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Biomedical subjects

R D Wynne

Publications and source records attributed to R D Wynne.

27 records · Page 2Linked to original sources

Electrolyte secretion by the isolated cat pancreas during replacement of extracellular bicarbonate by organic anions and chloride by inorganic anions.

1. The effect of replacing extracellular bicarbonate and chloride by other anions on the volume and composition of secretin-stimulated pancreatic juice has been analysed in the isolated, perfused cat pancreas. 2. The anions of some aliphatic carboxylic acids were able partially to substitute for bicarbonate in sustaining pancreatic secretion. The order of effectiveness was: acetate greater than proprionate greater than butyrate greater than formate. 3. The rate of secretion in the presence of 25 mM-acetate was 42% of that achieved with 25 mM-bicarbonate. The concentration of acetate in the secretion varied with flow rate, reaching a maximum of 120 mM at high flow rates and declining at lower flow rates, with reciprocal changes in chloride concentration. Bicarbonate was always present in the secretion at a concentration of 5--7 mM. 4. Inorganic anions were able totally or partially to substitute for chloride in sustaining secretion. In relation to chloride, their degree of effectiveness was: chloride = bromide = or greater than nitrate greater than iodide greater than sulphate greater than methyl sulphate greater than isethionate. Those anions which had no effect on secretion rate (i.e. bromide and nitrate) also had no effect on the bicarbonate concentration of the secretion and themselves appeared in the secretion in place of chloride. Those anions which inhibited secretion increased the bicarbonate concentration in the secretion in proportion to the degree of inhibition they caused (i.e. the increase was greatest with isethionate). 5. When perfusate chloride was only partially replaced by bromide or iodide the ratios of chloride: bromide and chloride: iodide in the secretion were approximately equal to those in the perfusate. 6. The carbonic anhydrase inhibitor acetazolamide reduced secretory rate and bicarbonate concentration when added to normal perfusion fluid or chloride-substituted fluids, but had no effect following replacement of perfusate bicarbonate by acetate. 7. These observations illustrate that an extracellular source of permeant anions is required for optimal pancreatic bicarbonate secretion to occur. This may indicate the participation of an anion exchange carrier in the transport events responsible for this secretory process.

Acetazolamide↗

The origin and secretion of pancreatic juice bicarbonate.

1. The rate of secretion from a saline-perfused preparation of the cat's pancreas is directly proportional to the perfusate bicarbonate concentration. When all bicarbonate is omitted, secretion completely or almost completely ceases.2. Incorporation of [(14)C]bicarbonate into the perfusion fluid results in its prompt appearance in the juice. The radioactive label is concentrated four to five times in the juice just as the total juice bicarbonate is four to five times greater than perfusate bicarbonate.3. These two observations suggest that about 95% of pancreatic juice bicarbonate is derived from perfusate (plasma) bicarbonate.4. The inhibition of pancreatic secretion from the perfused gland by acetazolamide is similar to that observed in the intact animal.5. There is a fall in pH and rise in P(CO2) in the perfusion fluid leaving the gland which is greater during secretion than at rest.6. It is therefore suggested that during secretion, hydrogen ions pass from the gland into the perfusate (plasma), thus increasing the production of carbon dioxide from circulating bicarbonate. This carbon dioxide diffuses into the cell, is rehydrated (partly under the influence of carbonic anhydrase) and finally is secreted, thus establishing the necessary gradient for the continued diffusion of carbon dioxide into the cell.

Acetazolamide↗

Renal excretory actions of furosemide, of hydrochlorothiazide and of the vasodilator flosequinan in healthy subjects.

The responses of urine and urinary solute outputs and flows to single doses of 80 mg furosemide, 25 mg hydrochlorothiazide, and 100 or 200 mg flosequinan were investigated in healthy subjects using a double-blind, randomized, crossover design. Treatment days were separated by 7 days. Volumes of urine passed between 0 and 3, 3 and 6, 6 and 9, 9 and 12, and 12 and 24 h after drug administration were determined and urinary concentrations of chloride, sodium, potassium, calcium, magnesium, phosphate, zinc, urate, urea and creatinine were measured. Venous blood was taken before and 6 and 24 h after dosing and the serum was analysed for the same solutes as urine. Excretions of urine and urinary solutes accumulated at the end of each collection period after each formulation were fitted by the UY function, whose derivative provided corresponding flows as functions of time. Instantaneous renal clearances of solutes 6 and 24 h after dosing were evaluated from the flows. This approach showed that 80 mg furosemide and 25 mg hydrochlorothiazide were equipotent 24-h natriuretics. Rapid urinary responses which then rebounded compared with the control responses were produced by 80 mg furosemide, whereas changes after 25 mg hydrochlorothiazide were smooth. Neither 100 or 200 mg flosequinan showed any important effect on urinary excretion.

Adolescent↗