Fumihiro Iwata

Role of gap junctions in inhibiting ischemia-reperfusion injury of rat gastric mucosa

Gap junctional intercellular communication (GJIC) is known to be important in the maintenance of tissue homeostasis. However, the role of GJIC in gastric mucosa has not been well investigated. We tested the hypothesis that maintenance of GJIC protects rat gastric mucosa against ischemia-reperfusion (I/R) stress by using irsogladine, an activator of GJIC, and octanol, an inhibitor of GJIC. Intragastric perfusion with octanol before ischemia resulted in a significant increase in 51Cr-EDTA clearance after reperfusion. Intraduodenal pretreatment with irsogladine attenuated the increase in 51Cr-EDTA clearance produced by octanol in a dose-dependent manner. Epithelial gap junctions reacted with anticonnexin-32 monoclonal antibodies were not changed after I/R stress alone. Intragastric perfusion with octanol caused a significant reduction in immunoreactive connexin-32 spots, which was completely reversed by irsogladine. These results indicate that inhibition of GJIC weakens the barrier function of gastric mucosa and subsequently causes damage of the barrier function in combination with I/R. Facilitation of GJIC and maintenance of gap junctions protect gastric mucosal barrier functions by potentiating cellular integrity.

Functional evidence linking potassium channels and afferent nerve-mediated mucosal protection in rat stomach

Adenosine triphosphate-dependent potassium (K+ATP) channels in several types of vascular smooth muscles mediate the vasodilation induced by calcitonin gene-related peptide (CGRP). Upon stimulation, primary afferent nerve terminals in the gastric mucosa release CGRP which mediates a protective hyperemia. We tested the hypothesis that a potassium channel blocker aggravates gastric mucosal injury by impairing afferent nerve-mediated hyperemia in the gastric mucosa. Rats were treated with K+ATP channel blocker, glybenclamide (20 mg/kg intravenously). Intragastric added ethanol (0.15 N HCl, 15% ethanol) and intragastric capsaicin (160 microM) were also administered. Glybenclamide aggravated the acidified ethanol-induced mucosal injury, and attenuated the mucosal hyperemia (hydrogen gas clearance) induced by intragastric acidified ethanol and intragastric capsaicin. These findings suggest for the first time that K+ATP channels modulate primary afferent nerve-mediated mucosal defense mechanisms in the gastric mucosa.

Role of endogenous nitric oxide in ischaemia‐reperfusion injury of rat gastric mucosa

It has been suggested that endogenous nitric oxide may act as a protective factor for gastric mucosa since nitric oxide increases blood flow and may scavenge certain oxyradicals. We tested the hypothesis that nitric oxide protects rat gastric mucosa against ischaemia‐reperfusion stress. Gastric ischaemia was induced by clamping the left gastric artery for 20 min. Rats were treated with two kinds of specific inhibitors of nitric oxide production, NG‐nitro‐L‐arginine or NG‐monomethyl‐L‐arginine. Gastric mucosal integrity was continuously monitored by measuring the blood‐to‐lumen clearance of [51chromium]‐labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. Oxidative stress in gastric mucosa was assessed by measuring dichlorofluorescein (DCF) fluorescence intensity before ischaemia and after reperfusion. Blockade of nitric oxide resulted in a significant increase in [51Cr]‐EDTA clearance and DCF fluorescence intensity after reperfusion. These effects of nitric oxide inhibitors were attenuated by pretreatment with L‐arginine. In conclusion, these findings support the hypothesis that endogenous nitric oxide acts as an important protective factor against ischaemia‐reperfusion stress in rat gastric mucosa.

Role of complement regulatory membrane proteins in ischaemia–reperfusion injury of rat gastric mucosa

Background : The role of complement in ischaemia–reperfusion injury has not been well investigated. 5I2 is a monoclonal antibody (mAb) directed against a rat membrane inhibitor of the C3 convertase step, which is the rat counterpart of mouse Crry/p65. 6D1 is a mAb against rat CD59 which inhibits the formation of membrane attack complexes.

Familial occurrence of congenital bile duct cysts

Congenital bile duct cysts are now a well‐documented anomaly of the biliary tree, and have become more common in Japan. Familial occurrence of congenital bile duct cysts, however, is extremely rare, with only six reported cases in the literature. We report a familial pattern of congenital bile duct cysts in a mother and her daughter. A 33‐year‐old female was admitted for evaluation of right upper quadrant abdominal pain and fever 6 days after an uneventful delivery of her second child. A com‐ puted tomography (CT) and ultrasound scan (US) revealed an obstructed biliary tract. Percutaneous transhepatic biliary drainage was then performed, and a cholangiogram revealed a Scholtz type B choledochocele without an anomalous connection of the pancreaticobiliary ducts. Endoscopic US demonstrated that the choledochocele was associated with a stone in the cyst. A pylorus‐preserving pancreatoduodenal resection was performed, and a histological study revealed that the choledochocele was lined by biliary mucosa without evidence of malignancy. The newborn infant had an abdominal tumour. An US and CT revealed a congenital bile duct cyst. An operation was performed and the intraoperative cholangiogram showed an Alonso‐Lej type I congenital bile duct cyst with an anomalous connection of the pancreaticobiliary ducts. Whether congenital bile duct cysts are hereditary remains to be elucidated.

A Case of Familial Adenomatous Polyposis Associated with Colon Cancer, Ureteral Cancer and Two Early Gastric Cancers

A rare case of Familial Adenomatous Polyposis (FAP), associated with colon cancer, ureteral cancer and two early gastric cancers, is reported. A 42‐year‐old male was admitted to our hospital for evaluation of bloody stools and macrohematuria. There were six FAP patients in his family line, spanning four generations, and five had developed colon cancers. A barium enema revealed diffuse and scattered polyposis throughout the colon and an apple core sign in the descending colon. Abdominal CT disclosed right hydronephrosis with a markedly dilated ureter. Surgery was undertaken and included total colectomy, mucosal proctectomy, ileoanal anastomosis and right nephrectomy with ureteral resection, under a diagnosis of colon cancer and complete right ureteral stenosis. The resected specimens revealed a colon cancer in the descending colon, 50×32×15 mm in size and a ureteral cancer in the lower part of the right ureter, 30×16×16 mm in size.