Leonardo Marzio

Coccoid Helicobacter pylori Not Culturable In Vitro Reverts in Mice

An experimental rodent model was used to demonstrate the viability of the coccoid form of Helicobacter pylori. Concentrated suspensions were prepared for the two different morphologies: at 2 days incubation for the bacillary forms and at 20 days incubation for the “dormant” forms. The strains used for incubation were two fresh isolates from humans with duodenal ulceration, and two collection strains. Five hundred microliters of culture (OD550 = 5 Mc Farland) of Helicobacter pylori with bacillary (2‐5×109 CFU/ml) and coccoid (0 CFU/ml) morphology were inoculated intragastrically in BALB/c mice. The gastric mucosa of the mice was colonized by Helicobacter pylori with the administration of fresh bacillary and coccoid cultures and not with the established cultures. Helicobacter pylori was isolated at 1 week after inoculation with the administration of fresh bacillary cultures, while fresh coccoid Helicobacter pylori was recovered in mice stomachs after 2 weeks of inoculation. After colonization, histopathologic changes occurred after 1 month from inoculation; all colonized mice showed a systemic antibody response to Helicobacter pylori. These results support the thesis of the viability of coccoid Helicobacter pylori non‐culturable in vitro and confirm that concentrated bacterial suspensions are able to colonize and to produce gastric alterations in this suitable animal model.

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.

H2‐receptor antagonists are scavengers of oxygen radicals

Abstract. Potential oxygen radical scavenging properties of the H2‐receptor antagonists cimetidine, ranitidine and famotidine were investigated. These drugs, although ineffective against superoxide anion and hydrogen peroxide, can scavenge hydroxyl radical (OH·) with a very high rate constant, which is about tenfold higher than that of the specific scavenger mannitol for famotidine (1·7 × 1010 mol−1 s−1) and cimetidine (1·6 × 1010 mol−1 s−1), ranitidine displaying a rate constant of 7·5 × 109 mol−1 s−1. These OH· scavenging effects are significant beginning from 10, 28 and 100 μmol 1−1 concentration for famotidine, cimetidine and ranitidine, respectively, thus suggesting that the drugs may effectively act as OH· scavengers in vivo especially in the gastric lumen. Only cimetidine can apparently bind and inactivate iron, which further emphasizes its antioxidant capacity. Moreover, all drugs, even at 10 μmol 1−1 concentration, show powerful scavenging effects on hypochlorous acid and monochloramine, which are cytotoxic oxidants arising from inflammatory cells, such as neutrophils. These data suggest that some therapeutical effects of H2‐receptor antagonists in peptic ulcer may also be related to their antiradical‐antioxidant capacity, and that these drugs could potentially be used in other disease entities characterized by free radical‐mediated oxidative stress in vivo.

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.

Sodium cromoglycate in the treatment of eosinophilic gastroenteritis

Two patients suffering from eosinophilic gastroenteritis (EG) were treated with sodium cromoglycate (SCG). Before treatment they showed enteric and cutaneous symptoms, such as abdominal pain, nausea, vomiting, diarrhoea and recurrent urticaria and angioedema. The histological findings were a notable amount of eosinophilic infiltration in the lamina propria and gastric glands, a villous shortening and thickening and weak eosinophilic inflammation in the duodenum. The patients were treated with 300 mg SCG, 4 times daily, for 4/5 months. During treatment, the clinical symptoms disappeared and at the end of treatment a reduced inflammation with an almost complete decrease of eosinophilic infiltration was observed. The results provide evidence of SCG efficacy in the treatment of EG and suggest its employment as an alternative to the steroids commonly used in EG.

Gallbladder kinetics in obese patients

Gallbladder contractility has been studied in 21 obese patients >130% ideal weight) and 30 nonobese subjects before and at regular intervals after the administration of a regular solid-liquid meal, and after a low-calorie, low-fat meal used conventionally for weight-loss purposes (Modifast®). Gallbladder volume was determined by means of real-time ultrasonography, using a linear array scanner with a 3.5 MHz probe. In seven of the obese patients, gallbladder contractility was also evaluated after a 10-day regimen with Modifast. The obese group showed a statistically significant greater gallbladder fasting volume and blunted contractility than controls both after the ordinary and the low-calorie meal. The 10-day low-calorie regimen was associated with a statistically significant increment in fasting gallbladder volume, while the percent volume reduction after Modifast did not change. It is suggested that, in addition to metabolic factors, gallbladder hypocontractility in the obese may contribute to the high incidence of cholesterol gallstones noted in these patients. A low-calorie, low-fat diet augmenting gallbladder volume may favor bile stasis and therefore the likelihood of developing gallstones.

Treatment ofHelicobacter pyloriInfection

Antibiotic resistance has resulted in unsatisfactory eradication results with dual and now triple therapy in many countries. Newer antibiotics and changes in dosing and duration of therapy may overcome resistant strains but may only provide limited improvement in eradication rates. Sequential therapy with amoxicillin (1 g twice a day) and a proton pump inhibitor (PPI) (twice a day) given for 5 days followed by a PPI plus clarithromycin (500 mg twice a day) and tinidazole (500 mg twice a day) for 5 days is now a first‐line therapy for Helicobacter pylori in some countries. Standard triple therapy is effective in regions where clarithromycin resistance is low. Levofloxacin based triple therapy is an effective alternative to quadruple therapy in second‐line treatment. Adjuvant therapy may reduce side‐effects and improve compliance. Molecular and genomic research on H. pylori may result in the development of targeted antibiotic therapy; however, more research is required in this field. Further research in vaccination is also necessary before this can become an option in clinical practice.

Gallbladder hypokinesia and normal gastric emptying of liquids in patients with dyspeptic symptoms. A double-blind placebo-controlled clinical trial with cisapride.

Gastric and gallbladder emptying after a standard liquid meal were studied in 65 patients with early satiety, bloating, pain at the right hypochondrium or the epigastrium, nausea, and occasionally vomiting. Fifty normal subjects were studied as a control group. Gastric and gallbladder emptying were evaluated by means of real-time ultrasonography (RUS). Serial RUS scans were made after a 12-hr fast and every 15 min after a standard meal for 2 hr. Patients were considered to have delayed gastric emptying or hypokinetic gallbladder when gastric diameters and gallbladder volume evaluated 45 min after meal were 2sd above the corresponding mean values of the normal subject group. Fifteen patients (23%) were found with delayed gastric emptying and 20 (30.7%) a reduced gallbladder emptying. None of our patients showed delayed gastric emptying and hypokinetic gallbladder simultaneously. The 20 patients with reduced gallbladder emptying were included in a double-blind randomized, placebo controlled, change-over study with cisapride (10 mg three times a day) for 30 days. Cisapride treatment reversed the gallbladder hypomotility within the normal range while placebo did not change the response to meal. Symptom score improved significantly after cisapride and placebo. It is concluded that in dyspeptic patients with reduced gallbladder response to a meal, cisapride may be of help in improving the kinetic abnormality. Dyspeptic symptoms, however, do not seem to be corrected with the described gallbladder motor abnormality.

Gallbladder contraction and its relationship to interdigestive duodenal motor activity in normal human subjects

Gallbladder volume and interdigestive gastric and duodenal motor activity were evaluated simultaneously in 12 normal subjects. After overnight fasting, gallbladder volume was monitored every 4 min in each subject by means of real-time ultrasonography, and gastroduodenal motor activity was measured by means of a probe consisting of three polyvinyl catheters with one side opening for each catheter, placed 15 cm apart and constantly perfused with deionized water. Real-time ultrasonography and intestinal manometry were performed by different investigators and continued until at least two consecutive spontaneous phase III activities of migrating motor complexes were observed. The results show a cyclic variation of gallbladder volume, which reached its minimum value before the end of phase II in the proximal duodenum and its maximum in early phase II, 25 min after the beginning of phase III. These results suggest that there is a relationship between the cyclic gallbladder volume changes, which occur during fasting in humans, and with the various phases of duodenal migrating motor complex.