Induction of mononuclear cell infiltration into liver by Japanese herbal medicine.

Juzen-Taiho-To (JTT) is a Japanese herbal medicine that has been administered mainly to patients weakened by long illness. Currently, it has also been used for cancer patients and showed antitumor effects that have been reported as phagocytosis enhancement, cytokine induction and antibody production. In this study, we examined the effect of oral administration of JTT in mice on the immunological restoration of the liver, especially focused on natural killer (NK) T-cell induction. Mice were grouped to receive JTT or placebo orally for a period of 1, 3 and 7 days. After sacrifice, the liver tissue was fixed, embedded and stained with hematoxylineosin and some antibodies by common staining methods. Transmission electron microscope (TEM) observation was also carried out. Although the JTT-treated mice had the same appearance as the non-JTT-treated mice, their livers were infiltrated by massive mononuclear cells, some of which were aggregated in clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of interleukin (IL)-12 and massive infiltration of mononuclear cells with large granules in the liver of JTT-treated mice. Oral administration of JTT may induce the expression of IL-12 and be followed by immunological restoration such as NK T-cell induction in liver

[A case of hemolytic uremic syndrome caused by verotoxin producing enteropathogenic Escherichia coli (O157:H7) with prolonged cerebrovascular dysfunction].

A 56-year-old woman was admitted to our hospital because of bloody watery diarrhea. Stool cultures on admission revealed the verotoxin producing enteropathogenic Escherichia coli (VTEC) (O157:H7). Hemolytic uremic syndrome (HUS) appeared on the 4th hospital day. Plasma exchange was performed from the 4th day to the 11th day. Mental confusion appeared on the 6th day, and was aggravated until the 18th day, and slowly improved afterwards. Serial cranial CT in series demonstrated low density areas in the bilateral parietooccipital lobes on the 26th day, and the left one diminished but the right one became more evident on the 49th day. The series of single photon emission computed topography (SPECT) revealed that in the region of the temporoparietooccipital lobe cerebral blood flow decreased on the left side on the 30th day, on both sides on the 39th day, and on the right side on the 82nd day. There are few reports of prolonged cerebrovascular dysfunction observed in serial studies of SPECT in a patient of HUS by VTEC (O157:H7). We should be aware, however, of the appearance of the CNS involvement in the recovery stage because the prolonged cerebrovascular dysfunction may occur as our case.

[New combination therapy with FTM [5-FU, pirarubicin (THP) and MMC] for treatment of inoperable advanced gastric cancer].

Clinical usefulness of a new combination FTM therapy consisting of 5-FU, Pirarubicin (THP) and MMC for the treatment of advanced gastric cancers was investigated. 5-FU, THP or MMC was administered at a dose of 600 mg/m2 on day 1, 8, 22 and 29, 30 mg/m2 on days 1 and 22, and 10 mg/m2 on day one only of each course, respectively. Eighteen patients with inoperable advanced gastric cancer were treated with FTM. All drugs were investigated by intravenously by one shot. The tumor response rate was 50% [9 of 18 showed PR]. The survival rate was higher in responders than in nonresponders (18.1% vs 11.1%) (p < 0.05). Side effects in the gastrointestinal tract were minimal. Cardiotoxicity and nephrotoxicity were not detected, but myelosuppression was prominent in most cases. G-CSF was given in sixteen patients (88%), and platelet transfusion was performed in two patients (11%). New combination FTM therapy is an effective treatment regimen even for advanced inoperable gastric cancer.

Effects of intraduodenal administration of a low dose of cholecystokinin (CCK) antagonist (CR-1505) on plasma CCK concentration, intestinal CCK content, and levels of CCK mRNA.

The effects of the intraduodenal administration of a low dose of CR-1505 for 3-7 days on the gene expression of cholecystokinin (CCK), plasma CCK concentration, and CCK content in the intestinal mucosa were examined in rats. The simultaneous changes of protein and enzyme content in the pancreas were also determined. CR-1505 was infused continuously into the duodenum at a dose of 3 mg/kg per day, calculated to correspond to a dose of 150-200 mg/day in humans. Seven days after the administration of CR-1505, a liquid meal (4.5 kcal/3 ml) was introduced into the stomach and changes in the intestinal CCK content and plasma CCK concentration were examined. The level of CCK mRNA in the intestine was significantly higher in rats treated with CR-1505 than in control rats. The plasma CCK concentration, the CCK content of the intestinal mucosa, and the composition of pancreatic enzymes did not significantly differ in rats treated with CR-1505 and the untreated controls. In control rats, the administration of the liquid meal increased the plasma CCK concentration and significantly decreased the intestinal CCK content in water extracts, but did not affect the amount extracts in acid whereas the ingestion of the meal did not cause any significant changes in rats treated with CR-1505. These findings indicate that a low dose of CR-1505 stimulates the gene expression of CCK without enhancing CCK release or exerting an effect on the pancreas.

Effect of long-term exercise under restricted-feeding on intestinal content of cholecystokinin and on the pancreas in aging rats.

The effects of exercise (5000 m/day running from 100 to 600 days of age) on the cholecystokinin (CCK) content in the proximal intestine, and the enzyme and insulin contents of the pancreas were examined in food-restricted rats. Food restriction decreased the body weight and the wet weights of the pancreas and proximal intestine but not the wet weight of the stomach. Food restriction also decreased the chymotrypsin content of the pancreas but not its amylase content. The contents of enzymes in the pancreas were not affected by exercise. The insulin content of the pancreas was lower in lean rats produced by food restriction and/or exercise than in controls. Exercise increased the wet weight of the proximal intestine and the CCK content of the intestine. The increase in the CCK content may be due to compensational change in the efficiency of digestion of luminal nutrients induced by exercise.

Two mechanisms of inhibition by bile on luminal feedback regulation of rat pancreas.

BACKGROUND: Pancreatic exocrine secretion in conscious rats is regulated by luminal protease activities. A decrease in protease activities results in pancreatic hypersecretion (luminal feedback regulation). Although bile has been known to affect this regulation, the mechanism is not clear. In the present study, the effect of bile in the intestinal lumen on luminal feedback regulation was examined. METHODS: Rats were prepared with separate cannulas for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. Because the rate of enzyme secretion varies in individual rats, porcine trypsin was infused instead of pancreatic juice. Graded doses of porcine trypsin were infused with bile or Tris buffer containing 10 mmol/L CaCl2 instead of bile. RESULTS: The trypsin activities in the proximal quarter of the small intestine were similar in rats infused with bile and with Tris buffer containing 10 mmol/L CaCl2 (without bile); however, increments of pancreatic secretions of fluid and protein were significantly higher in rats without bile infusion than in those with bile infusion. Infusion of calcium-free Tris buffer resulted in significantly lower trypsin activity. CONCLUSIONS: The results indicate that bile has two inhibitory mechanisms on pancreatic secretion, one stabilizing luminal trypsin, the other independent of luminal trypsin activity.

Different response of brain cholecystokinin content to intragastric administration of trypsin inhibitor (camostate) in young and old rats.

The tissue concentrations of cholecystokinin in the intestine and the brain in young (4-8-month-old), and old (26-29-month-old) rats before and after intragastric administration of synthetic trypsin inhibitor (camostate) were examined. The total cholecystokinin content in the proximal intestine was significantly higher in old rats, whereas that in the brain was similar in young and old rats. Intragastric administration of camostate significantly increased the plasma cholecystokinin concentration and decreased the intestinal cholecystokinin content in both young and old rats. It also decreased the cholecystokinin content in the brain of old rats but not of young rats. These results suggest that the effect of aging on changes in the tissue content of cholecystokinin varies in different tissues.

Evidence for the effect of aging on tissue contents of gastrin, cholecystokinin and somatostatin in the rat.

The changes associated with aging in the tissue concentrations of cholecystokinin, somatostatin and gastrin in young (7-month-old), middle-aged (13-month-old) and old (25-26-month-old) rats were investigated. The concentrations and total contents of somatostatin and gastrin significantly decreased in the antrum in 13- and 25-26-month-old rats compared with the young controls. The cholecystokinin concentration in the proximal intestine and its total content significantly increased in the old rats. Somatostatin concentrations in the intestine and cerebral cortex did not change with age. Cholecystokinin content in the cerebral cortex decreased in old rats because of the decrease of tissue wet weight. We conclude that the effects of aging on the changes of peptide concentrations in tissues vary depending on peptide specie and in different tissues studied.

Manifestations of experimental acute pancreatitis in young and old rats.

Two kinds of experimental pancreatitis were induced in young (4-6 month) and old (25-27 month) female Wistar rats: acute edematous pancreatitis was induced by intraperitoneal administration of a high dose of cerulein (40 micro/kg x 2) and acute hemorrhagic pancreatitis was intraductal injection of 1% deoxycholic acid. After these treatments, the plasma amylase concentration and pancreatic wet weight were determined and the pancreas was examined histologically. In the groups with cerulein induced pancreatitis one of eight old rats died, whereas all five young rats survived. There was no specific finding macroscopically in the liver, kidney, lung or heart of old rats at autopsy after cerulein injection. The plasma amylase concentration and the pancreatic wet weight were significantly increased by administration of cerulein or deoxycholic acid in both young and old rats. There was no significant difference in the plasma amylase concentrations in young and old rats after the induction of acute pancreatitis. The increase in pancreatic wet weight was less in old rats than in young ones after deoxycholic acid treatment, but similar in the two groups after cerulein injection. The extents of histological changes were also similar in young and old rats. Thus, no evidence that aging increases susceptibility to pancreatitis was obtained.