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Biomedical subjects

J K Aronson

Publications and source records attributed to J K Aronson.

At least 127 records · Page 7Linked to original sources
PubMed1982

The effects of digoxin and dopamine on the oxygen consumption, lactate production and haemodynamic performance of an isolated, perfused, working guinea-pig heart.

We have adapted an established technique for perfusing the isolated, working rat heart to the guinea-pig heart and characterized its biochemical and haemodynamic performance. After 20 min of anoxia the heart recovers about 50% of its pre-anoxic performance ('post-anoxic cardiac failure') and after 90 min of continuous work total cardiac output falls to 50% of its initial, stable value ('spontaneous cardiac failure'). We have studied the effects of digoxin (10(-7) M and 2 x 10(-7) M) and dopamine (10(-5) M) on these two forms of cardiac failure and shown that digoxin improves the haemodynamic performance of the heart without altering its metabolism and therefore increases its efficiency. In contrast dopamine improves the haemodynamic performance of the heart at the expense of increased aerobic and anaerobic metabolism. The preparation is of value in studying the effects of cardioactive drugs on hearts subjected to constant pre-load and after-load.

Animals↗
PubMed1982

The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man.

1 We have investigated the disposition and metabolism of sulphasalazine (SASP) in eight adults with and without inflammatory bowel disease. 2 SASP is poorly absorbed (less than 12%) and the half-time measured in the serum, 10.2 h, is probably the half-time of absorption and therefore an overestimate of the true half-time. The apparent volume of distribution is low (less than 9 l). Renal and biliary clearance rates are low (5.5 and 2.1 ml min-1 respectively) probably due to a high degree of protein binding. Of the absorbed SASP, two thirds is excreted in the urine and one third in the bile. 3 Most of the SASP reaches the colon and is there split by bacteria, forming sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA). 4 SP is almost completely absorbed and, with its metabolites, is excreted in the urine (SP renal clearance rate 32.1 ml min-1). There is no enterohepatic recirculation. 5 Of the 5-ASA released in the colon at least 25% is absorbed and rapidly eliminated in the urine after acetylation. At least 50% is eliminated in the faeces. 6 There are no differences in disposition characteristics when comparing patients with and without inflammatory bowel disease but the metabolism of SASP is markedly reduced in patients taking antibiotics and after removal of the large bowel.

Adult↗
PubMed1982

Distribution and metabolism in healthy volunteers of disodium azodisalicylate, a potential therapeutic agent for ulcerative colitis.

A series of experiments has been performed in healthy male volunteers to investigate the disposition of orally administered disodium azodisalicylate, a potentially useful drug for the treatment of ulcerative colitis. The drug was given by mouth in doses of up to 2 g a day for six weeks and there were no adverse effects. Serum concentrations of the intact compound were low and the serum half-time was 4-12.8 days, probably because of a combination of a low clearance rate and a high apparent volume of distribution. Less than 5% of the ingested dose was excreted unchanged in the urine. Circulating concentrations of 5-ASA and N-acetyl-5-ASA were low and 30% of the equivalent daily dose was excreted in the urine, predominantly as N-acetyl-5-ASA. In most subjects more than 30% of the equivalent daily dose of 5-ASA was recovered from the faeces, either as 5-ASA itself or as the acetylated derivative. As 5-ASA has been shown to be the active therapeutic moiety of sulphasalazine, disodium azodisalicylate appears to be suitable for therapeutic trial in ulcerative colitis.

Adult↗
PubMed1981

Techniques for studying the pharmacodynamic effects of cardiac glycosides on patients' own erythrocytes during glycoside therapy.

We have measured the effects of digoxin on the cation transport mechanisms of patients' erythrocytes during treatment with digoxin for atrial fibrillation and cardiac failure in sinus rhythm. The results show that during short-term treatment with digoxin there is occupation of erythrocytic cardiac glycoside receptors by digoxin with resultant inhibition of active cation transport. These effects correlate well with the patients' clinical responses to treatment. During long-term treatment, however, these effects are not seen, suggesting that there is pharmacological tolerance to the effects of digoxin. The clinical implications of these results are discussed.

Atrial Fibrillation↗
PubMed1980

Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan.

1 The metabolism of three oral doses of L-tryptophan (50, 25 and 10 mg/kg) in healthy young males has been investigated. 2 There was a linear relationship between both peak and area under curve of the total plasma tryptophan concentrations whilst the relationship between these parameters and plasma free tryptophan was hyperbolic. 3 Before the tryptophan load about 85% of plasma tryptophan was bound to albumin. As plasma tryptophan concentrations increased there was a hyperbolic increase in free tryptophan. Scatchard analysis revealed 1.4 binding sites/molecule albumin with a dissociation constant (Kd) of 57.9 microM. Following administration of L-tryptophan (50 mg/kg) twice daily for 7 days there was no alteration in the number of binding sites but the dissociation constant (Kd) had decreased to 30.9 microM. 4 L-Tryptophan (50 mg/kg twice daily for 7 days) markedly increased both basal plasma total and free tryptophan. However following a further load the total tryptophan curve was comparable to that seen after acute administration. The plasma free tryptophan curve was lowered relative to that seen after an acute dose. 5 Increasing the tryptophan dose shortened the plasma half-life and decreased the volume of distribution and the rate of clearance. Longer term tryptophan administration had no significant effect on plasma half-life or volume of distribution but did decrease the rate of plasma clearance. 6 The plasma kynurenine concentration increased with increasing tryptophan dose and basal concentrations increased markedly after longer term tryptophan administration. 7 Tryptophan administration either acutely or chronically produced little change in urinary tryptophan or 5-hydroxyindole acetic acid excretion. Urinary kynurenine and indole acetic acid excretion increased with increasing doses of tryptophan. 8 Data are discussed in relation to the administration of L-tryptophan for the treatment of depression.

Administration, Oral↗
PubMed1980

Metabolism of an oral tryptophan load. II: Effect of pretreatment with the putative tryptophan pyrrolase inhibitors nicotinamide or allopurinol.

1 The effect of seven days administration of either allopurinol (300 mg daily) or nicotinamide (500 mg twice daily) on the metabolism of an oral L-tryptophan load (50 mg/kg) has been investigated. 2 Administration of either drug failed to alter the plasma total or free tryptophan or plasma kynurenine curve. Nor was the urinary excretion of tryptophan, kynurenine, 5-hydroxyindoleacetic acid or indole acetic acid influenced. 3 Allopurinol pretreatment did increase the volume of distribution of tryptophan. 4 These data suggest that allopurinol and nicotinamide are unlikely to be of value as tryptophan pyrrolase inhibitors in vivo and therefore would not increase the therapeutic effect of L-tryptophan when it is given to treat depressive illness.

Administration, Oral↗
PubMed1980

The use of colour vision measurement in the diagnosis of digoxin toxicity.

Colour vision has been measured, using the Farnsworth-Munsell 100-Hue test, in control subjects and in patients taking digoxin. In 10 patients with digitalis toxicity, of whom only two described symptomatic abnormalities, colour vision was impaired compared with that of both control subjects and non-toxic patients who had been taking digoxin for more than two months. Withdrawal of digoxin from toxic patients led to improved colour vision. Colour vision scores correlated well with (a) log plasma digoxin concentrations, and (b) various measures of the pharmacodynamic effects of cardiac glycosides on cation transport in the patients' own erythrocytes. These results suggest that colour vision assessment may be of use in screening for digitalis toxicity at the bedside and in assessing the degree of digitalis intoxication in an individual patient as an aid to clinical research.

Adult↗
PubMed1979

Tranylcypromine ('Parnate') overdose: measurement of tranylcypromine concentrations and MAO inhibitory activity and identification of amphetamines in plasma.

A case of tranylcypromine overdose is reported. Tranylcypromine, amphetamine methamphetamine and phenylethylamine were detected in the plasma by gas chromatography and their identity confirmed by mass spectrometry. The data suggested that the amphetamines were metabolic products of tranylcypromine. Platelet monoamine oxidase activity was more than 95% inhibited during the 72 h after the overdose despite complete clinical recovery by that time. The possible role of amphetamines and phenylethylamine in causing the clinical manifestations of tranylcypromine overdose is discussed.

Amphetamine↗
PubMed1979

The characteristics of the binding of 12-alpha-[3H]-digoxin to the membranes of intact human erythrocytes: relevance to digoxin therapy.

1 The characteristics of the binding of 12-alpha-[3H]-digoxin to the membranes of intact human erythrocytes are described. 2 Only one class of binding site can be demonstrated. Binding is time- and temperature-dependent, saturable and slowly reversible; it is inhibited by other cardiac glycosides and by potassium. 3 Pre-incubation with unlabelled digoxin reduces the subsequent binding of 12-alpha-[3H]-digoxin in stoichiometric fashion. 4 The possible application of the measurement of the binding of 12-alpha-[3H]-digoxin to the study of biochemical pharmacological events occurring during digoxin therapy is discussed.

Cardiac Glycosides↗
PubMed1979

Changes in cardiac glycoside receptor sites, 86rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients receiving digoxin during the early phases of treatment of cardiac failure in regular rhythm and of atrial fibrillation.

1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocytic 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells of patients receiving digoxin in the short-term for atrial fibrillation or cardiac failure in regular rhythm. 2 During the first few days of treatment [3H]-digoxin binding and 86rubidium uptake fall and intraerythrocytic sodium concentrations rise. 3 Subsequently parallel fluctuations occur in [3H]-digoxin binding and 86rubidium uptake but not in intraerythrocytic sodium concentrations and the significance of the fluctuations is discussed. 4 The values of all three measurements correlate significantly with the response of the heart in sinus rhythm as measured by QS2I. 5 Plasma digoxin concentrations do not correlate with QS2I.

Adult↗