Phosphorus homeostasis in sheep. I. Effects of ligation of parotid salivary ducts

1974 ◽  
Vol 25 (3) ◽  
pp. 475 ◽  
Author(s):  
FM Tomas ◽  
M Somers

The effects of bilateral parotid duct ligation upon calcium and phosphorus concentrations in blood plasma and upon phosphorus excretion in urine and faeces have been examined. Five Merino wethers were used, of which three were given a phosphorus-deficient diet (0.304 g phosphorus/day) and two a phosphorus-sufficient diet (1.454 g phosphorus/day) for 32 days prior to ligation of the parotid ducts. Blood samples were taken every 6 hours for 2 days before and 4 days after parotid duct ligation followed by less frequent sampling for a further 3 days. Parotid duct ligation caused an increase in plasma inorganic phosphorus levels after the first day in the phosphorus-supplemented sheep and in one of the deficient animals. Plasma calcium concentrations tended to be inversely related to plasma phosphorus levels and showed marked variations on the fourth day following duct ligation, coinciding with a sudden fall in plasma phosphorus levels of 30-50 %. Urinary phosphorus excretion in the phosphorus-sufficient animals was increased 20 to 50-fold following ligation and reached a peak of about 600 mg/day on the fourth day, but there was no significant change in phosphorus balance. Marked alterations in the daily urinary output of phosphorus tended to be associated with a change in plasma phosphorus levels in the reverse direction. Four of the sheep were re-examined 22 months after duct ligation and the elevated urinary output of phosphorus was found to have persisted in three of the four animals. It appears that there is a relationship between the salivary secretion of phosphorus to the gut and the urinary phosphorus excretion which contributes towards maintenance of the phosphorus homeostasis in sheep.

1974 ◽  
Vol 25 (3) ◽  
pp. 495 ◽  
Author(s):  
FM Tomas

The interrelationships between the urinary and faecal pathways for phosphorus excretion in sheep have been examined under conditions allowing direct proportional control of the major portion of endogenous phosphorus secretion to the gut which is contributed by the parotid salivary glands. Two rumen-fistulated Merino wethers were fitted with permanent bilateral re-entrant parotid duct cannulas which allowed continuous collection and return of parotid saliva. During experimental periods, a proportion of the phosphorus secreted by the parotid glands during control periods was returned to the rumen in artificial saliva, and the remaining quantity not returned in this manner was infused intravenously over a corresponding time period. Diversion of the secreted parotid salivary phosphorus from the rumen to the blood led to an increase in urinary phosphorus excretion which was proportional to the fractional amount of secreted phosphorus withheld from the rumen. Phosphorus balance remained unaltered, which indicated a virtual substitution between the two excretory pathways. The increased urinary excretion of phosphorus is attributed partly to increased plasma phosphorus levels and partly to a reduced efficiency of renal tubular reabsorption of phosphorus. No direct evidence for any hormonal action could be seen. The data show that the pathway of excretion of phosphorus can be determined quantitatively by the rate of endogenous phosphorus secretion into the gut. This mechanism is of fundamental importance among factors contributing to phosphorus homeostasis in sheep. ____________________ *Part II, Aust. J. Agric. Res., 25: 485 (1974).


PEDIATRICS ◽  
1962 ◽  
Vol 30 (6) ◽  
pp. 884-892
Author(s):  
L. S. Taitz ◽  
C. D. de Lacy

Hypocalcemic tetany does not occur in South African Bantu infants with very gross bone changes of rickets. Rachitic children with hypocalcemic tetany have significantly lower phosphorus excretion indices than those with normal or moderately decreased calcium levels. Tetany appears to occur in a specific group of subjects with moderately severe bone changes, decreased phosphorus clearance, and relatively high plasma phosphorus levels. It is suggested that this group represents either failure of the compensatory parathyroid response or secondary "pseudo-hypoparathyroidism." Certain cases of idiopathic infantile tetany may be the result of premature failure of the compensatory parathyroid response to deficiency of vitamin D.


1999 ◽  
Vol 10 (5) ◽  
pp. 980-985 ◽  
Author(s):  
JANE L. FINCH ◽  
ALEX J. BROWN ◽  
EDUARDO SLATOPOLSKY

Abstract. 1,25-Dihydroxy-vitamin D3 [1,25-(OH)2D3] suppresses the secretion and synthesis of parathyroid hormone (PTH) and has been used in the treatment of secondary hyperparathyroidism. However, 1,25-(OH)2D3 can induce hypercalcemia, which often precludes its use. Therefore, an analog of 1,25-(OH)2D3 that would retain its therapeutic effects but produce minor effects on calcium and phosphorus metabolism could be an ideal tool for the treatment of secondary hyperparathyroidism. It has been shown that 19-nor-1,25-dihydroxy-vitamin D2 [19-nor-1,25-(OH)2D2], an analog of 1,25-(OH)2D3, can suppress PTH levels in uremic rats at doses that do not affect plasma ionized calcium levels. The experiments presented here, using parathyroidectomized rats fed diets deficient in either calcium (0.02%) or phosphorus (0.02%), were performed to compare the effects of 1,25-(OH)2D3 and 19-nor-1,25-(OH)2D2 on calcium and phosphorus resorption in bone. Parathyroidectomized rats received daily intraperitoneal injections of vehicle, 1,25-(OH)2D3 (100 ng), or 19-nor-1,25-(OH)2D2 (100 or 1000 ng) for 9 d. Plasma calcium and phosphorus levels were monitored during the study, and ionized calcium levels were determined at the end of the study. By 9 d, 1,25-(OH)2D3 (100 ng/d) increased total calcium levels to 12.4 ± 0.26 mg/dl, compared with 6.32 ± 0.25 mg/dl (P < 0.001) in control animals. The same dose of 19-nor-1,25-(OH)2D2 (100 ng/d) was much less potent (9.45 ± 0.28 mg/dl, P < 0.001). Similar results were seen with ionized calcium levels [19-nor-1,25-(OH)2D2, 3.61 ± 0.12 mg/dl; 1,25-(OH)2D3, 5.03 ± 0.16 mg/dl; P < 0.001]. Ionized calcium levels were also lower in rats receiving the higher dose (1000 ng) of 19-nor-1,25-(OH)2D2 (4.59 ± 0.09 mg/dl, P < 0.05). Similar results were seen in rats fed the phosphorus-deficient diet. 1,25-(OH)2D3 (100 ng) increased plasma phosphorus levels from 4.30 ± 0.39 mg/dl in vehicle-treated rats to 7.43 ± 0.26 mg/dl (P < 0.001). The same dose of 19-nor-1,25-(OH)2D2 had no effect (5.19 ± 0.32 mg/dl), whereas the high dose (1000 ng) increased plasma phosphorus levels (7.31 ± 0.24 mg/dl) in a manner similar to that of 1,25-(OH)2D3 (100 ng). Therefore, 19-nor-1,25-(OH)2D2 is approximately 10 times less effective in mobilizing calcium and phosphorus from the skeleton, compared with 1,25-(OH)2D3. With its ability to suppress PTH at noncalcemic doses, 19-nor-1,25-(OH)2D2 is a potential therapeutic tool for the treatment of secondary hyperparathyroidism in chronic renal failure.


1984 ◽  
Vol 102 (3) ◽  
pp. 365-368 ◽  
Author(s):  
T. Matsui ◽  
Y. Kanagawa ◽  
H. Yano ◽  
R. Kawashima

ABSTRACT Three thyroidectomized sheep were infused intravenously with porcine calcitonin at a rate of 30 mi.u./h per kg and three sham-operated sheep were infused with vehicle for 5 h. Saliva was collected from the left parotid duct by cannulation for 10 min in every hour. Salivary secretion rates were not changed in either thyroidectomized or sham-operated sheep throughout the experiment. Before the infusion, salivary phosphorus excretion was less in thyroidectomized sheep than in sham-operated animals. Calcitonin infusion increased salivary phosphorus excretion and decreased serum phosphorus concentrations in thyroidectomized sheep. Vehicle infusion did not affect salivary phosphorus excretion in sham-operated sheep. Serum concentrations and salivary excretion of calcium were decreased by calcitonin infusion into thyroidectomized sheep but were not changed in sham-operated sheep infused with vehicle. Calcitonin infusion increased serum parathyroid hormone concentrations in thyroidectomized sheep after the decrease of serum calcium concentrations. However, vehicle infusion did not affect serum parathyroid hormone concentrations in sham-operated sheep. There was little change of cyclic AMP excretion during the experiment in either thyroidectomized or sham-operated sheep. It is concluded that calcitonin increases salivary phosphorus excretion in sheep. J. Endocr. (1984) 102, 365–368


1997 ◽  
Vol 12 (5) ◽  
pp. 961-964 ◽  
Author(s):  
D. Rosenbaum ◽  
S. Holmes-Farley ◽  
W. Mandeville ◽  
M. Pitruzzello ◽  
D. Goldberg

Author(s):  
Andrew J. King ◽  
Jill Kohler ◽  
Cyra Fung ◽  
Zhengfeng Jiang ◽  
Allison Quach ◽  
...  

The majority of patients with chronic kidney disease (CKD) receiving dialysis do not reach target serum phosphorus concentrations, despite treatment with phosphate binders. Tenapanor is a non-binder, sodium/hydrogen exchanger isoform 3 (NHE3) inhibitor that reduces paracellular intestinal phosphate absorption. This pre-clinical study evaluated the effect of tenapanor and varying doses of sevelamer carbonate on urinary phosphorus excretion, a direct reflection of intestinal phosphate absorption. We measured 24-hour urinary phosphorus excretion in male rats assigned to groups dosed orally with vehicle or tenapanor (0.3 mg/kg/day) and provided a diet containing varying amounts of sevelamer (0-3% w/w). We also evaluated the effect of the addition of tenapanor or vehicle on 24-hour urinary phosphorus excretion to rats on a stable dose of sevelamer (1.5% w/w). When administered together, tenapanor and sevelamer decreased urinary phosphorus excretion significantly more than either tenapanor or sevelamer alone across all sevelamer dose levels. The Bliss statistical model of independence indicated that the combination was synergistic. A stable sevelamer dose (1.5% w/w) reduced mean (±standard error of the mean) urinary phosphorus excretion by 42±3% compared with vehicle; together, tenapanor and sevelamer reduced residual urinary phosphorus excretion by an additional 37±6% (P < 0.05). While both tenapanor and sevelamer reduce intestinal phosphate absorption individually, administration of tenapanor and sevelamer together results in more pronounced reductions in intestinal phosphate absorption than if either agent is administered alone. Further evaluation of combination tenapanor plus phosphate binder treatment in patients receiving dialysis with hyperphosphatemia is warranted.


2009 ◽  
Vol 29 (5) ◽  
pp. 562-567 ◽  
Author(s):  
Daniel O. Young ◽  
Steven C. Cheng ◽  
James A. Delmez ◽  
Daniel W. Coyne

Background Hyperphosphatemia remains a significant problem for patients requiring dialysis and is associated with increased mortality. Current treatment options include dietary restriction, dialysis, and phosphate binders. Treatment using the latter is frequently limited by cost, tolerability, and calcium loading. One open-label trial found niacinamide to be effective at decreasing serum phosphorus values in hemodialysis patients. Niacinamide may effectively reduce phosphorus levels in peritoneal dialysis (PD) patients already receiving standard phosphorus-lowering therapies. Methods An 8 week, randomized, double blind, placebo-controlled trial to evaluate the effectiveness of niacinamide to reduce plasma phosphorus levels in PD patients. Patients had to demonstrate a baseline phosphorus value > 4.9 mg/dL. Patients were randomized to niacinamide or placebo and prescribed 250 mg twice daily, with titration to 750 mg twice daily, as long as safety parameters were not violated. Phosphate binders, active vitamin D, and cinacalcet were kept constant during the study. The primary end point was change in plasma phosphorus. Secondary end points included changes in lipid parameters. Results 15 patients started on the study drug (8 niacinamide, 7 placebo) and 7 in each arm had at least one on-study phosphorus measurement. The niacinamide treatment group experienced an average 0.7 ± 0.9 mg/dL decrease in plasma phosphorus and the placebo-treated group experienced an average 0.4 ± 0.8 mg/dL increase. The treatment effect difference (1.1 mg/dL) was significant ( p = 0.037). No significant changes in high- or low-density lipoproteins or triglycerides were demonstrated. Two of the 8 patients randomized to the niacinamide treatment arm had to withdraw from the study due to drug-related adverse effects. Adverse effects may limit the use of niacinamide in PD patients. Conclusion Niacinamide, when added to standard phosphorus-lowering therapies, resulted in a modest yet statistically significant reduction in plasma phosphorus levels at 8 weeks. [ClinicalTrials.gov number NCT00508885 (ClinicalTrials.gov)]


1973 ◽  
Vol 24 (6) ◽  
pp. 913 ◽  
Author(s):  
RC Clark ◽  
OE Budtz-Olsen ◽  
RB Cross ◽  
P Finnamore ◽  
PA Bauert

Urinary and faecal phosphorus excretion were measured in five sheep for 4 days after acute intravenous infusion of 3.38 g of phosphorus as potassium dihydrogen phosphate. Urinary phosphorus excretion was increased for 12 hr after the infusion, but urinary phosphorus output was small compared with the marked increase in faecal phosphorus output. The increase in faecal phosphorus excretion coincided with and followed the appearance in the faeces of Cr-EDTA, which had been introduced into the rumen as a marker at the time of the phosphate infusion. This suggests that secretion of phosphorus into gut regions below the reticulo-rumen is not quantitatively altered in response to intravenous phosphorus loading, and that phosphorus absorption is also unaffected (at least not on a short-term basis). The additional phosphorus entered the alimentary canal at the level of the reticulo-rumen, and it was deduced that this occurred predominantly via the salivary glands. Persistence of the increase in faecal phosphorus excretion for some time after the Cr-EDTA marker had been cleared emphasizes the importance of the phosphorus recirculation system to ruminants like the sheep.


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