No abstract
In 1959 we described elevated plasma concentrations of transcortin during pregnancy and after the administration of estrogens (1,2). Since then, a number of investigations utilizing a variety of methodologies to ascertain the binding of cortisol to transcortin have confirmed our observations (3-8). The different techniques used and the diverse arithmetic approaches employed all indicate that the plasma concentration of transcortin rises about threefold during pregnancy or after estrogen therapy. These findings (3)(4)(5)(6)(7)(8) are in essential agreement with our original, less sophisticated observations and calculations. An important contribution has been the isolation by Seal and Doe (9, 10) of a highly purified plasma transcortin preparation, making it possible to ascertain the amino acid composition of the protein and many of its physical properties. They have shown that transcortin has one binding site for cortisol and a molecular weight of approximately 45,000 (9, 10). More recently, these workers have demonstrated, by means of isolation studies, that the plasma transcortin concentration is approximately 2.5 mg per 100 ml in normal subjects and 7.5 mg per 100 ml in estrogen-treated subjects (7). These and other values for normal, estrogen-treated, and pregnant subjects (3-8) are higher than our original calculations (1).Our low values can be attributed to the crudeness of the early techniques and the less critical theoretical physicochemical approaches utilized. The methods used in our laboratory now obviate these shortcomings and yield values similar to those obtained by other workers.
The mechanism of excretion of nitrofurantoin in the kidney was studied in anesthetized dogs by direct collection of urine from ureteral catheters. The method of stop flow analysis, involving a period of occlusion of the ureter, was applied in order to determine in which part of the nephron nitrofurantoin is excreted; in addition, simultaneous nitrofurantoin and creatinine clearance determinations were performed on four dogs at varying levels of urinary pH and plasma CO2 combining power. The results showed that nitrofurantoin is handled by glomerular filtration and tubular reabsorption. Tubular reabsorption was greater when the urine was acid. Alkalinizing the urine resulted in higher nitrofurantoin concentrations in the urine and less tubular reabsorption. TVTITROFUBANTOIN has been employed for the 1* treatment of urinary infections with increas¬ ing frequency, owing to its proved effectiveness against the majority of common urinary patho¬ gens x and the paucity of serious side reactions which it has occasioned.When nitrofurantoin (Furadantin) is given orally in appropriate dosage, clinically significant blood levels cannot be obtained; yet up to 50% of the ingested dose may be recovered from the urine in a 6 to 8 hour period.2 Previous studies of the uri¬ nary excretion of nitrofurantoin revealed a marked variability of excretion rate and concentration of the drug in different individuals and in the same individual at different periods of time.3 These find¬ ings coupled with periodic discrepancies between in vitro sensitivities to the medicament and its clin¬ ical effectiveness prompted us to study the mecha¬ nisms involved in the renal transport of nitro¬ furantoin by means of the technique of stop flow analysis 4 and clearance studies.Since nitrofurantoin is a weak acid with a pKa of 7.2, it is more dissociated in alkaline than in acid solution. The undissociated form of weak acids are able passively to penetrate the cell membrane, while the dissociated ions are unable to cross the lipid barrier.5 This weak acid property could per¬ haps explain the variability in the clinical results noted in the treatment of pyelonephritis with nitro¬ furantoin.6 Theoretically, greater renal tissue con¬ centration of nitrofurantoin would occur in an acid urine. The increase in hydrogen ions would by the law of mass action drive more of the nitrofurantoin into the undissociated form, allowing greater move¬ ment of the nitrofurantoin into the tubular cells from the urine. Alkalinization of the urine would result in a higher urine nitrofurantoin concentra¬ tion since a greater portion would be in the nonpenetrating dissociated form.The purpose of this study was twofold; first to determine the site within the nephron governing the urinary excretion of nitrofurantoin, and second the response of this mechanism to changes in uri¬ nary and plasma pH.Stop flow analysis offers a precise method where¬ by the location of the tubular site of secretion or reabsorption can be determined and graphically displayed. This technique was utilized...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.