Clarithromycin Versus Metronidazole as First-line Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Controlled Study in Japan.

BACKGROUND: Helicobacter pylori eradication rates achieved with a first-line regimen of clarithromycin (CLR) combined with amoxicillin (AMX) and a proton pump inhibitor have recently fallen to ≤80% because of the increasing incidence of CLR resistance in Japan. This randomized multicenter trial aimed to compare the eradication success of 2 first-line triple therapy regimens: rabeprazole, amoxicillin, and clarithromycin (RAC) versus rabeprazole, amoxicillin, and metronidazole (RAM). METHODS: A total of 124 consecutive patients infected with H. pylori were randomized into one of two 7-day therapeutic regimens: RAC (n=60) or RAM (n=64). Eradication was confirmed by the C-urea breath test. Adverse effects were also assessed. RESULTS: Intention-to-treat and per protocol H. pylori eradication rates were 73.3%/77.2% in the RAC group and 90.6%/93.5% in the RAM group. The eradication rate of RAM therapy was significantly higher than that of RAC therapy. CLR, metronidazole, and AMX resistance was found in 36.2%, 2.1%, and 0% of patients, respectively. In addition, no relevant differences in adverse effects were observed. CONCLUSIONS: Metronidazole-based therapy (RAM) was superior to standard CLR-based therapy (RAC) for first-line H. pylori eradication. This reflects the progressive increase in CLR resistance observed in Japan.

Effect of supplementation with rebamipide for Helicobacter pylori eradication therapy: a systematic review and meta-analysis.

BACKGROUND AND AIM: Several studies have reported that the application of rebamipide during the eradication of Helicobacter pylori can improve the eradication rate. However, the efficacy and safety are controversial. The present study systematically evaluated whether rebamipide improves the eradication rate of H. pylori by conducting a meta-analysis based on randomized controlled trials (RCTs). METHODS: Literature searches were conducted in the following database: PubMed, the Cochrane Library, and the Igaku-chuo-zasshi database in Japan. A meta-analysis of all RCTs comparing rebamipide supplementation with non-rebamipide-containing therapy was performed. RESULTS: We identified six randomized trials (611 patients). Pooled H. pylori eradication rates by per-protocol analysis were 73.3% and 61.4% for patients with or without rebamipide, respectively. The odds ratio was 1.74 (95% confidence interval. 1.19-2.53). CONCLUSIONS: Supplementation with rebamipide might be effective in increasing the H. pylori eradication rates of proton-pump inhibitor-amoxicillin dual therapy.

Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction.

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the ¹³C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.

Involvement of Src family kinase activation in angiotensin II-induced hyperresponsiveness of rat bronchial smooth muscle.

Angiotensin II (Ang II) might be an important mediator in pathogenesis of airway hyperresponsiveness (AHR) that is the asthmatic characteristic feature of asthma, although the mechanisms of AHR caused by Ang II are not yet clear. Presently, the RT-PCR analyses revealed that all the Src family kinases (SFKs), such as Fyn, Lck, Lyn, Hck, Src, Yes, Blk, Fgr and Frk, were expressed in the lungs and main bronchi of rats. The phosphorylation (activation) of SFK (Tyr416) was increased in bronchial smooth muscle (BSM) by Ang II. The Ang II-induced SFK phosphorylation was inhibited by pretreatment with SU6656, an SFK inhibitor. The concentration-contraction curves to carbachol (CCh) were shifted to the left in the presence of Ang II. The maximal contraction of CCh was also significantly increased by pretreatment with Ang II. These results indicate that Ang II causes BSM hyperresponsiveness. The Ang II-induced BSM hyperresponsiveness was significantly inhibited by SU6656, although the carbachol (CCh)-induced contraction itself was not changed by SU6656. In conclusion, Ang II induced a BSM hyperresponsiveness through activation of SFK, and might play an important role in pathophysiology of bronchial asthma.

Angiotensin II induces hyperresponsiveness of bronchial smooth muscle via an activation of p42/44 ERK in rats.

Angiotensin II (Ang II) might be an important mediator in the pathogenesis of bronchial asthma, although the mechanisms of airway hyperresponsiveness caused by Ang II are not yet clear. Whether p42/44 ERK contributes to the Ang II-elicited bronchial smooth muscle (BSM) hyperresponsiveness in rats was presently examined. The RT-PCR analyses revealed that Ang II AT(1A), AT(1B), and AT(2) receptors, angiotensinogen, angiotensin-converting enzyme, but not renin, were expressed in the lungs, trachea, and main bronchi of rats. Only a small and transient contraction was induced by the application of Ang II in the main bronchial smooth muscle; the contraction was inhibited by losartan, an AT(1) receptor antagonist. The contractions induced by carbachol (CCh), high K(+) depolarization, and sodium fluoride (NaF; a G protein activator) were augmented by pretreatment with Ang II. The BSM hyperresponsiveness induced by Ang II was abolished by losartan. Furthermore, the Ang II-induced BSM hyperresponsiveness to CCh was attenuated by pretreatment with U-0126, a p42/44 ERK kinase (MEK-1/2) inhibitor. In conclusion, Ang II-induced BSM hyperresponsiveness through the activation of p42/44 ERK may play an important role in the pathophysiology of bronchial asthma, although Ang II itself caused a small force development in the bronchial smooth muscle.

The physiological and behavioral effects of subchronic intracisternal administration of TGF-beta in rats: comparison with the effects of CRF.

We studied the physiological and behavioral effects of subchronic intracisternal administration of transforming growth factor-beta (TGF-beta) for 7 days. Subchronic intracisternal administration of TGF-beta significantly inhibited the increase in body weight of rats but did not affect food intake. In the measurement of locomotor activity after the final intracisternal administration on day 7, the total count for 1.5 h increased significantly in the TGF-beta group compared with the vehicle group. However, that for 10 h was not different between both groups. Furthermore, significant elevations in oxygen consumption were observed in the TGF-beta group during both light and dark phase. Subchronic TGF-beta treatment induced a significant decrease in the number of total leukocytes and lymphocytes and the relative weight of the thymus, and a significant increase in brown adipose tissue weight. Corticotropin-releasing factor (CRF) is the primary neuroendocrine factor released in response to stress. Subchronic treatment with CRF, as a positive control, significantly affected body weight, food intake, oxygen consumption, total leukocyte and lymphocyte counts, and thymus and adrenal weight. Subchronic TGF-beta administration partially mimicked the stress responses, implicating a role for TGF-beta in the brain in stress.