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Biomedical subjects

B D Ross

Publications and source records attributed to B D Ross.

At least 163 records · Page 9Linked to original sources
PubMed1980

Activation of oxoglutarate dehydrogenase in the kidney in response to acute acidosis.

1. Activation by H+ and by Ca2+ of 2-oxoglutarate dehydrogenase extracted from mitochondria of normal or acidotic rat kidney is described. This effect, first shown for the enzyme from heart by McCormack & Denton [Biochem. J. (1979) 180, 533--544], is of a regulatory importance in kidney, in which organ, in contrast with heart, increased flux occurs during acute acidosis. 2. In renal-cortical tubules, 2-oxoglutarate concentration fell within 1 min of decreasing the pH and rose again 1--3 min after increasing the pH of the medium. The extent of the decrease in 2-oxoglutarate was directly related to the decrease in pH. A similar fall in the oxoglutarate concentration in the whole perfused kidney was noted within 5 min of inducing acidosis. 3. In tubules, the rates of gluconeogenesis and ammoniagenesis from 1 mM-glutamine were increased by 64 and 33% respectively on decreasing pH to 7.0, the increase in rates being proportional to the fall in pH between 7.4 and 7.0. 4. The increased rates of renal ammoniagenesis and gluconeogenesis seen in acute acidosis in vitro can be accounted for by the increased activity of 2-oxoglutarate dehydrogenase and the tissue concentrations of 2-oxoglutarate when calculated from the Km determined at normal and acidotic pH. 5. The decrease in 2-oxoglutarate concentration seen in acute acidosis implies a fall in intramitochondrial pH in kidney, and is the result of two phenomena, accelerated disposal via 2-oxoglutarate dehydrogenase and maintenance of near equilibrium of glutamate dehydrogenase.

Acidosis, Renal Tubular↗
PubMed1979

Ammoniagenesis by the isolated perfused rat kidney: the critical role of urinary acidification.

1. The effect of metabolic acidosis simulated in vitro on ammoniagenesis was investigated by using the isolated kidney of the rat perfused with an albumin Krebs-Henseleit medium containing glutamine and glucose. 2. Addition of HCl to a perfusate of normal bicarbonate concentration resulted in a prompt increase in urine flow rate, decrease in fractional sodium reabsorption and decrease in urine pH. 3. A minimum urine pH as low as 5.15 was achieved, with an average value of 5.92, indicating that this preparation has the capacity to acidify normally. 4. In contrast with studies in vitro with other preparations, with the functional perfused kidney a diminution in perfusate bicarbonate concentration resulted in a prompt increase in ammonia production, which was strikingly correlated with the decrease in urine pH. 5. The increase in ammonia production was diminished in studies carried out with a non-urinating kidney, in comparison with those that exhibited significant urine acidification. 6. These data suggest that a decrease in urine pH with trapping of ammonia in the urine may be a critical stimulus for increased ammonia production in acute metabolic acidosis.

Acidosis↗
PubMed1979

Characteristics of renal handling of human immunoglobulin light chain by the perfused rat kidney.

1. The renal handling of purified human immunoglobulin light chain has been studied with an isolated perfused rat kidney preparation. 2. Human immunoglobulin light chain was freely filtered and largely reabsorbed. Fractional reabsorption was characteristic for each of four light chains and varied between 56% and 86%. No renal tubular maximum for human light chain was obtained. 3. Light chains at concentrations up to 10 times those seen in human myeloma were without effect on glomerular filtration rate or sodium and potassium reabsorption in experiments lasting up to 2 h. 4. Filtered and reabsorbed light chain returned ultimately to the perfusion medium, indicating a unique property of the tubular handling of this protein. None of the inhibitors tested (ouabain, frusemide, acetazolamide, probenicid) influenced light chain reabsorption. 5. The results are taken to indicate that light chain reaches the site of the transport enzyme, Na+,K+-dependent ATPase, at concentrations which vary with the nature of the light chain. This may provide a mechanism for renal damage in patients with myeloma, after prolonged exposure.

Absorption↗
PubMed1978

The metabolic fate of glutamine nitrogen in the perfused rat kidney.

The fate of glutamine amide and amino nitrogen was determined in the perfused rat kidney. There is a deficit of about 40% in the recovery of glutamine nitrogen and NH3 in the perfusion medium. After correction for the tissue conetent of glutamine, the remaining nitrogen was fully accounted for by small amounts of NH3, glutamate, aspartate and a compound that liberated glutamate on acid hydrolysis, probably 5-oxopyrrolidine-2-carboxylate (pyroglutamate). The latter accounted for 8% of the glutamine metabolized.

Animals↗
PubMed1978

Evaluation of hypertonic citrate flushing solution for kidney preservation using the isolated perfused rat kidney.

The isolated perfused rat kidney has been used to study the effects of cold ischaemia during ice storage. Tissue adenine nucleotide levels in freeze-clamped kidneys were closely correlated with their function after circulation had been reestablished in the perfusion circuit. The ATP content was depleted to a greater extent than total adenine nucleotide after 8 hr of cold ischaemia but both were considerably diminished after 24 hr. The model was also used to compare four solutions which are available clinically for preliminary flushing of organs in the ice storage preservation technique. The results indicated that for periods of 8 and 24 hr of cold ischaemia, renal function and adenine nucleotide content were significantly better maintained with a solution based on hyperosmolar citrate than with Collins, Sacks, or Perfudex solutions. This study confirmed recent observations of the clinical efficacy of citrate solution, while demonstrating how the isolated perfused rat kidney could be used for rapid screening of modifications in preservation techniques.

Adenine Nucleotides↗
PubMed1977

Effects of analgesics and related compounds on renal metabolism in rats.

1. The metabolic effects of p-aminophenol have been compared with those of paracetamol and other analgesics in studies of rat liver and kidney in vitro. 2. p-Aminophenol injected into rats inhibited gluconeogenesis from lactate in renal cortical tubules, but not in isolated hepatocytes, and reduced kidney ATP content without affecting the ATP content of liver. Perfused kidneys from rats previously injected with p-aminophenol showed a 50% reduction of ATP content, severe inhibition of Na+ reabsorption and reduction of inulin clearance without significant inhibition of gluconeogenesis from lactate. 3. Paracetamol, p-phenetidine, phenazone and aspirin, when given intravenously to rats, had no effect on renal tubular glucose synthesis from lactate or pyruvate. Paracetamol and aspirin both slightly inhibited renal glucose synthesis from several different substrates when added directly to tubules. 4. Paracetamol (4 mmol/l) inhibited glucose synthesis from lactate and other substrates by 50% or more in isolated hepatocytes. Glucose synthesis from lactate was inhibited 30% by concentrations of paracetamol as low as 0.5 mmol/l. 5. These results indicate that p-aminophenol is a potent inhibitor of proximal tubular function, with its main site of action the inhibition of ATP synthesis and energy production, and they confirm the primary hepatotoxic effect of paracetamol.

Adenosine Triphosphate↗