A reevaluation of the cause of acute hypercalcemia following intravenous administration of lead acetate.
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Biomedical subjects
Publications and source records attributed to R V Talmage.
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Acute changes in plasma calcium and 45Ca were studies in young adult male thyroparathyroidectomized (TPTX) rats injected with moderate doses of parathyroid hormone (PTH). For plasma calcium changes, comparison was made between rats fasted or fed prior to PTH injection. For plasma 45Ca changes, the effect of the time of administration of the radionuclide was also studied; this included rats injected with PTH 1 h after radionuclide ("1 h 45Ca"), 18 h later ("18 h 45Ca") and more than 6 days later ("6 day 45Ca"). The results can be summarized as follows: (1) Plasma calcium changes were greater when PTH was injected into "fed" rather than into "fasted" rats. (2) PTH always produced a relative increase (compared to controls tested concurrently) in plasma 45Ca concentrations. This increase was the same in the "1 h 45Ca" and the "18 h 45Ca" group. (3) Plasma 45Ca rose at least temporarily following PTH injection in the "18 h 45Ca" group. (4) The 45Ca rise following PTH was always greater in "fed" than in "fasted" groups. (5) Plasma 45Ca specific activities (S.A.) tended to rise in the "6 day 45Ca" group and to fall in the "18 h 45Ca" group, following PTH injection. However, the 45Ca S.A. was always higher in fed than fasted groups. (6) In a few experiments in which 32P was injected with 45Ca, specific activity changes in plasma 45Ca following PTH injection were not accompanied by similar changes in 32P specific activity. These results could not be adequately explained by PTH effects on bone resorption, but the data supported the postulate that PTH controls plasma calcium concentrations by increasing transport of calcium through the osteocyte-lining cell (osteoblast) bone cell complex from the bone fluid compartment to the ECF.
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Daily fluctuations in plasma calcium, phosphate and their radionuclides (injected 5 or more days previously) were determined in rats maintained on a closely controlled feeding and light schedule. Male rats (150-300 g) were trained to a 7a.m.-7p.m. "light" schedule with food available 9 p.m. to 9 a.m. All prarmeters dropped rapidly at the start of each feeding period and then rose during the day. The daily changes in radionuclide concentrations were several orders of magnitude greater than for the stable ions. Continuous access to food produced an earlier fall (5 p.m.) in all plasma values. In thyroidectomized rats (with parathyroid transplants) plasma calcium and phosphate remained relatively constant during the 24 h period. If the time of availability of food was moved 6 h earlier (no change in light cycle), the drop in these plasma values also occurred 6 h earlier. Closer examination of these daily changes indicated that all values fell at least 1 h prior to feeding. In fasted rats, plasma calcium and phosphate concentrations fell as usual; however, 45Ca and 32P rose instead of falling. It was concluded that, in normal rats, changes in endogenous calcitonin secretion may actually increase rather than decrease daily pertubations of plasma calcium and phosphate. Daily changes in these values are influenced by a condition reflex developed due to the feeding habits of the rats. Finally, it is suggested that intestinal hormones rather than calcium may be the primary control of calcitonin secretion, and that the gastrointestinal tract plays a major role, in addition to absorptive activity, in both calcium and phosphate homeostasis.
Young male rats were administered 45Ca 5 days to 2 weeks prior to use. All rats were either parathyroidectomized (PTX) or thyroparathyroidectomized (TPTX) and given several days to recover from surgery. The first group of rats were maintained on a 12 h dark-fed and 12 h light-fasted daily cycle. The remainder of the rats were used for parathyroid hormone (PTH) studies (0.1-0.6U/g body weight) following which blood samples were obtained from the tail for 1 to 6 h. Two groups of these rats were bilaterally nephrectomized 18 h before PTH injection. Two contrasting results were obtained: in PTX (or TPTX) rats maintained on the closely regulated food and light regime, plasma 45Ca concentrations rose markedly each day at the start of the fasting period and then fell slowly. Total plasma calcium values fell throughout the fasting period. A similar rise and fall was also observed in 45Ca values of rats experimentally fasted after being maintained with food continuously available. In contrast, in all PTX or TPTX rats, PTH injections was followed by an equal rise in both plasma calcium and 45Ca values so that for the first few hours plasma 45Ca specific acitvity was unchanged. These data are consistent with the concept of a bone fluid compartment (BFC) separated by a cellular interface from the primary extracellular fluid space (ecf). It is postulated that through this cellular interface calcium is actively "pumped" from the BFC to the ECF. The rise in plasma 45Ca values at the start of fasting is explained on the basis of decreased entry of stable calcium from the gastrointestinal tract and a continued movement of calcium and 45Ca from the BFC to the ECF. The concomitant increase in plasma calcium and 45Ca during the first few hours after PTH injection is explained by a rapid action of PTH to increase the rate of calcium movement from BFC to ECF by its action at the cellular interface, without altering 45Ca specific activity until such time as dissolution of bone crystals is required as a supply of calcium.
Daily fluctuations in plasma calcium concentrations in rats trained to a closely regulated feeding pattern have been compared to corresponding plasma gastrin and calcitonin concentrations. The time period studied was that extending from 4 hr prior to the start of the feeding. Both plasma calcium and phosphate levels fedd prior to the start of the feeding period and remained low at least for the first 2 hr of feeding. This pattern was also observed in rats in which food was withheld for 2 hr past the regular feeding time. Plasma 45Ca and 32P concentrations (radionuclide injected at least one week prior to sampling) did not follow the pattern of their stable counterparts. Instead, these values rose or remained constant until after feeding had commenced, after which they fell precipitously. Both plasma calcitonin and gastrin levels rose rapidly after the start of the feeding period. The primary point of emphasis is that calcitonin secretion was produced in these rats by an intestinal related stimulus and not by a rise in plasma calcium concentration.
Histopathological findings in the lungs, livers, bone marrows, small intestines, gonads, kidneys, and other tissues of the four pocket mice (Perognathus longimembris) that survived the Apollo XVII flight were evaluated in the light of their immediate environment and as targest of HZE cosmic ray particles. Results of this study failed to disclose changes that could be ascribed to the HZE particle radiation. Decreased numbers of erythropoietic cells in the bone marrow of the flight mice were probably related to the increased oxygen pressure. The small intestine showed no changes. Ovaries and tests appeared normal. Two of the three surviving male flight mice displayed early stages of spermatogenesis, just as ground-based controls did at the same season. Abnormalities were also not found in the thyroid, parathyroids, adrenals, or kidneys. The status of the juxtaglomerular apparatus could not be evaluated. The lungs exhibited nonspecific slight rections. A variety of incidental lesions were noted in the livers of both the flight mice and their controls. The heart muscle showed nothing that could be regarded as pathological. Sections of skeletal muscle examined were free from significant change.
The ability of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP; 40 milligrams per kilogram of body weight per day) to reduce the hypercalcemic effect of parathyroid hormone in thyroparathyroidectomized rats was confirmed. However, treatment with this large dose of EHDP enhanced the hypophosphatemic effect of a low dose of parathyroid hormone (10 international units per100 grams of body weight), apparently by promoting the renal excretion of phosphate. The data suggest that EHDP may have a direct effect on the renal action of parathyroid hormone and, in this way, may also affect vitamin D metabolism by the kidney.
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