TRPV2 channel inhibitors attenuate fibroblast differentiation and contraction mediated by keratinocyte-derived TGF-ß1 in an in vitro wound healing model of rats.

BACKGROUND: Keratinocytes release several factors that are involved in wound contracture and scar formation. We previously reported that a three-dimensional reconstruction model derived from rat skin represents a good wound healing model. OBJECTIVE: We characterized the role of transient receptor potential (TRP) channels in the release of transforming growth factor (TGF)-ß1 from keratinocytes and the differentiation of fibroblasts to identify possible promising pharmacological approaches to prevent scar formation and contractures. METHODS: The three-dimensional culture model was made from rat keratinocytes seeded on a collagen gel in which dermal fibroblasts had been embedded. RESULTS: Among the TRP channel inhibitors tested, the TRPV2 inhibitors SKF96365 and tranilast attenuated most potently keratinocyte-dependent and - independent collagen gel contraction due to TGF-ß signaling as well as TGF-ß1 release from keratinocytes and α-smooth muscle actin production in myofibroblasts. Besides the low amounts detected in normal dermis, TRPV2 mRNA and protein levels were increased after fibroblasts were embedded in the gel. TRPV2 was also expressed in the epidermis and keratinocyte layers of the model. Both inhibitors and TRPV2 siRNA attenuated the intracellular increase of Ca2+ induced by the TRPV agonist 2-aminoethoxydiphenyl borate in TGF-ß1-pretreated fibroblasts. CONCLUSION: This is the first study to show that compounds targeting TRPV2 channels ameliorate wound contraction through the inhibition of TGF-ß1 release and the differentiation of dermal fibroblasts in a culture model.

Severe erosive esophagitis developing after gastric ulcer formation.

A 90-year-old woman visited to our institute due to postprandial obstructive sensation of the esophagus. She had suffered from ischemic heart disease and diabetes mellitus, and taken low-dose aspirin for prophylaxis. She also had a history of a large ulcer located on the upper gastric body at 81 years-old. Esophago-gastric junction was normal excepting mild hiatal hernia at that time. The esophagogastroduodenoscopy showed a lump of food at the lower esophagus with severe stricture and mucosal injury. Rabeprazole 20 mg per day was given, and both the inflammatory change and the symptoms improved after the prescription. A probable reason of the development is impaired gastroesophageal motility and acid regurgitation induced by gastric deformity caused after ulcer formation.

Metronidazole-induced neurotoxicity developed in liver cirrhosis.

A 68 year-old-male with hepatitis C-positive liver cirrhosis was admitted because of liver abscess. After metronidazole was initiated against the infection, mental disturbance appeared. Hepatic encephalopathy was suspected at first, however, the brain MRI showed hyperintense lesion of the bilateral basal dendric nuclei which indicated metronidazole-associated encephalopathy. The symptoms became well after cessation of the drug. Metronidazole is a widely used medicine against various infections. Recent case reports describe that this medicine can induce reversible encephalopathy. However, there have been few reports regarding metronidazole-induced encephalopathy occurred in patients with cirrhosis. Here we report on a case of hepatic cirrhosis and abscess in which reversible metronidazole-induced encephalopathy developed.

Endoscopic hemostasis techniques for upper gastrointestinal hemorrhage: A review.

Upper gastrointestinal hemorrhage (UGIH) is an urgent disease that is often encountered in daily medical practice. Endoscopic hemostasis is currently indispensable for the treatment of UGIH. Initially, when UGIH is suspected, a cause of UGIH is presumed from the medical interview and physical findings. After ample primary treatment, urgent endoscopy is performed. Many methods of endoscopic hemostasis are in wide use, including hemoclip, injection and thermo-coagulation methods. Although UGIH develops from a wide variety of diseases, such as esophageal varices and gastric and duodenal ulcer, hemostasis is almost always possible. Identification of the causative diseases, primary treatment and characteristic features of endoscopic hemostasis are needed to allow appropriate treatment.

Gastroduodenal mucosal injury in patients taking low-dose aspirin and the role of gastric mucoprotective drugs: possible effect of rebamipide.

The present study was conducted to investigate the prevalence of mucosal injury in patients taking low-dose aspirin in Japan and examine the effect of gastric mucoprotective drugs on aspirin-related gastroduodenal toxicity. We selected 530 patients who had taken low-dose aspirin for 1 month or more after undergoing esophagogastroduodenoscopy from 2005 through 2006 at Teikyo University Hospital, Tokyo, Japan. Endoscopic records were retrospectively reviewed to determine the presence of massive bleeding and mucosal injury (ulcer or erosion). The influence of clinical factors, including co-administration of gastroprotective drugs, was also examined. Hemorrhage was observed in 25 patients (3.7%) and mucosal injury (36.2%) in 192 patients. The presence of Helicobacter pylori antibody was a significant risk factor associated with mucosal injury. Patients taking any gastroprotective drug showed a significantly lower rate of mucosal injury than those not taking these drugs. Patients taking rebamipide concomitantly with proton pump inhibitors or histamine 2 receptor antagonists had mucosal injury less frequently than those taking acid suppressants plus other mucoprotective drugs. In conclusion, these results show the possible gastroprotective effects of rebamipide, suggesting that it may be a good choice in aspirin users with gastroduodenal toxicity that is not suppressed by acid suppressants alone.

Prevalence of erosive esophagitis among Japanese patients taking low-dose aspirin.

BACKGROUND AND AIM: The risk for erosive esophagitis (EE) with low-dose aspirin (ASA) remains unknown, especially among Japanese patients. We conducted the present study to compare the risk of EE with that of gastroduodenal mucosal injury among Japanese patients taking ASA. METHODS: From 5555 patients undergoing upper gastrointestinal endoscopy from January 2005 to December 2006 at Teikyo University Hospital, Tokyo, Japan, 159 patients (76 males and 83 females, mean age: 69.3 +/- 11 years) fulfilling the following conditions were selected: (i) taking ASA (less than 100 mg/day) continuously; (ii) not taking acid suppressants; and (iii) no history of gastrointestinal tract surgery, malignancies, severe cardiac failure, or liver cirrhosis. Age- and sex-matched patients not taking aspirin were randomly chosen as controls (n = 159). Two well-experienced endoscopic examiners evaluated endoscopic records to determine the presence or absence of esophageal hiatal hernia, EE, and gastroduodenal ulcers. RESULTS: The prevalence of EE in patients taking aspirin (9.4%) was not different from that of the controls (6.3%, odds ratio [OR]: 1.5, 95% confidence interval [CI]: 0.7-3.2), whereas peptic ulcers were found more frequently in the aspirin group (14%) than in the control group (4%, OR: 3.6, 95% CI: 1.5-8.8). CONCLUSION: In Japanese patients taking ASA, EE was not as common as peptic ulcers.

Diagnosis of Helicobacter pylori infection using RAPIRUN H. pylori antibody detection kit.

Accurate diagnosis of Helicobacter pylori infection is essential in today's clinical settings. Additionally, because of the widespread prevalence of this infection, noninvasive and convenient techniques are required for screening purposes. RAPIRUN H. pylori antibody detection kit (Otsuka Pharmaceutical Co., Ltd, Tokyo, Japan) enables a diagnosis within 20 min using a random, single-voided urine specimen. Thus it is especially suited for use in point-of-care settings. The sensitivity and specificity are acceptable and comparable with other available methods. Here we provide an overview of the RAPIRUN kit.