Biomedical subjects

K R Emslie

Publications and source records attributed to K R Emslie.

23 records · Page 2Linked to original sources

PubMed1982

Metabolism of paracetamol by the isolated perfused kidney of the homozygous Gunn rat.

1. Isolated kidneys from homozygous Gunn rats were perfused with paracetamol in concentrations lower and higher than Km for paracetamol oxidation in the albino rat kidney. 2. Glucuronylation of paracetamol was not detected at either concentration. 3. An increase in oxidative metabolism at the higher concentration, similar to that seen with the Sprague-Dawley rat kidney, did not occur with kidneys from homozygous Gunn rats. 4. This finding does not support the hypothesis that the enhanced nephrotoxicity of paracetamol observed in the homozygous Gunn rat in vivo is due to increased intrarenal formation of reactive metabolites.

Acetaminophen↗

PubMed1981

Selective distal nephron damage during isolated kidney perfusion.

The morphologic characteristics of the isolated perfused rat kidney were examined by light and electron microscopy. Following perfusion for 90 min, the cortex appeared normal except for the development of spaces in glomerular mesangial regions and ultrastructural abnormalities in very few proximal tubular cells. In the medulla, descending limbs of the loops of Henle and Collecting tubules appeared normal. During perfusion, however, even under optimal conditions, consistent and reproducible changes rapidly developed in cells of the thick ascending limb of Henle's loop, more specifically, in cells of the straight portion of the distal tubule in the inner stripe of the outer medulla. The changes became progressively more severe as perfusion continued and ranged from swelling of mitochondria at 15 min to complete cellular disruption by 90 min. Horseradish peroxidase added to the perfusion medium was found in and between damaged cells and in the interstitial tissue adjacent to affected areas. The pathogenesis of these selective medullary distal tubular abnormalities may relate to the specialized functional activity of this segment of the nephron. Such abnormalities may contribute to the specific functional defects of the preparation.

Animals↗

PubMed1981

Paracetamol and the isolated perfused kidney: metabolism and functional effects.

1. Renal metabolism of paracetamol has been studied in the isolated perfused rat kidney. 2. The major metabolites of paracetamol normally observed in vivo were present in low concentrations in the urine of the isolated perfused rat kidney. 3. Paracetamol was bound covalently to kidney protein in a linear relationship to dose up to 31.9 mM paracetamol in the perfusate. 4. Using Michaelis-Menten kinetics, the apparent Km of 5.5 mM and Vmax of 139 nmol/h/g wet wt. for renal paracetamol oxidation were observed. 5. Concn. of paracetamol greater than 14.2 mM induced immediate diuresis and diminished sodium reabsorption. Lower concn. were without effect on function.

Acetaminophen↗

PubMed1981

Induction of paracetamol metabolism in the isolated perfused kidney.

1. At a perfusate concn. of 3.5-4.0 mM, 59 plus or minus 9 nmol of paracetamol h per g wet wt. were oxidized by isolated rat kidney. 2. Approx. half the paracetamol undergoing oxidation was converted to a mercapturic acid metabolite and the remainder was covalently bound to kidney protein. 3. Addition of GSH to the perfusate decreased the level of covalent binding. Depletion of cellular GSH, by prior administration of diethyl maleate, significantly decreased formation of the mercapturic acid metabolite. 4. The metabolic pathways of glucoronylation, sulphation and mercapturic acid formation were induced either by 3-methylcholanthrene pretreatment or by prolonged feeding of aspirin or paracetamol; covalent binding of paracetamol to kidney protein was not increased.

Absorption↗

PubMedDate not supplied

Pathogenesis and treatment of acute hematogenous osteomyelitis: evaluation of current views with reference to an animal model.

Antibiotic therapy and surgical drainage of the bone are the most commonly accepted forms of therapy for acute hematogenous osteomyelitis; the efficacy of these two treatment modalities, however, has not been fully established. Treatment regimens remain empiric and open to much controversy. Many contentious issues concerning the management of this disease have arisen because the natural history of the untreated condition has not been properly understood, because therapeutic regimens alternative to those empirically initiated and perpetuated have not been adequately tested, and because most follow-up studies have dealt with small numbers of patients over relatively short periods. A highly reproducible animal model of acute hematogenous osteomyelitis was developed and utilized in a reexamination of issues regarding the natural history and pathology of the disease and the influence of appropriate treatment.

Acute Disease↗