Masahiro Yoshinaga

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 13C-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.

Two Endothelin Receptors (ETA and ETB) Expressed on Circular Smooth Muscle Cells of Guinea Pig Cecum

BACKGROUND/AIMS The functional receptors for endothelin (ET) in colonic smooth muscle are still unknown. This study investigated the expression of ET receptors in isolated circular smooth muscle cells of guinea pig cecum. METHODS Inhibition of 125I-ET-1 binding was examined using unlabeled ET-1, ET-2, ET-3, sarafotoxin 6c (S6c), and ETA antagonists. Expression of the ET-receptor message was investigated using reverse-transcription polymerase chain reaction. The contractile potency of the ET family and the inhibitory effect of ETA antagonists on ET-1-induced contraction were also investigated. RESULTS Unlabeled ET-1, ET-2, and ET-3 inhibited the specific binding of 125I-ET-1 in a concentration-dependent manner, but the inhibitory effect of ET-3 was smaller than those of ET-1 and ET-2. At a 10(-6) mol/L concentration of S6c, the specific binding of 125I-ET-1 was 24.7%. S6c had clearly reached maximal inhibition. Abundant polymerase chain reaction products for both the ETA and the ETB message were observed. ET-1 and ET-2 showed similar contractile potency, but ET-3-induced and S6c-induced contractions were significantly less potent than the ET-1-induced contraction. A significant response to S6c was obtained at a concentration as low as 10(-10) mol/L. The ETA antagonists BQ-123 and FR 139317 significantly inhibited ET-1-induced contraction. CONCLUSIONS The results show a direct contractile effect of ETs on circular smooth muscle of guinea pig cecum and the presence of both ETA- and ETB-receptor subtypes.

Rectal carcinoid tumor: endoscopic ultrasonographic detection and endoscopic removal

Eight patients with rectal carcinoid tumors were examined by endoscopic ultrasonography (EUS) to assess the depth of invasion of the rectal wall. All resected tumors were contained within the submucosa and their depth of invasion was correctly diagnosed by EUS before treatment. Perirectal lymph nodes were not delineated by EUS. Four patients who were treated only with endoscopic polypectomy were completely cured as were four patients who had a surgical resection. EUS is useful in selecting the candidates for endoscopic removal or local resection and thus may help to avoid unnecessary radical surgery.

Direct contractile effect of motilin on isolated smooth muscle cells of guinea pig small intestine

We examined the direct effect of motilin on longitudinal and circular smooth muscle cells isolated from the guinea pig small intestine. In addition, the effects of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate hydrochloride (TMB-8, an inhibitor of intracellular Ca(2+)-release), verapamil (a voltage-dependent Ca(2+)-channel blocker), and removal of extracellular Ca2+ were investigated to evaluate the role of intracellular Ca2+ stores and extracellular Ca2+ on the muscle contraction induced by motilin. The effects of atropine (a muscarinic receptor antagonist), spantide (a substance P receptor antagonist) and loxiglumide (a CCK-receptor antagonist) were also examined to determine whether the motilin-induced contraction was independent of those receptors. Motilin induced a contraction of the longitudinal and circular smooth muscle cells in a dose-dependent manner with the maximal effect attained after 30 seconds of incubation. The ED50 values were 0.3 nM and 0.05 nM, respectively. TMB-8 suppressed completely the motilin-induced contraction of both types of smooth muscle cells. Verapamil had only a slight suppressive effect. Removal of extracellular Ca2+ did not have any significant influence on motilin-induced contraction. The contractile response to motilin was not affected by atropine, spantide or loxiglumide. Our findings showed that:1) motilin has a direct contractile effect on both longitudinal and circular smooth muscle cells; 2) this contractile effect is not evoked via muscarinic, substance P or CCK receptors, and 3) the intracellular release of Ca2+ plays an important role in the contractile response to motilin on both types of smooth muscle cells.

Vitamin C inhibits corpus gastritis in Helicobacter pylori-infected patients during acid-suppressive therapy

Previous studies have shown that gastric acid suppression worsens corpus gastritis in Helicobacter pylori (H. pylori)‐positive patients. We evaluated the effect of acid‐suppressive therapy and vitamin C on H. pylori‐associated gastritis.

The Simultaneous Expression of Peroxisome Proliferator-Activated Receptor Delta and Cyclooxygenase-2 May Enhance Angiogenesis and Tumor Venous Invasion in Tissues of Colorectal Cancers

We conducted this study to evaluate the impact of the expression of peroxisome proliferator-activated receptor delta on angiogenesis in tissue samples of colorectal cancer. We examined 52 samples of primary human colorectal carcinomas and matched normal adjacent tissues to evaluate the expression of peroxisome proliferator-activated receptor delta, cyclooxygenase-2, vascular endothelial growth factor-A, and CD34 through immunohistochemical analysis. Peroxisome proliferator-activated receptor delta was expressed in 25 (48.1%), and cyclooxygenase-2 was expressed in 26 (50.0%) of total colorectal cancer tissues. Tissue samples were divided into four groups, according to the expression of peroxisome proliferator-activated receptor delta and cyclooxygenase-2. The positive rate of vascular endothelial growth factor-A, the levels of microvascular density, and the incidence of venous vessel invasion in peroxisome proliferator-activated receptor delta (+)/cyclooxygenase-2 (+) samples exceeded significantly those in the other three groups of tissue samples (P < 0.05). The results suggest that the axis of the cyclooxygenase-2/peroxisome proliferator-activated receptor delta signal pathway might play a crucial role in the development of colorectal cancers by enhancing angiogenesis.

The 15-lipoxygenase-1 expression may enhance the sensitivity to non-steroidal anti-inflammatory drug-induced apoptosis in colorectal cancers from patients who are treated with the compounds

Background and Aim:  Non‐steroidal anti‐inflammatory drugs (NSAIDs) can prevent colorectal cancer (CRC), but their effect is limited. Recent studies have shown the involvement of 15‐lipoxygenase‐1 (15‐LOX‐1) in NSAID‐induced apoptosis in colorectal carcinoma cells. We evaluate whether 15‐LOX‐1 expression influences the sensitivity of NSAID‐induced apoptosis in CRCs.

Direct contractile effect of endothelin-1 on isolated circular smooth muscle cells of guinea pig caecum

Smooth muscle cells isolated from the circular muscle layers of the guinea pig caecum were used to determine whether endothelin-1 (ET-1) can cause contraction by exerting a direct action on smooth muscle cells. In addition, the inhibitory effects of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of intracellular Ca2+ release, verapamil, a Ca2+ channel blocker, and removal of extracellular Ca2+ on the ET-1-induced muscle contraction were examined. ET-1 elicited a contractile response of isolated smooth muscle cells in a dose-dependent manner (ED50: 2 nM). TMB-8, verapamil, and removal of extracellular Ca2+ significantly inhibited the contraction produced by ET-1. These results strongly suggest that ET-1 has a direct contractile effect on circular smooth muscle cells of the guinea pig caecum, and that this contraction depends on both intracellular and extracellular Ca2+.

Accelerated communication the direct contractile effect of gastrin releasing peptide on isolated gastric smooth muscle cells of the guinea pig

Abstract Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to determine whether gastrin releasing peptide (GRP) can cause contraction by exerting a direct action on muscle cells. In addition, the inhibitory effect of 8-( N,N-diethylamino )-octyl-3,4,5-trimethoxybenzoate hydrochloride ( TMB-8 ), an inhibitor of intracellular Ca2+ release, and verapamil, a Ca2+ channel blocker, on the GRP-induced contraction of gastric smooth muscle cells were examined. GRP elicited a contractile response of gastric muscle cells in a dose-dependent manner. The ED50 was 13 pM. TMB-8 significantly inhibited the contractile effect of GRP in gastric muscle cells. These results demonstrate the direct action of GRP on the gastric smooth muscle cells of the guinea pig, and the importance of Ca2+-release from intracellular calcium stores in the contractile response to GRP.

Paclitaxel-Based Chemotherapy for Advanced Pancreatic Cancer after Gemcitabine-Based Therapy Failure: A Case Series of 5 Patients

Background/Objectives: Gemcitabine (GEM) is a gold-standard chemotherapy agent for advanced pancreatic cancer. Because of the malignant character of the disease, nearly all patients show disease progression despite treatment with GEM-based chemotherapy; therefore, second-line chemotherapy may be beneficial for these patients. We report a retrospective analysis of 5 patients with advanced pancreatic cancer, treated with a paclitaxel-containing regimen as second-, third- or fourth-line chemotherapy after various therapies, such as a GEM-based regimen, S-1 regimen, and chemoradiation. We retrospectively analyzed the efficacy and adverse events, and evaluated the paclitaxel-containing regimens. A review of the literature is also discussed. Results: The median overall survival from the start of salvage therapy was 10.7 months. The disease control rate of the paclitaxel-containing regimen according to RECIST criteria was 60%, including complete response in 0 patients, partial response in 3, and stable disease in 2. Two patients had malignant ascites at the start of this salvage therapy, and in both of them the ascites and clinical complaints improved. Grade 3 and 4 hematological adverse events were observed in 2 patients and 1 patient, respectively. Conclusion: Salvage paclitaxel-based therapy could be beneficial to advanced pancreatic cancer patients who maintain good performance status after several chemotherapy failures.