Treatment of functional dyspepsia in Chinese adult patients with domperidone: A multicenter, randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: This pilot study aimed to evaluate the efficacy and safety of domperidone for the treatment of Chinese patients with functional dyspepsia (FD) who were diagnosed according to the Rome IV criteria and to identify the FD subtypes that potentially responded better to domperidone. METHODS: This multicenter prospective study was conducted in China from August 2018 to July 2020, consisting of a 1-week screening phase and a 2-week double-blind treatment phase. Participants were randomized to receive domperidone 10 mg or matching placebo tablets thrice daily for 14 days. The primary end-point was the overall treatment effect (OTE) response rate after 2-week therapy. RESULTS: Altogether 160 patients were included, with 80 patients in each group. The OTE response rate after 2-week therapy was significantly higher for domperidone compared with placebo (60.7% vs 46.0%; relative risk [RR] 1.318, 95% confidence interval [CI] 0.972-1.787). Moreover, the OTE response rate after 2-week domperidone or placebo treatment was 60.3% versus 54.9% for postprandial distress syndrome (PDS) (RR 1.098, 95% CI 0.750-1.607) and 60.6% versus 35.2% for overlapping PDS-epigastric pain syndrome (EPS) (RR 1.722, 95% CI 0.995-2.980). Adverse events were reported by seven patients in the domperidone group and 12 patients in the placebo group. None of the adverse events in the domperidone group were serious. CONCLUSION: Domperidone showed a positive pattern regarding OTE response rates after 2-week therapy compared to placebo in patients with FD, as well as in subtypes of PDS and overlapping PDS-EPS. No new safety issue was observed.

Are bowel symptoms and psychosocial features different in irritable bowel syndrome patients with abdominal discomfort compared to abdominal pain?

BACKGROUND: The Rome IV criteria eliminated abdominal discomfort for irritable bowel syndrome (IBS), which was previously included in Rome III. There are questions as to whether IBS patients with abdominal discomfort (seen in Rome III but not Rome IV) are different from those with abdominal pain (Rome IV). AIM: To compare bowel symptoms and psychosocial features in IBS patients diagnosed with Rome III criteria with abdominal discomfort, abdominal pain, and pain & discomfort. METHODS: We studied IBS patients meeting Rome III criteria. We administered the IBS symptom questionnaire, psychological status, and IBS quality of life. Patients were classified according to the predominant abdominal symptom associated with defecation into an only pain group, only discomfort group, and pain & discomfort group. We compared bowel symptoms, extraintestinal symptoms, IBS quality of life, psychological status and healthcare-seeking behaviors, and efficacy among the three groups. Finally, we tested risk factors for symptom reporting in IBS patients. RESULTS: Of the 367 Rome III IBS patients enrolled, 33.8% (124 cases) failed to meet Rome IV criteria for an IBS diagnosis. There were no meaningful differences between the pain group (n = 233) and the discomfort group (n = 83) for the following: (1) Frequency of defecatory abdominal pain or discomfort; (2) Bowel habits; (3) Coexisting extragastrointestinal pain; (4) Comorbid anxiety and depression; and (5) IBS quality of life scores except more patients in the discomfort group reported mild symptom than the pain group (22.9% vs 9.0%). There is a significant tendency for patients to report their defecatory and non-defecatory abdominal symptom as pain alone, or discomfort alone, or pain & discomfort (all P < 0.001). CONCLUSION: IBS patients with abdominal discomfort have similar bowel symptoms and psychosocial features to those with abdominal pain. IBS symptoms manifesting abdominal pain or discomfort may primarily be due to different sensation and reporting experience.

Anorectal dysfunction in patients with mid-low rectal cancer after surgery: A pilot study with three-dimensional high-resolution manometry.

BACKGROUND: The quality of life in patients who develop low anterior resection syndrome (LARS) after surgery for mid-low rectal cancer is seriously impaired. The underlying pathophysiological mechanism of LARS has not been fully investigated. AIM: To assess anorectal function of mid-low rectal cancer patients developing LARS perioperatively. METHODS: Patients diagnosed with mid-low rectal cancer were included. The LARS score was used to evaluate defecation symptoms 3 and 6 mo after anterior resection or a stoma reversal procedure. Anorectal functions were assessed by three-dimensional high resolution anorectal manometry preoperatively and 3-6 mo after surgery. RESULTS: The study population consisted of 24 patients. The total LARS score was decreased at 6 mo compared with 3 mo after surgery (P < 0.05), but 58.3% (14/24) lasted as major LARS at 6 mo after surgery. The length of the high-pressure zone of the anal sphincter was significantly shorter, the mean resting pressure and maximal squeeze pressure of the anus were significantly lower than those before surgery in all patients (P < 0.05), especially in the neoadjuvant therapy group after surgery (n = 18). The focal pressure defects of the anal canal were detected in 70.8% of patients, and those patients had higher LARS scores at 3 mo postoperatively than those without focal pressure defects (P < 0.05). Spastic peristaltic contractions from the new rectum to anus were detected in 45.8% of patients, which were associated with a higher LARS score at 3 mo postoperatively (P < 0.05). CONCLUSION: The LARS score decreases over time after surgery in the majority of patients with mid-low rectal cancer. Anorectal dysfunctions, especially focal pressure defects of the anal canal and spastic peristaltic contractions from the new rectum to anus postoperatively, might be the major pathophysiological mechanisms of LARS.

Efficacy and safety of lubiprostone for the treatment of functional constipation in Chinese adult patients: A multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Functional constipation is a gastrointestinal disorder prevalent around the world. Lubiprostone is the first locally acting type-2 chloride channel activator to be used for treating constipation. This study aimed to evaluate the efficacy and safety of lubiprostone in Chinese adults with functional constipation. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. Patients with functional constipation were randomized to receive either lubiprostone (24 mcg twice daily) or placebo for 4 weeks. The primary end-point was the frequency of spontaneous bowel movements (SBMs) during the first week of treatment. The secondary end-points included the median time of the first SBM, SBM frequency at weeks 2, 3 and 4, weekly response rate of SBMs, the stool consistency score and average number of complete spontaneous bowel movements (CSBMs) per week. RESULTS: In total, 259 patients were randomized, with 130 in the lubiprostone group and 129 in the placebo group. SBM frequency was higher in the lubiprostone group (4.88 ± 4.09/wk) than that in the placebo group (3.22 ± 2.01/wk) at week 1 (P < 0.0001). SBM frequency was also higher in the lubiprostone group at weeks 2, 3 and 4. The average number of CSBMs and the stool consistency score in the lubiprostone group were significantly higher than that in the placebo group at each week. No drug-related serious adverse events (AEs) occurred. The most commonly reported AE was nausea. CONCLUSION: Lubiprostone was superior to placebo in treating Chinese patients with functional constipation, together with good safety profile.

Ethnic differences in genetic polymorphism associated with irritable bowel syndrome.

Genetic polymorphism is associated with irritable bowel syndrome (IBS) in terms of susceptibility and clinical manifestations. Previous studies have shown that genetic polymorphism might play a key role in the onset and progression of IBS by modulating components of its pathogenesis such as the gut-brain axis, gastrointestinal motility, inflammatory activity, and immune status. Although underlying pathophysiological mechanisms have not been fully clarified, the potential ethnic differences that are present in worldwide genetic studies of IBS deserve attention. This review surveyed numerous studies focusing on IBS-associated single nucleotide polymorphisms, and investigated the ethnic disparities revealed by them. The results demonstrate the need for more attention on ethnic factors in IBS-related genetic studies. Taking ethnic backgrounds into accounts and placing emphasis on disparities potentially ascribed to ethnicity could help lay a solid and generalized foundation for transcultural, multi-ethnic, or secondary analyses in IBS, for example, a meta-analysis. Broader genetic studies considering ethnic factors are greatly needed to obtain a better understanding of the pathophysiological mechanisms of IBS and to improve the prevention, intervention, and treatment of this disease.

Effect of high-fat, standard, and functional food meals on esophageal and gastric pH in patients with gastroesophageal reflux disease and healthy subjects.

OBJECTIVES: To investigate the effects of different test meals on esophageal and intragastric pH in patients with gastroesophageal reflux disease (GERD) and healthy subjects and to demonstrate the relationship between esophageal acid exposure (EAE) and gastric pH. METHODS: We enrolled patients with reflux esophagitis (RE; n = 15), nonerosive reflux disease (NERD; n = 12) and healthy subjects (n = 10). Four pH electrodes were used to monitor the pH of the distal esophagus, upper border of the lower esophageal sphincter, gastric fundus, and gastric body for 26 hours. Isocaloric and isovolumetric high-fat, standard, and functional meals were supplied randomly to the participants. The EAE and gastric acidity of each meal in fasting and postprandial states were compared. RESULTS: High-fat meals significantly increased postprandial EAE in patients with RE and NERD. EAE was higher after a high-fat meal than after a standard or functional food meals at the fourth hour postprandially in patients with RE (P < 0.05). Patients with NERD reported fewer symptoms after a functional food meal than after high-fat and standard meals (0 [interquartile range {IQR} 0-1] vs 1 [IQR 0-2] vs 3 [IQR 1-4], P = 0.014). Compared with high-fat and standard meals, functional food meal significantly decreased gastric acidity in patients with RE. EAE was significantly related to gastric acidity in patients with RE. CONCLUSIONS: High-fat meals increased EAE in patients with RE and NERD. Functional food could serve as adjuvant therapy in GERD patients. EAE was related to gastric acidity in RE patients.

Predictors of healthcare-seeking behavior among Chinese patients with irritable bowel syndrome.

AIM: To analyze predictors of healthcare-seeking behavior among Chinese patients with irritable bowel syndrome (IBS) and their satisfaction with medical care. METHODS: Participating patients met IBS Rome III criteria (excluding those with organic diseases) and were enrolled in an IBS database in a tertiary university hospital. Participants completed IBS questionnaires in face-to-face interviews. The questionnaires covered intestinal and extra-intestinal symptoms, medical consultations, colonoscopy, medications, and self-reported response to medications during the whole disease course and in the past year. Univariate associations and multivariate logistic regression were used to identify predictors for frequent healthcare-seeking behavior (≥ 3 times/year), frequent colonoscopies (≥ 2 times/year), long-term medications, and poor satisfaction with medical care. RESULTS: In total, 516 patients (293 males, 223 females) were included. Participants' average age was 43.2 ± 11.8 years. Before study enrollment, 55.2% had received medical consultations for IBS symptoms. Ordinary abdominal pain/discomfort (non-defecation) was an independent predictor for healthcare-seeking behavior (OR = 2.07, 95%CI: 1.31-3.27). Frequent colonoscopies were reported by 14.7% of patients (3.1 ± 1.4 times per year). Sensation of incomplete evacuation was an independent predictor for frequent colonoscopies (OR = 2.76, 95%CI: 1.35-5.67). During the whole disease course, 89% of patients took medications for IBS symptoms, and 14.7% reported they were satisfied with medical care. Patients with anxiety were more likely to report dissatisfaction with medical care (OR = 2.08, 95%CI: 1.20-3.59). In the past year, patients with severe (OR = 1.74, 95%CI: 1.06-2.82) and persistent (OR = 1.66, 95%CI: 1.01-2.72) IBS symptoms sought medical care more frequently. CONCLUSION: Chinese patients with IBS present high rates of frequent healthcare-seeking behavior, colonoscopies, and medications, and low satisfaction with medical care. Intestinal symptoms are major predictors for healthcare-seeking behavior.

The impact of soluble dietary fibre on gastric emptying, postprandial blood glucose and insulin in patients with type 2 diabetes.

Dietary fibre plays an important role in controlling postprandial glycemic and insulin response in diabetic patients. The intake of dietary fibre has been shown to delay the gastric emptying in healthy subjects. The relationship between gastric emptying and postprandial blood glucose in diabetic patients with fibre-load liquids needs to be investigated. To investigate the impact of soluble dietary fibre (SDF) on gastric emptying, postprandial glycemic and insulin response in patients with type 2 diabetes. 30 patients with type 2 diabetes (DM) and 10 healthy subjects (HS) matched for gender and age were randomized to receive SDF-free liquid (500 mL, 500 Kcal) and isoenergetic SDF liquid (oat ß-glucan 7.5 g, 500 mL, 500 Kcal) on two separate days based on a cross-over with 6-day wash-out period. Gastric emptying was monitored by ultrasonography at intervals of 30 min for 2 hours. Fasting and postprandial blood was collected at intervals of 30-60 min for 180 min to determine plasma glucose and insulin. Proximal gastric emptying was delayed by SDF-treatment both in DM (p=0.001) and HS (p=0.037). SDF resulted in less output volume in the distal stomach in DM (p<0.05). SDF decreased postprandial glucose (p=0.001) and insulin (p=0.001) in DM subjects. Postprandial glucose (r=-0.547, p=0.047) and insulin (r=-0.566, p=0.004) were negatively correlated with distal emptying of SDF in DM subjects. Distal gastric emptying was delayed significantly in DM subjects with HbA1c levels ≥6.5% (p=0.021) or with complications (p=0.011) by SDF, respectively. SDF improved postprandial glycaemia which was related to slowing of gastric emptying.

Diagnosis of functional constipation: agreement between Rome III and Rome II criteria and evaluation for the practicality.

OBJECTIVE: To investigate the agreement between Rome III and Rome II criteria for diagnosing functional constipation (FC) and to evaluate the accuracy of each constipation symptom for FC diagnosis. METHODS: Patients with chronic constipation underwent rigorous biochemical and endoscopic/imaging tests to exclude organic and metabolic diseases. The questionnaires including general information, constipation symptoms, and the most troublesome constipation symptoms were completed in a face-to-face survey. The accuracy of constipation symptoms for FC diagnosis was examined using the likelihood ratio. RESULTS: Among 184 patients (43 males and 141 females) with chronic constipation, 166 (90.2%) met Rome II criteria and 174 (94.6%) met Rome III criteria for FC, while 166 met both criteria. There was a good diagnostic agreement between the two sets of criteria, with a kappa value of 0.69 and the overall agreement rate was 95.7% (P < 0.001). Based on Rome III criteria, the most accurate symptom for FC diagnosis was sensation of anorectal blockage, followed by straining during defecation and infrequent bowel movements. The most troublesome symptoms reported by patients were lumpy or hard stools, straining during defecation, sensation of incomplete evacuation. More patients indicated that 'the symptoms in the past 3 months' was better than 'those within the past one year' to reflect their constipation (36.7% vs 6.0%, P < 0.001). CONCLUSIONS: There is good agreement between Rome III and Rome II criteria for FC diagnosis. Rome III criteria are more practical than Rome II criteria for Chinese patients.

Gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia.

AIM: To study the evolution of gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia (FD). METHODS: From June 2008 to November 2009, a total of 1049 patients with FD (65.3% female, mean age 42.80 ± 11.64 years) who visited the departments of gastroenterology in Wuhan, Beijing, Shanghai, Guangzhou, and Xi'an, China were referred for this study. All of the patients fulfilled the Rome III criteria for FD. Baseline demographic data, dyspepsia symptoms, anxiety, depression, sleep disorder, and drug treatment were assessed using self-report questionnaires. Patients completed questionnaires at baseline and after 1, 3, 6 and 12 mo follow-up. Comparison of dyspepsia symptoms between baseline and after follow-up was explored using multivariate analysis of variance of repeated measuring. Multiple linear regression was done to examine factors associated with outcome, both longitudinally and horizontally. RESULTS: Nine hundred and forty-three patients (89.9% of the original population) completed all four follow-ups. The average duration of follow-up was 12.24 ± 0.59 mo. During 1-year follow-up, the mean dyspeptic symptom score (DSS) in FD patients showed a significant gradually reduced trend (P < 0.001), and similar differences were found for all individual symptoms (P < 0.001). Multiple linear regression analysis showed that sex (P < 0.001), anxiety (P = 0.018), sleep disorder at 1-year follow-up (P = 0.019), weight loss (P < 0.001), consulting a physician (P < 0.001), and prokinetic use during 1-year follow-up (P = 0.035) were horizontally associated with DSS at 1-year follow-up. No relationship was found longitudinally between DSS at 1-year follow-up and patient characteristics at baseline. CONCLUSION: Female sex, anxiety, and sleep disorder, weight loss, consulting a physician and prokinetic use during 1-year follow-up were associated with outcome of FD.

Temperature can influence gastric accommodation and sensitivity in functional dyspepsia with epigastric pain syndrome.

BACKGROUND: Functional dyspepsia-epigastric pain syndrome (FD-EPS) is characterized pathophysiologically by visceral hypersensitivity, but the effect of the temperature stimulation on gastric function has been seldom studied. AIM: The purpose of this study was to investigate the effects of liquid nutrients at different temperatures on the gastric accommodation, sensitivity, and gastric-wall compliance of healthy subjects (HS) and FD-EPS patients. METHODS: Ten FD-EPS patients (Roma III criteria) and ten HS were recruited into the study. Intragastric pressure (IGP) and gastric perfusion were measured and compared following the administration of liquid nutrients at 37 °C on day 1 and at 8 °C on day 2. RESULTS: Seven patients developed abdominal discomfort or abdominal pain after being given cold liquid nutrient. The administration of liquid nutrient at 8 °C resulted in an increase of IGP in HS (P=0.044), a significant decrease in gastric perfusion (P<0.0001), a marked increase in IGP (P=0.015), and a dramatic reduction in gastric wall compliance (P=0.012) in patients compared to the effects of liquid nutrient at 37 °C. In addition, IGP in patients was lower than that in HS at 37 °C liquid nutrient (P=0.036), and the gastric perfusion volume in patients at maximal satiety was also significantly reduced at 8 °C liquid nutrient compared with HS (P=0.017). CONCLUSIONS: Cold stimulation can increase the IGP in HS and FD-EPS patients, elevate the visceral sensitivity and reduce the gastric volume of FD-EPS patients. FD-EPS patients who are sensitive to cold may develop epigastric discomfort or pain.

[Multi-centered stratified clinical studies for psychological and sleeping status in patients with chronic constipation in China].

OBJECTIVE: To survey the emotional and sleeping status of patients with chronic constipation (CC) and analyze the relationship between psychological status and constipated symptoms. METHODS: From January 2009 to April 2010, 5 centers and 25 stratified hospitals were selected as the representatives of different regions of mainland China. The CC questionnaires including constipated symptoms, emotional and sleeping status, previous treatments and self-reported impact of constipation on health status, etc. Questionnaires were completed by well-trained physicians or investigators during face-to-face interviews. CC was diagnosed in accordance with the Rome III criteria. RESULTS: A total of 909 valid questionnaires analyzed. There were 258 males and 651 females with a mean age of (49 ± 19) years. 41.5% (377 cases) reported "tense feelings" and 38.3% (348 cases) "felt downcast" over the past 3 months. The patients feeling tense and(or) downcast "frequently" and "most of time" were around 11.3% (103 cases) and 9.4% (85 cases). And 43.8% (398 cases) patients reported sleeping disorders over the past 3 months. Regional differences existed in the comorbidities of psychological and sleeping disorders in CC patients, especially in those from tertiary hospitals. And it was the highest in Beijing area for tense feelings and downcast. The sleeping disorders were the most common in the patients from secondary hospitals, of which 66.1% (37/56) and 65.0% (39/60) were from Wuhan and Xi'an respectively. They were higher than Beijing and Guangzhou (39.7% (23/58), 29.0% (9/31), all P = 0.001). The patients from rural primary clinics suffered more sleeping disorders than those from urban primary cares (P = 0.026). About 35.0% (318 cases) and 28.4% (258 cases) patients reported their constipation was related with emotional and sleeping disorders. The comorbidities of psychological and sleeping disorders were more common in severe constipated patients than mild and moderate counterparts and resulted in more hospital visits (both P = 0.000). CONCLUSIONS: The CC patients often have the comorbidities of psychological and sleeping disorders with regional differences. The patients from the hospitals at various levels may present different spectrums of comorbidities of psychological and sleeping disorders. And the severity of CC influences the moods, sleeps and hospital visits.

[Symptomatic features and psychosocial factors in patients with belching disorders].

OBJECTIVE: To explore the symptomatic features and psychosocial factors in patients with belching disorders. METHODS: At Peking Union Medical College Hospital Outpatient Clinic from September 2010 to January 2011, 21 consecutive patients with repetitive belching were profiled by symptom questionnaires, including general demographics, spectrum of symptoms, disease course, predisposing factors, previous treatment, psychosocial factors, mental status and personality traits, etc. Pearson's correlation analysis and exact probability were used. RESULTS: Among them, 20 patients fulfilled the Rome III criteria of belching disorders. There were 5 males and 15 females with an age range of (49 ± 10) years. Among them, the belching patterns were daily (n = 18), meal-related (n = 16), spontaneous (n = 15), controllable (n = 16) and symptomatic overlapping (n = 17). The most common symptoms were functional dyspepsia (FD) (n = 13) and gastroesophageal reflux disease (GERD) (n = 11). Sixteen patients experienced mental stimulation/negative events and 13 patients were related to family tension, work stress and overwork. There were 12 patients with anxiety and/or depression and 8 with neurotic personality. The number of overlapping symptoms was related to anxiety states (r = 0.47, t = 2.14, P < 0.05). But the severity of belching was unrelated to with or without depression and anxiety state (P = 0.096). CONCLUSIONS: There are a variety of clinical manifestations in patients with belching disorders. Belching disorders is often related to emotional change and environmental stress and accompanied by abnormal mental and personality characteristics. Belching may be an abnormal behavior reaction to gastrointestinal discomfort symptoms. The psychological and social factors probably play an important role in the pathogenesis of belching disorders.

Chinese National Consensus on diagnosis and management of Barrett's esophagus (BE): revised edition, June 2011, Chongqing, China.

To standardize the diagnosis and management of Barrett's esophagus (BE) in China, the Chinese Society of Gastroenterology convened the Second National Conference on BE in June 2011 in Chongqing, China. After intense discussion among experts in this field and an extensive review of the literature, a revised consensus on the diagnosis and management of BE was generated.

[A clinical analysis of 61 cases of protein-losing enteropathy].

OBJECTIVE: To increase the understanding in protein-losing enteropathy (PLE). METHODS: Sixty-one PLE patients were enrolled in the study and the clinical characteristics, complicated disease, diagnosis and treatment were analyzed. RESULTS: The age of the patients was 16 - 77 (40 ± 15) years, and the gender ratio was 35:26 (female:male). The main clinical manifestations were bilateral lower limb edema in 51 cases, ascites in 41 cases, bilateral pleural effusion in 23 cases, pericardial effusion in 13 cases, abdominal pain in 16 cases and diarrhea in 33 cases. The prominent abnormality in laboratory examinations was hypoalbuminemia. The underlying diseases include systemic lupus erythematosus (SLE) in 28 cases, intestinal lymphangiectasia in 12 cases, hepatic cirrhosis in 5 cases, heart diseases in 5 cases, Crohn's disease in 3 cases, membranous nephropathy in 2 cases, Budd-Chiari syndrome in 1 case. Four cases happened after abdominal operation and 1 case after radiation therapy of gastric cardia cancer. Thirty-seven cases were diagnosed by (99)Tc(m)-labelled human serum albumin scintigraphy and 24 cases were diagnosed clinically. Treatment was focused on underlying diseases. The clinical manifestations in 21 cases of SLE improved after SLE was controlled. In 2 cases of intestinal lymphangiectasia and one with Crohn's disease, the clinical manifestations improved after surgery. The other patients had no improvement. CONCLUSIONS: PLE was not uncommon in clinical practice. Its predominant characteristics were severe hypoalbuminemia, edema and dropsy of serous cavity. PLE can complicate other diseases such as SLE, intestinal lymphangiectasia. Treatment should be focused on primary disease.

Elevated expression of c-fos in central nervous system correlates with visceral hypersensitivity in irritable bowel syndrome (IBS): a new target for IBS treatment.

BACKGROUND AND AIMS: Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its molecular mechanisms are still poorly understood. c-fos is a well-established marker of cell activation. Accumulating evidence demonstrates that norepinephrine (NE) system is dysregulated in IBS; however, very little is known on its mechanism. It is our hypothesis that elevated expression of c-fos in central nervous system (CNS) correlates with visceral hypersensitivity in rat model of IBS. Furthermore, we explored the changes of NE system in IBS patients. METHODS: The rat model of IBS was induced by heterotypic chronic and acute stress. Tissues obtained from rat model were analyzed for c-fos levels in CNS (frontal lobe, hippocampus, cornu dorsale) and colon by immunohistochemistry. Real-time reverse transcription polymerase chain reaction was used to detect tyrosine hydroxylase (TH) in the colonic tissues obtained from IBS patients. RESULTS: The rat model of IBS was associated with increased expression of c-fos in different parts of CNS (P = 0.001, P = 0.002, and P = 0.002, respectively), but normal in colon (P = 0.207). The clinical parameters (colonic motility and sensation) of rat model were significantly correlated with elevated c-fos in CNS (P < 0.05). Enterochromaffin cells and serotonin in colon were related to the elevated c-fos in CNS (P < 0.05). The TH messenger ribonucleic acid (mRNA level of IBS-D patients was almost four times as much as that of controls. CONCLUSIONS: Elevated expression of c-fos in CNS might be one of key mechanisms in etiology of IBS. Therefore, regulation of CNS activation could be a major targeting effect when treating IBS patients.

[Evaluation of gastric sensitivity and accommodation by simultaneous determination of intra-gastric pressure in liquid load test].

OBJECTIVE: To extensively evaluate the method of simultaneous determination of intra-gastric pressure (IGP) in liquid load test (LLT) in healthy subjects (HS) and patients with functional dyspepsia (FD). METHODS: Forty HS and 67 FD patients (Rome III criteria) were recruited. All subjects were surveyed with regards to demographic characteristics, features of FD symptom spectrum and psychological status (Zung anxiety and depression scale). And the test of simultaneous determination of IGP in LLT was conducted. Finally all the data were collected and analyzed. RESULTS: HS group: no statistical difference was found in IGP divided by gender, age and body mass index (P > 0.05). The coefficient of variation of IGP at 15.3% was less than that of maximal intake volume (MIV). Twice repeated studies showed quite similar results and the linear interclass correlation coefficient of IGP was 0.806 (P = 0.002). As to the range of normal value from HS, the proportion of gastric hypersensitivity accounted for 35.0% and impaired accommodation for 25.0%. FD group: no statistical difference was found in IGP and MIV divided by gender, age and FD symptom subtype (P > 0.05). FD patients with abnormal psychological status had a lower IGP (4.2 +/- 1.2 mm Hg vs 4.8 +/- 1.1 mm Hg, P = 0.042) and MIV (450 +/- 138 ml vs 526 +/- 121 ml, P = 0.034) than those with normal status. IGP was not related to epigastric pain, epigastric burning, postprandial fullness or early satiation (F = 1.635, P = 0.190). Early satiation was significantly related to MIV (F = 4.682, P = 0.031; correlation coefficient was -6.8, P = 0.033). No statistical difference was found in gastric compliance among HS, all FD patients, patients with hypersensitivity or impaired accommodation (P > 0.05). The test had an excellent safety and tolerability. CONCLUSIONS: The method of simultaneous determination of IGP in LLT can differentiate gastric hypersensitivity from impaired accommodation. And it has an excellent feasibility, safety and reliability.

[Investigation of female chronic constipation: a multi-center cross-sectional clinical study].

OBJECTIVE: To analyze the characteristics of female chronic constipation (CC), contributing factors of severe constipation and the correlation between female CC and pelvic floor dysfunction (PFD) so as to provide references for the diagnosis and treatment of female CC. METHODS: Five hundred and sixty-one CC outpatients meeting Rome III criteria at clinics of gastroenterology from ten Beijing hospitals were recruited during March-May 2007. After data input and verification, formulated the standard of severe CC. RESULTS: The peak age of CC onset was 20 - 29 years in female patients while 60 - 69 years in male patients. F:M = 3.04:1. A wide range of CC symptoms were present and straining was the most common one (381, 76%). However, a significant difference between females and males was shown in defecation by manually pelvic floor supporting (female 26/69, 38%, male 3/20, 15% in manual assisted defecation, P < 0.05) and urinary incontinence when coughing (female 95/422, 22.5%, male 13/139, 9.4%, P < 0.01). Severity of CC, its manifestations and pelvic floor dysfunction were closely correlated with frequencies of pregnancy and delivery. CONCLUSION: Owing to anatomic features of female pelvic floor and physiological nature of pregnancy and delivery, the early onset of CC in female patients should attract sufficient attention of multi-disciplinary clinicians.

Platelet-activating factor in the enteric nervous system of the guinea pig small intestine.

Platelet-activating factor (PAF) is a proinflammatory mediator that may influence neuronal activity in the enteric nervous system (ENS). Electrophysiology, immunofluorescence, Western blot analysis, and RT-PCR were used to study the action of PAF and the expression of PAF receptor (PAFR) in the ENS. PAFR immunoreactivity (IR) was expressed by 6.9% of the neurons in the myenteric plexus and 14.5% of the neurons in the submucosal plexus in all segments of the guinea pig intestinal tract as determined by double staining with anti-human neuronal protein antibody. PAFR IR was found in 6.1% of the neurons with IR for calbindin, 35.8% of the neurons with IR for neuropeptide Y (NPY), 30.6% of the neurons with IR for choline acetyltransferase (ChAT), and 1.96% of the neurons with IR for vasoactive intestinal peptide (VIP) in the submucosal plexus. PAFR IR was also found in 1.5% of the neurons with IR for calbindin, 51.1% of the neurons with IR for NPY, and 32.9% of the neurons with IR for ChAT in the myenteric plexus. In the submucosal plexus, exposure to PAF (200-600 nM) evoked depolarizing responses (8.2 +/- 3.8 mV) in 12.4% of the neurons with S-type electrophysiological behavior and uniaxonal morphology and in 12.5% of the neurons with AH-type electrophysiological behavior and Dogiel II morphology, whereas in the myenteric preparations, depolarizing responses were elicited by a similar concentration of PAF in 9.5% of the neurons with S-type electrophysiological behavior and uniaxonal morphology and in 12.0% of the neurons with AH-type electrophysiological behavior and Dogiel II morphology. The results suggest that subgroups of secreto- and musculomotor neurons in the submucosal and myenteric plexuses express PAFR. Coexpression of PAFR IR with ChAT IR in the myenteric plexus and ChAT IR and VIP IR in the submucosal plexus suggests that PAF, after release in the inflamed bowel, might act to elevate the excitability of submucosal secretomotor and myenteric musculomotor neurons. Enhanced excitability of motor neurons might lead to a state of neurogenic secretory diarrhea.

Angiotensin receptors and actions in guinea pig enteric nervous system.

Actions of ANG II on electrical and synaptic behavior of enteric neurons in the guinea pig small intestine were studied. Exposure to ANG II depolarized the membrane potential and elevated neuronal excitability. The number of responding neurons was small, with responses to ANG II in 32% of submucosal neurons and 25% of myenteric neurons. Hyperpolarizing responses were evoked by ANG II in 45% of the neurons. The hyperpolarizing responses were suppressed by alpha2-noradrenergic receptor antagonists, which suggested that the hyperpolarizing responses reflected stimulation of norepinephrine release from sympathetic neurons. Exposure to ANG II enhanced the amplitude and prolonged the duration of noradrenergic inhibitory postsynaptic potentials and suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. The selective ANG II(1) receptor (AT1R) antagonists, ZD-7115 and losartan, but not a selective AT2R antagonist (PD-123319), suppressed the actions of ANG II. Western blot analysis and RT-PCR confirmed expression of AT1R protein and the mRNA transcript for the AT1R in the enteric nervous system. No expression of AT2R protein or mRNA was found. Immunoreactivity for AT1R was expressed by the majority of neurons in the gastric antrum and small and large intestine. AT1R immunoreactivity was coexpressed with calbindin, choline acetyltransferase, calretinin, neuropeptide Y, and nitric oxide synthase in subpopulations of neurons. The results suggest that formation of ANG II might have paracrine-like actions in the enteric nervous system, which include alterations in neuronal excitability and facilitated release of norepinephrine from sympathetic postganglionic axons. The enhanced presence of norepinephrine is expected to suppress fast and slow excitatory neurotransmission in the enteric microcircuits and to suppress neurogenic mucosal secretion.