Yutaka Hikasa

Angiomyolipoma of the colon: A new entity in colonic polypoid lesions

SummaryA 67-year-old man with angiomyolipoma on the sigmoid colon is reported. The colonic polyp was pedunculated and diagnosed histologically after endoscopic polypectomy. Angiomyolipoma is one of the benign hamartomas arising principally in the kidneys of patients with or without tuberous sclerosis. Extrarenal angiomyolipoma is rare and this may be the first report of colonic angiomyolipoma.

Fecal bile acid analysis in healthy Japanese subjects using a lipophilic anion exchanger, capillary column gas chromatography and mass spectrometry

SummaryDetailed fecal bile acid profiles of healthy Japanese subjects were studied using a lipophilic anion exchanger, capillary gas chromatography and mass spectrometry. Total daily excretion of bile acid into feces corrected for by fecal markers were between 127.99 to 366.33 μmole per day. Unconjugated bile acids constituted a major part, between 80 to 96%, of fecal bile acids. Glycine conjugated, taurine conjugated and sulfated bile acids were between 1 to 6, 0 to 3 and 1 to 10%, respectively. Esterified bile acids at C-24 position existed between 1 to 5%. Primary bile acids ranged from 0 to 55%. There were a number of epimers of hydroxy-and keto-bile acids, and lithocholic and deoxycholic acid were major secondary bile acids among them. A cholenoic acid was detected in the unconjugated fraction of one subject. It seems necessary to analyze the details not only on the type of bile acids but also on the mode of conjugation in biological samples. Thus, the methodology described in this study has made it easier to investigate on the role of bile acid in the physiology or pathophysiology of the gastrointestinal tract.

Influence of Helicobacter pylori infection on development of stress-induced gastric mucosal injury.

Abstract: Immediately after the Great Hanshin Earthquake in Kobe in 1995, the recurrence rate of peptic ulcer in patients infected with Helicobacter pylori was higher than that in patients in whom H. pylori had been eradicated. We evaluated the influence of H. pylori infection on stress-induced gastric mucosal injury in Mongolian gerbils and C57BL/6 mice. These animals were immersed in water for 30, 120, and 720 min 12 weeks after inoculation with H. pylori, and then killed to assess gastric mucosal damage, and to measure cytokine production (interleukin [IL]-1β, IL-4, IL-6, and IL-10; interferon [IFN]-γ; and tumor necrosis factor [TNF]-α) in the gastric tissue of the mice. The stress treatment for 30 min resulted in a significantly higher bleeding rate and bleeding index among infected gerbils and mice compared with results in uninfected animals. Conversely, the bleeding and ulcer indexes were significantly higher in uninfected gerbils after 720 min of the stress treatment than in infected gerbils. Prior to the stress treatment, gastric IL-1β and IFN-γ production was significantly higher in the infected group than in the uninfected group. After 120 min of the stress treatment, TNF-α production was increased in the infected group, and IL-1β and IL-10 production was increased in the uninfected group. However, the production of these cytokines showed no change at 30 min of the stress treatment. These results suggest that H. pylori infection influences the development of gastric mucosal injury in the early phase of stress exposure; cytokines do not play a major role in this process.

Effect of leukotriene C4D4 antagonist on colonic damage induced by intracolonic administration of trinitrobenzene sulfonic acid in rats

We examined the effects of eicosanoid antagonists on colonic damage induced by trinitrobenzene sulfonic acid (TNB) in a rat inflammatory bowel model. TNB (30 mg) dissolved in 0.25 ml of 50% ethanol, was given intrarectally. The appropriate doses of ONO-1078 (a leukotriene C4D4 antagonist), ONO-4057 (a leukotriene B4 antagonist), and OKY-046 (a thromboxane A2 synthetase inhibitor) were given to obtain the same blood level, either 4 h before (pre-treatment model) or 24 h after (the post-treatment model) the administration of TNB (n=8 in all groups). Drugs were given once daily for 6 days through a gastric feeding tube. Autopsy was performed on the 7th day. Colonie damage was assessed in terms of colonie damage scores, and myeloperoxidase (MPO) activity and eicosanoid concentrations in colonie tissues were measured. Compared with the group given TNB alone, the colonie damage score was reduced to 10% in the pre-treatment model with ONO-1078, but the score was not reduced in other groups, MPO activity was not changed in any group. The concentration of leukotriene C4 was reduced with ONO-1078 treatment, in both pre- and post-treatment models. These results demonstrated that a leukotriene C4D4 antagonist reduced colonie inflammation; however, its anti-inflammatory effect was limited in this colitis model.

High concentration and retained amidation of fecal bile acids in patients with active ulcerative colitis

SummaryFecal bile acid profiles of 14 patients with ulcerative colitis in the active phase were analyzed to study the potential significance of bile acids in the pathophysiology of this disease, and the results were compared with those in 12 healthy controls. The excretion levels of total bile acids (mean ± SD) in patients were higher than in controls, 445.1 ± 392.1 vs 215.5 ± 148.0 µmol/day, 3.1 ± 1.7 vs 1.6 ± 1.0 µmol/g wet feces (P<0.05), and 17.2 ± 9.2 vs 12.4 ± 13.3 µmol/g dry feces. Fecal profiles of individual bile acids showed higher levels of primary bile acids (52 ± 27%) in patients compared to those (26 ± 21%) in controls. Proportions of glycine and taurine conjugates in patients (26 ± 24%) were higher than in controls (5 ± 2%) (P<0.05), whereas proportions of unconjugates and sulfates were lower in patients than in controls. Accordingly the extent of deconjugation and dehydroxylation of bile acids was lower in patients than in controls. These trends were prominent in patients with more severe disease activity. A high concentration of bile acids in the intestine may have a significant role in the pathophysiology of ulcerative colitis at active phase.

Evaluation of polyethylene glycol-HT as a stationary phase for capillary column gas—liquid chromatography of trimethylsilyl ethers of bile acid methyl esters

Abstract Polyethylene glycol-HT was introduced as a polar stationary phase for bile acid analysis in capillary column gas—liquid chromatography. It has an excellent thermal stability compared with polyethylene glycol 20,000. Helium can be used as carrier gas. These characteristics show the superiority of this liquid phase to polyethylene glycol 20,000 which is of similar polarity. The relative retention times of some bile acid derivatives on a polyethylene glycol-HT capillary column are reported.

Leukotriene C4 D4 antagonist markedly reduced inflammation in a rat model of inflammatory bowel disease

The r o l e o f e i c o s a n o i d s in i n d u c i n g i n f l a m m a t i o n r a i s e s an i s s u e o f t h e t h e r a p e u t i c use of t h e i r a n t a g o n i s t s in i n f l a m m a t o r y bowel d i s e a s e . ~1~ We e v a l u a t e d t h e e f f e c t s of e i c o s a n o i d a n t a g o n i s t s on t h e r a t model o f i n f l a m m a t o r y bowel d i s e a s e i n d u c e d by t r i n i t r o b e n z e n e s u l f o n i c a c i d ( T N B ) / e t h a n o l . ~2~ S-D r a t s w e i g h i n g 1GO-190g were g i v e n a s i n g l e i n t r a c o l o n i c i n s t i l l a t i o n of 0 .25ml o f 50~ e t h a n o l c o n t a i n i n g 30mg of TNB v ia anus . E i c o s a n o i d a n t a g o n i s t s were O N O 4 0 5 7 ( l e u k o t r i e n e B4 a n t a g o n i s t ) , 0N0-1078 ( l e u k o t r i e n e C4 D4 a n t a g o n i s t ) and OKY-O4G(thromboxane A2 s y n t h e t a s e i n h i b i t o r ) o b t a i n e d f rom Ono P h a r m a c e u t i c a l C o . , L t d . ( O s a k a ) . C o n s i d e r i n g t h e a b s o r p t i o n r a t e s , 100mg, 30mg and 100mg/Kg body w e i g h t o f r e s p e c t i v e d r u g s were a d m i n i s t e r e d t o o b t a i n t h e s i m i l a r b lood l e v e l t h r o u g h a g a s t r i c t u b e once a day. The f i r s t a d m i n i s t r a t i o n was a t 1 h o u r b e f o r e t h e TNB t r e a t m e n t . The r a t s were k i l l e d 1 week l a t e r , and c o l o n i c damage was a s s e s s e d by t h e c o l o n i c damage s c o r e , as Score 0: no damage; Score 1: h y p e r e m i a w i t h o u t u l c e r ; Sco re 2: u l c e r w i t h t h i c k e n i n g of bowel w a l l ; and Sco re 3: u l c e r w i t h s e v e r e t h i c k e n i n g o f bowel wa i l i n v o l v i n g s e r o s a . C o l o n i c i n f l a m m a t i o n i n d u c e d by TNB/e thano l was s u p p r e s s e d by 0N0-1078, as s e e n by t h e r e d u c t i o n of c o l o n i c damage s c o r e ( t a b l e ) . By c o n t r a s t , c o l o n i c damage s c o r e was not changed in 0N0-4057 or OKY-046 t r e a t m e n t . I n c r e a s e d p r o d u c t i o n o f l e u k o t r i e n e s c o r r e l a t e d w i t h t h e i n f l a m m a t i o n of e x p e r i m e n t a l c o l i t i s . ~1~ The p r e s e n t r e s u l t s i n d i c a t e d t h a t l e u k o t r i e n e C4 D4 a n t a g o n i s t was e f f e c t i v e f o r r e d u c i n g c o l o n i c i n f l a m m a t i o n . Thus, i t i s a p o s s i b l e t h e r a p e u t i c a g e n t f o r p a t i e n t s w i th T a b l e . E f f e c t o f t r e a t m e n t w i t h i n f l a m m a t o r y bowel d i s e a s e , e i c o s a n o i d a n t a g o n i s t s a l t h o u g h i t s mechanism a w a i t s to be s t u d i e d . Group n S c o r e

Effects of 5β-chol-3-en-24-oic acid, and lithocholic acid and its sulfates on prostaglandin E2 output in perfusion of the rat colon

SummaryThe effects of bile salts on the output of prostaglandin E2(PGE2) were studied in rats by colonic perfusion. Bile salts and their concentrations in infusates were as follows; chenodeoxycholic acid sodium salt (CDCNa), sulfolithocholic acid disodium salt (SLCNa) and sulfotaurolithocholic acid disodium salt (STLCNa) were at 1 mmol/1, lithocholic acid sodium salt (LCNa) was at 0.6 mmol/1, 5β-chol-3-en-24-oic acid sodium salt (A3Na) was at 0.006 mmol/1, and sulfoglycolithocholic acid disodium salt (SGLCNa) was at 0.8 mmol/1. Median values of PGE2 outputs were 40.9, 52.4, 65.5, trace, 7.6, 9.8 and 9.8 pg/10 min/cm in the CDCNa, LCNa, Λ3Na, SLCNa, STLCNa, SGLCNa and control groups, respectively (control vs CDCNa, LCNa, Λ3Na, SLCNa group, p< 0.01 by median test). There was such a dissociation in PGE2 output and electrolyte concentration in the perfusates that high concentration of Na+ and Cl- ions was observed only in the SGLCNa group (p< 0.01 by t-test compared with the control group), whereas in the remainder of the groups substantial net movement of electrolytes and water was not observed. Light microscopy showed no evidence of morphological damage in any group. These results indicated that CDCNa, LCNa and Λ3Na increased PGE2 outputs in the colon at low concentration without functional or morphological changes.