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BACKGROUND & AIMS: Hypophosphatemia (HypoP) is associated with organ dysfunction and mortality. Despite its potential severe consequences, HypoP remains poorly characterized in terms of real prevalence and timing of onset. The primary objective was to determine the prevalence of HypoP defined as blood phosphate

Background: Burosumab, a recombinant anti-FGF23 monoclonal antibody, was recently introduced as a treatment for X-linked hypophosphatemia (XLH). Burosumab normalizes blood phosphate levels, thereby healing rickets, decreasing leg bowing, and reducing pain. We aimed to explore the body composition and cardiometabolic health of pediatric patients with XLH treated with burosumab. Methods: This observational real-life study was conducted on growing children and adolescents. The outcome measures included changes in sex- and age-adjusted anthropometric and body composition parameters [fat mass (FM), fat-free mass (FFM), appendicular skeletal muscle mass (ASMM), muscle-to-fat ratio (MFR)], blood pressure, laboratory evaluation, and radiographic rickets severity [Thacher Rickets Severity Score (TRSS)]. Body composition was assessed by bioelectrical impedance analysis (BIA). Percentiles for FFM% and ASMM% were calculated according to BIA pediatric reference curves. The delta variable was calculated as the variable at 12 months minus the variable at baseline. Results: A total of 15 pediatric patients with XLH are treated in our clinic; included in the analyses were 7 children and adolescents (3 males, mean age 8.7 ± 3.2 years) with XLH without comorbidities. Baseline BIA revealed an unfavorable physique, with increased body fat percentage in five patients and decreased muscle mass in six. Indices of lean body mass significantly increased after 6 and 12 months of treatment: FFM(kg) ( p = 0.001, p = 0.046, respectively) and ASMM(kg) ( p = 0.012, p = 0.034, respectively), without any significant change in FM(kg). The percentile of ASMM% increased significantly after 6 months of treatment ( p = 0.006) and stabilized thereafter. TRSS improved significantly after 12 months of therapy ( p = 0.005). Age was positively correlated with delta TRSS ( r = 0.814, p = 0.026), and delta TRSS was negatively correlated with delta MFR ( r = −0.826, p = 0.022). Conclusions: There was a heretofore unrecognized improvement in body composition of growing children and adolescents with XLH who were treated with burosumab. These findings highlight the need to initiate burosumab treatment at a younger age when rickets is less severe.

This paper reports the results for the pH of six buffer solutions free of chloride ion with compositions: (a) BES (0.03 mol·kg(-1)) + NaBES (0.09 mol·kg(-1)); (b) BES (0.02 mol·kg(-1)) + NaBES (0.04 mol·kg(-1)); (c) BES (0.04 mol·kg(-1)) + NaBES (0.08 mol·kg(-1)); (d) BES (0.04 mol·kg(-1)) + NaBES (0.04 mol·kg(-1)) (e) BES (0.05 mol·kg(-1)) + NaBES (0.05 mol·kg(-1)); and (f) (0.06 mol·kg(-1)) + NaBES (0.06 mol·kg(-1)). The remaining eight buffer solutions (g) to (n) have saline media of the ionic strength I = 0.16 mol·kg(-1), matching closely to that of the physiological sample. Conventional pa(H) values, designated as pH(s), for all six buffer solutions (a) - (f) without the chloride ion and eight buffer solutions with the chloride ion (g) - (n) at I = 0.16 mol·kg(-1) from (278.15 K to 328.15) K have been calculated. The operational pH values for five buffer solutions at T = 298.15 K and T = 310.15 K have been determined based on the difference in the values of the liquid junction potentials between the blood phosphate standard and the experimental buffer solutions. Five of these buffers are recommended as secondary standards for the physiological pH range 7.5 to 8.5.

The purpose of this study was to examine the effect of D-ribose supplementation on the changes of blood fatigue substances (lactate, ammonia, phosphate and hypoxanthine) after maximal exercise performance in college male students. The experimental trials of each subject were divided into the following conditions: placebo supplement trial and D-ribose supplement trial. The subjects exercised using a Concept II Indoor rowing ergometer for 2,000 m Single Skull event. The subjects ingested 200 mg/kg of D-ribose after breakfast, lunch, dinner, as well as thirty minutes before exercising, for six days. Blood fatigue substances were continuously measured before exercise, immediately after exercise, and thirty minutes after exercise. The results indicated a significant difference in blood phosphate and hypoxanthine levels between the two experimental trials in the 30 minute recovery period (p

Zusammenfassung In 26 Experimenten erhielten Kaninchen teils abgepresten Pflanzensaft, teils Extrakte aus frischen Pflanzen oder den Presruckstanden (Trester) von Trisetum flavescens oral verabreicht. Benutzte Praparationen: Pr 1, Pr 2: Abgeprester Pflanzensaft, lyophilisiert, nur teilweise wasserloslich. Pr 8: Abgeprester Pflanzensaft, mittels Chloroform von Pflanzenfarbstoffen und wasserunloslichen, lipophilen Bestandteilen befreit, wasserloslich. E1, EII: Extraktion mit Methanol-Wassergemisch (4:1), Behandlung mit Chloroform (wie oben), Lyophilisierung, wasserloslich. E Pr 2: Methanol-Extraktion, Methanol abgedampft, Lyophilisierung, wasserloslich. E Pr 8: Extraktion wie oben, zusatzlich Chloroform-Behandlung, Lyophilisierung, wasserloslich. Sowohl die Pressafte als auch die Extrakte bewirkten einen Anstieg der Konzentration an anorg. P im Blutplasma, sofern das Ausgangsmaterial von jungen Pflanzen stammte. Die Reaktion des Blut-Phosphatspiegels lies zu einem gewissen Grade eine Dosis: Wirkung-Beziehung erkennen. Da der Pressaft Pr 8 wie auch die wirksamen Extrakte E Pr 2 und E Pr 8 wasserloslich waren, kann fur die biologisch aktive Substanz die gleiche Losungseigenschaft unterstellt werden. Die nachgewiesene Wirkung entspricht derjenigen eines Vitamin-D-Metaboliten. Wahrscheinlich handelt es sich dabei um das eigentliche pathogene (kalzinogene) Prinzip der Pflanze. Da von anderer Seite auch Cholekalziferol in Trisetum flavescens nachgewiesen worden ist, scheinen in dieser Pflanze zwei Substanzen mit Vitamin-D-Charakter vorzukommen, die sonst nur im tierischen Organismus gebildet werden. Summary Trisetum flavescens: Evidence of a water-soluble active constituent In 26 experiments rabbits were given orally either the sap of crushed Trisetum flavescens, extracts of the fresh plant, or extracts of the residues of the crushed plant. The preparations used were: Pr. 1, Pr. 2: Crushed plant sap, lyophilized, only partially water-soluble. Pr. 8: Crushed plant sap, with pigments and water-insoluble lipophilic components removed by chloroform, water-soluble. E I, E II: Methanol: water (4:1)-extract, treated with chloroform (as above), lyophilized, water-soluble. E Pr. 2: Methanol-extract, methanol evaporated off, lyophilized, water-soluble. E Pr. 8: Extract (as above), treated again with chloroform, lyophilized, water-soluble. Administration of both the sap and the extracts resulted in an increase in the inorganic phosphorus concentration in the plasma, provided that the starting material comprised young plants. A certain dose-response relationship could be derived from the changes in the levels of blood phosphate. Since Pr. 8 (sap) and the active extracts, E Pr. 2 and E Pr. 8, were all water-soluble, it can be concluded that the biologically active substance was also water-soluble. The effects observed indicate that a Vitamin D metabolite was involved and it would seem that this may be the actual pathogenic active constituent (calcinogen) of the plant. Nevertheless, Trisetum flavescens has also been shown to contain cholecalciferol and it therefore appears that two substances with the properties of Vitamin D occur in this plant which are otherwise formed only in animal organisms. Resume Trisetum flavescens: Mise en evidence d'un principe actif soluble dans l'eau On a fait 26 experiences sur des lapins en leur administrant par voie orale, soit de la seve de Trisetum flavescens presse, soit des extrait de cette plante fraiche, ou des extraits des residus de la plante pressee. Les preparations utilisees etaient: Pr. 1, Pr. 2: Seve de plante, pressee, lyophilisee: — partiellement soluble dans l'eau. Pr. 8: Seve de plante pressee, extraite au chloroforme des matieres colorantes et des substances lipophiliques insolubles dans l'eau: — soluble dans l'eau. E I, E II: Extraction au methanol: eau (4:1), traitement au chloroforme (comme ci-dessus), lyophilisation, soluble dans l'eau. E Pr. 2: Extraction au methanol, methanol evapore, lyophilisation: — soluble dans l'eau. E Pr. 8: Extraction (comme ci-dessus), traitement supplementaire au chloroforme, lyophilisation, soluble dans l'eau. Si la matiere de base provient de plantes jeunes, aussi bien la seve que les extraits ont l'effet d'augmenter la concentration plasmatique du phosphore anorganique. La reaction du niveau phosphatique dans le sang permet de deceler a un certain degre un effet dose-reponse. Etant donne que, la seve, Pr. 8, ainsi que les extraits efficaces, E Pr. 2 et E Pr. 8, etaient solubles dans l'eau, on peut en deduire que la substance biologique active a la meme qualite de solubilite. L'effet observe correspond a celui d'un metabolite de la vitamine D. Probablement s'agit-il la du vrai principe actif pathogene (calcinogene) de la plante. Etant donne qu'il a egalement ete demontre que Trisetum flavescens contient du cholecalciferol, cette plante semble contenir deux substances avec des proprietes de la vitamine D qui ne se forment autrement que dans l'organisme animal. Resumen Tisetum flavescens: Indicacion de una substancia activa hidrosoluble En 26 experimentos se administro por via oral a conejos bien el jugo resultante de exprimir las plantas, bien extractos de plantas frescas o bien el orujo de Trisetum flavescens. Se usaron los preparados siguientes: Pr 1, Pr 2: jugo de plantas prensadas, liofilizado, solo hidrosoluble en parte. Pr 8: jugo de plantas prensadas, liberado mediante cloroformo de los colorantes vegetales y de los componentes lipofilos insolubles en agua, hidrosoluble. E 1, E 11: extraccion con una mezcla de metanol-agua (4:1), tratada con cloroformo (vease arriba), liofilizacion, hidrosoluble. E Pr 2: extraccion con metanol, evaporacion del metanol, liofilizacion, hidrosoluble. E Pr 8: extraccion como E Pr 2, tratada adicionalmente con cloroformo, liofilizacion, hidrosoluble. Tanto los jugos como los extractos producen un aumento de la concentracion plasmatica del P inorganico, siempre y cuando el material de partida provenga de plantas jovenes. La reaccion del nivel de fosfato en sangre dejaba reconocer hasta cierto punto una relacion entre la dosis y el efecto. Como el jugo exprimido Pr 8 y los extractos activos E Pr 2 y E Pr 8 eran hidrosolubles, pueden presumirse para la substancia biologica activa las mismas propiedades de solubilidad. El efecto comprobado es semejante al de un metabolito de la vitamina D. Tal vez se trate aqui del principio patogeno propiamente dicho (calcinogeno) de la planta. Puesto que otros autores tambien han verificado colecalciferol en Trisetum flavescens, parece ser que este vegetal posee dos substancias con el caracter de la vitamina D, las cuales comunmente solo son producidas por el organismo animal.

Exposure of a facultative air breather, Hoplosternum littorale, to 12.5, 25, and 37.5% of the water soluble fraction (WSF) of Urucu crude oil, resulted in a rapid increase in air-breathing frequency (ABF) sustained over the 45 min period of exposure. Following 4 h exposure to a graded increase in WSF up to 50%, there was no significant affect on haematocrit, or plasma [Na+] and [K+]. Crude oil ingestion resulted in some degree of ion regulatory impairment, however results were variable. A single oral dose of 3.0 ml/kg of Urucu crude elevated net whole body Na+ efflux and resulted in a 7% reduction in plasma [Na+] 72 h following ingestion. A single oral dose of 3.0 ml/kg resulted in a significant net whole body K+ efflux and a reduction in plasma [K+] 24 h after ingestion. No mortalities were observed in any exposure regime in this study. An oral dose of Urucu crude oil at 3.0 ml/kg also resulted in a 24% reduction in ATP:Hb ratio (from 0.206 to 0.157) and a 31% reduction in GTP:Hb ratio (0.455 to 0.315) 24 h following ingestion indicating that these fish may be hypoxemic. Taken together, these results indicate that exposure of H. littorale to Urucu crude oil affects gas exchange and ion regulation.

We examined the relationship between bone mineralization, measured by single photon absorptio-metry, and blood phosphate and alkaline phosphatase concentration in 71 preterm neonates. Although both alkaline phosphatase and phosphate concentrations were significantly related to bone mineral content, and alkaline phosphatase concentrations were related to bone mineral content relative to weight, each could only explain a small amount of the variation in bone mineralization. Hence, concentrations of neither could be used to identify those neonates with the greatest bone mineral deficits.

The inorganic phosphate of the blood has been studied extensively in recent years because of its relation to various problems of nutrition, metabolism, and disease. In cattle the effect of the phosphorus level of the food on the percentage of inorganic phosphorus of the blood has already been demonstrated by us (1) (2). During the collection of these data we were impressed by the fact that unaccountable, and frequently large fluctuations may occur from day to day. This result led us to adopt the mean of the blood phosphate values obtained on three consecutive days as the probable true value. The day-to-day fluctuations, however, remained unexplained. The physiological factors influencing the concentration of blood phosphate have not been studied extensively. Havard andRcay (3) seem to have been the only workers who have noted marked periodic fluctuations. They report that the concentration of blood phosphate is very unsteady in human blood studied at hourly intervals when the subject is not kept completely at rest. Ordinary movements of the subject about the laboratory cause large variations. Havard and Reay believe that these changes are the result of exercise which they later (4) showed causes first a small rise and then a rapid fall in blood phosphate. In these studies the lowest level was reached hour after the period of exercise. working with rabbits, observed

The work of Howland and Kramer1 on the level of the inorganic phosphate in the blood in human rickets, and some confirmatory experiments undertaken by Hess1 led to the conclusion that during the period of active rickets in children, the inorganic phosphate of the blood is reduced, and that during the process of cure by either sunlight or cod-liver oil, the phosphate rises again to its normal level.Since the experimental rickets produced in rats is comparable in most important respects to human rickets, it was thought of interest to determine whether the same changes in blood phosphate could be demonstrated in rats. In applying the work of Howland and Kramer to experimental rat rickets, we have obtained results which on the whole agree very well with those of theirs reported at a recent meeting of the Society of Biological Chemists.Because of the small quantities of blood which can be obtained from the animals, it seemed advisable to make the determinations on whole blood rather than plasma if possible. Ex...

Frolmi the observations of Bergstrand (1) and others (2, 3, 4) it has become an established fact that some cases of chronic renal insufficiency are accompanied by enlargement of the parathyroid glands. The condition was well exemplified by a case recently studied at the Massachusetts General Hospital in which chronic glomerular nephritis had existed for more than twenty years, and in which necropsy revealed tremendous enlargement of all parathyroid glands (5). The question as to the cause of the parathyroid enlargement arises. It was suggested by Albright, Baird, Cope and Bloomberg (6) that the phosphate retention in chronic renal insufficiency might be the determining factor. When the blood phosphate level is raised by intravenous phosphate administration, hypocalcemia and tetany ensue (7). It seemed not unlikely that either hyperphosphatemia or the resulting hypocalcemia might be a stimulus to parathyroid hyperplasia. The present investigations were undertaken to determine the effect of administration of parenteral phosphate on the parathyroid glands of rabbits.

Changes in the level of blood and serum calcium have been associated from time to time with sex and reproduction. In fowl, pigeons and doves the results are very striking during the egg-laying periods but in mammals the reports are very conflicting and of doubtful significance. The importance of the calcium intake in fowl during egg production, with normal shell formation, is well established (1, 2, 3, 4, 5, 6) and the hourly fluctuations in the blood-calcium values during laying periods have been beautifully demonstrated in fowl, pigeons and doves (6, 7, 8, 9, 10, 11). Fluctuations in the weights of ovaries, testes and thyroids with seasonal variations in blood-calcium in pigeons and doves were also noted by Reinhardt and Riddle (6). Macowan (10) also observed histological changes in the parathyroids of the laying pullet and showed that parathormone injections caused rises of 2 to 6.5 mg. of Ca per 100 cc. of serum in pullets but not in moulting hens or cockerels. In the pregnant mammal we also recognize...

SummaryDisodium dichloromethylene diphosphonate (Cl2MDP) administered at 10 mg P/kg/day sc for 3 days to rats leads to a decreased blood calcium and decreased blood phosphate. The treated animals responded to a calcium load administered ip or iv with a larger increase in blood calcium and to a phosphate load with a larger decrease in blood calcium. It is suggested that this diminished efficiency in regulating blood calcium is due to the inhibiting effect of the diphosphonate on bone resorption.

1. The effect of propranolol on adrenaline- and insulin-induced hypophosphataemia was studied in man. 2. β-Adrenergic blockade with propranolol almost completely abolished and significantly inhibited adrenaline- and insulin-induced hypophosphataemia respectively; in addition, the drug clearly prevented the normally observed rise in plasma lactate, while causing only a slight change in blood glucose levels. 3. It is suggested that the fall in blood phosphate values induced by adrenaline and, in part, that caused by insulin, is mediated by β-adrenergic receptors.

Publisher Summary Vitamin D is the antirachitic factor. It is the substance, or the group of closely related substances, whose most remarkable property is in relation to the calcification of newly forming bone—in other words, in preventing the deficiency disease, infantile rickets. Rickets can be defined as a disease seen principally in early childhood and characterized by an inadequate calcification of the bony structures, especially of the newly forming bone, with a liability to consequent bony abnormalities and deformities such as enlarged epiphyses, knock knees or bow legs, pigeon chest, etc. The characteristic biochemical abnormalities are the low levels of blood phosphate and, sometimes, of the blood calcium; the inadequate mineralization of the bones; and a raised blood phosphatase level. The hypocalcemia sometimes associated with rickets is the cause of tetany. The inadequate mineralization of the bone, especially at the growing end of the long bones, gives rise to the characteristic X-ray appearance, which is very useful in diagnosis and in following the effect of treatment.

OBSERVATION of a rapid fall in ‘inorganic phosphate’ of heparinized whole blood and plasma led to study of the phosphate changes in shed blood. The effect of heparin on blood phosphate in vivo has been reported1. Further study of the effect of heparin in vitro led to the view that the action of heparin may be associated with phosphate uptake.

This investigation of the inorganic blood phosphate was undertaken in order to determine its value as an early diagnostic sign of rickets. The blood phosphate was determined in rats receiving a control diet, the McCollum rachitic diet No. 3143, and the rachitic diet plus various substances which were being tested for antirachitic properties. The fluctuations in the blood phosphate of rachitic and non-rachitic rats due to age, anesthesia and injury were also investigated.The blood was drawn from anesthetized rats by cardiac puncture, and except in case of the very young rats determinations were made on individual samples. The latest Briggs' modification1 of the Bell and Doisy phosphate method was employed.Deep anesthesia increased the inorganic blood phosphate rapidly. Light anesthesia for 7 to 15 minutes increased it only 2 to 6 per cent. The struggling and injury involved in stunning and bleeding the rats, which are methods used by other investigators, caused much greater increases in blood phosphate tha...

In studies involving the fractionation of blood phosphate compounds by means of hydrolysis with N HCl certain difficulties were encountered in the determination of the resulting orthophosphate by Kuttner's colorimetric procedure.1 The results were usually too low, and analyses of known quantities of P under similar conditions likewise gave values below those expected. Although inclined to attribute our difficulties to the losses of HCl during hydrolysis, we had the same trouble even when we prevented such alterations in concentration. We had no more trouble when we substituted N H2 SO4 for the N HCl. Our analyses on known quantities of P were also entirely satisfactory when H2 SO4 instead of HCl was used for the hydrolysis. This led us to investigate the probable influence of different salts in high concentration on the orthophosphate values determined by the Kuttner method. We discovered subsequently that Rimington2 had already pointed out the effect which the concentration of various salts used as antic...

In connection with our studies of the antirachitic factor in cod liver oil and irradiated cholesterol, we determined the inorganic blood phosphate of rats, hoping that this information could be used, in addition to roentgenograms and histologic examination, as an aid in the diagnosis of the rachitic condition. The first determinations were made on rats about 6 months old, which had been obtained originally from Doure-Doure. At the age of from 3 to 4 weeks, they were placed on the McCollum rachitic diet 3143. 1 To the diet of one group of these rats was added 0.2 per cent of irradiated cholesterol and to another 0.2 per cent of nonirridiated cholesterol. Still another group of animals on diet 3143 was irradiated daily. The rats on the rachitic diet alone or on the rachitic diet plus nonirradiated cholesterol, developed rickets much less rapidly than young rats which we later bred in

In a previous communication1 it was shown that rachitic rats may respond to small amounts of irradiated ergosterol by a marked rise of the inorganic phosphorus of the blood, unaccompanied by any signs of healing at the epiphyses. It has also been pointed out2 by us that this phenomenon held true for infants who received dry milk which had been inadequately irradiated. In this communication we wish to add the observation that some infants which had been getting irradiated ergosterol (viosterol) for a period of several months, in the course of the winter, reacted in a similar way. These infants had been given small amounts of a standard preparation of irradiated ergosterol. Evidently in these instances this quantity was insufficient to afford complete protection; had a more potent preparation been given, complete protection would have resulted.Irradiated foods and sterols have a tendency to raise the phosphorus in the blood, irrespective of and apart from their antirachitic action. Therefore, an analysis of...

An investigation 1 undertaken somewhat more than a year ago showed that in infants the inorganic phosphate of the blood could be raised to the normal level by means of frequent exposures to the sun's rays. It was shown later 2 that the same result can be accompushed by irradiation with the carbon arc lamp. It seemed probable that this striking phenomenon—chemical equilibrium brought about by the action of light— is due to the ultraviolet, rather than to the visible rays of the spectrum. As a matter of fact, subsequent investigation has confirmed the view that some ultraviolet radiations possess this biologic action, for when they are filtered out from the spectrum the rays lose this power. 3 As is well known, the composition of the rays of the sun is not at all times the same. There is a marked seasonal variation in its spectrum—in the temperate zone