Studies of glucose-14C(U) and pyruvate-14C (U) metabolism in liver tissues obtained by needle biopsy under peritoneascopy from patients with acute hepatitis (convalescence), chronic hepatitis (active and inactive form), cirrhosis of the liver (types A, A' and B, and the nutritional), fatty liver and diabetes mellitus and in liver slices from rats in acute and chronic carbontetrachloride intoxication revealed the following: 1) Metabolic rates as measured by the incorporation of labeled carbon from glucose-14C(U) and pyruvate-14C(U) into CO2, glycogen, fatty acids and glucose with 10-15mg tissues of human liver were comparable to those obtained similarly with about 120mg slices of rat liver. 2) A statistically significant decrease in incorporation of labeled carbon from glucose-14C(U) into glycogen and an increase from pyruvate-14C(U) into fatty acids were found in convalescence from acute hepatitis. Incorporations of the radioisotope from glucose-14C(U) into CO2, glycogen and fatty acids tended to decline in chronic hepatitis (active form), diabetes mellitus, chronic hepatitis(active from) with diabetes mellitus and cirrhosis of the liver (types A and A'). Decreases in the total incoporation into CO2, glycogen and fatty acids appeared to be correlated with retarded restoration of blood sugar level in a oral glucose tolerance test. Similarly, cases with impaired oxidation of pyruvate-14C(U) by liver tissue showed a delay in restoration of blood pyruvate level towards the fasting value after the glucose load. 3) In acute carbontetrachloride intoxication of rats, increased procuctions of radioisotope CO2 and glycogen from glucose-14C (U) and decreased productions of the CO2 and glucose from pyruvate-14C (U) and an increased formation of 14C-glycogen from pyruvate-14C (U) were found to be statistically significant to control values. In chronic carbontetrachloride intoxication, productions of the CO2 and glycogen from glucose-14C(U) and oxidation of pyruvate-14C(U) were all significantly decreased; the results being similar to those observed with clinical cases of chronic hepatitis and cirrhosis of the liver.
Rat experiments were undertaken to examine the alterations of steps involved in the-transfer of BSP from blood to bile following the intravenous administration of liver hydrolysate (Proheparum, Nordmark-Kaken). 1) Biliary excretion of BSP was increased by the intravenous administration of liver hydrolysate. 2) Through the administration of liver hydrolysate, a significant increase of unconjugated BSP storage in the liver and a moderate degree of cholereis were demonstrated. No acceleration of BSP-gultathione conjugating enzyme activity, elevation of biliary BSP-Tm, inhibitionof BSP-binding affinity of serum albumin and release of BSP from BSP-bound serum were observed. 3) The above facts suggest that the most important factor to increase biliary excretion of BSP following the intravenous administration of liver hydrolysate may be an increased hepatic storage of BSP, namely, an increased permeability of hepatic cell membrane especially on the uptake side from the blood stream.
Rat experiments were undertaken to examine the alterations of steps involved in the transfer of BSP from blood to bile following the intravenous administration of bilirubin. 1) Biliary excretion of BSP and bile output were decreased by the administration of bilirubin. 2) Biliary BSP-Tm (transport maximum) was unchanged by the administration of bilirubin. 3) A decrease of BSP storage in the liver was demonstrated by the administration of bilirubin, which suggests a decrease of hepatic uptake of BSP from blood stream. 4) An acceleration of BSP-glutathione conjugating enzyme activity was noted by the addition of bilirubin in vitro, but the conjugation rate of the biliary BSP was somewhat decreased by the intravenous administration of bilirubin in vivo. 5) Inhibition of BSP-binding affinity of serum albumin and release of BSP from BSP-bound serum was not demonstrated by the addition of bilirubin in vitro. 6) The above facts gussest that the most important factor to decrease biliary excretion of BSP following the intravenous administration of bilirubin may be a decrease of hepaticuptake of BSP from blood stream.
Comparative studies between Indocyanine green (ICG) and bromphthalein sodium (BSP) in the steps involved in the movement of dyes from blood to bile following their intravenous administration were carried out in rat experiments. 1) Biliary excretion of BSP was increased by intravenous administration of sodium salicylate, while that of ICG was not increased by the same treatment. 2) Far less ICG was bound to bovine serum albumin than BSP in vitro. 3) Binding affinity of bovine serum albumin to both BSP and ICG was reduced by the administration of sodium salicylate. 4) The maximal transport rate of ICG into the rat bile (biliary ICG-Tm) was less than that of BSP. 5) A distinct depression of biliary BSP excretion was induced by the excess dosage of BSP, while the phenomenon was not remarkable in the case of ICG. 6) It was confirmed that the binding affinity of BSP to the serum protein is an important factor in the steps involved in the movement of BSP from blood to bile, but it is not important in the case of ICG.
Intestinal absorption of fat was studied experimentally with rats in both intragastric and intraduodenal administration in vivo and in vitro. Both administration of triolein, α-monoolein or oleic acid as oil, and the administration of mixed micellar solution containing oleic acid, α-monoolein and sodium taurocholate were performed. 131I-triolein, 131I-oleic acid and 125I-α-monoolein were used as tracers. Following results were obtained. 1) Gastric emptying played important role in digestion and absorption of fat. Upon the receptor controlling gastric emptying sited in duodenal mucosa, fatty acid had more stimulatory effect (inhibitory effect) upon gastric emptying than triglyceride. 2) Apparent absorption ratio based on total administered dose should be corrected by gastric emptying ratio. 3) The mechanism of uptake of micellar solution was considered as simple diffusion. Fatty acid and monoglyceride were released from micelles at the epthelial surface and each lipid was taken up by simple diffusion, not by unit uptake. Fatty acid was taken up more rapidly than monoglyceride from micellar solution. 4) Intact uptake of monoglyceride from micellar solution and subsequent biosynthesis of triglyceride via monoglyceride pathway in the intestinal mucosa was proved in vivo and in vitro. 5) The possible existence of the enzyme which hydrolized monoglyceride specifically was proved in the intestinal mucosa.