Gastroenterologia Japonica

Secretory leukocyte protease inhibitor (SLPI) is the dominant protease inhibitor in the mucus secretions of the repiratory and genital tracts, and local production seems likely, as immunoreactive SLPI has been found in the corresponding mucosa. To our knowledge, SLPI has not been previously demonstrated in intestinal epithelia or secretions. In an earlier study, however, we found surprisingly high levels of SLPI in peritonitis exudate from patients with gastrointestinal perforations. This study extends these observations by demonstrating the presence of immunoreactive SLPI in intestinal mucosa. In the small intestine, SLPI was present in Paneth cells and in scattered mucosa cells of goblet-type. In normal mucosa of the large bowel, SLPI was also found in scattered cells of goblet-type in the epithelium. In addition, immunoreactive SLPI was frequently found in colonic adenomas. The findings in this study raise several interesting questions on the possible role of SLPI in the gut epithelial defense against inflammatory assaults.

We report a case of Cruveihier-Baumgarten syndrome associated with portal vein thrombosis that developed, slowly during a 2-year period after, endoscopic variceal sclerotherapy. The thrombosis led to the disappearance of the venous hum and the dilated abdominal wall veins characteristic of this syndrome. A 73-year-old woman was hospitalized for treatment of esophageal varices in April 1988. Her spleen was markedly enlarged, and the histologic findings of her liver were not consistent with hepatic cirrhosis, but with idiopathic portal hypertension. A venous hum was audible in the upper abdomen. Superior mesenteric angiography revealed a porto-systemic shunt vessel under the abdominal wall, originating from the umbilical vein. She was injected four times with a sclerosant, and this brought about disappearance of the esophageal varices. Two years after the first admission, the venous hum was no longer audible, but there was a recurrence of the esophageal varices. More than 2 years later (4 years after the first admission), ultrasonographic study, computed tomography, and angiography showed a large thrombus, which completely obstructed the portal vein at the origin of the umbilical vein, and the development of collateral vessels, seen as a “cavernous transformation”.

To elucidate the relationship between the vagus nerve and circulating neurotensin release, mongrel dogs were given an intraduodenal infusion of a 50 ml water solution containing 10 g glucose (n = 4) or 5 g soybean oil (n = 7) over a period of 4 min before and after truncal vagotomy with pyloroplasty. In the prevagotomized animals only a slight increase of neurotensin-like immunoreactivity (NTLI) was observed following glucose infusion, while NTLI in response to fat infusion was significantly increased. After vagotomy, NTLI release following fat infusion was significantly decreased when compared to untreated control animals, suggesting that vagotomy causes a major alteration in circulating NTLI release and that the vagus nerve may play a definite role in fat-induced NTLI release.

Studies were conducted to investigate possible roles of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in liver cell necrosis/fatal hepatitis in mice which were injected withPropionibacterium acnes (P.acnes) and subsequently 7 days later with a small dose of lipopolysaccharide-endotoxin (LPS). Higher serum levels of TNF were observed in the model, and enhanced production of both TNF and IL-1 was also found in hepatic as well as splenic adherent cells that were isolated from mice pretreated withP.acnes and were stimulated by LPSin vitro. When TNF substituted for LPS in the model, fatal hepatitis was also induced within 24 hrs, although the replacement of LPS by IL-1 resulted in no lethality. Moreover, when a combination of a near non-lethal doses of TNF and IL-1 substituted for LPS, 100% lethality was observed within 4 hrs. These results strongly suggest that both TNF and IL-1 are crucial soluble factors which are released by infiltrating macrophages in both liver and spleen, and are responsible for the development of liver cell necrosis/fatal hepatitis. In particular, TNF is one of the principal mediators of liver injury and IL-1 may potentiate the lethal effect of TNF in an LPS-related experimental model of massive liver cell necrosis.

Factors that affect serum levels of 7α-hydroxycholesterol were studied in the rat. Serum levels of 7α-hydroxycholesterol differed in male and female rats fed regular chow (male; 0.2±0.1 nmol/ml (mean ±SD)n=8; female; 0.4±0.1 nmol/ml;n=8). When rats were fed with chow to which 3% cholestyramine had been added, the level increased significantly, particularly in female rats (male: 0.6±0.3 nmol/ml;n=8; female; 2.4±1.5 nmol/ml;n=8). The liver activity of cholesterol 7α-hydroxylase, the rate-limiting enzyme for degradation of cholesterol, did not show any sex differences, irrespective of whether the animals were fed with regular chow (male; 51±15 pmol/min per mg protein;n=8; female; 58±21 pmol/min per mg protein;n=8), or the cholestyramine-supplemented chow (male; 162±33pmol/min per mg protein;n=8; female; 172±33 pmol/min per mg protein;n=8). In contrast, the activity of 3β-hydroxy-Δ5-C27-steroid dehydrogenase, which acts after cholesterol 7α-hydroxylase in the catabolism of cholesterol, showed a marked difference between the sexes. In both sexes this enzyme activity was higher in cholestyramine-treated rats (male; 963±78 pmol/min per mg protein;n=8; female; 708±106 pmol/min per mg protein,n=8) compared to that in that rats received regular chow (male; 622±83pmol/min per mg protein;n=8). If the serum level of 7α-hydroxycholesterol depended solely on the enzyme activity of cholesterol 7α-hydroxylase, it would be difficult to explain these sex differences, since there were no sex differences in levels of cholesterol, 7α-hydroxylase. These results clearly indicate that, in the rat, the serum level of 7α-hydroxycholesterol depends not only on cholesterol 7α-hydroxylase activity but also on 3β-hydroxy-Δ5-C27-steroid dehydrogenase activity.

Rabbit colitis has been induced by injection of muramyl dipeptide emulsified with a long-chain fatty acid. The muramyl dipeptide emulsion was injected submucosally at six portions of the rectum and colon, 10cm proximal to the anus, using a flexible endoscope. Six rabbits were injected six times every 2 weeks and subsequently killed 2 weeks after the last injection. The histological changes of the colon that occurred in all 6 rabbits were mononuclear cell and histocyte infiltration with sporadic eosinophils, transmural infiltration, and well-maintained goblet cell populations. These changes were different in degree. In 4 of 6 rabbits histological examination of the liver showed pericholangitis and periductal fibrosis mimicking the pericholangitis frequently seen in patients with inflammatory bowel disease. Fibrosis bridging between the portal and portal veins occurred in 2 rabbits, and noncaseating granuloma was seen in 1 rabbit. These histological changes in our model have led to the suggestion that continuous stimulation with bacterial cell wall fragments may be involved in chronic intestinal inflammation and extraintestinal manifestations such as pericholangitis.