The effects of AMI-U-II, containing 8 essential amino acids and histidine (7.4%, W/V), on rabbits with ischemic acute renal failure were investigated in comparison with some amino acids solutions. Rabbits with ischemic acute renal failure were obtained by occulusion of the left renal artery and vein for 3 hours in right-nephrectomized rabbits. Amino acids solutions with 50% glucose solution (Cal/N=1060) were administered to the rabbits by the intravenous hyperalimentation method. The following results were obtained. 1) On the survival period, serum biochemical findings, N-balance, uremic toxins and amino gram, the groups infused by amino acids solutions were more excellent than the group without infusion. 2) On the survival period, serum urea nitrogen, creatinine, total protein, albumin, potassium, Ca, N-balance and body weight, the effects of AMI-U-II and AMI-U-II+ (Arg) were more excellent than those of other amino acids solutions. 3) Guanidino succinic acid (GSA) and guanidino butyric acid (GBA) were in low level by AMI-U-II infusion, on the other hand, in high level by AMI-U-II+(Arg) infusion. From these results, it was suggested that arginine was the precursor of uremic toxins such as GSA and GBA. 4) The serum amino gram pattern in rabbits with ischemic renal failure was resemble to those of reported in the patient chronic uremia. AMI-U-II caused the most pronounced increment of serum essential amino acids level in comparison with other amino acids solutions. 5) In conclusion, it seems that AMI-U-II is one of the most excellent amino acids solution for a nutritional therapy in renal failure.

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The effects of AMI-U-II, containing 8 essential ammo acids and histidine (7.4% w/v), on the incorporation of ¹⁵N (¹⁵Nurea) into serum albumin were investigated in rabbits with ischemic acute renal failure, and compared with those of AMI-U-II-(His) and reference solution (Ref-II) whichh was designated by Ministry of Health and Welfare of Japan. Amino acid solutions with 50% glucose solution (Cal/N=1060) were administered to rabbits by the intravenous hyperalimentation technique The following results were obtained. 1) ¹⁵N was found in serum albumin after administration of ¹⁵N-urea to rabbits. Therefore, it was suggested that urea nitrogen was reutilized as a nitrogen source of protein in rabbits as same: as in human being. 2) The degree of incorporation of ¹⁵N (¹⁵N-urea) into serum albumin was as follows: AMI-U-II>Ref-II>AMI-U-II-(His)>None. On the other hand, the inhibitory effect on SUN elevationn was in proportion to the degree of the incorporation of 15N (15N-urea) into serum albumin. 3) ¹⁵N was much incorporated into non-essential amino acids in albumin, but not into histidine and little incorporated into essential amino acids. From these results, AMI-U-II seemed to be one of the most excellent amino acid solutions for nutritional therapy of renal failure.

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Effects of AMI-U-II, containing 8 essential amino acids and histidine (7.4%, W/V), on rabbits with ischemic chronic renal failure produced by the method of Avioli et al., were investigated in comparison with reference solution (Ref-II) which was designated by Ministry of Health and Welfare of Japan. The following results were obtained. 1) The time course of changes of SUN, S-creatinine, Ccr, (U/P) osm and serum potassium in rabbits with ischemic chronic renal failure was similar to those in patients with chronic renal failure. 2) The most suitable ratio of Cal to nitrogen (Cal/N) for biological findings in the intravenous hyperalimentation (IVH) method was obtained as 1000 in rabbits with ischemic chronic renal failure. 3) More preferable tendencies of the body weight and biological findings of serum are showed in groups administered with glucose solution plus either AMI-U-II solution or Ref-II solution in comparison with none administered group. 4) On SUN and hematocrit, effects of AMI-U-II were more excellent than those of Ref-II. 5) In conclusion, it is obvious that AMI-U-II is one of the most excellent amino acids solu-tions for a nutritional therapy in renal failure.

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Seventy autopsy cases ranging from new born baby to ninety years of age which had no evidence with hypertension and renal diseases were examined histologically to clarify renal vascular changes with age. Thirty-three renal biopsy cases with essential hypertension ranging from twenty to sixty-one years of age were studied histologically to find influence on the aging process of the kidney. The vascular changes in arcuate arteries and afferent or efferent arterioles began at the end of 2nd decade. Those in relatively small interlobular arteries (under 80u in outside diameter) appeared at the beginning of 3rd decade. At the middle of 3rd decade, the vascular changes in interlobular arteries (over 80μ in outside diameter) were found at the end of 3rd decade. Those vascular changes increased according to age. Over the age of 45 year old, there were two groups. The changes of relatively small interlobular arteries and afferent arterioles developed gradually in the one group and in the other these did rapidly. The glomerular, tubular and interstitial changes were associated with the sclerotic changes of renal arteries, especially the changes in relatively small interlobular arteries. It is possible that the changes of arterial branches due to the cellular and strumal age changes in the renal tissues may play important role of mechanism of the aging process in the kidney. In hypertensive cases, renal sclerotic changes in interlobular arteries and afferent or efferent arterioles were usually found from the middle of 3rd decade. After the end of 4th decade, those changes in hypertensive cases increased rapidly with age and were much more frequent and severe than those in normo-tensive cases. It is suggested that age-induced renal vascular changes are influenced by the hypertension: and the hypertension is aggravated by aging.

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Involvement of microtubules in the cellular action of vasopressin was studied by physiological and biochemical procedures. 10^-5 to 10^-4M colchicine inhibited the hydro-osmotic response to both vasopressin and cyclic AMP in the toad urinary bladder acting only from the serosal side. This inhibitory effect was found to be time-and dose-dependent and was not prevented by the addition of pyruvate. Furthermore, the presence of tubulin in the extracts from the bladder epithelial cells was confirmed using colchicine-binding assay and disc gel electrophoresis. On the other hand, the osmotic water movement enhanced by 360mM urea (mucosal), 360mM mannitol (serosal) or 2μg/ml amphotericin B (mucosal) was not affected by 10-4M colchicine. The inhibitory effect of colchicine on the osmotic response to cyclic AMP was completely blocked by an increase in the concentration of Ca⁺⁺ of the serosal bathing medium from 1 to 8mM and the binding of colchicine to tubulin from the bladder epithelial cells, and bovine brain was also significantly inhibited by 8mM CaC1₂. However, exact mechanism of the effect of Ca⁺⁺ on colchicine inhibition could not be clarified. From these findings it may be concluded that the microtubules in the bladder epithelial cells play a role in the cellular action of vasopressin on steps subsequent to cyclic AMP formation ex-cept a directional cytoplasmic streaming process.

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Responses of renin, aldosterone, cortisol and dopamine β-hydroxylase (DBH) to insulin hypoglycemia were investigated in 9 normal subjects and 11 patients with essential hypertension. Patients with normal renin essential hypertension (NREH) showed a significant rise in plasma renin activity (PRA) in response to insulin hypoglycemia as well as in normal subjects, while in patients with low renin essential hypertension (LREH) no significant rise in PRA but a elevation of plasma aldosterone and cortisol were observed. The basal levels of serum DBH activity and ΔDBH values after the administration of insulin were lower in the LREH group than in the NREH group. These results suggest that the autonomic nervous system may be so hypotonic in the LREH that cause a hyporesponse of PRA to insulin hypoglycemia, and that the pituitary adrenal axis may be involved in the release of aldosterone under this condition instead of the renin-angio-tensin system.

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There are yet few reports dealing with scanning electron microscopy (SEM) observations of kidney biopsy tissue. The authors made SEM studies of the glomerulus, particularly the epitheial cells, in twenty patients with chronic glomerulonephritis. The morphological changes observed in the epithelial cells were classified into five stages ranging from 0 to 4 depending on the grade of deformity' Study of the correlation between grade of deformity and laboratory test results showed that as the grade progressed, the amount of urinary protein increased and GFR decreased, However, a set relationship with degree of hematuria, BUN and serum creatinin values could not be demonstrated. Further, the authors also observed abnormal proliferation in microvilli in the epithelial cell body and foot processes in cases with nephrotic syndrome.

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Serum and urinary β₂-microglobulin (β₂-m) were measured by radioimmunoassay in 60 patients with proteinuria (mostly chronic glomerulonephritis with and without azotemia not under hemo-dialysis), along with the measurement of retinol binding protein (RBP) and lysozyme (LZM). 1) Serum β₂-m from 75 control college students was 1.3±0.4 (0.2-2.5) mg/l and urinary β₂-m concentrations were 72±47 (14-280)μg/l on recumbent and 95±84 (22-550) μg/l on stand-ing position. 2) There was a significant correlation between serum β₂-m and creatinine concentrations. (r=0.85). Serum β₂-m concentration also linearly correlated to Ccr when logarithmic scales were used (r=-0.71). Thus β2-m appeared to be excreted by glomerular filtration through the kidney as an endogenous GFR substance (Fig. 1 and 2). 3) Simultaneous determination of β₂-m in serum and urine revealed no relationship between. β2-m concentrations of these specimens in control and non-azotemic chronic glomerulonephritis, groups. However, urinary, β₂-m concentration in azotemic chronic glomerulonephritis increased proportionately to serum, β₂-m after serum β2-m exceeded 5.0mg/l (r=0.52, p<0.025) indicating the renal threshold of (β₂-m around 3-5mg/l (Fig. 3). Tubular reabsorption rates (% TR) of β₂-m in chronic glomerulonephritis, assuming that 90% of β₂-m is filtered by glomerulus, range from 99.9 to 86%. Apparently tubular reabsorption was not saturated at high serum concentration of 10-50mg/l. Thus the tubular absorption process of β₂-m appeared to be characterized by a relatively low threshold, a high reabsorption capacity and a constant fractional absorption over a relatively wide range of serum concentration of β₂-m (Fig. 6 and 7). 4) β₂-m and RBP clearance ratio to transferrin clearance (Cβ₂-m/Ctrf and CRBF/Ctrf) were compared in three groups, those with highly, moderately and poorly selective groups of renal disease classified by CIgG/Ctrf. Clearance ratio of RBP was well correlated to that of IgG. Ho-wever, β₂-m clearance ratio showed no difference in the above groups. β₂-m appeared to be handled by the renal tubules with the different absorption process from that of IgG and REP (Fig. 5).

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