We investigated the effect of gastric hypoxia on the endogenous prostaglandins (PGs) in the gastric mucosa in vivo and in vitro experiments using rats. In vivo study, rats with gastric fistulation were instilled saline every 30min, and PGs released into gastric lumen were determined by radioimmunoassay. In control rats, releases of PGE2 and PGI2 were excessively high in the early experimental period followed by the gradual decrease, and then stable releases were obtained after 60min. Therefore, all the in vivo experiments were performed after 60min-resting time. By the ligation of left gastric artery, release of PGE2 was markedly increased. In vitro experiments, PGE2 and PGI2 released from rat isolated gastric wall were significantly decreased by bubbling with anoxic gas (N295%, CO25%) compaired with O2 saturated controls (O295%, CO25%). These results suggest that gastric hypoxia in vivo indirectly stimulates the synthesis of PGs in gastric mucosa. However, the mechanisms are still unelucidated.
The influence of taurocholate sodium (TCA) to rat gastric mucosa has been argued very much in the etiology of experimental gastritis. One hundred and twenty one Wistar male rats, weighing 150gm to 200gm, were placed in wire bottom cages and fed stock diet and 5mM TCA fluid supplied ad libitum. The animals were divided into 6 groups composed from the group treated with TCA for 1 month (A), group for 2 months (B), group for 3 months (C), group for 6 months (D), group for 10 months (E), and the control without treated (F). In these groups, gastric mucosal blood flow by means of hydrogen gas clearance method, potential difference (PD), and gastric mucosal pH were measured, and then these items were compared also with histological findings by HEstain, Azanstain and PASstain. Generative zone (G-zone) of rat gastric mucosa was studied by autoradiography, and the length of the glandular portion and tubular portion were measured. Atrophic gastritis showing chronic inflammatory cell infiltration, the shortening length of the glandular portion, the thinning of the epithelium was not clearly formed in this study, but gastritis was shown histologicaly. Blood flow decreased significantly (p<0.05) in C, D, E groups. PD did not change significantly, while pH slightly increased in C, E groups. It is concluded that gastric mucosal blood flow decreased prior to induction of atrophic gastritis treated with TCA.
Ultrastructural changes of the parietal cells and changes of intracellular cyclic AMP with histamine stimulation were sequentially observed in the isolated guinea pig gastric glands. Cells were classified morphologically into four groups: "Resting": tubulovesicles were dominant. "Stimulated": secretory canaliculi were expanded. "Partially stinulated": intermediate between former two groups. "Other": cells with collapsed secretory lumina or dense membranous profiles. And the proportions of numbers of these classified cells under each condition were investigated. At 10 minutes after stimulation with 10-3M histamine the proportion of "stimulated" increased, at 20 minutes "other" increased and at 40 minutes proportions returned to the same value as before stimulation. "Other" were considered to be the cells which were returning from "stimulated" to "resting" morphologically. The increase of "stimulated" at 10 minutes was in a dose-responsive manner and the addition of cimetidine blocked this increase. The proportion of "stimulated" paralleled to the intracellular cyclic AMP and a direct relationship between the activity of cyclic AMP and morphological changes in the parietal cell stimulated with histamine was suggested.
The gastric mucosal hemodynamics and oxygen sufficiency in 46 patients with liver cirrhosis and in 45 normal controls were studied by reflectance spectrophotometry during endoscopy. The reflectance spectra were taken from 10 different regions in the stomach. The estimated mucosal blood volume was greater and the estimated oxygen saturation of hemoglobin in the gastric mucosal capillaries was lower in patients with liver cirrhosis than in normal controls. These results suggest the stasis and dilatation of capillaries of the stomach in cirrhotic patients. The mucosal blood volume and oxygen saturation of hemoglobin in the capillaries of the stomach was smaller in the cirrhotic patients with esophageal varices than without esophageal varices. In conclusion, the microcirculation of the gastric mucosa in patients with liver cirrhosis was disturbed, and this disturbance of microcirculation may play a role in the development of acute gastric mucosal lesions in these patients.
The effect of short and long-termly administrated ranitidine on serum gastrin response to the test meal was chronologically studied along the clinical course of therapy in 34 patients with gastric ulcer, 17 patients on the short-term and 17 on the long-term therapy respectively. As the short-term therapy, ranitidine 150mg was administrated b.i.d. for 8 weeks in 17 patients with gastric ulcer (Group 1), and as the long-term therapy, one group (Group 2) was given ranitidine 150mg, s.i.d. in 6 and the other (Group 3) sucralfate 1.0g, b.i.d. in 11 patients with healed gastric ulcer respectively. The short-term therapy was continued for 8 weeks, then succeeding to the long-term therapy without any delay. Serum gastrin response to the test meal was repeated twice at 2 and 8 weeks of the short-term therapy in Group 1 and at 0 and 3 months of the long-term therapy in Group 2 and 3. As the results, serum gastrin response was observed significantly increasing during the short-term therapy in Group 1, still increasing during the long-term therapy in Group 2. On the other hand, in Group 3, where ranitidine was withdrawn, gastrin response was observed decreasing back to the pre-treatment level. These results would suggest the possible relation of cause and effect between increased gastrin response level and high ulcer recurrence after the withdrawal of H2 blocker ranitidine.
Effects of glucagon and effervescent granules on gastrointestinal MRI (magnetic resonance imaging) were studied. Identification and differentiation of the abdominal organs on the images obtained by multi-direction and multi-slice methods were tested before and after the oral administration of effervescent granules followed by intramuscular glucagon injection. The following effects were seen after the administration of contrast-gas. Indentification of the abdominal organs was improved remarkably on the transverse, coronal, and sagittal images of the stomach. Identification of the pancreas was improved on the transverse and sagittal images. Visualization of the border between adjacent organs, such as between the stomach and the pancreas, the left lobe of the liver and the stomach, the stomach and the intestine, and the stomach and the spleen was improved on both the transverse and sagittal images. This technique is useful in demonstrating gastric and other organic morphology.
Upper intestinal content was collected after giving a test meal and analyzed. In patients with ileal disease and with ileal resection, total bile acids concentration was reduced and the percentage of the total lipid in the micellar phase was decreased. It was thought that these reduction may cause fat malabsorption. A trial of bile acid replacement with ursodeoxycholic acid (UDCA) was undertaken in these patients. After one month of oral UDCA administration (300mg/day), increase of total bile acids concentration, improvement of reduced percentage of the total lipid in the micellar phase, and decrease of fecal fat excretion were demonstrated. The UDCA percentage was increased to 22.4% of total conjugated bile acids and cholic acid/chenodeoxycholic acid ratio was decreased after UDCA administration. These results showed that UDCA administrated was absorbed through intestinal mucosa and changed into the conjugated form in the liver and involved in the micellar solubilization of lipid.
Our previous study has revealed that both cholinergic and adrenergic nerves exist abundantly in the rat colonic mucosa and that the unmyelinated nerve fibers are located near the true capillaries and glandular epithelial cells. However, the functional relationship between mast cells and cholinergic nerve still remains unclear. This study is designed to elucidate the functional and morphological relation between mast cells and the colonic mucosal microcirculation. Wistar strain male rats weighing 250-300g were divided into the three groups: control group, compound 48/80 group and tranilast + compound 48/80 group. Compound 48/80 (1mg/kg b.w.) was infused via a catheter inserted into the abdominal aorta at the level of the mesenteric artery. Tranilast (100mg/kg b.w., p.o 2x a day) was pretreated for two days. The hemodynamics of the microcirculatory system in the colonic mucosa was observed in each group by in vivo microscopy following the transillumination method. A variety of the microcirculatory disturbances such as the increased permeability of the mucosal venules and capillaries, sludge phenomenon and stasis, were noted one minute after the compound 48/80 administration. The colonic mucosal blood flow measured by the hydrogen gas clearance method was remarkably decreased (32.5± 7.8ml/min/100g, mean±SEM) compared with that before compound 48/80 administration (112.2±8.0, P<0.001) and that in the tranilast + compound 48/80 group (76.4±10.9, P<0.005). By endoscopy (GIF P3, Olympus), the colonic mucosa appeared to be edematous and the venules were dilated. In the Eponembedded and toluidine blue-stained preparations, a large number of mast cells were found to be degranulated in the lamina propria mucosae as well as in the submucosa by compound 48/80 treatment, leading to a decrease in the number of mast cells. In the toluidine blue-stained 4 micron sections fixed by absolute ethanol, the number of the detectable mast cells were obviously less in the compound 48/80 group (9.9±2.6/mm2, mean±SD) than in the control (26.4±4.9, P<0.001). In the tranilast + compound 48/80 group, the mast cell degranulation was significantly prevented (15.9±3.7, P<0.001). In conclusion, the microcirculatory disturbances of the rat colonic mucosa are caused by mast cell degranulation induced by compound 48/80 and they are significantly suppressed by tranilast pretreatment.
Five cases of urolithiasis were experienced among 58 cases of total proctocolectomy. In two cases the stone components were analyzed to be uric acid and ammonium urate, respectively. 1) Urinary pH after total proctocolectomy was lower than normal or partial colon resction. Urinary pH after ileo-rectal anastomosis, in which rectum was preserved 10 to 15cm in length, distributed in a wide range and its mean value was between that of proctocolectomized state and normal cases. As to urinary pH, ileo-rectal anastomosis is thought to be a limit to keep the urinary lithogenesity at a minimum level. 2) Urine after total proctocolectomy frequently precipitated into sediment. Chief components of the sediment were uric acid and calcium oxalate, the ratio 73:27. When urinary pH was under 5.6 and was incubated at 4°C, the sediment appeared in 88.6% of cases. On the other hand, it was observed in only 21.4% of cases, if the urinary pH was over 5.7. Urinary Na/K and sodium excretion lowered in total proctocolectomized cases. 3) Causes of uric acid stone after total proctocolectomy is thought to be due to lowered urinary pH and decreased urinary sodium and water output.
Effects of vasoactive intestinal polypeptide (VIP) on liver blood flow were studied in rats by means of hydrogen gas clearance method using needle electrode. The liver blood flow in control group was 49.2± 3.2ml/min/100g. The administration of 0.002 to 20μg/kg of VIP through the tail vein induced biphasic effects on liver blood flow; 0.2μg/kg of VIP caused 40% increase, while 20μg/kg of VIP induced 30% reduction. However, intraportal administration of VIP showed no changes in liver blood flow. In order to clarify the mechanism of VIP action, the effects of atropine or hexamethonium pretreatment on VIP effects on liver blood flow were examined. The pretreatment with atropine and hexamethonium, which were known as a cholinergic blocker or ganglion blocker, inhibited VIP induced increase of liver blood flow. The administration of anti-VIP antiserum induced no changes in liver blood flow. These data suggest that VIP increases liver blood flow by acting selectively on hepatic artery and its effects may be mediated via cholinergic systems.
To evaluate a diagnostic utility of digital subtraction angiography on liver tumor, 52 patients with liver tumor were studied. Contrast material on DSA was administered via either intravenous (DSA-IV) or intraarterial (DSA-IA) route. As the procedure of DSA-IV was less invasive and easier than that of conventional angiography, DSA-IV was able to be done with no events on elder patients, patients with poor to reliability to conventional angiography and out-patients. Tumors could be detected 66.7% on DSA-IV. Dose of contrast material on DSA-IA was under the half dose of conventional angiography, and clerer image was obtined (80.1%) on DSA-IA, especially of portography. Draw back of DSA were (A) difficulty in image creation due to movement of intestinal gas and intraabdominal organs and (B) limited observation field.
The endoscopic ultrasonography (referred to as "EUS" hereafter) was employed in the diagnosis of gallbladder diseases in order to overcome diagnostic limitations of the conventional ultrasonography. Eighteen normal cases in autopsy and 90 clinical cases with gallbladder diseases underwent EUS. The instrument used in this study was the third prototype EUS with a 7.5 MHz trnasducer (Olympus GF-UM1). The gallbladder wall was demonstrated by EUS as 3 layers in the clinical examinations as well as in the normal autopsy specimen in water-bath. The comparison between findings by EUS and by histology made it possible to reveal the kind of tissue components to be matched with these ultrasonography layers. The 1st and most inner layer with slightly high echoic level meant the mucosal layer, the 2nd thin layer with low echoic one implicated the muscular layer and the 3rd high echoic layer was supposed to represent the subserosal and serosal layer. The gallbladder wall in case of adenomyomatosis came into sight as 2 layers consisting of a low echoic and thick layer and another high echoic layer. And the small cystic echoes were visualized in the inner low echoic layer by EUS. Concerning protruded lesions of the gallbladder, EUS enabled us to have a clear view of the cholesterol polyps in the gallbladder as a multiple granular structure composed of high echoic spots. EUS, also, made it possible to disclose the polypoid type of gallbladder cancer as the papillary irregular low echoic mass. The tumor infiltration into the gallbladder wall was clearly demonstrated by EUS as the destruction of 3 layers of the gallbladder wall. This appearance also might help differentiate cancer from the other benign polypoid lesions.
The renal tubular reabsorption of amylase was studied in 7 healthy volunteers by measuring urinary excretion of amylase and determing isoamylase pattern before and during inhibition of tubular reabsorption by a 20-minutes infusion of arginine at a rate of 0.6g/min. The excretion of amylase was compared with that of beta-2-microglobulin. The excretion of beta-2-microglobulin rose from a mean baseline excretion of 0.14±0.08μg/min to a peak of 18.63±2.72μg/min, a 137-fold increase. The maximal values were found during infusion of arginine in all cases. The excretion of amylase rose from a mean basal excretion of 3.90±0.32 Somogyi Unit (SU)/min to a mean peak value of 8.33±1.33SU/min during arginine infusion, a 2.1-fold increase. These results indicate that amylase is reabsorbed in the tubular cells, but only a very modest degree compared to beta-2-microglobulin. Amylase isoenzyme analysis revealed that the elevation of urinary amylase excretion was mainly due to an increase of salivary-type isoamylase activity. Thus, the ratio of pancreatic to salivary-type isoamylase in urine decreased during arginine infusion, a clear indication of tubular reabsorption of salivary-type isoamylase. The present study suggests that the high tubular reabsorption of salivary-type isoamylase contributes to the high renal clearance of pancreatic-type isoamylase compared to that of salivary-type isoamylase.
In order to clarify the correlation between exocrine pancreatic function and morphological changes in minimal pancreatic damage, numbers and size of zymogen granules of pancreatic acinar cells were stereologically estimated at the ultrastructural level, and PFD tests were carried out. The results of PFD test revealed lower than normal ranges in 41% of the patients with biliary tract diseases and all patients with chronic pancreatitis. Mean diameter of zymogen granules varied widely in size from 0.4 to 1.5μm, were significantly smaller in the patients with chronic pancreatitis and biliary tract diseases with impaired exocrine pancreatic function as compared to the patients with biliary tract diseases with normal exocrine pancreatic function. Urinary PABA recovery rate was observed significantly correlated with mean diameter and quantities of zymogen granules in unit volume of acinar cell cytoplasm. These findings suggest that ultrastructural changes of zymogen granules are closely related to the exocrine pancreatic function, and may explain the pathogenesis of pancreatic dysfunction.