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Biomedical subjects

M Walser

Publications and source records attributed to M Walser.

At least 145 records · Page 8Linked to original sources
PubMed1974

Urea metabolism in chronic renal failure.

Urea degradation was measured during 16 experiments in 13 chronic uremic patients being treated with essential amino acids or their analogues. [(14)C]Urea was injected i.v. and the clearance of labeled urea from its volume of distribution was compared with the simultaneous renal clearance of ordinary urea, which averaged 2.0 liters/day. The difference, extrarenal clearance of urea, averaged 3.1 liters/day as compared with a previously reported mean of 18 liters/day in normal subjects. Thus urea-splitting activity in the gut of uremic subjects expressed in these terms is far less than in normal individuals. Nevertheless, the amount of ammonia N formed from urea in these patients, 3.5 g/day, is not significantly different from normal, owing to their elevated plasma urea. In the same subjects, urea appearance rate was measured as the sum of urea excretion and the daily change in the urea pool. No negative correlation was noted between urea appearance and urea degradation, as might be expected if portal ammonia were being utilized for protein synthesis. However, urea production was positively correlated (r = 0.76) with urea degradation, suggesting that most of the resulting portal ammonia is converted back to urea. The results fail to support the view that degradation of urea in the gut promotes N conservation in uremic subjects maintained on low protein diets.

Ammonia↗
PubMed1974

Nitrogen sparing induced by a mixture of essential amino acids given chiefly as their keto-analogues during prolonged starvation in obese subjects.

11 normal obese subjects were fasted for 33 days. In five, who served as controls, urine urea nitrogen excretion remained constant for 2 wk thereafter. The other six were given seven daily infusions containing 6-8 mmol each of the alpha-keto-analogues of valine, leucine, isoleucine, phenylalanine, and methionine (as sodium salts) plus 3-4 mmol each of the remaining essential amino acids (lysine, threonine, tryptophan, and histidine). Rapid amination of the infused ketoacids occurred, as indicated by significant increases in plasma concentrations of valine, leucine, isoleucine, alloisoleucine, phenylalanine, and methionine. Glutamine, glycine, serine, glutamate, and taurine fell significantly. Blood glucose, ketone bodies, plasma free fatty acids, and serum immunoreactive insulin concentrations were unaltered. Urine urea nitrogen fell from 1.46 to 0.89 g/day on the last day of infusions; 5 days later it was still lower (0.63 g/day) and in two subjects studied for 9 and 17 days postinfusion it remained below preinfusion control values. Urine ammonia, creatinine, and uric acid were unaltered. Nitrogen balance became less negative during and after infusions. The results indicate that this mixture of essential amino acids and their keto-analogues facilitates nitrogen sparing during prolonged starvation, in part by conversion of the ketoacids to amino acids and in part by altering mechanisms of nitrogen conservation. The latter effect persists after the ketoacids are metabolized.

Amino Acids↗
PubMed1973

Aldosterone action and sodium- and potassium-activated adenosine triphosphatase in toad bladder.

Urinary hemibladders obtained from toads soaked in water or saline were treated with aldosterone, 10(-6) M, either 1(1/2) or 16 h after mounting. After 2(1/2) h exposure to the hormone, short-circuit current was increased by 110-192% and open-circuit potential by 20-44% as compared with untreated paired hemibladders. Mucosal cells were then assayed for sodium-potassium-stimulated adenosine triphosphatase (ATPase). No increase occurred in activity per milligram protein or in the portion of total activity dependent on sodium. Activity at low sodium concentrations was also measured and analyzed by means of the Hill equation in terms of K, the apparent dissociation constant of the enzyme-sodium complex, and n, a number that expresses the degree of interaction between binding sites. Neither K nor n was significantly altered by aldosterone. A few experiments were also carried out at low ATP concentrations (0.3 mM); again no change in sodium-dependent activity was noted. The results indicate that aldosterone does not stimulate sodium transport by increasing the quantity of sodium-potassium adenosine triphosphatase in mucosal cells or the dependence of this activity on sodium or ATP concentrations.

Adenosine Triphosphatases↗
PubMed1973

The effect of keto-analogues of essential amino acids in severe chronic uremia.

Alpha keto-analogues of valine, leucine, isoleucine, methionine, phenylalanine, and (in one instance) tryptophan and histidine, along with the remaining essential amino acids, were administered orally to 10 patients with severe chronic uremia fed a diet low in protein but adequate in calories. Ketoacid dosage varied from 6 to 14 g daily, as sodium or calcium salts. Net nitrogen intake, calculated as intake minus urinary protein nitrogen, averaged 1.8 g/day. The urea space was either estimated or measured with [(14)C]urea and daily changes in the body urea pool were calculated. Urea appearance was measured as the sum of urea excretion and the change in urea pool. If these ketoacids were converted to amino acids and utilized for protein synthesis, a fall in urea nitrogen appearance should occur. In five subjects, ketoacids were given for 15-18 days and then withdrawn. Urea nitrogen appearance increased 1.55 g/day on withdrawing ketoacids, and corrected nitrogen balance decreased by 1.73 g/day. In two other subjects ketoacid administration was followed, on two occasions each, by a period of administration of nine essential amino acids. In three of these four instances, urea appearance rose significantly with amino acids. In four patients studied at high blood urea levels, ketoacid treatment was relatively ineffective; two of these patients responded more favorably when studied again after peritoneal dialysis. One of these improved enough clinically to be managed as an out-patient for short intervals, despite virtual anuria. No accumulation of ketoacids in plasma or urine could be detected, and no toxicity was identified.

Adult↗
PubMed1973

Synthesis of essential amino acids from their alpha-keto analogues by perfused rat liver and muscle.

Most essential amino acids can be replaced by their alpha-keto-analogues in the diet. These ketoacids have therefore been proposed as substitutes for dietary protein. In order to determine their fate in tissues of normal animals, isolated rat liver and hindquarter (muscle) preparations were perfused with keto-analogues of valine, leucine, isoleucine, methionine, or phenylalanine. When perfused at 1.5-2.0 mM, all five compounds were utilized rapidly by the liver of 48-h starved rats, at rates varying from 49 to 155 mumol/h per 200g rat. The corresponding amino acids appeared in the medium in significantly increased concentrations. Perfusion with phenylpyruvate also led to the appearance of tyrosine. Urea release was unaltered. Measurement of metabolite concentrations in freeze-clamped liver revealed two abnormalities, particularly at ketoacid concentrations of 5 mM or above: a large increase in alpha-ketoglutarate, and a moderate to marked decrease in tissue glutamine. This decrease was quantitatively sufficient to account for nitrogen appearing in newly synthesized amino acids. Isolated hindquarters of fed rats were perfused with the same ketoacids at concentrations of 1.3-8.0 mM. All were utilized at rates varying from 1.4 to 7.0 mumol/h per g muscle perfused. The corresponding amino acids were released at greatly increased rates. Alanine and glutamate levels fell in some perfusions, but the principal nitrogen donor in muscle was not identified; the content of glutamine in tissue, and its rate of release into the perfusate remained constant.

Acetoacetates↗
PubMed1972

Components of sodium and chloride flux across toad bladder.

The effect of transepithelial potential difference (psi) on Na and Cl flux across toad bladder was assessed by measuring isotopic flux between identical media at various values of psi. The contribution of edge damage to ionic permeability was eliminated, resulting in relatively high spontaneous psi (-97 +/-4 mv) and low electrical conductance g. Bidirectional Na fluxes were measured simultaneously. Unidirectional Cl fluxes were measured in paired hemibladders at psi = 0 mv or -97 mv. Net Na flux J(Na), at psi = 0 mv, was slightly less than short-circuit current (SCC). At psi = -97 mv, J(Na) averaged 17% of SCC, and was sometimes zero. DeltaJ(Na)/Deltapsi (= g(+)) averaged 60% of g between -97 mv and +75 mv; at -150 mv, g(+) fell, indicating rectification. Analysis of unidirectional Na fluxes indicates low passive conductance (1.5 mumho/mg wet weight), a bidirectional, electrically neutral flux of approximately 0.13 mua/mg, and relatively large conductance of the active transport path at psi >/= -97 mv. The absence of appreciable transstimulation of serosal (S)-to-mucosal (M) Na flux (in response to increasing mucosal Na concentration) indicates that the electrically neutral flux is not exchange diffusion in the usual sense. Analysis of Cl fluxes indicates similar values for passive conductance and neutral flux, suggesting linked neutral flux of Na and Cl. Either the electromotive force of the Na pump E, its conductance g(a), or both are strong functions of psi. The product of these two quantities, Eg(a), is a measure of the "transport capacity" at any given value of psi, independent of the direct effect of psi on J(Na) through the pump path. Eg(a) varies with psi. Hence estimation of the net Na flux or current at any one value of psi, including psi = 0, fails to reveal the maximal transport capacity of the pump, its resting electromotive force (when J(Na) = 0 through the pump), or the dependence of transport capacity on potential.

Animals↗
PubMed1969

Extracellular fluid in individual tissues and in whole animals: the distribution of radiosulfate and radiobromide.

Radiosulfate, (35)SO(4), and radiobromide, (82)Br, were administered simultaneously to rats and dogs. In rats, the apparent volume of distribution of (82)Br averaged 30% of body weight and was constant between 0.5 and 35 hr after injection. The apparent volume of distribution of (35)SO(4), corrected for urinary loss, increased by 6% body weight/hr: the extrapolated volume at zero time was 88% of bromide space. Analysis of individual tissues and carcasses for (82)Br and inorganic (35)SO(4) showed that equilibration of both isotopes in several organs and in the whole carcass was rapidly achieved within 1 to 2 hr: no further increase in measured spaces occurred in 24 hr. The carcass inorganic sulfate space was 92%+/-2% of the bromide space in intact rats, and showed no increase with time. However, a progressively greater fraction of the injected (35)SO(4) was not recovered, owing to metabolic alteration. In eviscerated rats, the inorganic sulfate space was a smaller and much more constant fraction (79.8% +/-0.4%) of the bromide space, showing that at least 20% of body bromide (and hence chloride) is nonextracellular. The viscera chiefly responsible for the higher ratio of spaces in the intact animal were the liver, small bowel, and kidney. In the last two organs, excess inorganic (35)SO(4) (beyond the bromide space) was attributable to trapped transcellular fluid in which sulfate had been concentrated more than chloride (or bromide). Excess sulfate in liver and cartilage could not be explained in this manner: the results suggest passive binding of sulfate, but could reflect active cell uptake in these tissues. No excess sulfate was found in skin or tail. The implications of these observations with respect to the distribution of body chloride and the measurement of extracellular space are discussed. The extracellular volume of the rat is estimated to be 24% of body weight.

Animals↗