[Efficacy and safety of compound azintamide on dyspepsia symptoms in a multicentre self-controlled trial].

OBJECTIVE: To investigate the efficacy and safety of compound azintamide on dyspepsia symptoms. METHODS: One hundred and eighty dyspepsia patients were divided into two groups according to dyspepsia symptom related with gastrointestinal disease (group A) or biliary system disease (group B), whose dyspepsia symptom were not improved by the Domperidone 10 mg tid for 2 weeks. Two tablets of compound azintamide were administered orally following a meal, tid for 2 weeks. The changes of symptoms score of upper abdominal distention, upper abdominal pain or discomfort anorexia and effective rate as well as adverse events were recorded. RESULTS: Compound azintamide greatly improved the symptoms of upper abdominal distention, upper abdominal pain or discomfort and anorexia. All symptoms scores were significantly decreased after 2 weeks of compound azintamide (P < 0.01). The effective rate of each symptom and total symptoms score were more than 84.9% and 92.5%. One patient reported mild rash at the fourteenth days, which disappeared 3 days later. CONCLUSION: Compound azintamide showed effective and safety in treatment of patient with dyspepsia symptoms when Domperidone therapy is not satisfactory.

Effects and mechanisms of electroacupuncture at PC6 on frequency of transient lower esophageal sphincter relaxation in cats.

AIM: To investigate the effects of electroacupuncture (EA) at neiguan (PC6) on gastric distention-induced transient lower esophageal sphincter relaxations (TLESRs) and discuss the mechanisms of this treatment. METHODS: Protocol I: Twelve healthy cats underwent gastric distention for 60 min on the first day. Electrical acupoint stimulation was applied at the neiguan or a sham point on the hip in randomized order before gastric distention, on the third day and fifth day. Those cats that underwent EA at neiguan on the fifth day were named "Neiguan Group" and the cats that underwent EA at a sham acupoint on the fifth day were named "Sham Group" (control group). During the experiment the frequency of TLESRs and lower esophageal sphincter (LES) pressure were observed by a perfused sleeve assembly. Plasma levels of gastrin (GAS) and motilin (MTL) were determined by radioimmunoassay. Nitrite/nitrate concentration in plasma and tissues were measured by Griess reagent. The nuclei in the brain stem were observed by immunohistochemistry method of c-Fos and NADPH-d dyeing. Protocol II: Thirty six healthy cats were divided into 6 groups randomly. We gave saline (2 mL iv. control group), phaclofen (5 mg/kg iv. GABA-B antagonist), cholecystokinin octapeptide (CCK-8) (1 microg/kg per hour iv.), L-Arginine (200 mg/kg iv.), naloxone (2.5 micromol/kg iv.) and tacrine (5.6 mg/kg ip. cholinesterase inhibitor) respectively before EA at Neiguan and gastric distention. And the frequencies of TLESRs in experimental groups were compared with the control group. RESULTS: Protocol I: Not only the frequency of gastric distention-induced TLESR in 60 min but also the rate of common cavity during TLESRs were significantly decreased by EA at neiguan compared to that of sham acupoint stimulation. C-Fos immunoreactivity and NOS reactivity in the solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) were significantly decreased by EA at neiguan compared to that of the sham group. However, the positive nuclei of C-Fos and NOS in reticular formation of the medulla (RFM) were increased by EA at neiguan. Protocol II: The inhibited effect of EA at neiguan on TLESR's frequency was completely restored by pretreatment with CCK (23.5/h vs 4.5/h, P < 0.05), L-arginine (17.5/h vs 4.5/h, P < 0.05) and naloxone(12/h vs 4.5/h, P < 0.05). On the contrary, phaclofen (6/h vs 4.5/h, P > 0.05) and tacrine (9.5/h vs 4.5/h, P > 0.05) did not influence it. CONCLUSION: Electric acupoint stimulation at Neiguan significantly inhibits the frequency of TLESR and the rate of common cavity during TLESR in cats. This effect appears to act on the brain stem, and may be mediated through nitric oxide (NO), CCK-A receptor and mu-opioid receptors. But the GABAB receptor and acetylcholine may not be involved in it.

Characteristics and therapeutic efficacy of sulfasalazine in patients with mildly and moderately active ulcerative colitis.

AIM: To investigate the characteristics and short-term efficacy of sulfasalazine (SASP) in patients with mildly and moderately active ulcerative colitis (UC). METHODS: Two hundred and twenty-eight patients with mildly and moderately active UC were recruited, 106 patients in 1993-1995, and 122 patients in 2000-2002, they were assigned as the 1990s group (n = 106) and the 2000s group (n = 122), prospectively. The general characteristics, clinical manifestations, colonoscopic and histological data were compared between the two groups. The short-term efficacy and safety of SASP 3 g per d were evaluated. RESULTS: Between 2000s and 1990s groups, the gender ratio of men to women was 1:1.18 and 1:1.04, 57.4% and 50.9% of the patients were between 30 and 49 years old. The gender ratio and age of UC patients were not significantly different. The total course of 50.0% and 37.1% of UC patients was less than 1 year (P<0.05), 10.6% and 31.2% of the cases had a duration of more than 5 years (P<0.05) in 2000s and 1990s groups, respectively. The most common clinical type was first episode in 2000s group and chronic relapse in 1990s group. The patients showed a higher frequency of abdominal pain and tenderness in 1990s group than in 2000s group. Erosions were found in 84.4% and 67.9% of patients in 2000s and 1990s groups (P<0.05). Rough and granular mucosa (67.9% vs 43.4%, P<0.05) and polyps (47.2% vs 32.8%, P<0.05) were identified in 1990s group more than in 2000s group. There were no significant differences in clinical, colonoscopic and histological classifications. After SASP (1 g thrice per d) treatment for 6 wk, the clinical, colonoscopic and histological remission rates were 71.8%, 21.8% and 16.4%, respectively. In 79 patients with clinical remission, 58.2% and 67.1% remained grade 1 in colonoscopic and histological findings, respectively. The overall effects in first episode type (complete remission in 10, 18.9%, partial remission in 28, 52.8%, and improvement in 9, 17.0%) were better than in chronic relapse type (complete remission in 3, 7.5%; partial remission in 16, 40.0%; and improvement in 15, 37.5%) and chronic persistent type (complete remission in 1, 5.9%; partial remission in 6, 35.3%; and improvement in 6, 35.3%) respectively (P<0.05). In 110 patients treated with SASP, 18 patients (16.4%) had adverse reactions. Except for two cases of urticaria and one case of WBC decrease, none of the patients had to stop the treatment because of severe adverse reactions. CONCLUSION: Patients with mildly and moderately active UC in 2000s group had a shorter disease course, milder clinical manifestations, more first episode type and higher frequency of acute mucosal lesions in colonoscopy than in 1990s group. The patients in 1990s group had higher proportion of chronic relapse type and chronic mucosal change in colonoscopy than in 2000s group. The short-term efficacy of SASP could be mainly remission of clinical manifestations. But more than half of the patients still had light inflammation in colonoscopy and histology. The overall effects of SASP in first episode type were better than those in other types. SASP was a safe and effective drug to treat mildly and moderately active UC.

[Clinical analysis of primary biliary cirrhosis: a report of 42 cases].

OBJECTIVE: To study the clinical features of primary biliary cirrhosis (PBC) in order to facilitate cognition of the disease. METHODS: Clinical data of 42 patients clinically and/or histologically diagnosed with PBC were reviewed. Anti mitochondrial antibody (AMA) negative/positive patients as well as the patients who were/were not associated with Sjogren Syndrome (SS) were compared in terms of clinical, biochemical and immunological features. RESULTS: Among the 42 patients, 78.6% (33/42) of the cases were females; the mean age at diagnosis was (61.1+/-10.8) years. The most frequent symptoms were fatigue. Serum alkaline phosphatase (ALP), gamma-glutamyltranspeptidase (gamma-GT) and total bile acid (TBA) levels were markedly elevated in the majority of the patients, whereas ALT and AST levels were mildly to moderately elevated. Thirty-one patients had a total bilirubin (TBil) level above normal. The levels of TBil and prothrombin time had positive correlationship with years of the course (P=0.000, r=0.696; P=0.005, r=0.424), whereas serum albumin level had negative correlationship with years of the course (P=0.002, r=-0.462). Thirty-seven patients had elevated serum IgM and 34 patients were AMA/AMA-M(2) positive. AMA negative and AMA positive patients were similar in terms of clinical manifestations and liver biochemistries findings. Serum IgM and IgA levels were significantly lower, whereas total cholesterol level was higher in AMA negative patients when compared with AMA positive cases. Fifteen cases were associated with SS, which were similar in terms of clinical, biochemical and immunological features when compared with the PBC patients were not associated with SS. CONCLUSION: PBC is mostly found in middle aged and old women. Elevated serum ALP, TBA and gamma-GT levels together with positive AMA/AMA-M(2) can help to diagnose PBC. AMA negative PBC patients are characterized by relatively lower serum IgM and IgA levels and higher total cholesterol level. PBC patients who are associated with SS have not substantial differences in the clinical, biochemical and immunological spectra of the disease.

Tegaserod inhibits noxious rectal distention induced responses and limbic system c-Fos expression in rats with visceral hypersensitivity.

AIM: To examine the effects of tegaserod, a serotonin (5-HT) 4 receptor partial agonist, on abdominal withdrawal reflex (AWR) to rectal distention (RD) and c-Fos expression in limbic system. METHODS: Neonatal Sprague-Dawley rats randomly received colonic irritation by acetic acid from postnatal day 8 to d 21 as a visceral hypersensitive model (group H) or by intrarectal saline as a control group (group C). When they became adults, rectal distention (RD) was performed by a balloon (6F; Fogarty arterial embolectomy catheter; length, 20 mm; diameter, 2 mm) which was rapidly inflated with increasing volumes of saline (0.4, 0.8 and 1.2 mL) for 20 s at five-minute intervals. Five subgroups of group H (H-saline, H-vehicle, H-Teg0.1, H-Teg0.3 and H-Teg1.0) were injected randomly with saline, vehicle (1-methyl-2-thpyrrolidone) or tegaserod at doses of 0.1, 0.3 and 1.0 mg/kg ip, respectively. Two subgroups of group C (C-Saline and C-Teg1.0) were injected with saline or tegaserod (1.0 mg/kg) ip. RD was performed 10 min after injection, AWR was recorded and c-Fos expression in limbic system was analyzed quantitatively by immunohistochemistry. RESULTS: Compared to saline, tegaserod significantly inhibited AWR in group H (0.4 mL: from 2.0 to 0.5; 0.8 mL: from 3.5 to 1.5; 1.2 mL: from 4.0 to 3.0, P<0.01), but had no significant effect on group C. Tegaserod dose-dependently attenuated the number of c-Fos positive neurons in limbic structures, anterior cingulate cortex (ACC) showed the greatest attenuation. In group H, tegaserod (1.0 mg/kg) resulted in a significant overall decrease to 57% of H-saline (283+/-41 vs 162+/-16, P<0.01), in ACC to 42% of H-saline (72+/-10 vs 31+/-8, P<0.01). In group C, tegaserod (1.0 mg/kg) resulted in an overall decrease to 77% of C-saline (214+/-13 vs 164+/-22, P<0.01), in ACC to 65% of C-saline (48+/-8 vs 31+/-7, P<0.01). CONCLUSION: Tegaserod inhibits the response to rectal distention in rats with visceral hypersensitivity and dose-dependently attenuates c-Fos expression in limbic system, especially in anterior cingulate cortex.

Expression and localization of c-Fos and NOS in the central nerve system following esophageal acid stimulation in rats.

AIM: To determine the distribution of neurons expressing c-Fos and nitric oxide synthase (NOS) in the central nerve system (CNS) following esophageal acid exposure, and to investigate the relationship between c-Fos and NOS. METHODS: Twelve Wistar rats were randomly divided into two equal groups. Hydrochloric acid with pepsin was perfused in the lower part of the esophagus for 60 min. As a control, normal saline was used. Thirty minutes after the perfusion, the rats were killed and brains were removed and processed for c-Fos immunohistochemistry and NADPH-d histochemistry. Blood pressure (BP), heart rate (HR), and respiratory rate (RR) during the experimental procedures were recorded every 10 min. RESULTS: There were no significant differences in BP, HR and RR between the two groups. c-Fos immunoreactivity was significantly increased in rats receiving acid plus pepsin perfusion in amygdala (AM), paraventricular nucleus (PVN), parabrachial nucleus (PBN), nucleus tractus solitarius and dorsal motor nucleus of vagus (NTS/DMV), nucleus ambiguous (NA), reticular nucleus of medulla (RNM) and area postrema (AP). NOS reactivity in this group was significantly increased in PVN, PBN, NTS/DMV, RNM and AP. c-Fos and NOS had significant correlation between PVN, PBN, NTS/DMV, RNM and AP. CONCLUSION: Acid plus pepsin perfusion of the esophagus results in neural activation in areas of CNS, and NO is likely one of the neurotransmitters in some of these areas.

[Alteration of Ca2+ mobilization and increased circular muscle contractility in colon of stressed rats].

OBJECTIVE: To investigate relationship between the cold-restraint stress induced colonic circular muscle contractility disorder and calcium-handling properties alteration of the affected muscle in rats. METHODS: Stress was conducted on rats to induce the fecal pellet output increased. Contractile responses to acetylcholine (Ach), KCl, and NaF were determined for colonic circular muscle. To investigate Ca(2+) mobilization, effects of Ca(2+)-free solution, high concentration of extracellular Ca(2+), and pinaverium bromide on the contractility of colon were determined. Prepared sarcoplasmic reticular (SR) of colonic muscle by differential centrifugation and measured Ca(2+)-ATPase activity with colorimetric assay. RESULTS: In stressed rats, contractile responses of colonic circular muscle to Ach, KCl, and NaF increased significantly; the contraction was more sensitive to high concentration of extracellular Ca(2+) than control. In Ca(2+)-free solution, contractions were significantly suppressed in both groups. Pinaverium dose-dependently blocked contractions acting with different sensitivity on the two preparations. The Ca(2+)-ATPase activity of the SR in stress was lower than control. CONCLUSIONS: Cold- restraint stress caused a marked increase in the contractility of the colonic circular muscle in rats. Stressed rats' colonic muscle shows an alteration in the homeostasis of intracellular Ca(2+), with appears to be the consequence of increased influx of extracellular Ca(2+), decreased release of intracellular stores of Ca(2+) and a decreased Ca(2+)-ATPase activity of the SR.

[Tegaserod inhibits noxious rectal distention induced response and spinal nNOS expression in rats with visceral hypersensitivity].

OBJECTIVE: To examine the effects of 5-HT4 receptor partial agonist tegaserod on response to rectal distention (RD) and on nNOS expression in spinal cord, and to investigate the mechanism of tegaserod influencing visceral sensation. METHODS: Neonatal SD rats randomLy received colonic irritation by acetic acid from postnatal day 8 to day 21 as visceral hypersensitive model (Group H); or by saline intrarectally as control group (Group C). Five subgroups of Group H were i.p. injected randomLy with saline, vehicle (1-methyl-2-thpyrrolidone) or tegaserod at doses of 0.1, 0.3 and 1.0 mg/kg, respectively. Two subgroups of Group C were i.p. injected with saline or tegaserod at dose of 1.0 mg/kg. Ten minutes after injection rectal distention was performed, AWR was recorded and nNOS expression in spinal cord (L6-S1) was analyzed quantitatively by NADPH-diaphorase histochemistry. RESULTS: Tegaserod significantly inhibited AWR in Group H, but had no effect in Group C. Tegaserod (1.0 mg/kg) inhibited AWR more significantly in Group H than in Group C at the largest volume of distention (1.2 mL). In Group H, tegaserod (1.0 mg/kg) significantly decreased overall nNOS positive cells in spinal cord to 40% of saline. The greatest attenuation was in dorsal horn (31% of H-saline). Tegaserod (0.1 mg/kg) did not affect the overall nNOS(P>0.20), but decreased the number of nNOS positive cells in central canal (79% of H-saline P<0.01). CONCLUSION: Tegaserod inhibits response to rectal distention in rats with visceral hypersensitivity and dose dependently attenuates spinal nNOS expression, especially in dorsal horn and central canal. nNOS may be involved in the modulation of visceral sensitivity by tegaserod.

Electroacupuncture at PC6 or ST36 Influences the Effect of Tacrine on the Motility of Esophagus.

Aim. To investigate the mechanisms of gastrointestinal side effects of tacrine, and find treatment methods with electroacupuncture (EA). Methods. Twenty-five healthy cats were randomly divided into 5 groups: gastric-distention group (model group), tacrine group (cholinesterase inhibitor), tacrine + sham acupoint group (control group), tacrine + PC6 (neiguan) group, and tacrine + ST36 (zusanli) group, with 5 cats in each group. Saline 2 mL i.p. was given 30 min before gastric distention in model group. Tacrine 5.6 mg/kg i.p. was given 30 minutes before gastric distention in the other groups. Tacrine + sham acupoint group (control group), tacrine + PC6 group, and tacrine + ST36 group received EA at corresponding acupoints during gastric distention. The frequency of TLESRs and LESP were recorded by using a perfused sleeve assembly. Results. Compared with the model group, tacrine significantly increased the frequency of gastric distention-induced TLESR (P < 0.05) but did not influence the rate of common cavity during TLESR. Tacrine significantly increased the LESP, which could not remain during gastric distention. EA at PC6 could decrease the frequency of TLESR and maintain the increase of LESP, but EA at ST36 did not have these effects. Conclusion. Tacrine can significantly increase the gastric distention-induced transient lower esophageal sphincter relaxations (TLESRs). Electroacupuncture (EA) at PC6 may reverse the above side effect.

The efficacy, safety and cost-effectiveness of hydrotalcite versus esomeprazole in on-demand therapy of NERD: A multicenter, randomized, open-label study in China.

OBJECTIVE: The aim of the study was to investigate whether hydrotalcite was comparable to esomeprazole, a proton pump inhibitor, in on-demand therapy for non-erosive reflux disease (NERD). METHODS: This was a multicenter, randomized, open-label clinical trial with initial and on-demand therapy. Patients who had complete symptom relief in the initial therapy were randomized to either hydrotalcite or esomeprazole in the on-demand therapy. The percentage of patients who quit on-demand therapy in the two groups and the cost-effectiveness of the treatment were evaluated as primary end points. The rate of symptom relief and the improvement of symptom score for initial therapy and the weekly average symptom score and weekly average number of days on treatment for on-demand therapy were evaluated as secondary end points. RESULTS: In total, 398 patients were recruited in the initial therapy group, among whom 253 were included in on-demand therapy, with 127 patients in the hydrotalcite group and the remaining 126 in the esomeprazole group. 14 (11.0%) patients in the hydrotalcite group and six (4.8%) in the esomeprazole group quit the on-demand therapy due to unsatisfactory symptom control (P = 0.065). Cost-effectiveness calculated as the ratio of the cost of hydrotalcite to that of esomeprazole (per person/day) was 35.3% in the on-demand therapy. Similar number of patients achieved symptom relief in both groups. CONCLUSION: Hydrotalcite is a good option of on-demand therapy for NERD patients due to its cost-effectiveness and speed of action.