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Relative effects of PTH and dietary phosphorus on calcitriol production in normal and azotemic rats.

In moderate renal failure, the serum calcitriol level is influenced by the stimulatory effect of high PTH and the inhibitory action of phosphorus retention. Our goal was to evaluate the relative effect that high PTH levels and increased dietary phosphorus had on calcitriol production in normal rats (N) and rats with moderate renal failure (Nx). Normal and Nx (3/4 nephrectomy) rats were divided into two groups: (1) rats with intact parathyroid glands (IPTG) and (2) parathyroidectomized rats in which PTH was replaced (PTHR) by the continuous infusion of rat 1-34 PTH, 0.022 microgram/hr/100 g body wt, using a miniosmotic Alzet pump. To test the effect of dietary phosphorus, rats received either a moderate (MPD, 0.6% P) or a high phosphorus (HPD, 1.2%) diet for 14 days. The experimental design included pair-fed N and Nx rats with either IPTG or PTHR. Serum calcitriol and PTH levels in N rats fed a MPD were 69 +/- 3 and 40 +/- 5 pg/ml, respectively. In Nx rats on a MPD, serum calcitriol levels decreased only if hyperparathyroidism was not allowed to occur (76 +/- 4 vs. 62 +/- 4 pg/ml in Nx-IPTG-MPD and Nx-PTHR-MPD groups respectively, P < 0.05). Even in N rats on a HPD, high PTH levels (67 +/- 8 pg/ml in the N-IPTG-HPD group) were required to maintain normal serum calcitriol levels (69 +/- 4 vs. 56 +/- 6 pg/ml in Nx-IPTG-HPD and Nx-PTHR-HPD groups, respectively; P < 0.05). In Nx rats on a HPD, the development of secondary hyperparathyroidism (286 +/- 19 pg/ml in the Nx-IPTG-HPD group) prevented a decrease in serum calcitriol levels (68 +/- 7 pg/ml). In contrast, serum calcitriol levels were low in the Nx-PTHR-HPD group (52 +/- 4 pg/ml, P < 0.05), which were deprived of the adaptative increase in endogenous PTH production. In conclusion, our results in rats indicate that in moderate renal failure, an elevated PTH level maintains calcitriol production and overcomes the inhibitory action of phosphorus retention.

Animals↗

Vitamin D3 and its metabolites have no role in calcium and phosphorus metabolism in Tilapia mossambica.

The physiological function of vitamin D in fishes still remains uncertain. Earlier we observed no relationship between vitamin D3 content of several freshwater fishes and their calcemic/phosphatemic status and bone mineral content. In the present study the effects of vitamin D3 and its metabolites, 25-hydroxy vitamin D3 (25-OH-D3) and 1,25-dihydroxy vitamin D3 [1,25-(OH)2D3], administration on serum calcium-phosphorus levels, intestinal calcium absorption, whole-body calcium-phosphorus uptake, and gill calcium binding protein (CaBP) activity in the freshwater fish, Tilapia mossambica (Tilapia) was examined. It was observed that vitamin D3 and its metabolites could alter neither serum calcium-phosphorus levels nor intestinal calcium absorption and gill CaBP activity in fish at various doses. Further, the whole-body uptake of labelled calcium and phosphorus was also unaffected by vitamin D3/1,25-(OH)2D3 at different levels and/or at various lengths of time. Thus these studies indicate that unlike in terrestrial vertebrates, vitamin D3 or its metabolites are not needed for calcium-phosphorus homeostasis in fish.

Animals↗

[A comparison of phosphorus-chelating effect of calcium carbonate versus calcium acetate before dialysis].

INTRODUCTION: The hyperphosphatemia, hypocalcemia and low calcitriol levels are pathogenic factors for secondary hyperparathyroidism in chronic renal failure. The phosphorus control is essential to prevent secondary hyperparathyroidism. There are not comparatives studies to test the efficacy of control of phosphorus binders in predialysis patients. AIM: To compare the efficacy of calcium carbonate vs calcium acetate as phosphate binder in predialysis patients. MATERIAL AND METHODS: The present study includes 28 patients with chronic renal failure (mean clearance of creatinine 21 ml/min). Patients were separated into two groups: Group 1: (n = 14) received calcium carbonate 2,500 mg/day (1,000 mg of calcium); Group 2: (n = 14) receives calcium acetate 1,000 mg (254 mg of calcium). Calcium and phosphorus were determined every 4 months; i-PTH, alkaline phosphatase and clearance of creatinine were determined every six months. RESULTS: Both groups were comparable regarding age, renal function, calcium, phosphorus, alkaline phosphatase and i-PTH on basal situation and the end of study were not different. The serum calcium increased, not significantly, in the calcium carbonate group (group 1) [from 9.2 to 9.8 mg/dl (p = 0.05)], however it was not modified in the calcium acetate group (group 2). The serum phosphorus decreased significantly (p < 0.05) in both groups, independently of the calcium levels. Alkaline phosphatase and i-PTH not was modified during the study period. CONCLUSIONS: 1) Both calcium carbonate and calcium acetate are similarly effective as phosphate binder. 2) The carbonate group required four fold greater doses of calcium that acetate group. 3) The calcium acetate has less hypercalcemic effect than calcium carbonate.

Acetates↗

Calcium and phosphorus supplementation of human milk for preterm infants.

BACKGROUND: Preterm infants are born with low skeletal stores of calcium and phosphorus. Preterm human milk provides insufficient calcium and phosphorus to meet their estimated needs. OBJECTIVES: To determine if addition of calcium and phosphorus supplements to human milk leads to improved growth and bone metabolism without significant adverse effects in preterm infants. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group (NRG) was used. This includes searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. SELECTION CRITERIA: All trials utilizing random or quasi-random allocation to supplementation of human milk with calcium and/or phosphorus or no supplementation in preterm infants within a hospital were eligible. DATA COLLECTION AND ANALYSIS: Data were extracted using the standard methods of the Cochrane NRG, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk and weighted mean difference. MAIN RESULTS: No studies which met selection criteria were identified. Excluded studies that were identified included minerals as one component of a multicomponent fortifier or reported only non-clinical outcomes (for example, urinary excretion of calcium). Two studies were excluded because of methodological concerns. REVIEWER'S CONCLUSIONS: There are no randomized controlled data evaluating clinical outcomes of calcium and phosphorus supplementation of human milk for preterm infants on which to base practice recommendations. Further trials should assess the clinical benefits and potential adverse effects of supplementation of human milk with minerals. This may best be done in the context of manipulation of the composition of human milk fortifiers containing multiple nutrients (carbohydrate, protein, and minerals).

Calcium↗

Balance sheet for phosphorus in the UK.

A balance sheet for the inputs, uses and outputs of phosphorus in the UK economy has been drawn up. The major import is fertilizer, amounting to about 200 kt P per year. After fertilizers, the other imports (in kt P) are in animal feeds (63), detergents (38) and human food (14). The major outputs are sewage (50), animal excreta (26) and refuse (21); soil losses are about 20 kt. The flowpaths for phosphorus through humans, animals and plants are described. The discrepancy of about 210 kt P/yr is explained by the fact that the amount of phosphorus in the soil increases each year by almost as much as the amount of fertilizer phosphorus added. In view of UK dependence on this imported resource it is suggested that priority is given to work which might eventually have some practical application in preventing or reversing the immobilization of phosphorus in the soil.

Agriculture↗

Classical syndromes in occupational medicine: Phosphorus necrosis--a classical occupational disease.

A disease nearly extinct in occupational health history is phosphorus necrosis, previously seen in near-epidemic proportions among workers making phosphorus-containing matches. Similar destructive lesions were encountered early in the 20th century among personnel fabricating fireworks. Through the diligent efforts of an economist and a supportive congressman, legislation was passed in 1912 placing a tax on phosphorus matches, and because of the fiscal burden resulting, a nontoxic substitute for elemental phosphorus was adopted by all manufacturers. Today phosphorus necrosis is extremely rare, but the former presence of the disease points up both apathy and courage in the identification and eradication of a remarkably disfiguring work-caused disease.

Adolescent↗

Determination of iron to phosphorus ratios of iron storage compounds in patients with iron overload: a chemical and electron probe X-ray microanalysis.

The amounts of phosphorus and iron in various isolated ferritin preparations were investigated by: chemical analysis on ferritin samples and electron probe X-ray microanalysis on ferritin particles from the same preparations. A high correlation was found between iron to phosphorus ratios obtained by both methods. Further investigation by electron probe X-ray microanalysis on lysosomes of hepatic cells of patients with idiopathic and secondary hemochromatosis revealed lysosomal iron to phosphorus ratios which were very similar in all parenchymal cells but different from ratios obtained in Kupffer cells. Lysosomal iron to phosphorus ratios in hepatocytes did not change after intensive phlebotomy treatment. It is postulated therefore that, during phlebotomy, iron and phosphorus are concomitantly lost from the hepatic lysosomes.

Bloodletting↗

Effects of estrogen on daylong circulating calcium, phosphorus, 1,25-dihydroxyvitamin D, and parathyroid hormone in postmenopausal women.

We studied the effects of estrogen on daylong circulating levels of calcium, inorganic phosphorus, parathyroid hormone (PTH), and 1,25-(OH)2D3 (calcitriol) in a group of 10 postmenopausal women (68.5 +/- 1.4 years, mean +/- SEM). The study was conducted under strict dietary control, with mean calcium and phosphorus intakes of 845 and 970 mg. After treatment with conjugated equine estrogens, 1.25 mg/day, for 1 month, significant decreases in fasting (0800 h) serum levels were observed for calcium (9.09 +/- 0.08 versus 9.46 +/- 0.10 mg/dl, p less than 0.01) and phosphorus (3.38 +/- 0.10 versus 3.73 +/- 0.08 mg/dl, p less than 0.01). On the 0800 h fasting specimen, midmolecule PTH concentrations were higher (44.0 +/- 7.9 versus 34 +/- 8.2 pg/ml, p less than 0.05), but intact PTH was unchanged (28.6 +/- 2.7 versus 29.1 +/- 1.7 pg/ml) and a rise in circulating calcitriol (39.8 +/- 4.3 versus 31.6 +/- 2.1 pg/ml) was marginally significant (p = 0.07). When data represented multiple samples averaged over 7 and 15 h, significant estrogen-related reductions in serum calcium and phosphorus concentrations were observed. In addition, estrogen was associated with a significant rise in the daylong (15 h) level of calcitriol (39.4 +/- 4 versus 30.5 +/- 2.4 pg/ml, p less than 0.01). Daylong mid- and intact PTH concentrations were unchanged on estrogen compared to baseline values. No significant correlations were observed between changes in fasting calcitriol level and changes in fasting concentrations of calcium, phosphorus, or PTH. Further, the rise in daylong calcitriol concentration did not correlate significantly with changes in fasting or integrated values of calcium or PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil.

A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability.

Animals↗

Effects of dietary calcium, magnesium and phosphorus on the formation of struvite stones in the urinary tract of rats.

After feeding various diets we studied the effects of dietary calcium, magnesium and phosphorus on the formation of struvite stones in rats with urinary tract infections, and also studied the effects of the administration of vitamin D3 and aluminium gel on stone formation. A low-magnesium diet decreased urinary magnesium and prevented stone formation, but a medium-calcium diet did not significantly decrease stone weight. A high-calcium diet decreased urinary phosphorus and inhibited stone formation. A high-calcium and high-phosphorus diet decreased urinary excretion of magnesium and inhibited stone formation. Although the administration of vitamin D3 did not inhibit stone formation, aluminium gel decreased the urinary level of phosphorus and prevented stone formation. A marked decrease in urinary magnesium and/or phosphorus may prevent struvite stone formation in rats with urinary tract infections.

Aluminum↗

Evaluation of mineral metabolism and bone turnover in osteoporotic females treated with phosphorus and salmon calcitonin.

Twenty-five patients with radiological and clinical evidence of osteoporosis were studied. Nineteen patients received oral phosphorus at a dose of 1,000 mg/die for 10 days followed by salmon calcitonin (100 U MRC/die) for 20 days. Six patients received only oral calcium at a dose of 1,000 mg/die). In the first group, a significant increase in serum osteocalcin and parathyroid hormone, after administration of phosphorus and persisting after treatment with salmon calcitonin, was found. No variation in the controls was observed. In a later study, a significant increase in serum 1,25 dihydroxyvitamin D (1,25(OH)2D3), after receiving phosphorus and persisting after salmon calcitonin, was demonstrated. In accordance with the authors' results, phosphorus could be considered a useful activator of bone formation and this stimulus by parathyroid hormone was mediated. Finally, the positive effects of phosphorus on circulating 1,25(OH)2D3 must be considered for a good treatment protocol of osteoporosis.

Administration, Oral↗

Total and cell wall phosphorus content in Bacillus megaterium in phosphate-limited media.

A comparative study of the amount of total and cell wall phosphorus in Bacillus megaterium ATCC 33085, grown in media with or without phosphate limitation was carried out. The phosphorus levels were investigated during six successive subcultures. A progressive decrease in total phosphorus was found in cells cultivated in a phosphate-limited medium. A decline in the cell wall phosphorus level was observed starting only from the third subculture in phosphate-limited medium, and no phosphorus was detected in the walls of cells in the fifth subculture.

Agar↗

Dynamic changes in serum phosphorus levels in diabetic ketoacidosis.

The dynamic changes in serum phosphorus levels in 69 episodes of ketoacidosis in 48 diabetic patients were retrospectively evaluated. The mean age was 41 +/- 2 years (mean +/- SEM), and the duration of diabetes mellitus was 7 +/- 1 years. The serum phosphorus levels determined within the first six hours of admission were analyzed. Before initiation of therapy, the incidence of hyperphosphatemia was 94.7 percent. At the end of 12 hours, the mean serum phosphorus level fell from 9.2 +/- 0.6 to 2.8 +/- 0.3 mg/dl. Before therapy, the serum phosphorus level correlated positively with the serum glucose level, the effective plasma osmolality, and anion gaps, and correlated negatively with the serum chloride level. It is concluded that hyperphosphatemia is common in diabetic ketoacidosis before therapy. The increase in serum phosphorus is likely to be due to a transcellular shift. Potential factors responsible for the shift are serum glucose, through its osmotic effect, and the organic anions.

Adult↗

Inorganic phosphorus and zinc concentrations in amniotic fluid: correlation with intra-amniotic infection and bacterial inhibitory activity.

Concentrations of zinc and inorganic phosphorus were determined in amniotic fluid from 41 patients with intra-amniotic infection and from 40 uninfected, control patients. Also determined was amniotic fluid inhibitory activity to an Escherichia coli test organism. Compared to amniotic fluid from control patients, that from patients with intra-amniotic infection had significantly higher mean concentrations of phosphorus. In specimens free of meconium, the mean concentrations of phosphorus were still significantly higher. Assays for inhibitory activity were performed with 62 samples of fluid (25 noninhibitory, 37 inhibitory). Although noninhibitory fluid had higher mean concentrations of phosphorus and zinc, these differences did not hold after meconium-stained samples were excluded. No correlation was found between phosphorus-to-zinc ratio and either intra-amniotic infection or inhibitory activity. However, there are important differences in population and techniques between this and related studies.

Amniotic Fluid↗

The regulation of calcitriol by parathyroid hormone and absorbed dietary phosphorus in subjects with moderate chronic renal failure.

The two best-recognized stimuli for calcitriol production are parathyroid hormone (PTH) and dietary phosphorus deprivation. We studied the relative importance of these two stimuli in subjects with moderate chronic renal failure (MCRF). We recruited 10 subjects with MCRF aged 49 +/- 13 years (mean +/- SD) and having a creatinine clearance rate of 31 +/- 24 mL/min. After an overnight fast, they received 400 IU human PTH 1-34 subcutaneously, and blood and urine samples were collected over the subsequent 24 hours. They then took aluminum hydroxide 30 mmol/d for 2 months to reduce gut phosphorus absorption, at the end of which the PTH stimulation test was repeated. Responses were compared with those obtained in 11 normal subjects aged 44 +/- 16 years and having a creatinine clearance rate of 102 +/- 37 mL/min who were only studied while on their normal diet. Following PTH stimulation in the normal subjects but not the MCRF subjects, there was a significant increase in plasma calcium and calcitriol levels, with a significant decrease in renal phosphorus threshold. In both groups there was a similar and significant increase in urine cyclic adenosine monophosphate (cAMP) levels. Following restriction of absorption of dietary phosphorus in MCRF subjects, plasma calcitriol levels increased compared with baseline values. This study shows that these MCRF subjects were unable to respond with an increase in calcitriol to a PTH stimulus that produced a similar urine cAMP response in normal subjects. However, they were capable of responding to a reduction in phosphorus absorption with an increase in calcitriol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Maturational increase in mouse brain creatine kinase reaction rates shown by phosphorus magnetic resonance.

In-vivo phosphorus fluxes in the reaction catalyzed by creatine kinase (CK) were measured in brains of mice from 3 to 40 days of age using high-field (8.45 T) phosphorus magnetic resonance and the saturation transfer technique. This technique gives the ratio of chemical flux to reactant concentration directly and allows the calculation of pseudo-rate constants for the forward direction from PC to ATP (kf) and for the reverse direction (kr). The spin-lattice relaxation times (T1) for phosphocreatine (PC) and for the nucleoside triphosphate (NTP) nuclei, estimated by the progressive saturation technique, did not change during this age period. The PC concentration doubled relative to the NTP concentration over the first month of life. The kf and the flux of phosphorus nuclei in the forward direction increased 2- to 3-fold in the very narrow time period from 12 to 15 days of age. Brain phosphorus flux from PC to ATP thus increased 4- to 6-fold in the first month of life. An increase at least that large occurred in the reverse direction, but the kr could not be measured consistently in the younger animals using the saturation transfer technique. Phosphorus fluxes were equal in the forward and reverse directions in the mature brain. The capacity to increase rates of glycolysis and tissue respiration in response to increased energy demand appears in the same narrow age period as the increase in CK-catalyzed reaction rates in the developing rodent brain. We propose that these coincident changes in brain energy metabolism reflect the maturation of mechanisms for coupling cell energy production to rapid changes in energy requirements.

Adenosine Triphosphate↗

Effects of recombinant human insulin-like growth factor 1 on renal handling of phosphorus, calcium, and sodium in normal humans.

The effects of insulin-like growth factor 1 (IGF-1) on renal handling of phosphorus, calcium, and sodium were evaluated in eight healthy men while they lived in a clinical research center for slightly more than 5 days. Subjects received a continuous intravenous infusion throughout the study of 0.45% saline and 2.5% d-glucose at 50 mL/hr (group 1, four subjects) or 150 mL/hr (group 2, four subjects). Recombinant human IGF-1 (rhIGF-1), 60 micrograms/kg body weight, was injected subcutaneously three times daily for 10 doses from day 2 until the beginning of day 5. After commencing the rhIGF-1 injections, there was a marked decrease in the fractional excretion of phosphorus in both groups that was sustained throughout the study. Urine phosphorus excretion also decreased significantly on days 2 to 5 in group 1 and on day 2 in group 2. In group 1, the fractional excretion of calcium decreased on day 2; urine calcium did not change. The fractional excretion of sodium decreased on days 2 and 4; urine sodium decreased significantly only on day 2. In group 2, the fractional and absolute urine excretion of calcium did not change. Fractional sodium excretion was not altered, and urine sodium increased only on day 5. The average serum phosphorus, calcium, and sodium did not change from baseline in groups 1 or 2. The pattern of the circadian rhythms for serum concentrations, urine excretion, and fractional excretion of phosphorus and calcium did not appear to be affected by the rhIGF-1 injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phosphorus-32 intracavitary irradiation of cystic craniopharyngiomas: current technique and long-term results.

PURPOSE: The management of patients with craniopharyngiomas is often multifaceted and multidisciplinary. The purpose of this study was to examine the results of phosphorus-32 intracavitary irradiation in the treatment of patients with predominately cystic craniopharyngiomas. METHODS AND MATERIALS: Thirty patients with cystic craniopharyngiomas underwent phosphorus-32 intracavitary irradiation at our center between 1981 and 1993. The median patient age was 26 years (range, 3-70 years). Thirteen patients had intracavitary irradiation as the primary surgery for their cystic tumors, whereas 17 patients had adjuvant intracavitary irradiation after microsurgical resection, fractionated radiotherapy, or both. Patients in the adjuvant treatment group were more likely to have preoperative anterior pituitary insufficiency (p = 0.008 Fischer exact test) and diabetes insipidus (p = 0.003 Fischer exact test). The median follow-up was 37 months (mean, 46 months, range, 7-116 months). RESULTS: Phosphorus-32 intracavitary irradiation resulted in cyst regression in 28 of 32 treated cysts (88%). Ten patients (33%) have had tumor progression requiring further surgical intervention. Three patients (10%) died: two of tumor progression, and one of unrelated causes. Visual acuity and fields improved or remained stable in 63% of the patients. Fifteen patients had residual anterior pituitary function before intracavitary irradiation and 10 (67%) retained their preoperative endocrine status. New-onset diabetes insipidus occurred in 3 of 17 patients (18%) who had normal posterior pituitary function preoperatively. Fourteen of 20 adult patients (70%) continued to perform at their preoperative functional level; 3 of 5 pediatric patients who were age appropriate at the time of treatment continued to develop normally. No difference was noted between primary and adjuvant treatment patients with respect to cyst control, visual deterioration, or endocrine preservation after phosphorus-32 intracavitary irradiation. CONCLUSION: The goals of craniopharyngioma management should be tumor control with preservation of visual, endocrine, and cognitive function. Phosphorus-32 intracavitary irradiation is an important option that enhances the likelihood of achieving these goals in patients with primarily cystic craniopharyngiomas.

Adolescent↗