Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: role of dietary phosphate.
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BACKGROUND: The abnormal control of parathyroid hormone secretion in chronic renal failure is attributed, in part, to down-regulation of the calcium-sensing receptor (CaR) in hyperplastic parathyroid tissue. The cause of this down-regulation is unknown. Here we examined the roles of uremia and parathyroid hyperplasia on parathyroid gland (PTG) CaR expression in the rat model of renal failure. METHODS: Rats made uremic by 5/6 nephrectomy were maintained for one month on diets containing 0.2% P (low phosphate), 0.5% P (normal phosphate) or 1.2% P (high phosphate); intact rats (controls) were maintained on the normal-phosphate diet. RESULTS: CaR mRNA was reduced only in uremic rats fed the high-phosphate diet (55% less than in controls, P < 0.05). Immunohistochemical staining revealed decreased CaR protein expression in uremic high-phosphate rat PTG compared with controls (41% decrease as determined by computer-assisted quantitation, P < 0.01). PTG size was increased in uremic rats fed the high-phosphate diet compared with controls (2.77 +/- 0.95 vs. 0.77 +/- 0.16 microgram/g body wt, P < 0.0001). There was no increase in PTG size in uremic rats fed the low-phosphate and normal-phosphate diets (0.92 +/- 0.31 and 1.01 +/- 0.31 micrograms/g) compared with controls (0.77 +/- 0.16 microgram/g body wt). Immunohistochemical staining for proliferating cell nuclear antigen in hyperplastic PTG from uremic rats showed that CaR was decreased primarily in areas of active cell proliferation. CONCLUSION: These results suggest that CaR down-regulation cannot be attributed to uremia per se, but rather, is associated with parathyroid cell proliferation. Furthermore, dietary phosphate restriction prevents both the parathyroid hyperplasia and decreased CaR expression in renal failure. (+info)
Excessive Ca and P intake during early maturation in dogs alters Ca and P balance without long-term effects after dietary normalization.
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Calcium (Ca) and phosphorus (P) balance is important for skeletal development. Although the effects of deficiencies are well known, reports on the effects of excessive Ca and P supply are relatively scarce. Epidemiologic data and a few controlled studies have shown that skeletal abnormalities may develop when Ca intake is excessive, particularly in periods of rapid growth. Changes in Ca and P balance during and/or after a high Ca intake are thought to underlie this phenomenon. In this study, the effects of excessive Ca (3.1 g/kg dry matter) or Ca and P (Ca 3.1 g/kg, P 2.8 g/kg) intake on Ca and P balance in young, rapidly growing dogs during (for the period from 3 to 17 wk of age) and after (for the period from 17 to 27 wk of age) high Ca and P intake were compared with findings in age-matched controls with normal Ca and P intakes (Ca 1.0 g/kg, P 0.8 g/kg). Dogs fed a high Ca diet developed hypercalcemia, and food intake and fractional absorption of Ca and P were significantly lower at 15 wk of age, whereas endogenous fecal and renal Ca excretion were significantly higher than in controls. This resulted in significantly higher Ca retention than in controls only at 9 wk of age, and in disproportionate absorption of Ca and P. In dogs fed a high Ca and P diet, normocalcemia was maintained, fractional absorption of Ca and P were significantly lower at 9 and 15 wk of age, but retention of both was significantly higher at 9 wk than in controls. The endogenous fecal Ca and renal P losses were significantly higher, but renal Ca excretion was not different from that in controls. After normalization of Ca and P intake, Ca and P balance did not differ among groups. In conclusion, excessive Ca and P intake during early maturation alters Ca and P balance, but does not influence Ca and P balance after dietary normalization. (+info)
Limit-feeding corn as an alternative to hay reduces manure and nutrient output by Holstein cows.
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Efficiency of limit-feeding a whole shelled corn-based diet as an alternative to a conventional forage-based diet for nonlactating dairy cattle was determined. Twelve nonlactating, multiparous Holstein cows (initial BW 642+/-50 kg) were used in a randomized complete block design. Nutrient digestibility, excretion of DM, N, and P, performance of cows, and feed costs were measured. Both diets were formulated to provide equal daily intakes of NE1, protein, vitamins, and minerals, according to National Research Council recommendations. Dry matter intake was restricted by 30% for cows fed the high-corn diet compared with the high-forage diet (6.8 vs 9.6 kg/ d, respectively); therefore, concentrations of nutrients in the high-corn diet were increased to compensate for decreased DMI. Diets were fed once daily, and cows had unlimited access to fresh water. After a 28-d adaptation period, cows were placed in metabolism stalls for a 6-d total collection of feces and urine. The limit-fed, high-corn diet had a 15% greater DM digestibility than the high-forage diet. A 29% decrease in DMI for the high-corn diet vs the high-forage diet resulted in a 40% decrease in fecal DM excretion. Starch digestibility and digestibility of whole corn kernels were not affected (P > or = .62) by diet. Despite similar N intakes, total N excretion was 22% greater (P < .01) for cows fed the high-forage diet than for those limit-fed the high-grain diet. Cow weight and condition score change did not differ (P > .10) between diets. Feed costs were reduced by $.38/d with the high-corn diet vs the high-forage diet. Limit-feeding a corn-based diet is an economically and nutritionally viable alternative to forage-based diets for nonlactating Holstein cows. (+info)
Effects of porcine sometotropin on calcium and phosphorus balance and markers of bone metabolism in finishing pigs.
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Six sets of four littermate barrows initially averaging 75.5 kg BW were equally fed (within blocks) fortified corn-soybean meal diets (1.30% lysine) containing two concentrations of Ca (.50 and 1.00%) and P (.45% and .90%) in a 34-d test. One-half of the pigs were injected with 4 mg of porcine ST (pST)/d. Following a 7-d adjustment period, total collection of feces and urine was performed during two periods (d 1 to 10 and d 20 to 30) for the determination of Ca and P apparent digestibility (absorption) and retention. Pigs were bled after each period (d 10, 20, and 30) for the determination of serum metabolites associated with Ca, P, and bone metabolism. Feed intake for the 30-d period averaged 2,020 g/d. There were no treatment x period interactions, so the absorption and retention data were pooled across periods. The absorption and retention of Ca and P were greater (P<.01) in pigs fed the higher Ca and P levels. Within each Ca and P level, pST reduced (P<.01) fecal Ca and P excretion. Administration of pST did not affect urinary P excretion, but it increased (P<.03) urinary Ca excretion in pigs fed the low-Ca diet. The absorption and retention of Ca and P were increased (P<.01) by pST; however, the increases in Ca retention and P absorption and retention on an absolute basis (g/d) were more pronounced in pST-treated pigs consuming the higher Ca and P diet (interaction, P<.10). Serum concentrations of 1,25-dihydroxyvitamin D3, osteocalcin, and IGF-I on d 10 and 30 were increased (P<.07) with pST administration. However, the increases in 1,25-dihydroxyvitamin D3 and osteocalcin in pST-treated pigs were more pronounced when the lower dietary Ca and P levels were fed (interaction, P<.08). Urinary excretion of hydroxyproline increased (P<.01) with pST administration, but this effect was more pronounced in pST-treated pigs fed the lower Ca and P diet (interaction, P<.09). These results suggest that pST increases the absorption and retention of Ca and P independent of dietary Ca and P level. However, serum measures associated with Ca, P, and bone metabolism in pST-treated pigs were dependent on the Ca and P content of the diet, suggesting an effect of pST on the homeostatic control of Ca, P, and bone metabolism. (+info)
Effect of dietary phosphorus on finishing steer performance, bone status, and carcass maturity.
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Yearling crossbred steers (n = 60; 386 kg) were individually fed in a completely randomized experimental design to determine their P requirement. Treatments were in a factorial arrangement with two levels of Ca (.35 or .70% of DM) and five concentrations of P (.14, .19, .24, .29, or .34% of DM). The finishing diet consisted of 34.5% dry-rolled corn, 22.5% brewers grits, 22.5% corn bran, 7.5% ground corncobs, 5% molasses, 3% fat, and 5% supplement. Supplemental P was provided as monosodium phosphate and Ca as limestone. Ash content was determined on the first phalanx bone from the lower front legs following slaughter, and rib bone breaking strength was determined with an Instron Universal Testing Machine. Carcass maturity and shear force were also evaluated on wholesale rib cuts. Because no interactions between Ca and P levels were detected, only main effects are presented. Daily gain, DMI, and feed efficiency were not affected by dietary P concentration or P intake. Bone ash (g or g/100 kg BW) and rib bone breaking strength were also unaffected by dietary P. Feeding .7% Ca decreased (P<.06) ADG and efficiency compared with feeding .35% Ca. Neither dietary Ca nor P had a significant effect on tenderness (shear force), skeletal maturity, or overall maturity. These results indicate that the P requirement for finishing yearlings is .14% of diet DM or less and that supplementing P above levels supplied by basal ingredients in many grain-based finishing diets is not necessary. (+info)
Regulation of intestinal Na+-dependent phosphate co-transporters by a low-phosphate diet and 1,25-dihydroxyvitamin D3.
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In a study of the rat intestinal P(i) transport system, an activator protein for rat Na/P(i) co-transport system (PiUS) was isolated and characterized. We also investigated the effects of restriction of vitamin D and P(i) (two of the most important physiological and pathophysiological regulators of P(i) absorption in the small intestine) on intestinal P(i) transport activity and the expression of Na/P(i) co-transporters that are expressed in rat small intestine. Rat PiUS encodes a 424-residue protein with a calculated molecular mass of 51463 Da. The microinjection of rat PiUS into Xenopus oocytes markedly stimulated Na(+)-dependent P(i) co-transport activity. In rats fed with a low-P(i) diet, Na(+)-dependent P(i) co-transport activity was increased approx. 2-fold compared with that of rats fed a normal P(i) diet. Kinetic studies demonstrated that this increased activity was due to an elevation of V(max) but not K(m). The PiUS mRNA levels showed an approximate doubling in the rats fed with the low-P(i) diet compared with those fed with the normal P(i) diet. In addition, after the administration of 1, 25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] to vitamin D-deficient animals, the P(i) uptake was significantly increased in the Na(+)-dependent component in the brush border membrane vesicle (BBMV) at 24 and 48 h. In addition, we found a further high-affinity Na/P(i) co-transport system in the BBMV isolated from the vitamin D-replete animals. The levels of type III Na/P(i) co-transporter PiT-2 mRNA were increased 24 and 48 h after 1,25-(OH)(2)D(3) administration to vitamin D-deficient animals, whereas PiUS and the type IIb Na/P(i) co-transporter mRNA levels were unchanged. In conclusion, we first cloned a rat activator protein, PiUS, and then studied its role along with that of other type III Na/P(i) co-transporters. PiUS and PiT-2 might be important components in the regulation of the intestinal P(i) transport system by P(i) restriction and 1,25-(OH)(2)D(3). (+info)
Calcium phosphate supersaturation regulates stone formation in genetic hypercalciuric stone-forming rats.
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BACKGROUND: Hypercalciuria is the most common metabolic abnormality observed in patients with nephrolithiasis. Hypercalciuria raises urine supersaturation with respect to the solid phases of calcium oxalate and calcium phosphate, leading to an enhanced probability for nucleation and growth of crystals into clinically significant stones. However, there is little direct proof that supersaturation itself regulates stone formation. Through successive inbreeding of the most hypercalciuric progeny of hypercalciuric Sprague-Dawley rats, we have established a strain of rats, each of which excrete abnormally large amounts of urinary calcium and each of which forms calcium phosphate kidney stones. We used these hypercalciuric (GHS) rats to test the hypothesis that an isolated reduction in urine supersaturation, achieved by decreasing urine phosphorus excretion, would decrease stone formation in these rats. METHODS: Thirty 44th-generation female GHS rats were randomly divided into three groups. Ten rats received a high-phosphorus diet (0.565% phosphorus), 10 a medium-phosphorus diet (0.395% phosphorus), and 10 a low-phosphorus diet (0.225% phosphorus) for a total of 18 weeks. The lowered dietary phosphorus would be expected to result in a decrease in urine phosphorus excretion and a decrease in urinary supersaturation with respect to the calcium phosphate solid phase. Every two weeks, 24-hour urine collections were obtained. All relevant ions were measured, and supersaturation with respect to calcium oxalate and calcium hydrogen phosphate were determined. At the conclusion of the experiment, each rat was killed, and the kidneys, ureters, and bladder were dissected en block and x-rayed to determine whether any stones formed. A decrease in stone formation with a reduction in urinary supersaturation would support the hypothesis that supersaturation alone can regulate stone formation. RESULTS: Decreasing the dietary phosphorus intake led to a progressive decrease in urine phosphorus excretion and an increase in urine calcium excretion, the latter presumably caused by decreased intestinal calcium phosphate binding and increased calcium absorption. With decreasing dietary phosphorus intake, there was a progressive decrease in saturation with respect to the calcium phosphate solid phase. Fifteen of the 20 kidneys from the 10 rats fed the high-phosphorus diet had radiographic evidence of kidney stone formation, whereas no kidneys from the rats fed either the medium- or low-phosphorus diet developed kidney stones. CONCLUSIONS: A decrease in urine phosphorus excretion not only led to a decrease in urine supersaturation with respect to the calcium phosphate solid phase but to an elimination of renal stone formation. The results of this study support the hypothesis that variation in supersaturation alone can regulate renal stone formation. Whether a reduction of dietary phosphorus will alter stone formation in humans with calcium phosphate nephrolithiasis remains to be determined. (+info)
Efficacy of yeast phytase in improving phosphorus bioavailability in a corn-soybean meal-based diet for growing pigs.
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Crossbred barrows (n = 66; 6 wk old) were used in a 6-wk experiment to evaluate the efficacy of phytase from yeast or Aspergillus niger on performance, tibial characteristics, and serum inorganic P concentration. We also investigated the stability of these phytases in acidic solutions with pepsin, which simulated gastric conditions. Pigs were fed a P-adequate diet containing .34% nonphytate-P or a low-P diet containing .20% nonphytate-P. The low-P diet was supplemented with 0, 1,000, 2,000, or 4,000 phytase units (PU; the activity at optimal pH, i.e., pH 4.2 for yeast phytase and pH 5.5 for phytase from Aspergillus niger)/kg of yeast phytase, or 1,000 PU/kg phytase from Aspergillus niger. The graded level of yeast phytase linearly increased ADG (P = .047), tibial weight (P = .091), tibial density (P < .001), and P concentration in tibial cortex (P = .018). Aspergillus niger phytase also increased ADG (P = .022), serum inorganic P concentration (P < .001), tibial density (P = .007), and tibial P concentration (P = .025). The pigs given 1,000 PU/kg Aspergillus niger phytase showed greater ADG (P = .091), tibial density (P= .001), and tibial P concentration (P = .062) than those given 1,000 PU/kg yeast phytase. No measurements differed (P > .31) between the pigs given 1,000 PU/kg Aspergillus niger phytase and those given 4,000 PU/kg yeast phytase. These results suggested that yeast phytase improves bioavailability of P in the diet for growing pigs but the efficacy of yeast phytase is less than that of Aspergillus niger phytase. During incubation in acidic solutions with pepsin, yeast phytase (P < .001) lost more of its activity than Aspergillus niger phytase. This lesser stability of yeast phytase may be responsible for the poorer efficacy of yeast phytase than that of Aspergillus niger. In summary, supplementation of swine diets with yeast phytase is beneficial, but its efficacy is less than that of Aspergillus niger phytase. (+info)