A possible accumulation of the physiologically active macromolecules was studied on the sera of the patients with chronic renal disease consisting of 61 patients who were under treatment with hemodialysis, 36 with nephritis and 2 with nephrosis. These macromolecules, alkaline ribo-nuclease, amylase and γ-glutamyltranspeptidase are usually excreted and/or degradated by normal kidney. The effect of hemoidalysis on the enzymatic, activity was examined on the patients with chronic renal failure.1. Serum alkaline ribonuclease activity is correlative positively to the amount of serum creatinine and negatively to renal blood flow of the patients without hemodialysis. It seems to be a suitable index of the severity of renal dysfunction.2. Ribonuclease activity of the patients treated with hemodialysis showed exceedingly high activity (91.60 ± 27.12 units/ml) as compared with normal adults (7.78 ± 5. 74 units/ml) without any exceptions.3. Generally, the activity of ribonuclease, γ-glutamyltranspeptidase and amylase is increased by a single course of hemodialysis.4. Among the patients treated with hemodialysis, the ribonuclease activiy showed a tendency to increase as the time for hemodialysis accumulates and daily output decreases. But the activity, i. e. protein assesment in γ-glutamyltranspeptidase and amylase, did not differ much from the pre-treatment in its amount because of their chemical instability.5. We discussed the relationship between immunodeficiency and chronic toxic effect of ribonuclease andothef macromolecules which possibly accumulate in the sera of the patients with chronic renal failure.6. Assay of serum alkaline ribonuclease activity can be regarded as one of clearance tests and be a very useful i, Jol for examining clearance of macromolecules.

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In 45 regular hemodialysis patients the serum transferrin levels were estimated, and the relationship between the changes of transferrin and intake of nutrition were investigated. Following conclusions were made ; 1) In hemodialysis patients without administration of anabolic steroids, iron deficiency, hepatic disease and infection, the serum transferrin levels correlated well with the dietary intake, and they are regarded as an indicator of dietary intake, and also useful as an indicator of protein intake when caloric intake is not insufficient. 2) In patients with iron deficiency, the serum transferrin levels are not so useful as an indicator of dietary intake, although they reflected dietary intake to some extent. 3) In patients with low serum iron and low U. I. B. C., the serum transferrin levels are not useful as an indicator of dietary intake. 4) Serum transferrin levels increased in patients with acute hepatic disease, and decreased in those with infection. And in such cases the serum transferrin levels are not useful as an indicator of dietary intake. 5) By administration of anabolic steroids, serum transferrin levels were elevated. And they are not useful as an indicator of dietary intake. 6) In patients without administration of anabolic steroids, iron deficiency, hepatic disease and infection, the serum transferrin levels correlated significantly with the serum total protein and albumin values. But the latter two are less sensitive as an indicator of dietary intake than serum transferrin levels. 7) After the beginning of long-term hemodialysis, serum transferrin levels were elevated, probably due to iron deficiency and increase of dietary intake. 8) From the viewpoint of the serum transferrin levels, it is conceivable that hemodialysis patients need caloric intake at least more than 30 Cal/kg, and protein intake at least more than 1.0 g/kg.

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For the purpose of analysis of concentrating mechanism of urine we studied about the mor-phology of the collecting duct and its surrounding interstitial space of normal rabbit kidney light-microscopically and electron-microscopically as well. The following results were obtained. 1) The outer diameter of the collecting ducts increased to papilla. The ratio of outer diameter of collecting duct at different levels of outer medulla, inner medulla and papilla was proven to be about 1 : 2 : 3 The inner diameter of the collecting duct, however did not always increase its size at papilla, and some collecting ducts even narrowed themselves at the same level. That suggested the fact that the inner inner diameter of collecting ducts will be easily changed under the normal condition.2) Collecting ducts fused each other and decreased in number qlong the distance from outer medulla to papilla. It was found that the ratio of total numbeer of collecting ducts at the level of inner medulla and papilla was about 6 : 1.3) The total lumens occupied by collecting ducts decreased from inner medulla to papilla. The ratio was from 8 : 1 to 2.8 : 1.4) The ratio of interstitial volume at outer medulla, inner medulla and papilla was 1: 6.2 : 17.7.5) Electron-microscopically The size of epithelial cell of collecting duct at papilla becomes larger than those of outer medulla. Mitochondria of epithelial cell appear to be about same number at outer medulla and inner medulla as well. The interstitial cell was found to having irregular cytoplasmic processes and to touch closely the vessels and thin limbs of Henle's loop.

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This study was attempted to clarify the quantum chemical nature of thiazide diuretics from the electoronic aspect. Hückel's LCAO-MO Method was applied to thiazide diuretics and diazo-xide to caluculate their quantum chemical indices. The results show that the k value of the lowest vacant energy level of thiazide diuretics is low and nearly equal to that of FAD, and that of diazoxide is higher than that of thiazide diuretics and nearly equal to that of NAD⁺. Therefore, it was assumed that thiazide diuretics and diazoxide have the electron accepting nature and the former is more potent than the latter. This may explain the difference of the pharmacological actions between thiazide diuretics and diazoxide. To demonstrate the electron accepting nature of thiazide diurtics and diazoxide experimentally, the nanosecond flash laser photolysis and fluorescence quenching studies of pyrene-thiazide and pyrene-diazoxide systems were performed. Transient absorption spectrum of their nanosecond flash laser photolysis revealed a decrease of pyrerene anion absorption. The fluorrecence of pyrene was dynamically quenched by thiazide diurertics but not by diazoxide. These facts suggest that thiazide diuretics and diazoxide could scavenge an electron of pyrene anion, and an electron of a singlet excited pyrene could be transf erect to thiazide but not to diazoxide. The difference of a quantum chemical nature between thiazide diuretics and diazoxide was demonstrated by the result of the latter experiment. Finally, concerning the mechanism of the action of thiazide diuretics the author proposed a concept that the agent can be assumed as a functionally denaturating agent of the renal tubural membrane or an inhibitor of energy production which reacts with some electron donating groups of the renal tubular membrane or the biological electron transfer system in the renal tubular cell.

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