Citations

The concentrations of copper in organs of white male rats were measured. Highest concentrations were in the kidney (5.1 µg/g wet wt.), liver (4.4), heart (4.5), and pituitary (about 5). Hair contained about 30 µg/g. From the weights of the organs and their copper concentrations, the total copper contents of the organs and of the whole rat were calculated. The whole rat (250 g) contained slightly less than 0.5 mg, of which about half was in the skin and muscle. Balance studies indicated that approximately 300 µg of copper was excreted daily, almost exclusively in the feces. Relatively small amounts of copper were excreted in urine. When expressed as proportion of body weight, the weights of testes, pancreas, skin, and eyes were larger in the rat than in man, and adrenals, brain, and thyroid were considerably smaller.

Varying doses of Cu64-labeled cupric acetate were given orally or intravenously to adult male rats. The urinary and fecal excretion of Cu64 was measured in intact rats and in rats with obstruction of the common duct. In addition, the biliary Cu64 was assayed in rats with biliary fistula. Only about half to two-thirds of doses up to 1 µg of copper were absorbed; the site of absorption seemed to be the upper portion of the small intestine. With larger doses, the percentage absorbed fell, but the absolute amount increased. Much less copper was excreted in the feces when the rat had a biliary fistula, the difference being accounted for by the biliary Cu64. Fecal excretion was not prevented by duodenostomy below the pancreatic and biliary ducts and therefore presumably reflects excretion through the gut mucosa. Significantly more copper was excreted in the bile and in the urine when the Cu64 was given intravenously. Very little of the biliary Cu64 was absorbed from the gut of intact rats when it was given by stomach tube.

The isolated, perfused rat liver has been used to study the metabolic pathways of I131-labeled l-thyroxine (T4), l-3,5,3'-triiodothyronine (T3), their partially deiodinated derivatives, and d-thyroxine. l-Thyroxine was metabolized less rapidly than the l-thyronines with fewer iodine atoms. l-T4 accumulated in the liver more rapidly than l-3,3',5'T3 or l-3,3'T2 but less rapidly than l-3,5,3'T3 or d-T4. Conjugation with glucuronic acid proceeded in the liver most rapidly from 3,5,3'T3 and at much lower rates from d-T4, l-T4, l-3,3',5'T3, and l-3,3'-diiodothyronine (T2). Deiodination of l-3,3',5'T3 and l-3,3'T2 proceeded most rapidly.

Radioiodinated Hippuran was injected into the inferior vena cava of three unilaterally and three bilaterally nephrectomized dogs. Radioactivity was recorded over the precordium and remaining kidney in the former group and the precordium and renal fossa in the latter. The disappearance of I131 from plasma was analyzed and interpreted by two-compartment and three-compartment systems. Theoretical curves for cardiac and renal areas (constructed from analysis of arterial plasma samples) agreed well with curves from in vivo counting. Analyzed by either model, the first compartment exceeded the plasma volume severalfold, part seeming to be in the kidney. Extravascular compartments, impossible to sample, were not identified. About 15% of whole-blood radioactivity was in erythrocytes. Biliary excretion of Hippuran I131 was insignificant unless nephrectomy was bilateral; then up to 60% was excreted in the bile in 24 hr. Protein binding could not be demonstrated. Radiorenograms converted to fairly accurate rate constants may prove more useful than descriptive methods currently employed. Understanding the distribution and excretion of Hippuran appears helpful to accurate interpretation of the radiorenogram.

This study was undertaken to determine the site of maximal absorption of Co60-labeled vitamin B12 in the small intestine of the male albino rat. Animals were sacrificed at intervals after ingestion of the labeled vitamin. The highest concentration of radioactivity was found in the wall of the upper and mid-ileum 1/2–3 hours after ingestion. Accordingly, the absorption of tagged vitamin B12 was estimated by fecal and urinary excretion methods in animals with resections of portions of the small intestine, including the portion containing the ileocecal valve, and in normal controls. Resection of the middle half of the small bowel (the upper and mid-ileum) was found to produce significant impairment of vitamin B12 absorption. It is concluded that in the male albino rat the upper and mid-ileum is specifically adapted to most efficient absorption of vitamin B12.

The concentration and distribution of sodium and potassium in small consecutive portions of kidneys of potassium-depleted and vitamin D-intoxicated hydropenic rats were estimated by a procedure based on the principle of specific activity. By this method sodium and potassium could be measured in bits of tissue weighing less than 2 mg. The results were correlated with the corresponding urinary osmolality. In both experimental groups, a marked impairment of the elaboration of osmotically concentrated urine was observed. The relative distribution of sodium and potassium in the kidney was not altered significantly. Associated with the decreased osmolality of the urine, however, was an approximately proportionate or slightly greater reduction in the content of sodium in the papilla. The findings suggest that a failure to establish maximal medullary hypertonicity, as indicated by the diminished accumulation of sodium, may be an important factor in the impairment of concentrating mechanisms.

A study was made of the disappearance of sodium diatrizoate-I131 from the plasma of ten dogs after single intravenous injections. The plasma disappearance curves suggested a two-compartment system. The renal plasma clearance of diatrizoate-I131 calculated from these curves and the conventional renal plasma clearance of creatinine were not statistically different. Clearances calculated from the urinary excretion and midperiod plasma concentration of radioactivity in four experiments yielded values averaging 10% less than the creatinine clearance. Chromatographic studies of commercially available diatrizoate-I131 revealed the presence of about 5% free iodide and of about 5% of unidentified impurities. These impurities seem to account, partly at least, for the differences found between diatrizoate clearance and creatinine clearance. Biliary excretion and erythrocytic uptake of diatrizoate were minimal and did not appear to influence the analysis.

Urinary-excretion and fecal-recovery methods were employed in the study of intestinal absorption of cobalt60-labeled vitamin B12 in the normal male albino rat. a) The logarithm of the fecal excretion, as well as of the urinary excretion augmented by an intraperitoneal flushing dose of unlabeled vitamin, increased linearly with the logarithm of the oral dose. This same relation of fecal excretion to oral dose is also apparently true in man. b) Increasing the intraperitoneal flushing dose over a wide range brought about a progressive increase in the percentage of the labeled oral dose excreted in the urine, but this increase was of small magnitude. c) The optimal time for administration of the intraperitoneal flushing dose in the rat appeared to be about 2 hours after administration of the labeled oral dose. d) The male albino rat seems to be an excellent experimental animal for use in the study of vitamin B12 absorption.

Forty-two male and female mice, 8 weeks old, were given radioiron (Fe59) in doses of 0.006–0.1 µc, containing 0.013–0.17 µg of iron, by intraperitoneal or intravenous routes. Assays of the radioactivity of the whole body revealed an initial rapid loss of Fe59 (15–20%) lasting about 6 days. Thereafter the Fe59 left the mice at a steady rate of 0.39%/day (half-life 180 days). One 34-year-old normal man was given 10.6 µc of Fe59, containing 8.2 µg of iron, intravenously. Based on counts from the entire body, the biologic rate of loss of the Fe59 was about 0.14%/day (half-life 500 days), and there was little or no initial loss such as occurred in the mouse. The Fe59 in the circulating erythrocytes was essentially unchanged for the first 3 months. It then fell to a new level of about 90% of the previous one; the mid-point of the fall was about 120 days after the administration of the radioiron. The difference in the rates of loss of radioiron from mice and man seems to be related primarily to the life span of the circulating red cells.