An Evaluation of Radiosulfate for the Determination of the Volume of Extracellular Fluid in Man and Dogs 1

Walser, Mackenzie; Seldin, Donald W.; Grollman, Arthur P.

doi:10.1172/jci102739

Cited by 161 publications

(37 citation statements)

References 38 publications

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“…Although newer methods for estimating extracellular water voluine have been devised [radiolabeled inulin or polyethylene glycol (13)], there are difficulties with these techniques. Both indicators require a prolonged, continuous infusion to enable adequate distribution of the marker in the extracellular fluid space (14), which would have been a difficult procedure in extremely ill, dehydrated animals. Because chloride may not be entirely excluded from the cerebral cell (1 5), the true anatomic meaning of the chloride space in the brain has been a subject of much dispute.…”

Section: Discussionmentioning

confidence: 99%

Taurine and Osmoregulation: Taurine Is a Cerebral Osmoprotective Molecule in Chronic Hypernatremic Dehydration

et al. 1988

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ABSTRACT. We studied the effect of 8-wk dietary taurine depletion on the vulnerability to hypernatremic dehydration in postweanling kittens. While experimental taurine depletion was not associated with increased susceptibility to acute hypernatremia (1.5 M NaCl/NaHC03 35 ml/kg body weight, single injection), there was an increase in Recent evidence suggests that in many animal species taurine, a p-aminosulfonic acid formed in the metabolism of methionine and cysteine or present in the diet, acts as an osmoprotective molecule under stressful conditions (I). Hypernatremic dehydration is a formidable problem in clinical pediatrics. Rapid onset of hypernatremia and hasty rehydration are associated with the occurrence of cerebral shrinkage or swelling, respectively, caused by two distinct phenomena (2). The first is the slow diffusion of solute through the "blood brain bamer" so that an osmolal gradient will be initially relieved by the movement of water alone causing a volume change in the brain. The cerebral volume change is gradually attenuated by a second process that is oper-

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Section: Discussionmentioning

confidence: 99%

Taurine and Osmoregulation: Taurine Is a Cerebral Osmoprotective Molecule in Chronic Hypernatremic Dehydration

et al. 1988

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“…2). The sulfate ion has been used to estimate interstitial fluid volume since it is distributed without obstruction into the extracellular space, yet its renal clearance occurs only at a relatively slow rate (48,49). Control experiments demonstrated that GRGDS mock-labeled with sodium borohydride was equally effective as the unlabeled peptide in blocking cellular adhesion to fibronectin, thereby demonstrating that the labeling procedure did not affect the biological activity of GRGDS.…”

Section: Specificity Ofpeptide Inhibition Ofexperimental Metastasismentioning

confidence: 99%

Investigation of the biological effects of anti-cell adhesive synthetic peptides that inhibit experimental metastasis of B16-F10 murine melanoma cells.

Humphries¹,

Yamada²,

Olden³

1988

J. Clin. Invest.

155

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The experimental metastasis of B16-F10 murine melanoma cells is blocked by the anti-cell adhesive pentapeptide GlyArg-Gly-Asp-Ser (GRGDS) derived from the central cellbinding domain of fibronectin. In this report, we show that peptide treatment substantially extends the survival time for mice injected intravenously with B16-F1O cells (8/8 vs. 0/8 mice alive at 150 d), thereby demonstrating the potential efficacy of GRGDS treatment in protection against metastatic colonization. We have also examined the specificity of GRGDS activity by testing a series of related homologues for their effects on experimental metastasis. The overall profile of the relative inhibitory activities of these peptides closely matched their previously established capacity to disrupt adhesion in vitro. Lung retention studies with radiolabeled B16-F1O cells revealed an accelerated rate of cell loss from the lung 0-6 h after coinjection with the active peptide GRGDS. This early effect of GRGDS was consistent with its short circulatory half-life, which was found to be 8 min. Taken together, these results suggest that peptide-mediated inhibition of pulmonary colonization is due to interference with B16-F1O cell adhesion to structures in the target organ. Possible peptide interference in tumor cell-blood cell interactions was examined in order to assess (a) possible biological side-effects of peptide treatment and (b) whether such interactions might be an alternative mechanism for GRGDS-mediated inhibition of pulmonary colonization. GRGDS was found to retain full inhibitory activity when coinjected with B16-F10 cells into mice in which platelet function was impaired by acetylsalicylic acid treatment or into thrombocytopenic mice treated with antiplatelet serum (76-93% inhibition of colony formation). These data suggest that platelet involvement in the effects of the peptide is minimal. Similarly, GRGDS was also found to be a potent inhibitor of experimental metastasis in natural killer (NK) cell-deficient beige mice (86% inhibition), thereby discounting the possibility that GRGDS artifactually enhanced NK cell activity. We conclude as a result of these studies that cell-binding fibronectin peptides are specific inhibitors of experimental metastasis that prolong survival, that they appear to function by blocking the adhesion of B16-F1O cells to structures in the target organ, and that they do not appear to act through side effects on certain metastasis-related blood cell functions. In the future, deriva-

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“…It is also evident in Table III that the radiosulfate space as determined in man is less than that obtained by the use of other agents (mannitol, inulin, thiocyanate, sucrose). Because of this discrepancy, which has been discussed elsewhere (8), all determinations were made on paired normotensive and hypertensive subjects of similar body build.…”

Section: Resultsmentioning

confidence: 99%

“…For the determination of extracellular volume by radiosulfate,2 carrier-free S' in the form of H,SO was used in doses of 100 microcuries as described elsewhere (8). …”

Section: Methodsmentioning

confidence: 99%

The Volume of the Extracellular Fluid in Experimental and Human Hypertension 1

Grollman¹,

Shapiro²,

Gafford³

1953

J. Clin. Invest.

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Several lines of investigation have indicated the existence of abnormalities in salt and water metabolism in hypertensive cardiovascular disease. It has been shown, for example, that the electrolyte and water contents of the tissues in the hypertensive animal deviate from that in the normal (1) and that there is an increased rate of excretion of antidiuretic substance in the urine in experimental and human hypertension (2). The effect of a sodium restricted diet on the blood pressure level (3) and the difference in the rate of urinary excretion of salt and water in the hypertensive subject as compared to the normal (4) also point to some fundamental deviation from normal in the salt and water metabolism of the hypertensive subject. Because of the importance of this problem to a better understanding of the basic mechanisms underlying hypertensive cardiovascular disease, the present study was undertaken to compare the extracellular fluid volume in experimental and human hypertension with that of the normal. MATERIALS AND METHODSThe extracellular fluid volume was determined in a series of dogs rendered hypertensive by the application of a figure-of-eight ligature to the right kidney and ablation of the left organ (5). At least six months had intervened between the operation and the time of the experiments to permit the establishment of a stabilized blood pressure. Determinations were made simultaneously on a group of normotensive animals. Because of the uncertainty and difficulties attendant upon the determination of the extracellular volume, both mannitol and radioactive sulfate were utilized for this purpose. Although the use of inulin is considered to be the method of choice in man, erratic results are obtained when this substance is applied to the dog because of the large and variable blanks obtained in analysis of the blood under apparently constant conditions. The use of a constant infusion of mannitol (6) gave consistent and reproducible results. The radiosulfate method only was used in the experiments on the human.LAided by a grant from the Vaughn Fund. (7) with minor modifications. The animals were fasted for 12 to 14 hours prior to the determination but were allowed access to water at all times. They were trained to lie quietly on the animal board during the course of the procedure with only slight restraint.For the determination of extracellular volume by radiosulfate,2 carrier-free S' in the form of H,SO was used in doses of 100 microcuries as described elsewhere (8).

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An Evaluation of Radiosulfate for the Determination of the Volume of Extracellular Fluid in Man and Dogs 1

Cited by 161 publications

References 38 publications

Taurine and Osmoregulation: Taurine Is a Cerebral Osmoprotective Molecule in Chronic Hypernatremic Dehydration

Taurine and Osmoregulation: Taurine Is a Cerebral Osmoprotective Molecule in Chronic Hypernatremic Dehydration

Investigation of the biological effects of anti-cell adhesive synthetic peptides that inhibit experimental metastasis of B16-F10 murine melanoma cells.

The Volume of the Extracellular Fluid in Experimental and Human Hypertension 1

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