Saul J. Farber

Production of eicosanoids by the killifish gills and opercular epithelia and their effect on active transport of ions.

Gills and opercular epithelia of the killifish (Fundulus heteroclitus) homogenized and incubated with radiolabeled arachidonic acid were found to produce prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids. These metabolites were identified using thin-layer chromatography, autoradiography, reverse-phase high-performance liquid chromatography, and ultraviolet spectroscopy. Addition of glutathione and epinephrine to the incubation mixture caused a diminution in the production of most eicosanoids (cyclooxygenase and lipoxygenase products) whereas indomethacin decreased only the cyclooxygenase metabolites. The effects of eicosanoids on short-circuit and potential difference across opercular epithelia mounted in a Ussing-type chamber were examined. Prostaglandin E2 had an inhibitory effect on ion transport whereas the sulfidopeptide leukotrienes (LTC4, LTD4, and LTE4) had a stimulatory effect. These results indicate that gills and opercular epithelia have the capacity to synthesize eicosanoids and that some of these metabolites may play a role in the regulation of ion transport in the kill fish.

The Effect of Intravenously Administered Digoxin on Water and Electrolyte Excretion and on Renal Functions

Digoxin causes a prompt and considerable water and salt diuresis in congestive heart failure. This may occur with little or no change in renal hemodynamics, but usually is associated with decreased venous pressure. At times, increased glomerular filtration rate may contribute to the diuresis. In patients with noncardiac edema and without edema, Digoxin may also initiate a slight but definite sodium diuresis. This effect is not as great as in patients with congestive heart failure and apparently is not associated with changes in renal hemodynamics, cardiac output or venous pressure.

Cardiovascular Hemodynamic Functions in Complete Heart Block and the Effect of Isopropylnorepinephrine

In 8 patients with complete heart block, cardiac and hemodynamic functions were determined by methods based on cardiac catheterization. The data characterize the impairment in these functions in asymptomatic subjects and indicate, in addition, the further changes over the course of several years in the same subject, the deleterious effects associated with congestive heart failure, and the changes toward normal induced by isopropylnorepinephrine, a sympathomimetic amine known to stimulate the heart and increase ventricular rate in heart block.

ELECTROLYTE AND WATER EXCRETIONS AND RENAL HEMO-DYNAMICS DURING INDUCED CONGESTION OF THE SUPERIOR AND INFERIOR VENA CAVA OF MAN

It is apparent that the kidney is the organ ultimately responsible for the salt and water retention, hence the edema formation, in congestive heart failure, but why the kidney fails to excrete these substances normally in this disease state remains to be determined. Venous congestion, and renal venous congestion in particular, has been postulated as one of the factors playing a role in the decreased electrolyte and water excretions. Recent observations in animals and man lend support to this concept.

Cardiovascular Dynamics, Blood Volumes, Renal Functions and Electrolyte Excretions in the Same Patients during Congestive Heart Failure and after Recovery of Cardiac Compensation

Largely on the basis of acute observations in cardiac patients during congestive heart failure and in noncardiac control subjects, two assumptions have been made: (a) that congestive heart failure develops as cardiovascular and renal functions change from the type found in the control subjects to the type found in decompensated cardiac patients, and (b) that a return to, or toward, the normal occurs in these functions as cardiac compensation is regained. That these assumptions are not necessarily valid is indicated by the herein reported simultaneous measurements of cardiovascular dynamics, renal functions, blood volumes and electrolyte excretions in eight patients during cardiac decompensation and after recovery of compensation.

Mucopolysaccharides and Sodium Metabolism

This paper deals with the possible relationship between a native, negatively charged polyelectrolyte, chondroitin sulfate, and sodium metabolism. The physical chemical property of decreased activity of the cations Na, K and Ca in chondroitin sulfate is described. The data of experiments indicating an alteration in the mucoprotein metabolism of the cartilage of the rabbits ear in response to the depletion of salt are presented.

Hyperkalemia and hyperchloremic acidosis in chronic pyelonephritis

Abstract A report is presented concerning 13 patients with chronic pyelonephritis. Spontaneous hyperkalemia occurred in 11 of these patients and spontaneous hyperchloremic acidosis in 10. Administration of ammonium chloride to 6 patients whose serum chloride and potassium concentrations were close to the normal range resulted in the development of hyperchloremic acidosis and hyperkalemia. Administration of oral potassium loads to 3 patients resulted in the development of hyperkalemia. In the 1 patient whose urinary potassium was measured following a potassium load an abnormally slow excretion of potassium was found. It is suggested that a number of factors may be implicated in the causation of hyperkalemia in chronic pyelonephritis. Among these factors are included diminished renal potassium excretion, slow cellular uptake of dietary potassium and the effect of acidosis. The data also suggest that the hyperchloremic acidosis observed in these patients may be due in part to the reabsorption of ammonium chloride from the urinary tract.

Renal Excretion of Mannitol.

Conclusions I. The renal clearance of mannitol is frequently less than the simultaneous clearance of inulin in man. 2. The intravenous injection of manitol depresses the inulin clearance in man. 3. The clearance of inulin is equal to that of creatinine in the dog, but the mannitol clearance is usually less than that of creatinine. 4. mannitol undergoes metabolic alteration in man, and therefore, cannot be utilized in the infusion pump technique for measuring the rate of glomerular filtration. 5. Inulin appears to be the most generally useful substance for the measurement of glomerular filtration in man.

Composition of glycosaminoglycans (Mucopolysaccharides) in rabbit renal papillae

Abstract Glycosaminoglycans were isolated from rabbit renal papillae. The crude extract contained sulfated and non-sulfated fractions in approximately equal amounts. Galactosamine and glucosamine were identified as the major amino sugars. Fractionation of the crude material was accomplished by complexing with cetylpyridinium chloride and by column chromatography, paper chromatography, chemical determinations,automatic amino acid analysis and enzymic degradation. The isolated glycosaminoglycans were further characterized in the solid state by infrared spectroscopy and in solution by circular dichroism and the amino acid analyzer. The major constituents of rabbit renal papillary glycosaminoglycans were found to be hyaluronic acid and chondroitin sulfates.

Effect of growth hormone on water metabolism in hypophysectomized dogs.

Summary and Conclusions Continued administration of purified growth hormonc significantly improves the hypophysectomized dogs impaired response to water load. Concomitantly it increases the daily water exchange to levels seen in surgically induced diabetes insipidus. Growth hormone increases the glomerular filtration rate and renal plasma flow of hypophysectomized dogs but not to the pre-operative levels. It is suggested that growth hormone is one of the factors concerned with the maintenance of normal water metabolism.