K. Kinjo

Studies on the hepatic transport and metabolism of dyes

bile drainage after the surgery. Experimental analysis, using dogs with obstruction of the common bile duct and successive reconstruction procedures, revealed the same as seen in the human. Results obtained in 7 cases of portal hypertension, including 4 cases of cirrhotics and 3 cases of non-cirrhotic intrahepat ic portal hypertension (2 cases of end-to-side portacaval shun t and 5 cases of direct interruption surgery of esophageal varices such as proximal gastrectomy) revealed that the radioactive tracing test reflected the change of the hepatic blood flow at the first place. The results also reflected the change of hepatic functions after surgery at the second place. Though there is some question on the extrahepatic uptake of the radioactive BSP, this simplified external procedure could be helpful to examine the situation of the hepatic blood flow and the function before and after the surgical t rea tment in those hepatobiliary diseases.

Examination of dye metabolism in liver (VII) with respect to bind with serum protein to I.C.G. (Indocyanine green)

ConclusionThe data suggested that the binding activity of I.C.G. with serum protein provided by concentration of albumin, α1 globulin and α2 globulin.

Studies of dye metabolism in liver diseases (VI)

The incorporat ion of 4 14C delta aminolebulinic acid (ALA)and 2 14C glycine into heme, fecal coproporphyrin (FCP) and stercobil in (STB) were studied in cases with various disorders. Following the adminis t ra t ion of 4 14C ALA, activi t ies of FCP and STB appeared and declined within 4 or 5 days and the changes of two kinds of activity were associated with each other. This relat ionship suggested tha t they were produced from the common source. When 2 14C glycine was given, the r ise and the fall of FCP activity was independent of those of STB act ivi ty and FCP showed activi ty only on earl iest few days and no activity at the t ime of the end of red cell life span. STB activi ty kept a plateau for several days after the disappearance of FCP activity and then declined to lower level. The incorporat ion of 2 14C glycine into heme was active whereas tha t of 4 14C ALA was minimal. These re la t ions suggested the exis tence of two components of early appearing stercobilin. The first component associated with FCP activity and was independent of erythropoiesis and the second component was free f rom FCP product ion and dependent on erythropoiesis. In two cases of normal red cell life span who received 2 14C glycine the first component of STB was much less than the second component in each case (1 : 3.7, 1 : ]0.4). FCP activit ies showed no relat ion to the red cell destruct ion but associated with hepatic production of b i l i rubin tha t was observed in 4 14C ALA exper iments . It seems likely from these relat ions tha t FCP is of hepatic in origin.

Studies on hepatic excretion and metabolism of dyes (V) Relative storage capacity and maximal biliary transport of ICG in hepatic disease

The mechanism of BSP clearance are not yet completely clarified because of the limitations in the colorimetric measurement of BSP. Effort has been made to determine the maximal removal capacity (V max) by the liver, using ~sS-BSP, which had enabled us the measurement of trace dose BSP clearance. Intravenous injections of 10~20 uCi ~S-BSP with carriers (upto 5 mg/kg) were performed in normal subjects and patients with hepatic diseases, following the blood sampling at 2 or 3 minutes intervals for 30 minutes. Plasma disappearance rates were calculated graphically after counting the radioactivity in each plasma smaples. The amount cleared in initial disappearance phases (V rag/rain) can be obtained by multiplying the clearance rate constant (k) by the initial dose administered (D). After plotting V values logarithmically against the various initial doses, it was found that the BSP removal amount approached gradually to the maximal value (V max). This relationship was analyzed by Line-weaver-Burks method and V max was calculated by the following formula: 1 1 v = a + b ~ -

Dye excretion and metabolism in liver diseases

of bilirubin in the supernatant fraction was minimal 3 minutes af ter the injection, while a large amount of radioactivity was incorporated into bilirubin in the microsome fract ion in the same minutes. However, when bilirubin-l*C was intravenously given, most of radioactivity of bilirubin in lever was found in the supernatant fract ion in the first 3 minutes af ter the injection, and thereafter it migrated to the microsome and mitochondria fract ions in 15 and 30 minutes. These facts suggest a pathway of direct hepatic synthesis of bilirubin f rom glycine through &aminolevulinic acid in rat liver. Next, kinetics of plasma bilirubin was studied with 14C or 3H-labeled bilirubin, in order to obtain the quantitative informations about the bilirubin ell iminating functions of the liver as well as bilirubin turnover in human subjects, when three compar tment model was applied for this purpose.