Rabbit Responses to Human Threshold Doses of A Bacterial Pyrogen

There is little available information regarding the quantitative relationship between the rate of secretion of antidiuretic hormone (ADH) and the rate of reabsorption of water by the renal tubules. From the work of Shannon (1) and Lauson (2) it has been suggested that in both dogs and adult humans the rate of secretion of ADH is equivalent to the intravenous administration of vasopressin at rates varying from less than 0.1 to more than 0.7 milliunit per hour per kilogram of body weight. Utilizing the endogenous creatinine U/P ratios as an index of the renal response, these authors both demonstrated a curvilinear relationship between the rate of infusion of vasopressin and the response of the kidney. The lowest rates of infusion of vasopressin studied were sufficient to produce a marked reduction in the rate of urine flow and increase in the endogenous creatinine U/P ratios, and there do not appear to be any data which define the quantitative relationship between ADH and the renal reabsorption of water in the range in which the concentration of the urine is generally less than that of the plasma. The current studies were designed to establish this relationship with the additional hope that its characteristics might provide some insight with respect to the mode of action of ADH. The subjects were all apparently healthy young adult men of ages twenty to thirty-five. No food or water was allowed for 10 to 12 hours prior to all but three of the experiments. In three studies (R

Section: Resultsmentioning

confidence: 99%

A Study of the Quantitative Relationship Between Antidiuretic Hormone (Vasopressin) and the Renal Tubular Reabsorption of Water1

Hollander¹,

Williams²,

Fordham³

et al. 1957

“…Each lot was tested for pyrogen (14) and cultured for bacterial and fungal contamination before use.…”

Section: Metiiodsmentioning

confidence: 99%

Effect of Starvation on the Turnover and Metabolic Response to Leucine

Sherwin¹

1978

127

A B S T R A C T L-Leucine was administered as a primed continuous 3-4-h infuision in nonobese and obese subjects in the postabsorptive state and for 12 h in obese subjects after a 3-day and 4-wk fast. In nonobese and obese subjects studied in the postabsorptive state, the leucine infusion resulted in a 150-200% rise in plasma leucine above preinftusion levels, a small decrease in plasma glucose, and unchanged levels of plasma insulin and gltucagon and blood ketones. Plasma isoleucine (60-70%) and valine (35-40%) declined to a greater extent than other amino acids (P < 0.001).After 3 days and 4 wk of fasting, ecquimolar infusions of leucine resulted in two-to threefold greater increments in plasma leucine as compared to postabsorptive subjects, a 30-40% decline in other plasma amino acids, and a 25-30% decrease in negative nitrogen balance. Urinary excretion of 3-methylhistidine was however, unchanged. Plasma glucose which declined in 3-day fasted subjects after leucine administration, surprisingly rose by 20 mg/100 ml after 4 wk of fasting. The rise in blood glucose ocetrred in the absence of changes in plasma glucagon and insulin and in the face of a 15% decline in endogenous glucose production (as measured by infusion of [3-3H]glucose). On the other hand, fractional gluicose utilization fell by 30% (P < 0.001), thereby accouinting for hyperglycemia.The estimated metabolic clearance rate of leucine fell by 48% after 3 days of fasting whereas the plasma delivery rate of leucine was uinchanged, thereby accouinting for a 40% rise in plasma leuicinie during early starvation. After a 4-wk fast, the estimated metabolic clearance rate of leuicine declined further to 59% below base line. Plasma leucine nevertheless fell to postabsorptive levels as the plasma delivery rate of leucine decreased 65% below postabsorptive valtues.Dr.

“…and stored at 40C until used. Each lot was tested for pyrogen (10) and cultured for bacterial contamination before use. Before administration, sterile, pyrogen-free water was added to the Na DL-P-OHB solution to achieve a final solute concentration in the infusate which varied between 3.6 and 7.1 g/100 ml.…”

Section: Methodsmentioning

confidence: 99%

Effect of ketone infusions on amino acid and nitrogen metabolism in man.

Sherwin¹,

Hendler²,

Felig³

1975

328

123

A B S T R A C T To evaluate the role of hyperketonemia in the hypoalaninemia and decreased protein catabolism of prolonged starvation, Na DL-P-hydroxybutyrate was administered as a primed continuous 3-6-h infusion in nonobese subjects and in obese subjects in the postabsorptive state and after 3 days and 3-51 wk of starvation. An additional obese group received 12-h ketone infusions on 2 consecutive days after 5-10 wk of fasting.The ketone infusion in nonobese and obese subjects studied in the postabsorptive state resulted in total blood ketone acid levels of 1.1-1.2 mM, a 5-15 mg/100 ml decrease in plasma glucose, and unchanged levels of insulin, glucagon, lactate, and pyruvate. Plasma alanine fell by 21% (P <0.001) in 3 h. In contrast, other amino acids were stable or varied by less than 10%. Infusions lasting 6 h reduced plasma alanine by 37%, reaching levels comparable to those observed in prolonged starvation. Equimolar infusions of NaCl and/or administration of NaHCOs failed to alter plasma alanine levels.During prolonged fasting, plasma alanine, which had fallen by 40% below prefast levels, fell an additional 30% in response to the ketone infusion. In association with repeated prolonged (12 h) infusions in subjects fasted 5-10 wk, urinary nitrogen excretion fell by 30%, returning to base line after cessation of the infusions and paralleling the changes in plasma alanine. Ketone infusions resulted in two-to fourfold greater increments in blood ketone acids in fasted as compared to postabsorptive subjects.It is concluded that increased blood ketone acid levels induced by infusions of Na DL-P-hydroxybutyrate result in hypoalaninemia and in nitrogen conservation in starvation. These data suggest that hyperketonemia may be a contributory factor in the decreased availability of circulating alanine and reduction in protein catabolism characteristic of prolonged fasting. INTRODUCTIONIn fasting man survival is dependent upon the conservation of body protein stores as well as the continuous supply of energy-yielding fuels for brain metabolism (1). The need for gluconeogenesis and concomitantly the rate of protein breakdown progressively decline in prolonged starvation as ketone acids replace glucose as the major fuel consumed by the brain (2). The diminution in hepatic gluconeogenesis in prolonged fasting is mediated by a reduction in circulating glucogenic amino acids, particularly alanine, and a decrease in the outflow of these amino acids from muscle (3, 4). After a prolonged fast, plasma alanine decreases to a greater extent than that of all other amino acids, while splanchnic uptake and peripheral release of alanine are reduced to less than 50% of postabsorptive levels (3, 4).