Spinal microglia initiate and maintain hyperalgesia in a rat model of chronic pancreatitis.

BACKGROUND & AIMS: The chronic, persistent pain associated with chronic pancreatitis (CP) has many characteristics of neuropathic pain, initiated and maintained by the activation of spinal microglia. We investigated whether activated microglia in the thoracic spinal cord contribute to chronic pain in a rat model of CP. METHODS: CP was induced in Sprague-Dawley rats by an intraductal injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the measurement of mechanical sensitivity of the abdomen and nocifensive behavior to electrical stimulation of the pancreas. Three weeks after induction of CP, spinal samples were analyzed by immunostaining and immunoblot analyses for levels of CD11 (a marker of microglia, determined with the antibody OX42) and phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated protein kinase signaling). We examined the effects of minocycline (inhibitor of microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia in rats with CP. RESULTS: Rats with CP had increased sensitivity and nociceptive behaviors to mechanical probing of the abdomen and electrical stimulation of the pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained activated microglia (based on increased staining with OX42), with an ameboid appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42-positive cells. Intrathecal injection of minocycline reversed and prevented the increase of nocifensive behaviors and levels of P-p38 in rats with CP. Fractalkine induced hyperalgesia in rats without CP, which was blocked by minocycline. CONCLUSIONS: Activated spinal microglia have important roles in maintaining and initiating chronic pain in a rat model of CP. Microglia might be a target for treatment of hyperalgesia caused by pancreatic inflammation.

Elevated serum dopamine increases while coffee consumption decreases the occurrence of reddish streaks in the intact stomach.

BACKGROUND AND AIM: Reddish streaks in an intact stomach are an endoscopic feature of duodenogastric reflux. This study aimed to identify which factors are associated with gastric reddish streaks and thus help prevent mucosal damage from duodenogastric reflux. METHODS: Demographic data, personal habits, stressful life events, and psychological distress were compared between subjects with only gastric reddish streaks and those with normal mucosa who underwent upper gastrointestinal endoscopy as part of a self-paid physical checkup. Stress hormones dopamine and cortisol were also checked by high-performance liquid chromatography and radioimmunoassay methods respectively. RESULTS: There were 95 subjects with gastric reddish streaks and 52 subjects with normal mucosa. No significant differences in age, gender, blood groups, education levels, marital status, religion, aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, smoking habit, alcohol consumption, and intake of tea was found between the two groups, but intake of coffee was borderline more common in subjects with normal mucosa (38.5% vs 22.1%, P = 0.055). Subjects with gastric reddish streaks had lower Helicobacter pylori infection rate (37.8% vs 19.3%, P < 0.05). There were no significant differences in psychological distress and stressful life events between the two groups. Multivariate analysis shows that serum dopamine concentrations (odds ratio = 11.31, 95% confidence interval = 2.11-60.48, P = 0.005) and being without the consumption of coffee (odds ratio = 2.97, 95% confidence interval = 1.27-6.94, P = 0.012) were associated with gastric reddish streaks. CONCLUSIONS: Elevated serum dopamine and less coffee consumption are associated with gastric reddish streaks. These findings implicate that increased dopamine level plays a role for abnormal duodenogastric reflux.

Additional corpus biopsy enhances the detection of Helicobacter pylori infection in a background of gastritis with atrophy.

BACKGROUND: The best sites for biopsy-based tests to evaluate H. pylori infection in gastritis with atrophy are not well known. This study aimed to evaluate the site and sensitivity of biopsy-based tests in terms of degree of gastritis with atrophy. METHODS: One hundred and sixty-four (164) uninvestigated dyspepsia patients were enrolled. Biopsy-based tests (i.e., culture, histology Giemsa stain and rapid urease test) and non-invasive tests (anti-H. pylori IgG) were performed. The gold standard of H. pylori infection was defined according to previous criteria. The sensitivity, specificity, positive predictive rate and negative predictive rate of biopsy-based tests at the gastric antrum and body were calculated in terms of degree of gastritis with atrophy. RESULTS: The prevalence rate of H. pylori infection in the 164 patients was 63.4%. Gastritis with atrophy was significantly higher at the antrum than at the body (76% vs. 31%; p<0.001). The sensitivity of biopsy-based test decreased when the degree of gastritis with atrophy increased regardless of biopsy site (for normal, mild, moderate, and severe gastritis with atrophy, the sensitivity of histology Giemsa stain was 100%, 100%, 88%, and 66%, respectively, and 100%, 97%, 91%, and 66%, respectively, for rapid urease test). In moderate to severe antrum or body gastritis with atrophy, additional corpus biopsy resulted in increased sensitivity to 16.67% compare to single antrum biopsy. CONCLUSIONS: In moderate to severe gastritis with atrophy, biopsy-based test should include the corpus for avoiding false negative results.

Asian consensus report on functional dyspepsia.

BACKGROUND AND AIM: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared with the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. METHODS: Consensus team members were selected from Asian experts and consensus development was carried out by using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using a keypad voting system. A grade of evidence and strength of recommendation were applied to each statement according to the method of the GRADE Working Group. RESULTS: Twenty-nine consensus statements were finalized, including seven for definition and diagnosis, five for epidemiology, nine for pathophysiology, and eight for management. Algorithms for diagnosis and management of functional dyspepsia were added. CONCLUSIONS: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.

Placebo effect in patients with irritable bowel syndrome.

The placebo effect has evolved from being considered a nuisance factor in clinical research to a hot topic of scientific investigation. New research findings show that a placebo has real psychobiological and biological effects that are attributable to the overall therapeutic context. Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract that shows a significant placebo response of around 40­50% among different clinical trials.A positive patient-practitioner relationship can enhance the placebo effect in IBS patients.Emerging literature using functional brain imaging has started to document the neuronal changes associated with the placebo phenomenon in IBS patients, showing aberrant neural network during visceral placebo analgesia when compared to controls. Further promotion and integration of laboratory and clinical research are encouraged to advance the understanding of placebo mechanisms in IBS patients.

The clinical significances of irritable bowel syndrome in Taiwan.

BACKGROUND AND AIM: According to the Rome III definition, irritable bowel syndrome (IBS) has been a biopsychosocial dysfunction. We tried to know whether the IBS clinical manifestations were comparable to other countries. METHOD: We have reviewed the IBS publications in Taiwan, thus its clinical significances are summarized and compared to others. RESULTS: Among a selected population of paid physical checkup, the Rome I & II criteria defined prevalences were 17.5% and 22.1%, respectively without an observed female predominance. However, female was a factor leading to constipation predominant IBS (C-IBS). Taiwan IBS patients did excessively consume society resource in terms of physician visits and absenteeism. They also had more chance of cholecystectomy, whereas normal appendix was often found in case of appendectomy. Overlapping extra-colonic manifestations, e.g. dyspepsia and lower urinary tract symptoms were common. Helicobacter pylori infection and female gender were closely related to the coexisted dyspepsia. Various psychiatric disturbances were also confirmed here. Intestinal transit correlated well with bowel symptoms, e.g. slow in constipation but fast in diarrhea. Diminished cholinergic activity was observed among the C-IBS patients. Various agents including mebeverine, pinaverium, peppermint oil, smectitie and tegarserod did somewhat improve IBS symptoms. Unfortunately, the IBS knowledge was not well understood among the medical professionals. CONCLUSIONS: IBS is common in Taiwan, its impacts on the society are similarly observed while female gender often results in severe impacts. Disordered motility and cholinergic nervous system are likely some of its pathogeneses. Current recommended treatments are effectively demonstrated.

A radioimmunoassay for rat ghrelin: evaluation of method and effects of nonylphenol on ghrelin secretion in force-fed young rats.

Antiserum YJC 13-31 against the rat ghrelin conjugated to bovine serum albumin (BSA) was produced in the rabbit and a double antibody radioimmunoassay (RIA) for ghrelin has been developed. Characterization results of this antiserum revealed no cross-reaction with human growth hormone and somatostatin. Weak cross-reactions with insulin (0.1%), rat growth hormone (0.1%) and glucagon (0.3%) were observed, which scarcely interfered the assay system. The sensitivity of this RIA was 5 pg per assay tube. With the rat serum samples, the within-assay precision was 7.1% and the between-assay precision was 12.3%. The RIA was also available to detect the ghrelin in rat tissue extracts with good parallelism to the rat ghrelin standard. In application, the serum ghrelin and corticosterone levels in weaned rats were measured by RIA. Gavage of saline was sufficient to raise serum ghrelin from 2.6 +/- 0.18 to 6.7 +/- 0.7 ng/ml (P < 0.01). Gavage with nonylphenol (NP) suppressed the elevation of serum ghrelin levels in a dose-dependent manner. Besides, gavages of saline elevated the serum levels of corticosterone from 108.8 +/- 13.5 to 188.7 +/- 23.5 ng/ml (P < 0.01) but the elevation effects of corticosterone from gavages were overcome by NP in the low dose of 50 mg/kg. It can be speculated that ingestion of NP is harmful to young animals during growth and environmental adaptation.

Estrogen rapidly modulates 5-hydroxytrytophan-induced visceral hypersensitivity via GPR30 in rats.

BACKGROUND & AIMS: Sex hormones have been reported to modulate visceral hypersensitivity (VH). Estrogen regulates neurons not only by binding to estrogen receptors (ERalpha and ERbeta) to initiate transcription but also via the G-protein coupled receptor GPR30, which binds and rapidly mediates actions of estrogen. We examined the role of sex hormones in a VH model without colonic inflammation. METHODS: 5-Hydroxytryptophan (5HTP) was injected subcutaneously into awake female rats to induce VH; the 5HT3 antagonist (granisetron) or saline (control) were injected 30 minutes later. Immunohistochemistry was used to quantify calcitonin gene-related peptide-immunoreactive (CGRP-IR) neurons in the dorsal root ganglion (DRG). 5HTP-induced VH was evaluated in ovariectomized rats injected with 17beta-estradiol, progesterone, or both. ER alpha/beta agonist, GPR30 agonist, ER antagonist (ICI-182,780) or GPR30 antisense oligodeoxynucleotide were given to 5HTP-primed, estrogen-treated ovariectomized rats. RESULTS: Rats given 5HTP had increased VH that was inhibited by granisetron, accompanied by a decrease in CGRP-IR in the DRG. Ovariectomy eliminated 5HTP-induced VH, whereas estrogen and the combination of estrogen and progesterone, but not progesterone alone, restored the VH. The GPR30 agonist, but not the ERbeta agonist, rapidly restored VH. VH was preserved by coadministration of ICI-182,780 and estrogen but was absent after administration of the GPR30 antisense oligodeoxynucleotide. GPR30 colocalized with 5HT3 in DRG neurons; no significant inflammation occurred in colonic mucosa. CONCLUSIONS: In the absence of mucosal inflammation, estrogen can rapidly modulate 5HTP-induced VH. Loss of gonad hormones suppresses VH, whereas estrogen replacement restores it. Estrogen-mediated VH appears to act through GPR30.

Increasing trend of the incidence of esophageal squamous cell carcinoma, but not adenocarcinoma, in Taiwan.

Epidemiologic data on esophageal cancer in Asia are extremely limited. We examined temporal trends in the incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA) in Taiwan. Patients with esophageal cancer were identified from the Taiwan Cancer Registry between 1979 and 2003. Age-standardized incidences of ESCC and EA were calculated based on the national census and world standard population. Trends in incidence rates were estimated by calculating the annual percentage change (APC). The age-standardized incidence of ESCC increased progressively (from 1979-1983 to 1999-2003: 2.63 to 4.37 per 100,000-year), with an APC higher in male (3.27%, P < 0.0001) than that in female (1.23%, P = 0.03). Though the crude incidence of EA progressively increased in both gender (male: 0.28-0.49 per 100,000-year; female 0.07-0.11 per 100,000-year), the age-standardized incidence of EA is similar along the study period with an APC of 0.72% (P = 0.20) in male and 1.59% (P = 0.30) in female. In Taiwan, the incidence of ESCC significantly increased from 1979 to 2003, whereas the incidence of EA remained unchanged. Although EA incidence has not recently increased, it could in the future.

Prevalence of Helicobacter pylori infection in duodenal ulcer and gastro-duodenal ulcer diseases in Taiwan.

BACKGROUND AND AIM: The prevalence of Helicobacter pylori-negative duodenal ulcer (DU) is increasing in Western countries but is rare in Japan. We aimed to examine the prevalence of H. pylori infection and the characteristics in DU and gastro-duodenal ulcer (GDU) diseases in Taiwan. STUDY: All patients with an endoscopic diagnosis of DU or GDU from September 2003 to May 2004 at Taipei Veterans General Hospital were included. Rapid urease test was done for all patients, while urea breath test was carried out on those with negative rapid urease tests. A patient was considered infected if either test was positive. RESULTS: The prevalence of H. pylori was 88.7% (555/626) in DU and 90.5% (95/105) in GDU patients. There was no difference in sex and prevalence of H. pylori between the two groups but age was higher in the GDU patients (60.1 +/- 15.5 vs. 55.4 +/- 15.5, P = 0.005). Of H. pylori-negative DU patients, 28.2% (20/71) reported using non-steroidal anti-inflammatory drugs (NSAIDs)/aspirin, which were used by all 10 H. pylori-negative GDU patients (100%) (P < 0.001). There was no difference in sex and age between H. pylori-positive and negative DU patients. The prevalence rate of H. pylori in DU was not statistically different among outpatients, inpatients, and physical check-up subjects (86.8% vs. 93.3% vs. 90.7%, P = 0.163). CONCLUSION: The prevalence of H. pylori infection in DU appears to be decreasing in Taiwan. Thus, eradication therapy without confirming the presence of H. pylori in DU patients cannot be recommended. NSAIDs/aspirin is the major risk factor for H. pylori-negative DU patients, especially those with co-morbid gastric ulcer.

Electrogastrographic characteristics in subjects with stomach remnant.

BACKGROUND AND AIMS: Slow wave (SW) is an essential component in mediating stomach motility. The purpose of the present study was to investigate the SW characteristics in subjects with stomach remnant. METHODS: We consecutively enrolled 58 distal radical subtotal gastrectomy (RSG) patients (male/female: 44/14, age: 33-79 years) to receive an electrogastrographic (EGG) measurement. Their Helicobacter pylori status and dyspeptic score were simultaneously assessed. In addition, EGG data of 58 age- and sex-matched healthy subjects were compared. Based on power spectral analysis, the following EGG parameters were derived: dominant frequency (DF)/power (DP), percentage of normal rhythm (2-4 cpm), power ratio (PR) referring the postprandial power change, etc. RESULTS: Visual analysis occasionally found a short period of approximately 11 cpm myoelectricity-like rhythm. Distal RSG patients had lower fasting (1.90 +/- 0.69 vs 2.97 +/- 0.58 cpm, P < 0.001) and postprandial (2.03 +/- 0.72 vs 3.35 +/- 0.27 cpm, P < 0.001) DF values, while their fasting (36.2 +/- 22.3% vs 67.1 +/- 23.4%, P < 0.001) and postprandial (33.4 +/- 19.9% vs 82.2 +/- 16.7%, P < 0.001) percentages of normal rhythms were diminished. In contrast, fasting DP, its meal response and PR (2.99 +/- 2.40 vs 2.45 +/- 2.63, NS) were comparable to those of controls. Neither gender, age, type of gastroenterostomy, Helicobacter pylori colonization, dyspeptic score nor elapsed time after surgery had an obvious influence on EGG parameters. CONCLUSIONS: Distal RSG patients may have decreased SW frequency and less meal ingestion changed EGG parameters in terms of SW frequency, normality and stability, whereas their EGG power remained unchanged irrespective of meal ingestion.

Asian consensus on irritable bowel syndrome.

BACKGROUND AND AIMS: Many of the ideas on irritable bowel syndrome (IBS) are derived from studies conducted in Western societies. Their relevance to Asian societies has not been critically examined. Our objectives were to bring to attention important data from Asian studies, articulate the experience and views of our Asian experts, and provide a relevant guide on this poorly understood condition for doctors and scientists working in Asia. METHODS: A multinational group of physicians from Asia with special interest in IBS raised statements on IBS pertaining to symptoms, diagnosis, epidemiology, infection, pathophysiology, motility, management, and diet. A modified Delphi approach was employed to present and grade the quality of evidence, and determine the level of agreement. RESULTS: We observed that bloating and symptoms associated with meals were prominent complaints among our IBS patients. In the majority of our countries, we did not observe a female predominance. In some Asian populations, the intestinal transit times in healthy and IBS patients appear to be faster than those reported in the West. High consultation rates were observed, particularly in the more affluent countries. There was only weak evidence to support the perception that psychological distress determines health-care seeking. Dietary factors, in particular, chili consumption and the high prevalence of lactose malabsorption, were perceived to be aggravating factors, but the evidence was weak. CONCLUSIONS: This detailed compilation of studies from different parts of Asia, draws attention to Asian patients' experiences of IBS.

Gastric reddish streaks in the intact stomach: endoscopic feature of reactive gastropathy.

The pathogenesis of reddish streaks in the intact stomach is unclear. Sixty-three functional dyspeptic patients with gastric reddish streaks were recruited for the study. Fifty-five patients (group I) had only reddish streaks while nine patients (group II) had additional lesions such as reddish patches or spots randomly scattered throughout the stomach. Updated Sydney system and parameters of reactive gastropathy were used to score the biopsy specimens from reddish streaks separately. Helicobacter pylori infection rate was found to be markedly lower in group I than group II patients (13% vs 89%, P < 0.001). H. pylori-infected patients had higher scores for acute and chronic inflammation (P < 0.001) and foveolar hyperplasia (P < 0.005) than non-infected patients, while other parameters for gastritis and gastropathy were similar between infected and non-infected patients. In H. pylori-non-infected patients all biopsy specimens had at least one histological feature of reactive gastropathy. Bile reflux was observed in 54% of patients (34/63). Only 7.9% used non-steroidal anti-inflammatory drugs and 4.9% drank alcohol. The present data indicate that the fundamental histological features of gastric reddish streaks are reactive gastropathy with low H. pylori infection, and are probably enterogastric reflux related in etiology. Coincidental H. pylori infection increased acute and chronic inflammatory cell infiltration, and enhanced the grade of foveolar hyperplasia.

At the cutting edge: ghrelin gene products in food intake and gut motility.

Ghrelin, a 28-amino acid peptide, was recently identified from the stomach as the first endogenous ligand for growth hormone secretagogue receptors (previously known as orphan receptors). Ghrelin was discovered by 'reverse pharmacology'. The acyl ghrelin peptide features a unique post-translational modification of O-n-octanoylation at serine 3, and is the only gastrointestinal signal that increases meal size. However, des-acyl ghrelin accounts for the major forms in the plasma. Most recently, obestatin, a novel 23-amino acid peptide, was derived from the mammalian preproghrelin gene, which also encodes ghrelin, by a bioinformatic approach. This at-the-cutting-edge review focuses on three ghrelin gene products: acyl ghrelin, des-acyl ghrelin, and the newly identified obestatin. Their updated orexigenic and anorexigenic effects on food intake, their signal transduction pathways from the periphery to the brain, as well as their roles in modulating gastrointestinal motility, and potential applications in the many fields of medicine such as eating disorders, obesity/anorexia-cachexia, and gastrointestinal dysmotility under different conditions, are critically addressed.

Gastric mucosal injury in systemic lupus erythematosus patients receiving pulse methylprednisolone therapy.

AIMS: Whether glucocorticoids induce gastric mucosal injury remains uncertain. We investigated whether very high-dose steroids caused gastric mucosal injury in systemic lupus erythematous (SLE) patients and evaluated the possible risk factors for mucosal injury. METHODS: In this prospective paired study, 67 SLE patients who had received pulse methylprednisolone therapy were enrolled. Each patient underwent endoscopic examination and tissue and blood sampling before and after pulse steroid therapy. Mucosal injury was diagnosed if the follow-up injury scale was higher than the initial scale. Examined parameters included Helicobacter pylori infection, cyclooxygenase (COX)-1 and COX-2 activity, and current nonsteroidal anti-inflammatory drug (NSAID) usage including aspirin. RESULTS: Eleven (16.4%) of 67 cases who developed gastric mucosal injury after pulse therapy had significantly higher rates of peptic ulcer history, NSAID/aspirin use, lower gastric thromboxane B(2) and prostaglandin E(2) levels when compared with cases without gastric mucosal injury (P < 0.05). Infection by H. pylori was not a risk factor for gastric mucosal injury. Multivariate logistic regression analysis showed that NSAID/aspirin use was the only risk factor for gastric mucosal injury in these patients (odds ratio 26.99, 95% confidence interval 4.91, 148.57, P < 0.0001). Pulse steroid therapy alone did not induce gastric mucosal injury in fifty SLE patients without taking any NSAID/aspirin. CONCLUSIONS: Use of NSAIDs/aspirin, but not H. pylori infection, increases gastric mucosal injury in SLE patients receiving pulse methylprednisolone therapy. Very high-dose steroids de novo seem not to induce gastric mucosal injury in these patients. A larger case-controlled study enrolling a heterogeneous population is needed to clarify the role of glucocorticoids in gastric mucosal injury.

Splanchnic hyposensitivity to glypressin in a hemorrhage-transfused common bile duct-ligated rat model of portal hypertension: role of nitric oxide and bradykinin.

BACKGROUND/AIMS: The portal hypotensive effect of vasopressin during hemorrhage is less effective than that during stable condition in cirrhotic patients or experimental portal hypertension (the so-called hyposensitivity phenomenon). Recent studies have demonstrated that constitutive nitric oxide activities and bradykinin in hemorrhage-transfused partially portal vein-ligated rats are responsible, at least partly, for the splanchnic hyposensitivity to glypressin (a long acting vasopressin analogue). This study investigated the relative contribution of nitric oxide synthase isoforms and the role of bradykinin in the pathogenesis of splanchnic hyposensitivity in rats with cirrhosis induced by common bile duct-ligation (BDL). METHODOLOGY: Five weeks after BDL, systemic and portal hemodynamics were measured in stable or bleeding BDL rats receiving intravenous infusion of glypressin (0.2 mg/kg). In the treatment groups, N(G)-nitro-L-arginine methyl ester (L-NAME, a non-selective nitric oxide synthase inhibitor), L-canavanine (a specific inducible nitric oxide synthase inhibitor) or HOE 140 (a bradykinin B2 receptor antagonist) was administered 45 minutes before the infusion of glypressin. In rats with a hypotensive hemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or various inhibitors. RESULTS: Splanchnic hyposensitivity to glypressin was demonstrated in the hemorrhage-transfused BDL rats. The infusion of L-NAME elevated the mean arterial pressure in the bleeding BDL rats without the modulation of portal pressure. The addition of L-NAME or HOE 140, but not L-canavanine, significantly and similarly potentiated the portal-hypotensive effects of glypressin. CONCLUSIONS: Constitutive nitric oxide synthase and bradykinin play major roles in the development of splanchnic hyposensitivity to glypressin observed in hemorrhage-transfused rats with biliary cirrhosis.

Treatment of irritable bowel syndrome using complementary and alternative medicine.

The therapeutic objectives for irritable bowel syndrome (IBS) patients are to improve their functioning in society. Accordingly, recommended management is to develop a logical strategy including a positive diagnosis, consideration of the patient's agenda and emotional state, critical appraisal of the efficacies of various drugs and a graded therapeutic response. Unfortunately, none of the currently available drugs (e.g. antispasmodics, antidiarrheals, osmotics, cathartics, bulking agents, tranquilizers, sedatives) are globally effective in treating all IBS symptoms, and the advanced receptor-targeted drugs are not always successfully and safely marketed. Consequently, more than half of patients may seek complementary and alternative medicine (CAM) to treat the annoying bowel symptoms. Physicians have considered these CAM measures to have an "enhanced placebo effect". For example, many herbal medicine and plant products are globally used to treat IBS, whereas their efficacies are often inconclusive because of small sample sizes, inadequate data analyses and lack of standardized preparations. Meta-analyses do not establish their true efficacy. Acupuncture has long been employed by patients themselves to treat functional gastrointestinal disorders with satisfactory response, but its effect on IBS does not seem to be promising. Peppermint oil, melatonin and clay-like materials are effective in treating some IBS symptoms, while their true pharmacology remains enigmatic. In conclusion, IBS treatment is usually tailored to the individual's manifestations, ranging from reassurance to psychotherapy. Apart from conventional medications, CAM may be considered individually as a supplement or alternative to treat IBS patients that is at least equal in effect to placebo if patients do not exhibit any intolerable or serious side effects.

Can computed tomography with coronal reconstruction improve the diagnosis of choledocholithiasis?

BACKGROUND AND AIM: Many technical developments of computed tomography (CT) made in recent years have improved imaging quality. However, the diagnostic efficacy of CT with coronal reconstruction for choledocholithiasis remains uncertain. This study aimed to investigate if CT with coronal reconstruction can aid in the diagnosis of choledocholithiasis. METHODS: Two hundred and sixty-six patients with clinically suspected choledocholithiasis undergoing abdominal CT before endoscopic retrograde cholangiopancreatography were recruited. Among them, 163 patients confirmed with choledocholithiasis were divided into three groups: group 1, 92 patients undergoing CT using 5-mm thick sections with coronal reconstruction; group 2, 32 patients undergoing CT using 5-mm thick sections without coronal reconstruction; and group 3, 39 patients undergoing CT using 7-mm thick sections without coronal reconstruction. The diagnostic rate of CT for choledocholithiasis, the stone size and biochemical data among the three groups were analyzed. RESULTS: The sensitivity and specificity of CT in diagnosing choledocholithiasis were 77.3% and 72.8%. There was no significant difference of CT diagnostic rate among the three groups (75.0%, 81.2% and 79.5%, respectively). The diameter of common bile duct (CBD), size of CBD stones and white cell count showed significant differences between CT true-positive and false-negative cases in group 1 patients. The CT diagnostic rate was significantly lower in patients with choledocholithiasis of less than 5 mm than in patients with choledocholithiasis of 5 mm or more (56.5% vs 81.2%). CONCLUSION: The coronal reconstruction of CT imaging did not increase its diagnostic efficacy on choledocholithiasis. The stone size affects the diagnostic rate of abdominal CT for detecting choledocholithiasis.

Vasopressin response and shunting modulation in cirrhotic rats by chronic nitric oxide inhibition.

BACKGROUND AND AIM: Nitric oxide (NO) plays a significant role in the vascular hyposensitivity to vasoconstrictors in cirrhosis. Chronic NO inhibition improves the portal-systemic collateral responsiveness to arginine(8)-vasopressin (AVP) and ameliorates shunting degree in rats with prehepatic portal hypertension. This study investigated whether long-term NO inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME) enhances the collateral vascular responsiveness to AVP and alleviates the severity of shunting in cirrhotic rats. METHODS: Bile duct-ligated (BDL) rats received L-NAME in tap water (25 mg/kg/day) or tap water only (control) for 1 week from the 36th day after BDL. On the 43rd day, the mean arterial pressure and portal pressure were measured. With an in situ perfusion model of portal-systemic collateral vasculature, different concentrations of AVP (10(-10)-10(-7) mol/L) with a constant flow rate (12 mL/min) were applied to assess the perfusion pressure changes of collaterals. In addition, flow pressure curves were obtained with different flow rates (6-18 mL/min): the slopes serve as indices of collateral vascular resistance and the higher resistance indicates less collateral. RESULTS: The mean arterial pressure was significantly increased after L-NAME treatment (P < 0.05), whereas the heart rate and portal pressure were not significantly modified. As compared with the controls, the L-NAME group exerted significantly higher perfusion pressure changes to AVP at the concentrations of 3 x 10(-8), 10(-7) and 3 x 10(-7) mol/L. In addition, chronic L-NAME administration induced collateral vascular resistance elevation, suggesting the attenuation of portal-systemic shunting. CONCLUSION: Chronic NO inhibition improves the collateral vascular responsiveness to AVP and ameliorates portal-systemic shunting in BDL cirrhotic rats.

Simvastatin for rats with thioacetamide-induced liver failure and encephalopathy.

BACKGROUND AND AIM: Nitric oxide (NO) inhibition aggravates hepatic damage and encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure. Statins enhance NO synthase expression beyond their lipid-lowering capability, but the impact on encephalopathy remains unexplored. The aim of this study was to assess the effects of simvastatin on rats with TAA-induced acute liver damage and hepatic encephalopathy. METHODS: Sprague-Dawley rats received TAA (350 mg/kg/day) or normal saline (NS) by intraperitoneal injection for 3 consecutive days. Two days before injections, each group was divided into three subgroups, taking (i) distilled water; (ii) simvastatin (20 mg/kg/day); or (iii) simvastatin plus N(G)-nitro-l-arginine methyl ester (L-NAME, 25 mg/kg/day) by oral gavage for 5 days. On the fifth day, severity of encephalopathy was assessed and plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and ammonia were measured. RESULTS: The TAA subgroups showed higher ALT, AST, bilirubin and ammonia levels and lower motor activity counts as compared with the NS subgroups. Among the TAA-treated subgroups, rats with simvastatin treatment exerted higher motor activity counts and survival rate (P = 0.043), and a trend of lower ALT, AST, bilirubin and ammonia levels than those receiving saline. All rats that underwent simvastatin plus L-NAME treatment died during or after TAA injections. CONCLUSIONS: Simvastatin improved encephalopathy and survival in TAA-administered rats. The beneficial effect was offset by L-NAME, suggesting the role of NO in liver damage and encephalopathy.