Surface tension, proteinuria, and the urine bubbles of Hippocrates.

Hippocrates noted that bubbles in urine were associated with kidney disease. We examined changes in surface tension responsible for bubble formation in urine, to investigate whether surface tension could be a more accurate and continuous linear predictor of 24-h proteinuria than currently available tests on spot urine.

Edema, oncotic pressure, and free entropy: novel considerations for the treatment of edema through attention to thermodynamics.

Over 170 years after Richard Bright and a century after Ernest H. Starling, the development, location, and severity of edema in patients with renal impairment continue to baffle the predictions of most nephrologists. While much of the phenomenon can be explained by levels of serum proteins, or hydrostatic pressures, there are stunning exceptions well known to any practicing nephrologist. Some of the derangement is undoubtedly due to unmeasured but well-known variables, such as membrane permeability; however, other factors such as free entropy of plasma are also clearly involved. The study of other polyelectrolyte colloids, similar to plasma proteins, for industrial purposes has led to the identification of various phenomena such as counterion condensation that can result in loss of entropy and consequently osmotic pressure. Variables known to result in a loss of free entropy, such as pH, oxidation products and ligand binding, are discussed. Older equations developed by van't Hoff and Donnan might require replacement by newer mathematical models such as the nonlinear Poisson-Boltzmann equation or the Monte Carlo simulator. Attempts to restore free entropy to plasma would be a more physiological treatment of edema than diuretic use. Implications are noted for future drug development to treat edema.

Adaptation to phosphate depletion in opossum kidney cells.

Dietary phosphate restriction produces an adaptive increase in renal tubular Na/Pi cotransport. A similar adaptation occurs during phosphate depletion in opossum kidney cells, a continuous line of cultured renal epithelial cells. We investigated the cellular changes associated with adaptation to phosphate depletion in OK cells, in isolation from the complex systemic changes that occur with in vivo phosphate restriction. Phosphate depletion for up to 24 hours was associated with increases in Na/Pi cotransport activity, Na/Pi cotransporter mRNA, and Na/Pi cotransporter protein. Moreover, the increases in Na/Pi cotransport, and Na/Pi cotransporter mRNA and protein occurred at physiologically relevant degrees of phosphate restriction. The experimental results suggest that increases in Na/Pi cotransporter mRNA and protein may mediate the increase in Na/Pi cotransport activity in OK cells during phosphate depletion.

Comparison of 1,2-dihydropyrido[3,4-b]pyrazines (1-deaza-7,8-dihydropteridines) with several other inhibitors of mitosis.

Several properties of four 1-deaza-7,8-dihydropteridines were compared with those of each other and with those of colchicine, nocodazole, podophyllotoxin, and vincristine. Compound NSC 370147 was more active than the other compounds of this type with respect to inhibition of proliferation of cultured L1210 cells and to increase of the mitotic index. On an equimolar basis it was more active than two of the 1-deaza-7,8-dihydropteridines, colchicine, and nocodazole and was comparable to podophyllotoxin and vincristine in inhibiting the polymerization of partially purified pig brain tubulin. All four of the 1-deaza-7,8-dihydropteridines caused decreases in the extent of binding of [3H]colchicine to partially purified tubulin and enhanced the binding of [3H]vincristine to the tubulin. Emphasis in further testing was placed upon NSC 370147, because it is easier to synthesize and is more stable than some of the other compounds of this type and because its greater solubility in water facilitates its formulation for therapeutic administration. Compound NSC 370147 inhibited competitively the binding of [3H]colchicine to purified tubulin and enhanced slightly the binding of [3H]vincristine to tubulin. It was also synergistic with vincristine in killing cultured L1210 cells and in increasing the life-spans of mice bearing P388 leukemia. It is suggested that it would be worthwhile to evaluate combinations of NSC 370147 and vincristine in tests with other experimental neoplasms.