Extrarenal handling of phosphate: effect of thyroparathyroidectomy, 1,25-dihydroxycholecalciferol, and dietary calcium.

It is known that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] mobilizes inorganic phosphate (Pi) from gut and bone, thus increasing the entry of Pi into the extracellular space (ECS). In this work, we have investigated whether 1,25(OH)2D3 could also facilitate the net exit of Pi out of this pool into certain soft tissue and/or bone compartments in thyroparathyroidectomized (TPTX) rats. Sham-operated, TPTX, and TPTX rats treated with 1,25(OH)2D3 (26 pmol/day ip for 1 wk) were infused with a known amount of Pi over a given time. The amount of Pi excreted in the urine in excess of base-line values and the rise of the phosphatemia ([Pi]p) were measured. The difference between these two parameters corresponded to the net retention of infused Pi in the whole animal (RAPi) for a given rise in [Pi]p. The results show that RAPi was markedly diminished in TPTX as compared with sham-operated animals. This decrease could be corrected by 1,25(OH)2D3 treatment. Chronic reduction in the level of calcemia in TPTX 1,25(OH)2D3-supplemented rats as induced by decreasing dietary Ca intake also diminished RAPi. These effects could not be ascribed to the known actions of the experimental maneuvers on the renal excretion of Pi. Since infusions were chosen to obtain similar rises in [Pi]p and started from same levels of [Pi]p in animals of the same weight, the differences in RAPi were not due to variation of Pi retention in the ECS.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal transport of bisphosphonates: accumulation by renal cortical slices enhanced by calcium phosphate ions.

Bisphosphonates have been recognized as useful therapeutic agents in metabolic bone disease. Earlier studies showed a net renal secretion of 1-hydroxy-ethylidene-1,1-bisphosphonate (HEBP). They suggested a renal cellular uptake of this compound. We further studied this concept by investigating the uptake in vitro of 14C-HEBP by rat renal cortex slices. HEBP was accumulated against a concentration gradient, a process that was dependent on time, temperature, and substrate concentration. Unlike that of 3H-p-aminohippurate, the uptake was not affected by change in medium Na+ or glucose and acetate concentration, or by anoxia and various metabolic inhibitors. It was, however, markedly increased by raising the medium calcium and inorganic phosphate concentration. Equilibrium dialysis with renal cortex homogenates suggests that HEBP binds to a cytosolic macromolecule through a process that exhibits saturability and calcium dependency. In conclusion, the results suggest that the bisphosphonate HEBP can penetrate kidney cells by a process that does not appear to be energy dependent, but is markedly influenced by the extracellular calcium-phosphate concentration.

In vivo determination of intestinal calcium absorption, with scandium-47 used as marker.

The 47scandium/47calcium ratio technique for studying intestinal absorption of calcium in humans offers the following advantages: neither blood sampling nor complete faecal collection are required, and there is no need for an additional marker or for knowledge of the precise dose of calcium isotope administered. In the study this technique was corrected and modified using a new equation that considerably simplifies the determination procedures. The new method was validated in rats with various intestinal calcium absorption rates. The value of scandium as an unabsorbed intestinal marker was confirmed by the use of 46scandium. A mean recovery of 96% was obtained after intragastric administration. The 47scandium/47calcium ratio technique gave results that correlated well with the faecal 47calcium recovery method over a wide range of intestinal calcium absorption rates obtained by treatment with 1,25-dihydroxycholecalciferol or 1-hydroxyethylidene-1,1-biphosphonate. Taking into account the advantages of the 47scandium/47calcium ratio technique, it appears useful not only in small animals but also in outpatients, particularly children.

Interference of dichloromethane diphosphonate with parathyroid hormone effects at the bone but not at the kidney level.

Treatment with dichloromethane diphosphonate (Cl2MDP, 10 mg P/kg s.c. for 3 days) did not abolish the rapid hypocalciuric effect of acute administration of parathyroid hormone (PTH) to thyroparathyroidectomized (TPTX) rats. Cl2MDP impaired, however, the slower hypercalcemic response to PTH. This latter effect of Cl2MDP did not result from increased renal excretion of calcium. Thus, Cl2MDP does not interfere with the kidney but with the bone effect of PTH. This finding explains, at least in part, why, under treatment with Cl2MDP, there is still an effective regulation of plasma calcium.

Regulation of the tubular transport of phosphate in the rat: role of parathyroid hormone and 1,25-dihydroxyvitamin D3.

The reduced capability of the tubular Pi transport to adapt to a high Pi diet in TPTX rats can be normalized by physiological doses of 1,25-(OH)2D3. This suggests that the chronic consequence of a lack of PTH could be due, at least in part, to the reduced production of 1,25-(OH)2D3. The mechanism of Pi adaptation appears to be the most important regulator of Pi excretion in the growing rats, since it can markedly alter the acute phosphaturic response to parathyroid hormone.

[Swiss physicians and their contribution to surgery of the hand]. / Quelques médecins suisses et leur apport à la chirurgie de la main.

The origins of five important Swiss contributions to plastic and hand surgery since the last third of the 19th century are described: free grafting of the epidermis (J.L. Reverdin), a pollicization (C. Roux), de Quervains's stenosing tendovaginitis, Secrétan's oedema and the first voluntary movable artificial hand (S. Stodola and F. Sauerbruch). These contributions are related to the development of general surgery. Their history illustrates the advantages which may result from prolonged contact and exchange between members of different cultures.

Renal secretion of diphosphonates in rats.

Diphosphonates, characterized by a P--C--P bond, are relatively new experimental drugs used for the treatment of myositis ossificans, dental calculus, nephrolithiasis and Paget's disease. These compounds are not metabolized and the fraction which is not taken up by the skeleton is excreted unchanged in the urine. In the present study, the renal clearances of two 14C-labelled diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (CEHDP) and disodium dichloromethylene diphosphonate (CC12MDP) have been measured in conscious rats. The clearances have been found to be higher than the glomerular filtration rate (GFR), Cdiphosphonate/GFR being about 1.5. This observation indicates net tubular secretion of both drugs. High plasma concentration of EHDP or Cl2MDP significantly depressed CEHDP, whereas CEHDP was not influenced by varying urine pH, by infusing NH4Cl or NaHCO3, or by simultaneous administration of high doses of para-aminohippurate (PAH), probenecid, N-methylnicotinamide or Ca-EDTA. High plasma concentration of inorganic phosphate depressed CEHDP and also depressed the in vitro ultrafiltrability of EHDP. In conclusion, these results provide evidence of an active renal transport of diphosphonates which appears distinct from the mechanisms handling organic acids, organic bases and EDTA in the rat kidney.

Secretion of inorganic phosphate in the rat nephron.

1. The existence of tubular secretion of inorganic phosphate (Pi) in the mammalian kidney has been investigated by studying the renal response of rats infused with sodium phosphate by three different techniques. 2. Clearance studies indicate that, in anaesthetized rats, the net tubular reabsorption decreases markedly in response to Pi infusion. In conscious rats, the clearance of Pi slightly exceeded that of inulin at high plasma Pi concentration. 3. Free-flow micropuncture in control rats showed a net tubular reabsorption of Pi along the proximal tubule, and probably between the end of the distal tubule and the ureteral urine. In phosphate-loaded rats, whether receiving parathyroid hormone or not, an apparent net secretion of Pi was observed between the end of the distal tubule and the reteral urine. In the phosphate-loaded group receiving parthyroid hormone, net secretion was also observed very early in the proximal tubule followed by a predominant reabsorption along this segment. Thus the early proximal tubule and probably also the terminal nephron can be the site of either net reabsorption or net secretion. 4. Microperfusions of proximal tubules show a fall in the specific radioactivity of the perfused radioactive Pi solution, indicating entry of Pi into the lumen.