Laurino Grossi

On the specificity of altered muscle function in experimental colitis in rats.

BACKGROUND Studies on muscle contraction in colitis yield conflicting data that may reflect differences in the manner in which colitis is induced. Therefore, we compared distal colonic longitudinal muscle contraction in four models of colitis in the rat. METHODS Distal colitis was induced by intrarectal administration of trinitrobenzene sulfonic, acetic acid, or Trichinella spiralis larvae, or by intraperitoneal injection of mitomycin C. Colonic myeloperoxidase activity was used to monitor acute inflammation. RESULTS Myeloperoxidase activity increased in each model of colitis. In trinitrobenzene-treated rats, contractile responses to carbachol, substance P, and KCl decreased by 64%, 76%, and 58%, respectively. In acetic acid treated rats, responses induced by carbachol, substance P, or KCl were each significantly decreased by 73%, 68%, and 55% and were similarly reduced by 42%, 77%, and 46%, respectively, in rats with T. spiralis colitis. In mitomycin-induced colitis, these respective responses also decreased significantly by 71%, 55%, and 54%. CONCLUSION Decreased contractility of longitudinal muscle in acute colitis in rats is independent of the manner in which the colitis is induced and is mediated at a receptor-independent locus on the muscle cell.

Role of antimicrobial susceptibility testing on efficacy of triple therapy in Helicobacter pylori eradication.

Helicobacter pylori treatment failure may be due to resistance to macrolides and 5‐nitroimidazoles.

SR140333, a substance P receptor antagonist, influences morphological and motor changes in rat experimental colitis

The etiology of inflammation, edema, and smoothmuscle contraction characteristic of inflammatory boweldisease is not clearly understood. There is evidencethat several neuropeptides, including substance P (SP), may play a role. In this study weevaluated the ability of a SP-antagonist (SR140333) tomodify the course of experimental colitis induced in therat by trinitrobenzene sulfonic acid (TNB). Colitis was induced in 24 rats using TNB applied byintrarectal enema. Twelve TNB-treated rats receivedSR140333, 0.1 mg/kg intraperitoneally, 30 min before theadministration of TNB and every 48 hr until death. Twelve rats receiving only intrarectal 0.9%saline served as controls. Rats of each group werekilled after 14 days. At day 14, the control groupshowed no signs of inflammation whereas the TNB-treated rats without SR140333 treatment exhibited awell-established colitis. The TNB-treated group had ahigher level of inflammation, as seen histologically andby the significantly greater weight of colon strips, compared to the controls (0.30 ± 0.09 gvs 0.13 ± 0.03 g, P < 0.001) and to theSR140333-treated rats (0.30 ± 0.09 g vs 0.14± 0.05 g, P < 0.001). In addition, smoothmuscle contractility was significantly reduced in the inflamedcolons of TNB-treated rats when compared with thecontrols (carbachol: 42.7 ± 20.3 vs 254.2± 69.78 mg/mm2± 10.02 vs 89.45± 23.17 mg/mm2 11.4 ± 2.2 vs 98.32 ± 33.57mg/mm21). However, SR140333-treated ratsshowed a recovery from inflammation and motoralterations caused by TNB (carbachol: 150.9 ±46.1 mg/mm21; SP: 32.5 ± 9.4 mg/mm25; KCl:125.7 ± 36.1 mg/mm21). In conclusion,treatment with SP antagonist SR140333 reduces theseverity of colitis and has beneficial effects on theconcomitant alterations of contractility. Thus, theblockade of substance P may represent a possibility inthe treatment of intestinal inflammation.

Role of the Preliminary Susceptibility Testing for Initial and After Failed Therapy of Helicobacter pylori Infection with Levofloxacin, Amoxicillin, and Esomeprazole

Background:  Levofloxacin has been proposed as an alternative to classic therapy in secondary resistance to Helicobacter pylori.

Effect of baclofen on oesophageal motility and transient lower oesophageal sphincter relaxations in GORD patients: a 48-h manometric study

Abstract  Little is known about prolonged effect of baclofen on oesophageal and lower oesophageal sphincter (LOS) motility. We aimed at investigating the oesophageal motility in gastro‐oesophageal reflux disease (GORD) patients 24 h before and after the administration of multiple doses of baclofen. Twenty‐one GORD patients underwent a 48‐h manometry recording the swallows, the oesophageal and the LOS motility. During the second 24‐h period, patients received baclofen 10 mg or placebo four times per day in a double‐blind randomized fashion. Baclofen increased the LOS basal tone in comparison with baseline (P = 0.02), with a concomitant reduction in the number of transient LOS relaxations (TLOSRs) (P = 0.01). Moreover, baclofen induced a decrease of the swallows (P = 0.02) and of primary oesophageal body waves (P = 0.04) with no changes in the amplitude. Multiple doses of baclofen determine a reduction in the number of TLOSRs and an increase in the LOS tone throughout the 24 h. The concomitant decreased number of swallows and of primary peristalsis could depend on the well‐known lower amount of reflux episodes induced by the drug. The potential therapeutic effect of baclofen could be expressed not only postprandially, but also in the fasting state when reflux episodes are present as well.

Gastric emptying of a solid-liquid meal measured with 13C octanoic acid breath test and real-time ultrasonography: a comparative study.

OBJECTIVES:The 13C octanoic acid breath test (OBT) has been proposed as a reliable noninvasive test to measure gastric emptying. OBT has been compared with scintigraphy; however, there are no data comparing it with gastric emptying measured with real-time ultrasonography (RUS) The aim of the study was to correlate gastric emptying of a solid–liquid meal, with OBT and RUS simultaneously evaluated in a group of normal volunteers.METHODS:A total of 14 normal subjects ingested a standard test meal (one scrambled egg with two slices of white bread, 10 g of butter, and 300 ml of tap water). The egg yolk was mixed with 0.1 ml of 13C octanoic acid. Breath samples for 13CO2 analysis were collected in breath bags and were analyzed by means of isotope-selective nondispersive infrared spectrometry (IRIS). RUS was simultaneously performed by calculating the antral area following a previous validated method. Breath samples and antral area were taken at baseline and every 15 min after the meal during the first 2 h and every 30 min for another 2 h. Lag time (Tlag) and gastric half emptying time (T1/2) were calculated for OBT and RUS. Data were analyzed by the Students t test for paired data, correlation coefficient, and regression line.RESULTS:The results show a statistically significant longer Tlag and T1/2 for OBT in comparison with RUS (p < 0.001). A significant correlation and positive regression line was computed between OBT and RUS for Tlag and for T1/2.CONCLUSIONS:Our results show that OBT overestimates gastric emptying parameters of a solid–liquid meal in comparison with RUS. However, both techniques give data in good correlation. Because OBT is less operator-dependent than RUS, it may be useful in comparative gastric emptying studies.

Proximal and Distal Gastric Distension in Normal Subjects and H. pylori-Positive and -Negative Dyspeptic Patients and Correlation with Symptoms

Aim of the study was to analyze gastricdistension with water in H. pylori-positive and-negative dyspeptic patients and normal subjects and thecorrelation with symptoms. Twenty dyspeptic patients and 19 normal subjects were studied. H. pylori wasdetermined in each dyspeptic patient with the rapid ureatest at endoscopy. Gastric distension was evaluated byreal-time ultrasonography with the ingestion of stepwise-increasing amounts of water up toa total of 600 ml. During distension, the symptom scorewas evaluated as well. The proximal stomach wassignificantly smaller in dyspeptic patients than in healthy controls, at 100-600 ml water (P <0.01). A larger distal stomach was observed at 500 and600 ml of water (P < 0.01). The score of bloating andfullness was greater in dyspeptics than in controls at 300 and 600 ml of water distension.The symptoms score was linearly correlated with proximaland distal gastric measurements in dyspeptic patientsand in controls. No significant difference was found in dyspeptic patients regarding theH. pylori status. In conclusion, dyspeptic patients showa defective adaptation of the whole stomach to waterdistension and an increased symptom perception score as compared to controls. H. pyloriinfection does not seem to be a determining factor inthese observed findings.

Transient Lower Esophageal Sphincter Relaxations and Gastroesophageal Reflux Episodes in Healthy Subjects and GERD Patients During 24 Hours

Still little is known about the 24-hr pattern of transient lower esophageal sphincter relaxations (TLESRs), particularly in patients with GERD. The aim of our study was to evaluate the 24-hr esophageal and LES motor pattern and esophageal pH and to identify the relationship between TLESRs and gastroesophageal reflux in healthy subjects and in GERD patients. Ten healthy subjects and nine patients with esophagitis (grade I–II) underwent a 24-hr pH manometric recording by means of a portable electronic device. The recording aimed at identifying the temporal relationships between reflux episodes and LES motor events. The GERD patients showed a greater number of either reflux episodes or TLESRs during the 24 hr as compared to controls. While most refluxes occurred during TLESRs in both groups, a small percentage of TLESRs was followed by reflux episodes in healthy people, with only a slight increase in GERD patients. In conclusion, although representing an important motor pattern during gastroesophageal reflux both in healthy subjects and in patients with GERD, TLESR could probably be considered one of the pathophysiologic mechanisms of gastroesophageal reflux more than the primary cause of reflux episodes.

Efficacy of four different moxifloxacin-based triple therapies for first-line H. pylori treatment

UNLABELLED Moxifloxacin has been used in the first-line treatment of Helicobacter pylori infection. The optimal dosage and duration have not been assessed. AIM To evaluate the effectiveness of moxifloxacin, amoxicillin and esomeprazole in four regimens, in previously untreated patients infected by H. pylori. METHODS AND PATIENTS Patients were randomly assigned to: esomeprazole 20 mg b.i.d., amoxicillin 1g b.i.d., and one of each of the four following dosages of moxifloxacin: moxifloxacin 400 mg b.i.d. for 10 days (EAM800x10), moxifloxacin 400 mg b.i.d. for 7 days (EAM800x7), moxifloxacin 400 mg b.i.d. for 5 days (EAM800x5), moxifloxacin 400 mg o.i.d. for 10 days (EAM400x10). Eradication was assessed by the Urea Breath Test (UBT) 2 months following the end of therapy. RESULTS Ninety-four, 102, 92 and 105 patients were recruited in EAM800x10, EAM800x7, EAM800x5, and EAM400x10 respectively. The eradication rate was for Intention-To-Treat (ITT) and Per Protocol (PP) analyses: EAM800x10 group ITT: 90.4%, PP: 94.4%; EAM800x7 group ITT: 80.3%, PP: 86.3%; EAM800x5 group ITT: 71.4%, PP: 75.2%; EAM400x10 group ITT: 80.0%, PP 84.8%. A statistically significant difference was reached between EAM800x10 vs. EAM800x7 (ITT and PP: P<0.05), and between EAM800x10 vs. EAM800x5 (ITT and PP: P<0.01) and vs. EAM400x10 (ITT: P<0.05; PP: P<0.04). Thirty patients treated unsuccessfully with EAM800x5 and EAM400x10 were re-treated with EAM800x10 with an eradication rate of 86.7% (ITT) and 92.2% (PP). Nineteen patients with positive UBT after EAM800x10 and EAM800x7 underwent a second-line rifabutin-based therapy with an eradication rate of 84.2% (ITT and PP). CONCLUSION A triple therapy with 800 mg of moxifloxacin a day for 10 days is more effective than the same treatment for 5 or 7 days and a treatment with 400mg of moxifloxacin a day for 10 days for the first-line eradication of H. pylori infection. The high cost of moxifloxacin-based treatment however, may limit its wide use as first-line treatment of H. pylori infection.

Migrating motor complex recorded spontaneously and induced by motilin and erythromycin in an ex vivo rabbit intestinal preparation

We investigated basal motility and the motor effects of motilin, erythromycin, and prostigmine on segments of rabbit gastrointestinal tract removed from extrinsic neural and vascular pathway and immersed in an oxygenated organ bath. Motility was recorded by means of four strain gauges sutured on the serosal surface of the segment. During basal recording, clusters of duodenal contractions that propagated distally, resembling phase III activity of migrating motor complex, were seen. Motilin (10(-6) M) and erythromycin (10(-6) M) induced a propagated cluster of contractions similar to the phase III recorded during the basal period. Prostigmine (10(-6) M) induced a simultaneous increase in gastric and small intestinal motility. Atropine (10(-5) M) prevented the motor effect of motilin, erythromycin, and prostigmine. Thus, MMCs do not appear to require central input for initiation and propagation. Motilin and erythromycin stimulate MMCs through an enteric cholinergic mechanism; therefore, the previously reported smooth muscle receptors for both substances were not apparent in the ex vivo preparation.