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Effectiveness of a traditional Chinese medicine, Wulingsan, in suppressing the development of nephrocalcinosis induced by a high phosphorus diet in young rats.

The development of nephrocalcinosis in rats fed a high phosphorus diet, and the effectiveness of the Chinese traditional medicine, Wulingsan, and its components (Poria, Alismatis Rhizoma, Atractylodis Rhizoma, Cinnamomi Ramus, Polyporus) in suppressing the development of calcinosis were studied. The rats were fed a high phosphorus diet (1.5% P) supplemented with Wulingsan or its individual components (0.5 g/kg body weight) as separate experimental groups for a 2-week period. Upon histological observation by light microscopy and electron microscopy, signs of nephrocalcinosis were observed in almost all areas of the kidney. Calculi, consisting mainly of needle-shaped crystals of hydroxyapatite, were observed in the proximal tubules, in the collecting ductal lumina, and in the mitochondria of the proximal tubular cells and the interstitial cells. X-ray microanalysis revealed that the calculi were composed of hydroxyapatite (Ca and P). In the group fed the diet supplemented with Wulingsan, the severity of calcinosis in the corticomedullary junction was only slight. In all groups fed individual components of Wulingsan, the severity of calcinosis was almost the same as that in the group fed the high phosphorus diet (1.5% P). Wulingsan suppressed the development of calcinosis in rats fed the high phosphorus diet supplemented with this Chinese medicine, whereas its individual components alone had no effect. The process of calcinosis and the mechanism responsible for the activity of this Chinese medicine in the suppression of calcinosis are discussed.

Animals↗

Phosphorus trichloride toxicity. Preliminary report.

A railroad accident in Somerville, Massachusetts, led to spillage of phosphorus trichloride liquid. Attempted clean-up with water led to the liberation of phosphorus trichloride, phosphoric acid, hydrochloric acid, and phosphorus oxides. Seventeen people exposed to this mixture were studied. Patients experienced eye irritation, lacrimination, nausea, vomiting, and dyspnea. Six patients had transient elevation of lactic dehydrogenase. Although all patients had normal chest roentgenographic findings, pulmonary function tests showed statistically significant decreases in vital capacity (p = 0.02), maximal breathing capacity (p = 0.02), forced expiratory volume in one second (p = 0.02), and maximal expiratory flow rate at 25 percent of vital capacity (p = 0.05) in those closest to the accident site. Further, patients exposed for less than one and a half hours had significantly greater maximal expiratory flow rates at 25 percent of vital capacity when compared with patients who had been exposed longer (p = 0.02). In seven patients, repeated pulmonary function tests one month later showed improvement, suggesting strongly that the acute effects may have been due to phosphorus trichloride toxicity.

Accidents, Traffic↗

Benefits of calcitriol therapy and serum phosphorus control in dogs and cats with chronic renal failure. Both are essential to prevent of suppress toxic hyperparathyroidism.

Daily oral calcitriol at low doses is safe and effective in the control of renal secondary hyperparathyroidism in dogs and cats. Low doses of calcitriol are most effective when started early in uremia before the advanced stages of renal secondary hyperparathyroidism. At early stages calcitriol both diminishes PTH synthesis in the parathyroid cells present and prevents the hyperplasia that, if unchecked, results in the most extensive an difficult-to-control hyperparathyroidism. The salutary effects on the dog's or cat's sense of well being, appetite, activity, strength, and lifespan as reported by the veterinarians of our survey are attributed primarily to keeping PTH levels below a toxic threshold. Additionally, some of the benefits achieved by calcitriol are likely a direct consequence of calcitriol interacting with the vitamin D receptor in a wide variety of tissues throughout the body. Phosphorus restriction through a combination of diet and intestinal phosphate binders is important to allow calcitriol therapy to successfully lower PTH levels, but it likely has no direct effects that are independent of interactions involving calcitriol. Phosphorus restriction is also important to minimize chances for adverse tissue mineralization. Calcitriol therapy can be considered for treatment of chronic renal failure after serum phosphorus has been decreased to less than 6.0 mg/dL in patients in whom it was initially elevated. Calcitriol supplementation to dogs and cats with chronic renal failure makes good endocrinologic sense. Calcitriol deficits cause increased PTH and, as these two hormones are designed to maintain calcium and phosphorus homeostasis, the PTH increase is initially adaptive. One of the important effects of PTH is to stimulate additional calcitriol formation as a powerful means to raise blood calcium through increased calcium absorption from the diet. With too great an increase in PTH, however, its effects become harmful to many tissues due to the widespread distribution of the PTH receptor in many cell types that are likely normally responsive only to the paracrine PTH-related peptide that shares the PTH receptor. Exogenous supplemental calcitriol administration allows concentrations of calcitriol in the bloodstream to remain normal without the toxic consequences of excessive PTH secretion that would otherwise be provoked. Studies involving young dogs with subtotal nephrectomy may not parallel those on older dogs and cats with spontaneous chronic renal failure. In particular, higher doses are needed to effect PTH change in these young dogs than we have found necessary for older dogs and cats. Because survey participants agreed most strongly with the idea that their calcitriol-treated dogs and cats were living longer than comparably uremic animals they had treated previously, further studies to evaluate the ability of calcitriol to retard the progression of renal lesions and loss of excretory renal function seem warranted. Additional studies to document the beneficial effects of calcitriol on the many organs adversely affected by excess PTH during uremia are also needed because findings thoroughly documented and proven in humans and rats may not always extrapolate to dogs and cats.

Animals↗

Diet and prostate cancer risk in a cohort of smokers, with a specific focus on calcium and phosphorus (Finland).

BACKGROUND: Calcium, phosphorus, fructose, and animal protein are hypothesized to be associated with prostate cancer risk, potentially via their influence on 1,25-dihydroxyvitamin D3. We examined these nutrients and overall diet and prostate cancer risk in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC Study). MATERIALS AND METHODS: The ATBC Study was a randomized 2 x 2 trial of alpha-tocopherol and beta-carotene on lung cancer incidence conducted among Finnish male smokers; 27,062 of the men completed a food-use questionnaire at baseline, and comprise the current study population. There were 184 incident clinical (stage 2-4) prostate cancer cases diagnosed between 1985 and 1993. We used Cox proportional hazards models to examine associations between dietary intakes and prostate cancer. RESULTS: We did not observe significant independent associations for calcium and phosphorus and prostate cancer risk. However, men with lower calcium and higher phosphorus intake had a multivariate relative risk of 0.6 (95% CI 0.3-1.0) compared to men with lower intakes of both nutrients, adjusting for age, smoking, body mass index, total energy, education, and supplementation group. Of the other foods and nutrients examined, none was significantly associated with risk. DISCUSSION: This study provides, at best, only weak evidence for the hypothesis that calcium and phosphorus are independently associated with prostate cancer risk, but suggests that there may be an interaction between these nutrients.

Age Factors↗

Phosphorus and protein restriction and parathyroid function in chronic renal failure.

Phosphorus retention as a result of chronic renal failure (CRF) induces secondary hyperparathyroidism (HPT II) while supplemented low-phosphorus low-protein diets (LPD) prevent it. The aim of this study was to assess in seven patients with advanced CRF and biological HPT II the effects of a LPD providing daily 5 to 7 mg/kg phosphorus, 0.4 g/kg protein, 300 mg calcium (Ca) and supplemented with amino acids, ketoacids, CaCO3 and vitamin D2, on the relationship between ionized Ca (iCa) and PTH concentrations. Hyper- and hypocalcemia were induced by CaCl2 and Na2-EDTA infusion. After three months of LPD, serum phosphorus decreased from 1.59 +/- 0.15 to 1.26 +/- 0.24 mmol/liter (mean +/- SEM, P < 0.02), basal PTH levels from 251 +/- 25 to 127 +/- 16 pg/ml (P < 0.03), while basal iCa and GFR did not vary. The sigmoidal PTH-calcium curve shifted downward with maximal PTH decreased from 482 +/- 86 to 319 +/- 60 pg/ml (P < 0.02) and minimal PTH from 35 +/- 4 to 21 +/- 4 pg/ml (P < 0.05). On the other hand, the slope of the % maximal PTH-iCa curve, which is an indicator of the sensitivity of the parathyroid cell to changes in iCa concentrations, did not vary significantly. The set point of Ca and calcitriol levels were not modified. These results demonstrate a direct inhibition of PTH secretion over a wide range of iCa concentration by LPD in patients with advanced CRF and mild HPT II over a three months period. This effect is independent of changes in plasma calcitriol levels.

Adult↗

The role of phosphorus in chemical evolution.

In this tutorial review we consider the role of phosphorus and its compounds within the context of chemical evolution in galaxies. Following an interdisciplinary approach we first discuss the position of P among the main biogenic elements by considering its relevance in most essential biochemical functions as well as its peculiar chemistry under different physicochemical conditions. Then we review the phosphorus distribution in different cosmic sites, such as terrestrial planets, interplanetary dust particles, cometary dust, planetary atmospheres and the interstellar medium (ISM). In this way we realize that this element is both scarce and ubiquitous in the universe. These features can be related to the complex nucleosynthesis of P nuclide in the cores of massive stars under explosive conditions favouring a wide distribution of this element through the ISM, where it would be ready to react with other available atoms. A general tendency towards more oxidized phosphorus compounds is clearly appreciated as chemical evolution proceeds from circumstellar and ISM materials to protoplanetary and planetary condensed matter phases. To conclude we discuss some possible routes allowing for the incorporation of phosphorus compounds of prebiotic interest during the earlier stages of solar system formation.

Cosmic Dust↗

Influence of dietary phosphorus deficiency with or without addition of fumaric acid to a diet in pigs on bone parameters.

The purpose of this study was to examine if substantial bone loss occurs in weaned pigs by feeding a phosphorus-deficient diet with or without fumaric acid. Eighteen weaned pigs were used. The animals were assigned to three groups: group C (control; 0.65% P on DM basis), group LP (low phosphorus; 0.37% P on DM basis) and group LPF (low phosphorus plus fumaric acid; 0.35% P on DM basis plus 2% fumaric acid). These three diets were fed to the groups for a period of four weeks after a two-week adaptation period. Blood samples were collected once a week. Carboxyterminal telopeptide of type I collagen (ICTP) in serum was used as a bone resorption marker. Osteocalcin (OC) and bone-specific alkaline phosphatase (bAP) were used as bone formation markers. Bone mineral density (BMD) and content (BMC) were determined by peripheral quantitative computer tomography. BAP activities significantly increased (24%) in group LPF, and at the last sampling day group LPF had significantly increased activities in comparison to group C. In contrast, ICTP concentrations significantly increased with time in group LP and LPF, and at the last sampling day group LPF had significantly increased activities in comparison to group C. BMD and BMC in femur and tibia significantly decreased in group LP and LPF. The results show that P-deficient diets induce a bone loss. Fumaric acid did not influence the degree of bone loss. With a better understanding of its effect on bone, dietary phosphorus requirements in pigs could be more precisely defined.

Adaptation, Physiological↗

Phosphorus 31 solid state NMR characterization of oligonucleotides covalently bound to a solid support.

31P cross polarization (CP) magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectra were acquired for various linear and branched di- and tri-nucleotides attached to a controlled pore glass (CPG) solid support. The technique readily distinguishes the oxidation state of the phosphorus atom (phosphate versus phosphate), the presence or absence of a protecting group attached directly to phosphorus (cyanoethyl), and other large changes in the phosphorus chemistry (phosphate versus phosphorothioate). However, differences in configurational details remote from the phosphorus atom, such as the attachment position of the ribose sugar (2'5' versus 3'5'), or the particulars of the nucleotide bases (adenine versus uridine versus thymine), could not be resolved. When different stages of the oligonucleotide synthetic cycle were examined, 31P CPMAS NMR revealed that the cyanoethyl protecting group is removed during the course of chain assembly.

Chemistry, Organic↗

Haemodynamics and myocardial metabolism of phosphorus depleted dogs: effects of catecholamines and angiotensin II.

The responses of arterial pressure and myocardial contractile force (VPM) to infusion of angiotensin II, noradrenaline and orciprenaline were examined in twelve dogs during a control phase, after 30 days of dietary phosphorus deprivation and after 21 days of phosphorus repletion. In the phosphorus depletion period, animals had low skeletal and heart muscle Pi content, low magnesium, ATP and creatine phosphate in skeletal and heart muscle with no change of ADP, AMP or energy charge. In the basal state, VPM was diminished with no change of end-diastolic and systolic pressure. Infusion of angiotensin II caused a significantly smaller rise of arterial pressure (angiotensin II resistance), and the stimulatory effect of noradrenaline and orciprenaline on VPM was diminished (catecholamine resistance). These effects were reversible with Pi repletion. In phosphorus depletion, arterial concentrations were increased for lactate, unchanged for FFA and decreased for acetoacetate/beta-hydroxybutyrate. Unchanged myocardial extraction of lactate or beta-hydroxybutyrate and preserved cell Pi uptake for glycogenolysis were observed. The initial rate of uptake of calcium and concentrating ability of myocardial sarcoplasmic reticulum were unchanged.

Angiotensin II↗

In vivo 31P-NMR studies of Desulfovibrio species. Detection of a novel phosphorus-containing compound.

The phosphorus metabolism of sulfate-reducing bacteria was, for the first time, probed by in vivo 31P NMR. A novel phosphoric anhydride diester compound was detected in Desulfovibrio desulfuricans ATCC 27774 at intracellular concentrations up to 5 mM. The compound has been extracted and partially purified by anion-exchange chromatography and analysed by 31P, 13C and 1H NMR. These studies show that the novel phosphorus-containing compound is formed by five carbon atoms and is probably cyclic, with a Mr of approximately 300. Various Desulfovibrio strains were examined in vivo for the presence of this phosphorus-containing compound. Detectable amounts of the novel metabolite were found in D. desulfuricans ATCC 27774 when grown on lactate/sulfate, lactate/thiosulfate or pyruvate/sulfate. The phosphorus-containing compound was not detected when this strain of D. desulfuricans was grown on lactate/nitrate or pyruvate; neither was it detected in two other strains which, like D. desulfuricans ATCC 27774, have the capability of utilizing nitrate as a terminal electron acceptor.

Desulfovibrio↗

Reduction of dietary phosphorus absorption by oral phoshorus binders.

The aim of this study was to study a possible new non-aluminum phosphate-binder to limit hyperphosphatemia in patients with renal failure. Zirconyl chloride octahydrate was evaluated as a dietary phosphate binder in rats. Aluminum chloride hexahydrate was used as a reference. Animals were divided into six groups (6 animals per group): One - control group (C), two - aluminum groups (Al1 and Al2) and three - zirconium groups (Zr1, Zr2 and Zr3) receiving different doses of zirconyl chloride octahydrate. Urines were collected during the experimental period. At the end of the treatment, the animals were sacrified and plasma and different organs were collected (liver, spleen, kidneys, brain and femur). Determination of phosphorus and calcium levels in plasma indicated that zirconyl chloride octahydrate yielded as good results as aluminum chloride hexahydrate did. Zirconyl chloride octahydrate significantly (p<0.01) reduced bone phosphorus burden. Urinary excretion of phosphorus indicated a severe phosphorus depletion in all treatments. Not even traces of zirconium could be determined in the different tissues, in urines or in plasma. Consequently, it is important to carry out experiments with zirconium compounds in order to develop non-aluminum-containing phosphate binders.

Administration, Oral↗

Phosphate replacement during treatment of diabetic ketosis. Effects on calcium and phosphorus homeostasis.

Thirty-five patients with diabetic ketosis were given initial intravenous (IV) potassium replacement as phosphate (N = 13) or chloride (N = 13), or received no potassium replacement other than that contained in a normal diet (N = 9). All patients experienced a slight decrease in serum calcium level by 12 hours after the start of insulin therapy, but there was no statistically significant change in serum ionized calcium values. The phosphorus-supplemented group had significantly lower serum phosphorus concentrations at 24 and 36 hours when compared with patients receiving no IV hydration and excreted significantly more phosphorus during the first 12 hours of the study than either of the other two groups of patients. Our use of phosphorus supplements (4.7 to 28.5 mg/kg) did not cause abnormalities in calcium metabolism but did not prevent late hypophosphatemia.

Adolescent↗

Growth and phosphorus metabolism in premature infants fed human milk, fortified human milk, or special premature formula. Use of serum procollagen as a marker of growth.

Human milk promotes less than optimal growth and is associated with phosphorus deficiency and decreased bone mineralization in very-low-birth-weight (VLBW) infants. In this study, the effects of feeding premature infants either human milk (HM), fortified human milk (FHM), or special premature formula (Similac Special Care [SSC]) on growth, phosphorus metabolism, and serum type I procollagen (pColl-I-C) were evaluated. Infants fed FHM exhibited a rate of weight gain and an increase in head circumference comparable with infants fed SSC and significantly greater than infants fed HM, despite the fact that both the FHM group and the HM group demonstrated biochemical evidence of phosphorus deficiency. The pColl-I-C concentrations in VLBW infants were tenfold to 20-fold greater than concentrations in normal children older than 2 years of age. The pColl-I-C levels correlated positively with weight gain and were significantly greater in the FHM and SSC groups than in the HM group. By contrast, serum alkaline phosphatase levels did not correlate with weight gain and were significantly lower in the rapidly growing SSC group than in either of the two groups with phosphorus deficiency and presumed poor bone mineralization. We conclude that the serum pColl-I-C concentration is a biochemical marker of growth in VLBW infants and may prove useful as a predictor of growth responses to various nutritional and therapeutic interventions.

Blood Proteins↗

Calcium, phosphorus, magnesium, and calcitonin concentrations in the serum and cerebrospinal fluid of children.

Mineral metabolism in the cerebrospinal fluid (CSF) of children is poorly understood. Recent reports have suggested a neuroregulatory role for calcitonin. We examined the hypotheses that in children (1) CSF levels of calcium and phosphorus might be low, (2) CSF levels of magnesium might be higher than serum levels of magnesium, and (3) immunoreactive calcitonin might be present in the CSF. We examined serum and CSF samples of 45 children, aged 8 days to 16 years, undergoing spinal taps for suspected meningitis or as part of leukemia therapy. Both serum and CSF levels of calcium correlated with those of magnesium. There was no correlation for CSF levels vs serum levels of calcium, magnesium, or phosphorus. The CSF levels of calcium and phosphorus were lower than the serum levels of these elements, but the CSF levels of magnesium were higher than the serum levels of magnesium. Calcitonin was detected in the CSF of 8% of samples assayed (range, 14 to 175 ng/L [14 to 175 pg/mL]). Two of these five samples had bacteriologically proven meningitis, and two samples were from patients less than 2 months of age. The CSF levels of calcitonin did not correlate with the serum levels of calcitonin. Thus, in children CSF levels of calcium and phosphorus are low, CSF levels of magnesium are higher than the serum levels, and the level of immunoreactive calcitonin is usually not present in the CSF but possibly is elevated in meningitis and early infancy.

Adolescent↗

A dual-tuned resonator for proton-decoupled phosphorus-31 chemical shift imaging of the brain.

A fully quadrature dome-shaped resonator is presented that has been dual-tuned for proton and phosphorus operation at 1.5 T. The resonator is 16.5 cm in length and 23 cm in diameter. Phantom studies were performed to demonstrate the utility of the resonator for proton imaging, shimming, and proton-decoupled phosphorus spectroscopy. In human subjects, proton-decoupled phosphorus chemical shift imaging spectra of the brain were acquired at 27 cm3 resolution in 34 min. Volunteer studies demonstrated improved resolution of phosphomonoesters, phosphodiesters, and nucleoside triphosphates due to proton decoupling. Sensitive coverage of the brain extended from the most superior cerebral cortex to the cerebellum. Acquisition of good quality 31P spectra over this volume is due to the dome structure as well as quadrature operation at both proton and phosphorus frequencies.

Brain↗

Modern mankind's influence on the natural cycles of phosphorus.

When the molten surface of the earth solidified over 4 X 10(9) years ago the quantity of phosphorus to be contained in the storehouse of the new planet had already been resolved. The phosphorus was locked in an igneous lithosphere as orthophosphate. With the advent of the first primitive rainstorms the slow endless process of liberating the phosphorus from the igneous rock strata had begun. It required about 3 X 10(9) years for this process to supply enough soluble phosphates for the seas of the earth to become saturated with respect to apatites. Today slightly more than half of the phosphate is contained in sedimentary deposits. The established phosphorus cycles of the earth were almost independent of the activities of mankind for more than 4 X 10(9) years. Only in the past 200 years has the influence been worthy of consideration and as late as the 1960s too few reliable data were available for us to assess the status of our activities on the natural cycles. Today a reasonably clear picture is emerging.

Cyclization↗

A simple method to release polyphosphate from activated sludge for phosphorus reuse and recycling.

In enhanced biological phosphorus removal processes, activated sludge microorganisms accumulate large quantities of polyphosphate (polyP). It was discovered that nearly all of the polyP could be released from activated sludge simply by heating it at 70 degrees C for about 1 h. The chain length of released polyP ranged from 100 to 200 phosphate (P(i)) residues. The addition of CaCl(2) precipitated approximately 75% of the total phosphorus without pH adjustment. The formed precipitate contained more P and less Ca than typical natural phosphorite deposits. Hence, in combination with enhanced biological phosphorus removal, the present method has potential for the development of a simple process for recovering phosphorus in a reusable form from wastewater.

Calcium Chloride↗

Possible complication regarding phosphorus removal with a continuous flow biofilm system: diffusion limitation.

Diffusion limitation of phosphate possibly constitutes a serious problem regarding the use of a biofilm reactor for enhanced biological phosphorus removal. A lab-scale reactor for simultaneous removal of phosphorus and nitrate was operated in a continuous alternating mode of operation. For a steady-state operation with excess amounts of carbon source (acetate) during the anaerobic phase, the same amount of phosphate was released during the anaerobic phase as was taken up during the anoxic phase. The measured phosphorus content of the biomass that detached during backwash after an anoxic phase was low, 2.4 +/- 0.4% (equal to 24 +/- 4 mg P/g TS). A simplified computer model indicated the reason to be phosphate diffusion limitation and the model revealed a delicate balance between the obtainable phosphorus contents of the biomass and operating parameters, such as backwash interval, biofilm thickness after backwash, and phase lengths. The aspect of diffusion is considered of crucial importance when evaluating the performance of a biofilter for phosphate removal.

Anaerobiosis↗