I observed that rabbits consistently develop biliary concrements and cholecystitis if 1% Dihydrocholesterol in incorporated in their diet. The gallstones were about as large as miliary or peasize. The gall bladders were growing larger and their walls were thickened by edema and often by fibrous tissue. Many granulos vacuoles that secreated from Golgi appararts appeares in Ultrastructure of gallbladder epithelium of experimentary animals. The fine structure of strawberry gallbladder epithelium showed lipid droplets in supra or infra nuclear gegend. In lamina propria, there were numbers of foamy cells that mainly consist of large lucent vacuoles and dense bodies.
Many contributory studies of the cholesterol gallstone formation have been done, and the phospholipids and the fatty acids as the important factor for cholesterol solubilization in bile were pointed. Quantitative gas-liquid chromatography has been used for the fatty acid analysis of cholesterol esters, triglycerides and phospholipids in bile. The analysis of bile from 51 cases of cholesterol gallstones clarified the following results. (1) The concentration of fatty acids and essential fatty acids of phospholipids were decreased in case of cholesterol gallstones with slight pathological changes of gallbladder wall. However, the change of the fatty acids pattern of cholesterol esters, triglycerides and phospholipids were not observed. It is assumed that the decrease of phospholipids may prevent cholesterol to be soluble in bile. (2) The ceoncentration of phospholipids was markedly decreased in case of cholesterol gallstones with strong inflammatory changes of gallbladder wall. The percentage of 14: 0, 18: 0 and 18: 1 of phospholipid was increased, and L/O ratio was decreased. The inflammatory changes of gallbladder may enhance the formation of cholesterol gallstones. (3) In white bile the decrease of essential fatty acids, L/O ratio, and the increase of saturated fatty acids were observed. (4) The contents of triglycerides, phospholipids and total fatty acids in gallbladder bile with cholesterol gallstones were decreased, but the changes of the lipid pattern in hepatic bile were not observed. Therefore, the gallbladder should play the most important role in the formation of cholesterol gallstones.
In order to investigate the correlation of morphological and functional changes of the gastric mucosa, the histochemical studies of human gastric mucosa with special reference to various dehydrogenases were performed. The enzymes studied were succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH) and malate dehydrogenase (MDH). Methods The biopsies of gastric mucosa were obtained from certain five areas of the antrum and body by gastrocamera-gastric biopsy method under fluoroscopy. The histochemical studies of the mucosa were done. SDH was examined by Nichlas's method. LDH, GDH and MDH were examined by modification of the Nachlas and Seligman method. Nitro-BT was used in all of their examinations. Results 1) SDH activity. The parietal cells (PC) showed positive SDH activity. The activity of the PC was decreased when atropnic changes of the mucosa was severe. The surface epithel (SE) usually showed negative activity. When the mucosa has severe atrophic change, especially metaplasic gastritis, the activity was positive in the SE, and duodenal mucosa showed also positive in the SE. 2) LDH The PC showed positive LDH activity. When atrophic changes of the mucosa was severe, the activity of the PC was decreased as the SDH activity. Most of the SE showed positive and the muscularis mucosae also showed positive. 3) GDH GDH activity was positive in the PC. But the activity was weaker than SDH or LDH activity. GDH activity was also positive in the SE but it was also weaker than the LDH activity. 4) MDH MDH activity was positive in the PC. But the activity was much weaker than the GDH activity. No obvious relation between atrophic changes of the mucosa and the MDH activity in the PC was observed. The MDH activity in the SE was positive in a half same as the GDH activity. 5) Correlation of gastric acidity and the SDH activity of the PC. The SDH activity was strongly positive in the PC of the stomach with hyperacidity. On the other hand, the activity was decreased in the PC of the stomach with hypoacidity. It is apparent that gastric acidity is about parallel with the SDH activity of the PC.
Nine cases of clinically suggested drug-induced hepatitis were diagnostically confirmed by determination of serum enzyme activities following provocative readministration of causative agents. Animal experimentation was also performed. 1) The cases studied consisted of 6 cases induced by erythromycin estolate (EME) and 1 case each by tetracycline, potassium phenethicillin and arsphenamin natrium respectively. Their symptoms and liver function tests were discussed. 2) After recovery of their clinical course, the 9 cases were readministrated about half a daily dose of their respective causative agents. The activities of glucose-6-phosphatase (G6P), phosphohexose isomerase, aldolase (ALD), lactic dehydrogenase, malic dehydrogenase, glutathione reductase, isocitric dehydrogenase (ICD), GOT, GPT, alkaline phosphatase and Ieucine aminopeptidase were chronologically determined. In 24-48 hours all cases showed a marked increase in G6P, ICD and ALD, but a slight increase in transaminases. A few cases complained of fever, abdominal pain or jaundice, showing increased transaminases. 3) Three control subjects who had experience of administration of EME showed no positive provocation sign on determination of serum enzyme activities. 4) Rabitts were intramusculary injected of 2-hydroxy-methylene-17α-methyl dihydrotestosterone (HMD) (3mg/kg) once daily 21 times following a ligation of the left renal pedicle. After recovery of their disturbed serum enzyme activities by discontinuance of injection, they were readministrated HMD and examined as to the activities. The results obtained were almost identical with those of human cases.
Although many theories on the genesis of gastric ulcer have been advocated, an authorized theory has not been shown. Since MacDonald reported that patients suffering from Carcinoid were often complicated with gastric ulcers, it has been supposed that hyperserotonemia of them plays some role in ulcer formation. In order to clarify the genesis of ulceration, 380 Wistar female rats weighing approximately 150g were sacrificed in this experiment. They were deprived of food for 24 hours before the experiment, but were given free access to water. Animals were injected 20mg/kg of Sero tonin Creatinin Sulphate once daily and then killed after 30min 1, 2, 4, 6, 12, 24 and 48 hours. Results: 1) pH of gastric content measured by Tokyo pH test paper showed a significant rise comparing with that of control group. 2) The volume and the acidity of gastric juice were also measured. The former showed a conspicuous decrease, while the latter showed the same tendency as pH. 3) Congestion, petechien, erosions or ulcers were developed gradually on the mucous membrane of the stomach. 4) Ulcer formation was observed in 16% of treated animals after 4 hours and 65% of them after 12 hours. 5) The amount of serotonin in the glandular stomach was measured by Udenfriend's method in 119 rats. It increased to maximum after 2 hours with the average of 6.2μg/g and then decreased gradually. 6) The amount of blood Serotonin was measured by Udenfriend's method in 27 rats. It increased to maximum after 2 hours with the average of 0.504μg/ml and then decreased gradually as observed in the glandular stomach. 7) The ulcers were observed along the greater curvature of the glandular stomach and necrosis of mucous membrane, partial destruction of muscularis mucosa, congestion, bleeding and edema in submucosa were observed histologically. However it was interesting that not all of tissues fell into necrosis, but some part of the structure of the gland remained without any lesions. From a pathological point of view, it seems to be ascribed to circulatory disturbance. Through the observation of Serotonin ulcer, it should be concluded that the destruction of the tissue is caused from regional anoxia which is considered to be related to vasoconstrictive action of Serotonin, but it has no relation to gastric acidity.