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.

No relationship between plasma desacyl-ghrelin levels and rabeprazole-related delay in gastric emptying : controlled study in healthy volunteers.

BACKGROUND AND OBJECTIVE: Recent studies have indicated that rabeprazole, a proton pump inhibitor, delays gastric emptying. However, the mechanism of action remains unclear. We conducted this study to clarify whether desacyl-ghrelin (the inactive form of the endogenous growth hormone secretagogue receptor ghrelin) is involved in rabeprazole-induced changes in gastric motor function. METHODS: Twelve healthy males underwent (13)C-acetate breath tests to evaluate gastric emptying of a liquid meal twice after administration of rabeprazole 20 mg/day for 3 days or no medication (control). Gastric emptying was evaluated by two parameters: half-emptying time and time to peak (13)CO(2) excretion. Plasma desacyl-ghrelin levels were measured in blood samples collected at three time points: immediately pre-test and 1 and 2 hours after ingestion of the test meal. RESULTS: Rabeprazole significantly delayed gastric emptying of the liquid meal. However, plasma desacyl-ghrelin levels after ingestion of the liquid meal showed little difference before or after rabeprazole administration. CONCLUSION: The results indicate that desacyl-ghrelin was not associated with changes in gastric emptying caused by rabeprazole.

Liver injury induced by levothyroxine in a patient with primary hypothyroidism.

We report a patient with primary hypothyroidism, who developed hepatocellular injury due to levothyroxine, synthetic thyroxine. A 63-year-old male was admitted to our hospital due to elevation of liver enzymes. The patient was diagnosed as having hypothyroidism and had been treated with levothyroxine for almost two months until admission. Drug-induced liver injury induced due to levothyroxine was suspected and liver enzymes were rapidly decreased after discontinuation of levothyroxine and dried thyroid powder, also containing thyroxine. Synthetic triiodothyronine, the deiodinated form of levothyroxine was administered instead, and was well tolerated by the patient. The drug-induced lymphocyte stimulation test (DLST) using levothyroxine was negative. Since triiodothyronine which structurally resembles levothyroxine did not cause liver injury, and DLST using levothyroxine was negative, it is unlikely that levothyroxine itself was targeted by the immune system. Rather, we assume that the complex of levothyroxine as the hapten and liver-related macromolecules in the body as the carrier might have acquired antigenicity in this patient and subsequently resulted in liver injury.

Reliability of rapid urinary test for antibody to Helicobacter pylori in adult patients with proteinuria.

A urinary test for detecting the anti-H. pylori antibody using immunochromatography (RAPIRAN) is considered suitable for the screening purpose. However, this may yield spurious results in the presence of proteinuria. The present study was conducted to evaluate the diagnostic performance of RAPIRAN in patients with proteinuria. Urine and serum samples of adult inpatients with proteinuria were used for analyses. The diagnosis of H. pylori infection was made based on the seropositivity of anti-H. pylori antibody using 2 different serum tests. Fifty-one subjects were eligible for analyses. The serum tests showed negative and positive in 25 and 26 patients, respectively. Two of 25 seropositive patients had a negative result in RAPIRAN, and 1 provided invalid data. All of seronegative patients showed negative in RAPIRAN. The overall accuracy was 95.0%. The present study showed that RAPIRAN has diagnostic quality enough to use clinically also in patients with proteinuria.

Reliability of urinary tests for antibody to Helicobacter pylori in patients with pulmonary tuberculosis.

AIM: Although the quality of currently available urinary tests for detecting antibody to Helicobacter pylori (H pylori) have been proved in some populations, the accuracy has not been studied regarding patients who suffer from pulmonary tuberculosis with multi-drug treatments. The present study was conducted to evaluate the accuracy of these urinary tests for antibody to H pylori in these patients. METHODS: Serum samples from 61 inpatients with pulmonary tuberculosis were tested using enzyme immunoassay, and urine samples were assayed by enzyme-linked immunosorbent assay method (URINELISA) and immunochromatography method (RAPIRAN). Medicines prescribed to the patients were recorded for medical charts, to evaluate the influences on the results of urinary tests. RESULTS: The sensitivity, specificity, and consistency of URINELISA against the serum test were 93.1%, 65.6%, and 78.6% respectively, and those of RAPIRAN were 86.2%, 93.7%, and 90.1% respectively, which were almost equal to the data previously reported. Prescribed medicines had little influence on the results. CONCLUSION: The two urinary tests for detecting H pylori antibody have a diagnostic accuracy in patients with pulmonary tuberculosis given multiple anti-tuberculosis drugs.

Modified 13C-octanoate breath test and impact of sampling points.

In recent years, the C-octanoate breath test has attracted attention as a simple and noninvasive method of assessing gastric emptying of solids. However, practical procedures for test meals, parameters used, and sampling points have not yet been established. Moving toward a more convenient method, here we examined the influences of sampling interval and duration on the C-octanoate breath test performed on 15 healthy subjects using a commercially-available instant cupcake. Breath samples were obtained every 15 minutes within 4 hours, and every 30 minutes in the subsequent 2 hours. Using computer simulation, the time it took for the fitting curve to peak (Tpeak) was calculated in each setting with each interval (15, 30, 60, and 120 minutes) and test duration (3, 4, 5, and 6 hours). When the sampling interval widened over 30 minutes, the difference from the original 6-hour data became larger than 20% of the coefficient of variance. When the sampling duration was shortened to 3 hours, no appropriate fitting curve could be achieved. These results suggest that a sampling duration of 4 hours at 30-minute intervals seems to be suitable for practical use of the test.