The motility of Helicobacter pylori was maximum at 37°C and at pH 6. A newly developed proton pump inhibitor, rabeprazole (RPZ), and its thioether derivative (RPZ-TH) markedly inhibited the motility of H. pylori. The concentrations of the drug necessary to inhibit 50% of the motility were 0.25, 16, 16, and >64 g/ml for RPZ-TH, RPZ, lansoprazole, and omeprazole, respectively. No such inhibitory effects were observed with H 2 blockers or anti-H. pylori agents. The motilities of Campylobacter jejuni and C. coli-but not those of Vibrio cholerae O1 and O139, Vibrio parahaemolyticus, Salmonella enterica serovar Typhimurium, and Proteus mirabilis-were also inhibited. Prolonged incubation with RPZ or RPZ-TH inhibited bacterial growth of only H. pylori, except for a turbid colony mutant. The results indicate that RPZ and RPZ-TH have a characteristic inhibitory effect against the motility of H. pylori (spiral-shaped bacteria), which is distinguished from that against bacterial growth.Helicobacter pylori, which colonizes the gastric mucosa, is closely associated with gastritis and peptic ulcers (7,17) and is even a bacterial risk factor for gastric cancer (9,10,24,25,27 (1,6,11,14,15,23) as well as urease activity (16,19,26) in vitro.H. pylori is a spiral-shaped, gram-negative bacterium with one or two turns along its axis. It has multiple (four to six) polar flagella, and exhibits strong motility (13). The motility conferred by the flagella is necessary for colonization of the gastric mucosa and development of gastritis by H. pylori (3,4). In this study, we examined the effects of a newly developed PPI, rabeprazole (RPZ), and its thioether derivative (RPZ-TH) on the motility of H. pylori. MATERIALS AND METHODSBacterial strains. H. pylori strains used (seven strains) were isolates from gastric biopsy specimens of patients with gastritis and peptic ulcers. The primary cultures of each isolate were stored frozen at Ϫ80°C in 3% skim milk (Difco Laboratories, Detroit. Mich.) supplemented with 5% glucose (Difco). The following motile, gram-negative bacteria were also employed: Campylobacter jejuni and Campylobacter coli for spiral-shaped bacteria; Vibrio cholerae O1 biotype El Tor strain EO8 (28), V. cholerae O1 biotype classical strain CI3 (28), and V. cholerae O139 strain T16 (30) for curved rods; and V. parahaemolyticus (e.g., strain 100B [29]), Salmonella enterica serovar Typhimurium, and Proteus mirabilis for rods. All bacterial strains except for P. mirabilis were isolates from patients with diarrhea. Media and bacterial growth. H. pylori, C. jejuni, and C. coli were grown on blood agar plates (Trypticase soy agar supplemented with 5% sheep blood; Becton Dickinson, Tokyo, Japan) for 2 (for C. jejuni and C. coli) to 4 (for H. pylori) days at 37°C in a microaerophilic atmosphere (10% O 2 and 10% CO 2 ). The colonies developed were then suspended in brain heart infusion (BHI) broth (Difco) containing 10% fetal bovine serum (FBS) (Gibco, Gaithersburg, Md.), followed by incubation for 18 to 20 h at 37°C in a microaerophilic a...

Caspase proteolytic activities, such as caspase-3, -2 and -6, of THP-1 human monocytic cells were markedly increased in a time-and dosedependent manner by treatment with purified Shiga toxin 1 (Stx1) or Stx2. Caspase-3 activation was strictly correlated with internucleosomal DNA fragmentation and chromatin condensation of the cells. In addition, the specific caspase-3 inhibitor, Ac-DEVD-CHO, decreased the percentage of apoptotic cells. The purified B-subunit of Stx1 did not induce apoptosis in THP-1 cells. Caspase-3 activation, DNA fragmentation and chromatin condensation caused by Stx were completely blocked by pretreatment of cells with brefeldin A, an inhibitor of Golgi functions. The findings suggest that Stx1 as well as Stx2 activate caspase-3, which plays a critical role in apoptosis, and that the apoptotic signals rise after Stx is transported to the Golgi apparatus. ß

, in marked contrast to norfloxacin. Azithromycin decreased the tumor necrosis factor alpha (TNF-␣), interleukin-1␤ (IL-1␤), and IL-6 production from Stx-treated human peripheral mononuclear cells or monocytes to a greater extent than did clarithromycin. In Stx-injected mice, azithromycin significantly suppressed Stx-induced TNF-␣, IL-1␤, and IL-6 levels in serum and improved the outcome as assessed by survival rate. In the STEC oral infection experiment using immature mice immediately after weaning (weaned immaturemouse model), all mice died within 7 days postinfection. Azithromycin administration gave the mice 100% protection from killing, while ciprofloxacin administration gave them 67% protection. The data suggest that azithromycin (at least at higher concentrations) has a strong effect on Stx production by STEC and on the Stxinduced inflammatory host response and prevents death in mice. Azithromycin may have a beneficial effect on STEC-associated disease.

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Caspase proteolytic activities, such as caspase-3, -2 and -6, of THP-1 human monocytic cells were markedly increased in a time- and dose-dependent manner by treatment with purified Shiga toxin 1 (Stx1) or Stx2. Caspase-3 activation was strictly correlated with internucleosomal DNA fragmentation and chromatin condensation of the cells. In addition, the specific caspase-3 inhibitor, Ac-DEVD-CHO, decreased the percentage of apoptotic cells. The purified B-subunit of Stx1 did not induce apoptosis in THP-1 cells. Caspase-3 activation, DNA fragmentation and chromatin condensation caused by Stx were completely blocked by pretreatment of cells with brefeldin A, an inhibitor of Golgi functions. The findings suggest that Stx1 as well as Stx2 activate caspase-3, which plays a critical role in apoptosis, and that the apoptotic signals rise after Stx is transported to the Golgi apparatus.