Mami Ogura

Role of endogenous platelet-activating factor in caerulein-induced acute pancreatitis in rats: Protective effects of a PAF-antagonist

The role of endogenous platelet‐activating factor (PAF) in the pathogenesis of acute pancreatitis was investigated by determining whether CV‐6209, a selective PAF‐antagonist, confers protection against caerulein‐induced acute pancreatitis in rats. Continuous intravenous infusion of caerulein (5 μg/kg x h) induced time‐dependent increase in serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas, and produced histologic evidence of acute pancreatitis. Pretreatment with CV‐6209 (1 mg/kg) significantly inhibited the elevation of serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas. Caerulein‐induced tissue oedema and recruitment of leucocytic cells were markedly ameliorated with CV‐6209. Platelet‐activating factor may be released endogenously and may play a role during acute pancreatitis.

Increased neutrophil chemotaxis in obstructive jaundice: an in vitro experiment in rats.

Background and Aims: Changes in neutrophil functions in obstructive jaundice have been poorly understood. An in vitro experimental study was performed to evaluate the effect of obstructive jaundice on the functions of macrophages (secretion of neutrophil chemoattractants) and neutrophils (chemotaxis and superoxide anion generation).

Anatomical variation of pancreatobiliary ducts in biliary stone diseases

Endoscopic retrograde cholangiopancreatography examinations were prospectively analyzed to determine whether anatomical variations of ductal systems have a role in the pathogenesis of cholecystolithiasis and choledocholithiasis. Included were 140 normal examinations (control group), 102 patients with cholecystolithiasis, and 68 patients with choledocholithiasis (primary stones in the common bile duct). Low entry of the cystic duct was observed frequently in patients with cholecystolithiasis (15.7% vs. 2.1% in control, p < 0.01). No preferential type of course of the cystic duct was observed in patients with cholecystolithiasis and choledocholithiasis. Separate openings of the bile and pancreatic ducts were significantly prevalent in patients with choledocholithiasis (53.5% vs. 30.6% in control, p < 0.01). Common channel was significantly short in patients with cholecystolithiasis. Incidence of juxtapapillary duodenal diverticula was significant in patients with choledocholithiasis. These observations suggest that some of the pancreatobiliary ductal anatomy may be closely implicated in the development of gallstone diseases.

Acquired intrahepatic portal vein aneurysm

With the recent improvement in imaging procedures, repor ted cases of the intrahepatic portal vein aneurysm have been increasing (1-7). The pathogenesis of the disease, however , has not been well known. It is controversial whether the disease is congenital or acquired. Some of the reported cases have been considered to be acquired, but not conclusively proven in any of the cases. Altered portal venous hemodynamics may contribute to the development of portal vein aneurysm because of the fact that a number of cases have underlying portal hyper tension (1-4). Here we report a case of intrahepatic portal vein aneurysm that was discovered in a cirrhotic patient during his medical follow-up after the treatment of esophageal varices b y endoscopic injection sclerotherapy. Periodic close observation using various imaging procedures disclosed the etiology of the acquired portal vein aneurysm. Portal blood shunting to hepatic vein via the aneurysm was also noted.

Effect of obstructive jaundice on neutrophil chemotactic activity: An in vivo assessment in zymosan-induced peritonitis model in rats

The effect of obstructive jaundice on local neutrophil accumulation in response to inflammatory stimulus was investigated in rats. Obstructive jaundice was produced by bile duct ligation for 7 days. Zymosan (200 mg) was injected intraperitoneally and 4h later myeloperoxidase activity in the peritoneal fluid was measured to quantify neutrophil recruitment. Zymosan‐induced neutrophil recruitment was significantly greater (more than two‐fold) in bile duct‐ligated rats than in sham‐ligated or normal animals. Depletion of peritoneal cells significantly suppressed neutrophil recruitment after zymosan injection in all three groups, with no significant differences between the groups. In normal rats, replacement of their peritoneal cells by those from bile duct‐ligated rats did not enhance zymosan‐induced neutrophil recruitment. In contrast, bile duct‐ligated rats treated with peritoneal cell replacement from normals showed significantly increased neutrophil recruitment after zymosan injection. In vitro neutrophil chemotaxis in response to formyl‐Met‐Leu‐Phe was significantly enhanced in bile duct‐ligated rats, compared with that in sham‐ligated animals. The results suggest that local neutrophil recruitment in response to inflammation may be enhanced in obstructive jaundice and that increased neutrophil chemotactic activity, not macrophage activity, may play a prime role in the mechanism.

Influence of biliary obstruction on neutrophil chemotaxis

Abstract: The effect of obstructive jaundice on neutrophil chemotactic function was investigated, with a potent chemotactic factor, IL-8 (recombinant rat GRO-β), in rats that received 7-day bile duct ligation. Carrageenin or IL-8 was injected into a preformed air pouch, and exudate was collected 4 h later for measurement of myeloperoxidase activity. In vitro chemotaxis of peripheral neutrophils to IL-8 was evaluated by a modified Boyden chamber method. Both carrageenin and IL-8 induced significantly pronounced intra-air pouch neutrophil recruitment in the bile duct-ligated group compared with a sham-ligated group. In vitro neutrophil chemotaxis was significantly increased in the bile duct-ligated group compared with the sham-ligated group. The present experimental model suggests enhanced neutrophil chemotaxis to IL-8 in obstructive jaundice.

Role of endogenous platelet-activating factor (PAF) in endotoxin-induced portal hypertension in rats

To determine the role of platelet‐activating factor (PAF) in endotoxin‐induced portal hypertension, we performed continuous recording of both blood pressure (BP) and portal venous pressure (PVP) in rats following the administration of intravenous PAF (25 ng/kg), intraportal PAF (25 ng/kg), intraportal endotoxin (2 mg/kg), and intraportal endotoxin (2 mg/kg) for 1 min subsequent to pretreatment with a specific PAF‐antagonist (CV‐6209, 1 mg/kg, i.v.). Basal resting values of both BP (102.3 ± 9.3 mmHg) and PVP (7.7 ± 1.2 mmHg) fell rapidly after intravenous infusion of PAF (BP: 36.7 ± 5.8 mmHg; PVP: 5.7 ± 0.8 mmHg) and followed by gradual return. Intraportal PAF infusion elicited a rapid but less severe depression of BP (57.2 ± 9.4 mmHg) as compared with intravenous PAF infusion, whereas PVP was increased transiently around 4 min after treatment (11.0 ± 5.3 mmHg). A similar degree of PVP elevation (10.7 ± 2.0 mmHg) was observed between 8 and 20 min after intraportal administration of endotoxin. Depression of BP was initiated 12 min after endotoxin administration but was not severe (76.6 ± 12.8 mmHg). CV‐6209 significantly alleviated the endotoxin‐induced elevation of PVP and completely inhibited the hypotension. These observations suggest that: (i) PAF‐induced elevation of PVP is a direct response of the liver to PAF; and (ii) endogenous PAF plays an important role in the endotoxin‐induced portal hypertension.

MR imaging in The Evaluation of the Therapeutic Effect of B-RTO for Gastric Varices

BACKGROUNDS/AIMS Balloon-occluded retrograde transvenous obliteration (B-RTO) has become a new treatment option for gastric varices. In the present study, mid-term follow-up data after B-RTO were presented, and the role of magnetic resonance imaging (MRI) and MR-portography in the assessment of therapeutic effect was evaluated. METHODOLOGY Twelve patients with gastric varices were treated with up to three sessions of B-RTO. The patients were followed up with MRI, MR-portography, and endoscopy for a mean of 12.3 months. RESULTS In ten patients, one (n = 8) or two (n = 2) sessions of B-RTO were effective to produce immediate (< 2 weeks) variceal obliteration on MRI and MR-portography. Endoscopic confirmation of variceal eradication was obtained within three (n = 9) or six (n = 1) months after B-RTO in these patients. The remaining two patients who underwent three sessions of B-RTO showed only a significant reduction in variceal size immediately after B-RTO, but variceal obliteration was observed within three months with subsequent variceal eradication. There were no signs of exacerbation of gastric varices on MRI and endoscopy in any patient during the follow-up period. CONCLUSIONS The results suggest that B-RTO is effective for the treatment of gastric varices. MRI and MR-portography may provide accurate assessment of therapeutic effect.

The Effect of Biliary Pressure on Antibiotic Excretion into Bile

Abstract: Biliary obstruction has been recognized to inhibit excretion of antibiotics into bile. In the present study, using cefpirome sulfate (CPR), we sought to determine the effect of biliary pressure on antibiotic transfer into bile in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Thirty‐six patients with a variety of biliopancreatic diseases (free of renal disease or hypoproteinemia) received a single intravenous dose of CPR (1 g) prior to ERCP. Under fluoroscopy a diagnostic catheter with a metal ball tip was advanced into the middle portion of the extrahepatic bile duct or, in cases of common bile duct obstruction, above the obstruction. Biliary pressure was measured via the same catheter using duodenal pressure as a reference. Subsequently, bile was aspirated, and blood was withdrawn simultaneously. The mean interval between CPR administration and the bile and blood samplings was 67±12 minutes. The bile CPR concentration and the bile/serum ratio of CPR concentrations showed a significant inverse correlation with biliary pressure, but the serum CPR concentration did not. The bile CPR concentration and the bile/serum ratio of CPR concentrations differed significantly between the group with normal biliary pressures, below 10 mmHg, and that with biliary pressures exceeding 10 mmHg. The serum CPR concentrations of the two groups were similar. These results suggest that biliary pressure plays an important role in determining antibiotic transfer into bile.

Role of endogenous platelet-activating factor in the regulation of pancreatic blood flow during caerulein stimulation

The role of endogenous platelet-activating factor (PAF) in the control of pancreatic blood flow during caerulein stimulation was investigated. Pancreatic blood flow in anesthetized rats was measured continuously by laser Doppler flowmetry for 2h during the intravenous infusion of caerulein (0.25 μg/kg per h). Pancreatic blood flow showed a gradual, consistent, and significant increase, reaching 114.2±2.3% of the basal value after 120 min. Changes in pancreatic blood flow induced by caerulein were completely inhibited by a cholecystokinin (CCK) antagonist (loxiglumide, 5 mg/kg per h, i.v.) and by a specific PAF antagonist (CV-6209, 1 mg/kg, i.v.-bolus). Systemic blood pressure remained stable in all groups. These results suggest an important role of endogenously yielded PAF in regulating pancreatic blood flow during caerulein stimulation to the pancreas.