pigmental gallstone, and 27 patients with non-gastroenterological diseases, as controls, underwent detection of the plasma DAO and serum endotoxin. Another 109 gallstone patients, 31 with cholesterol gallstone and 78 with pigmental gallstone, and 21 patients with nongastroenterological diseases, as controls, underwent detection of urine technetium-labeled diethylenetriamine-pentaacetate (99mTc-DTPA). RESULTS: The gallstone-forming rate of the guinea pigs of the GLN group was 44.4% was, significantly lower than that of the PS group (73.9%, P < 0.05). The plasma DAO, serum endotoxin levels, proportionality of urine lactulose/mannitol, and activity of biliary beta-glucuronidase of the PS group were all significantly higher than those of the CON group (P < 0.05 or P < 0.01). The plasma endotoxin level of the pigmental GLN group was significantly lower than that of the PS group (P < 0.01). The positive rate of bacteria in abdominal lymph node of the PS group was 80%, significantly higher than those of the CON and GLN groups (30% and 45% respectively, P < 0.01 and P < 0.05). The level of plasma DAO and endotoxin of the pigmental gallstone patients were significantly higher than those of the controls (P < 0.05 and P < 0.01). The urine 99mTc-DTPA excretion rate of gallstone patients was 11.4%, significantly higher than that of the controls (4.7%, P < 0.01). CONCLUSION: Intestinal barrier function is correlated with pigment gallstone forming. Intestinal barrier function disorder may promote pigment gallstone formation through bacteria translocation, endotoxemia, and increase of biliary beta-glucuronidase.

Sphincter of Oddi hypomotility and its relationship with duodenal-biliary reflux, plasma motilin and serum gastrin.

AIM: To detect whether patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux by measuring the radioactivity of Tc99m-labeled diethylene triamine penta-acetic acid (DTPA) in the bile and whether the patients with duodenal-biliary reflux have sphincter of Oddi hypomotility, by measuring the level of plasma and serum gastrin of the patients. Finally to if there is close relationship among sphincter of Oddi hypomotility, duodenal-biliary reflux and gastrointestinal peptides. METHODS: Forty-five patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group. The level of plasma and serum gastrin of the patients and of 12 healthy volunteers were measured by radioimmunoassay. Thirty-four were selected randomly to undergo choledochoscope manometry. Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF), duration of contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. RESULTS: Sixteen (35.6%) patients were detected to have duodenal-biliary reflux. SOBP, SOCA and CBDP in the reflux group were much lower than the control group (t=5.254, 3.438 and 3.527, P<0.001). SOD of the reflux group was shorter than the control group (t=2.049, P<0.05). The level of serum gastrin and plasma motilin of the reflux group was much lower than the control group (t= -2.230 and -2.235, P<0.05). There was positive correlation between the level of plasma motilin and SOBP and between the level of serum gastrin and SOBP and CBDP. CONCLUSION: About 35.9% of the patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux. Most of them have sphincter of Oddi hypomotility and the decreased level of plasma motilin and serum gastrin. The disorder of gastrointestinal hormone secretion may result in sphincter of Oddi dysfunction. There is a close relationship between sphincter of Oddi hypomotility and duodenal-biliary reflux.

Differences and significance of motilin, vasoactive intestinal peptide and gastrin in blood and gallbladder tissues of patients with gallstones.

BACKGROUND: The disorders of gallbladder motility may play an important role in the formation of gallstones. Many neural and hormonal factors and their interactions regulate gallbladder motility and bile flow into the duodenum. Further study in these factors may help to reveal the etiology of gallbladder diseases. This study was undertaken to assess the relationship of the levels of motilin, vasoactive intestinal peptide (VIP) and gastrin in blood and gallbladder tissues with the formation of cholelithiasis. METHODS: The levels of motilin, gastrin and VIP in blood and gallbladder tissues of 36 patients with gallbladder stones, 14 patients with gallbladder polyps, 10 healthy volunteers and 10 patients with common bile duct stones were measured by radioimmunoassay. RESULTS: The level of motilin in plasma and gallbladder tissues of the gallbladder stone group was higher than that of the control and gallbladder polyp groups (P<0.05). The levels of plasma VIP and serum gastrin were much higher than those of the other three groups (P<0.01). The level of VIP in gallbladder tissues was higher than that of the control and gallbladder polyp groups (P<0.01). CONCLUSIONS: The abnormal excretion of hormonal factors is closely related to gallstone formation. The high level of VIP in gallbladder tissues may be an important cause of gallbladder hypomotility. The abnormal level of serum gastrin may be related to the gastrointestinal symptoms of patients with gallstones.

Possible relationship between cholecystectomy and subsequent occurrence of primary common bile duct stones: a retrospective review of data.

BACKGROUND: Most reports on the prognosis of cholecystectomy have been short-term studied, and few long-term reports have suggested variable incidences of common bile duct stones after cholecystectomy. We retrospectively reviewed the data to find the possible association between cholecystectomy and the subsequent occurrence of primary common bile duct stones. METHODS: The data were reviewed retrospectively of 478 patients with primary common bile duct stones diagnosed and treated by endoscopic sphincterotomy at our hospitals between January 1994 and December 2003. RESULTS: Sixty-one (14.1%) of the 432 patients had a history of cholecystectomy, with an incidence rate markedly higher than that in the general population. The mean interval between cholecystectomy and the occurrence of primary common bile duct stones was 8.23 years, with the longest being 28 years and the shortest 2 years. Compared with the patients who had not undergone a prior cholecystectomy, those who had had a prior cholecystectomy more often accompanied with acute cholangiolitis (chi(2)=8.259, P<0.01), and multiple stones or sand-like stones were frequently found (chi(2)=9.030, P<0.01). CONCLUSIONS: These results suggest a possible relationship between cholecystectomy and the subsequent occurrence of primary common bile duct stones. Perhaps patients with primary common bile duct stones who have had a prior cholecystectomy have a higher probability of infection of the biliary system. The infection may be one of the causes of occurrence of primary common bile duct stones after cholecystectomy.

[The relationship between Oddi's sphincter and bile duct pigment gallstone].

OBJECTIVE: To investigate the relationship between anatomic abnormalities and malfunction of Oddi sphincter with formation of bile duct pigment gallstone. METHODS: One hundred and twenty-three patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group by measuring the amounts of radioactivity of (99m)Tc-DTPA in the bile. Among them 53 were selected randomly to undergo choledochoscopic manometry. Basal pressure of Oddi's sphincter (SOBP), amplitude of Oddi's sphincter (SOCA), frequency of contraction (SOF), duration of contraction (SOD), duodenal pressure (DP), common bile duct pressure (CBDP) were scored and analyzed. The level of plasma motilin and serum gastrin of 45 patients and 12 healthy volunteers were measured by radioimmunoassay. The incidence rates of duodenal descending part diverticulum in patients with bile duct pigment stones, patients without alimentary tract diseases, patients with gallbladder polyps, patients with gallbladder stones were studied by means of barium meal examination. The incidence rates of intraduodenal peri-ampullary diverticulum in patients with primary bile duct pigment stones, patients with bile duct stone and gallbladder stones, patients with bile duct stones originating from the gallbladder, patients with inflammation and stricture of the extremity of bile duct and papilla, patients with cancer of the extremity of bile duct and papilla, patients with post-cholecystectomy syndrome were detected by duodenoscope. RESULTS: Of the patients, 44 were detected with duodenal-biliary reflux (35.8%). SOBP, SOCA and CBDP in the reflux group were much lower than those in control group (P < 0.001). The level of serum gastrin and plasma motilin of the reflux group were much lower than those of control group (P < 0.01). Positive correlation was found between level of motilin and SOBP while level of gastrin was positively correlated with SOBP and CBDP. The incidence of duodenal diverticulum in patients with bile duct pigment stone was 36.62%, which was higher than that of the other 3 groups. The incidence rate of intraduodenal peri-ampullary diverticulum in patients with primary bile duct pigment stone was higher than that of patients with inflammation and stricture of the extremity of bile duct and papilla, patients with cancer of the extremity of bile duct and papilla and patients with bile duct stones originating from the gallbladder. CONCLUSIONS: The patients with bile duct pigment stone have apparent duodenal-biliary reflux and infection of the bile duct. The state of structure and function of Oddi's sphincter is correlated significantly with bile duct pigment stone. The anatomic abnormalities and malfunction of Oddi's sphincter played an important role in the formation of bile duct pigment stone.

Role of intestinal barrier in pathogenesis of pigment gallstone in a guinea pig model.

BACKGROUND: The function of the intestinal barrier has drawn more and more attention from researchers in recent years for its important role in many diseases such as burns, wounds, and pancreatitis. In our experimental studies on pigment gallstone, we found potential relationships between the function of the intestinal barrier and pigment gallstone formation. This study was undertaken to investigate the possible action and mechanism of the function of the intestinal barrier in the pathogenesis of pigment gallstone. METHODS: Eighty guinea pigs were divided into a normal group (CON), a pigment gallstone group (PS) and an intestinal mucosa protection group (GLN). Normal forage, pigment gallstone-forming forage and pigment gallstone-forming forage with supplemental intestinal mucosa protector (glutamine) were given to each group. In the gallstone-forming rate, morphology of intestinal mucosa, intestinal permeability, serum endotoxin and biliary beta-glucuronidase were assessed after 8 weeks. RESULTS: The rate of gallstone-formation was 73.9% in the PS group. Damage of intestinal mucosa, endotoxemia (from 77+/-43 X 10(-6) EU/L to 1,367+/-525 X 10(-6) EU/L, P<0.01) and increased activity of biliary beta-glucuronidase (endogenous beta-glucuronidase from 122.1+/-39.5 to 209.8+/-47.5 Fishman Unit, P<0.01, and exogenous beta-glucuronidase from 573.5+/-476.9 to 2,206.6+/-983.9 Fishman Unit, P<0.01) were observed in the PS group compared with the CON group. The rate gallstone-formation decreased significantly to 44.4% and the other indices except beta-glucuronidase were lower in the GLN group than in the PS group. CONCLUSIONS: The function of the intestinal barrier is correlated with pigment gallstone formation. Dysfunction of the intestinal barrier function may promote pigment gallstone formation through bacterial translocation, endotoxemia, and biliary beta-glucuronidase.

Expression of pituitary adenylate cyclase-activating polypeptide 1 and 2 receptor mRNA in gallbladder tissue of patients with gallstone or gallbladder polyps.

AIM: To detect the expression of pituitary adenylate cyclase-activating polypeptide receptor 1 (VPCAP1-R)and VPCAP2-R mRNA in gallbladder tissues of patients with gallstone or gallbladder polyps. METHODS: The expression of VPCAP1-R and VPCAP2-R mRNA in gallbladder tissues was detected in 25 patients with gallstone,8 patients with gallbladder polyps and 7 donors of liver transplantation by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The VPCAP2-R mRNA expression level in the control group (1.09+/-0.58) was lower than that in the gallbladder polyp group (1.64+/-0.56) and the gallstone group (1.55+/-0.45) (P<0.05) while the VPCAP1-R mRNA expression level in the control group (1.15+/-0.23) was not apparently different from that in the gallbladder polyp group (1.28+/-0.56) and the gallstone group (1.27+/-0.38). CONCLUSION: The abnormal expression of VPCAP2-R mRNA in gallbladder tissue may play a role in the formation of gallbladder stone and gallbladder polyps.

[Effects of different drugs on the sphincter of Oddi motility: study with choledochoscope manometry].

OBJECTIVE: This study assessed the effects of narcotic analgesics, nitrates drugs, somatostatin analogues on human sphincter of Oddi motility and the antagonistic effects of nitrates drugs and anticholinergic agents against morphine measured by choledochoscope manometry. METHODS: 157 patients who had a T tube after cholecystectomy and choledochotomy were assessed by choledochoscope manometry. They were randomly divided into 5 groups. Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF), duration of contractions (SOD), duodenal pressure (DP), common bile duct pressure (CBDP) were scored and analyzed. RESULTS: SOBP, SOCA and SOF increased after injection of morphine and Ap-237, CBDP increased after intramuscular administered morphine. No apparent change occurred after intramuscularly administered pethidine. SOBP and SOCA decreased after tramadol. After intravenous administration of stilamin in a dose of 250 microg/h, SOCA increased. After administration stilamin of 500 microg/h dose, SOCA and SOBP declined. After intravenous administration of sandostatin, CBDP increased obviously. BPOS and SOCA decreased significantly after administration of isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN), SOBP reduced evidently after application of pentaerythritol tetranitrate (PTN). SOBP, SOCA, SOF and CBDP increased evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased. As to associated application with PTN, SOCA and SOF decreased. After associated application of anisodamine or atropine, SOCA, SOBP declined, after injected buscopan, SOCA, SOBP, SOF all declined. CONCLUSION: The regular dose of morphine and Ap-237 shows excitatory effect on the sphincter of Oddi motility. Tramadol shows inhibitory effect on the sphincter of Oddi. The regular dose of pethidine and sandostatin shows no apparent effect on the sphincter of Oddi. Stilamin in low dose shows excitated effect on the sphincter of Oddi. Nitrates drugs show inhibited effects on SO motility. Nitrates drugs and anticholinergic agents can antagonize the excitated effect of morphine.

Effects of somatostatin analogues on human sphincter of Oddi pressure.

BACKGROUND: Somatostatin, a neuropeptide and hormone, exists in the biliary tract of several species. The effects of somatostatin and its analogues on the sphincter of Oddi motility have been controversial. The aim of this study was to observe the action of stilamin and sandostatin on the sphincter of Oddi via choledochofiberscope manometry. METHODS: Twenty patients who had had "T" duct after cholecystectomy and choledochotomy were divided into 2 groups randomly: stilamin and sandostatin. They were subjected to manometry via a choledochofiberscope through the "T" duct tract. The following data recorded included duodenal pressure (DP), sphincter of Oddi basal pressure (SOBP), sphincter of Oddi contractive amplitude (SOCA), frequency of the sphincter of Oddi (SOF), duration of the sphincter of Oddi, and the common bile duct pressure (CBDP). RESULTS: After intravenous administration of stilamin at a dose of 250 microg/h, the mean SOCA increased from 89.18(26.50) to 128.57(54.21) mmHg (P<0.05). After the administration of stilamin at a dose of 500 microg/h the mean SOCA declined to 92.18(42.81) mmHg (P<0.05), and mean SOBP declined from 17.63(13.36) to 8.16(4.01) mmHg (P<0.05). Although SOF had declined from 9.25(2.45) to 7.46(1.52) n/min, it was not significantly influenced. After intravenous administration of sandostatin at a dose of 100 microg, the mean CBDP increased obviously. CONCLUSIONS: Intravenous administration of stilamin at a dose of 250 microg/h stimulates the motility of the sphincter of Oddi whereas the injection of stilamin at a dose of 500 microg/h inhibits its motility. Intravenous injection of sandostatin of 100 mug has no effect on the sphincter of Oddi.

Nitroester drug's effects and their antagonistic effects against morphine on human sphincter of Oddi motility.

AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility. METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry. A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group, isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually. RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95+/-7.49 mmHg to 5.92+/-4.04 mmHg (P<0.05) evidently after application of PTN. BPOS increased from 7.37+/-5.58 mmHg to 16.60+/-13.87 mmHg, SOCA increased from 54.09+/-38.37 mmHg to 100.70+/-43.51 mmHg, SOF increased from 7.15+/-3.20 mmHg to 10.38+/-2.93 mmHg and CBDP increased 3.75+/-1.95 mmHg to 10.49+/-8.21 mmHg (P<0.01) evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN, SOCA and SOF decreased separately from 100.64+/-44.99 mmHg to 66.17+/-35.88 mmHg and from 10.70+/-2.76 mmHg to 9.04+/-1.71 mmHg (P<0.05) markedly. CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most significant.

Effects of narcotic analgesic drugs on human Oddi's sphincter motility.

AIM: To assess the effects of intramuscular analgesics (morphine, Ap-237, pethidine and tramadol) on human Oddi's sphincter motility with choledochoscope manometry. METHODS: A total of 70 patients having T tubes after cholecystectomy and choledochotomy were assessed by choledochoscope manometry. They were randomly divided into morphine group, Ap-237 group, pethidine group and tramadol group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions(SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. All narcotic analgesic drugs were administered intramuscularly. RESULTS: Levels of BPOS, SOCA and SOF were increased after injection of morphine and Ap-237 (P<0.05), level of CBDP was increased from 4.97+/-3.87 mmHg to 8.62+/-7.43 mmHg (10 min later) and 7.32+/-5.95 mmHg (20 min later) after injection of morphine (P<0.01). No apparent change occurred after intramuscular injection of pethidine. Level of BPOS was increased from 7.01+/-5.50 mmHg to 2.87+/-2.78 mmHg 10 min after injection of tramadol and SOCA was decreased from 63.34+/-35.29 mmHg to 45.90+/-27.86 mmHg (10 min later,P<0.05) and 35.97+/-24.30 (20 min later,P<0.01) after administration of tramadol. CONCLUSION: All these findings indicate that Oddi's sphincter manometry via choledochoscope is a practical and new way to study the dynamics of Oddi' s sphincter. The regular dose of morphine and Ap-237 could increase BPOS, SOF and SOCA. Morphine could increase the level of CBDP, demonstrating an excitatory effect on the sphincter of Oddi. Pethidine had no effect on Oddi's sphincter motility. Tramadol shows an inhibitory effect on the motility of the sphincter of Oddi and decreases levels of BPOS and SOCA.

Effect of morphine and M-cholinoceptor blocking drugs on human sphincter of Oddi during choledochofiberscopy manometry.

OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and the antagonism of anticholinergic agents against morphine. METHODS: The action of these drugs on the sphincter of Oddi (SO) was evaluated by means of choledochofiberscopy manometry in 40 operated patients with T-tube. The patients were divided randomly into 4 groups: anisodamine, atropine, buscopan, and control. The following data were recorded: duodenal pressure (DP), basal pressure of the sphincter of Oddi (BPSO), contractive amplitude of the sphincter of Oddi (CASO), contractive frequency of the sphincter of Oddi (CFSO), contractive duration of the sphincter of Oddi (CDSO), and pressure of the common bile duct (PCBD). Both morphine and anticholinergic agents were given intramuscularly. RESULTS: After injection of 10 mg morphine, BPSO, CASO, CFSO, and PCBD increased significantly. After injection of 15 mg anisodamine or 0.75 mg atropine, CASO, BPSO declined obviously, and after injection of 20 mg buscopan, CASO, BPSO, CFSO declined obviously, but in anisodamine, atropine and buscopan groups, they differed insignificantly. CONCLUSIONS: The results illustrate that SO manometry via choledochofiberscopy is a new method for SO dynamic study. Morphine can increase DP, BPSO, CASO, PCBD, but anisodamine atropine and buscopan can antagonize the effect of morphine.