André Ulmann

Early stimulation of alkaline phosphatase activity in response to 1α,25-dihydroxycholecalciferol

Abstract Alkaline phosphatase activity (APA) stimulation in response to 1,25-dihydroxycholecalciferol (1,25 (OH) 2 D 3 ) has been studied in vitamin-D-deficient rat intestinal brush borders prepared from ex - vivo -perfused duodeno-jejunal segments. Basal APA in intestines perfused with ethanol remained constant throughout the experiments. APA was significantly increased when intestines were perfused with 1,25 (OH) 2 D 3 (3 nM) for 30, 45 or 60 min. A dose-effect response was observed when 1,25 (OH) 2 D 3 increased in the perfusion medium. The maximal alkaline phosphatase activity after a 45-min perfusion (2404 ± 379 m T U/mg prot.) was observed when 1,25 (OH) 2 D 3 concentration was 6 nM. Cholecalciferol had no effect in this system.

Renal Magnesium and Phosphate Wastage in a Patient with Hypercalciuria and Nephrocalcinosis: Effect of Oral Phosphorus and Magnesium Supplements

We report a 29-year-old man with a mild decrease in glomerular filtration, nephrocalcinosis, hypercalciuria and a renal magnesium leak. He had other features of congenital magnesium-losing kidney, such as arthritis and hyperuricemia, short stature and recurrent urinary tract infections, but had no radiological chondrocalcinosis. In addition, pallidal calcification was found. The patient also had a renal phosphate leak. Phosphorus supplements resulted in a decrease in urinary calcium excretion, indicating that hypercalciuria was at least partially a consequence of phosphorus depletion. Plasma and urine magnesium were not affected by phosphorus supplements. Addition of magnesium supplements resulted in a transient and modest decrease in urinary calcium excretion, with no modification in plasma magnesium.

Phosphate fluxes in isolated enterocytes from vitamin D replete and vitamin D deficient rats -- early effects of calcitriol

In the present work we studied rapid in vitro effects of calcitriol (1,25(OH)2 vitamin D3) on the intestinal transport of inorganic phosphate (Pi). Enterocytes from vitamin D replete (D+) as well as vitamin D depleted (D−) rats were isolated mechanically from the duodeno-jejunum. In this model, Pi uptake was a temperature and Na+-dependent phenomenon. The in vitro-addition of calcitriol (1 pM) resulted in a significant enhancement of initial Pi uptake rate by enterocytes from D+ (P<0.01) and D− (P<0.05) rats. This effect which was Na+-dependent, was observed within the time of 20 min, but not before. A similar effect on Pi uptake rates of D+ or D− enterocytes could be elicited by the in vitro addition of the methyl ester of cis-vaccinic acid (MCVA) which is thought to increase membrane fluidity by modifying the lipid composition of the cell membrane. The stimulatory effect of calcitriol on Pi uptake rate was blunted in the presence of the methyl ester of transvaccinic acid (MTVA) thought to decrease membrane fluidity. Enterocyte Pi efflux rate constant (oKPi) remained unchanged in the presence of calcitriol (1 pM). In conclusion, the study demonstrates a rapid in vitro effect of calcitriol on Pi uptake by isolated enterocytes from D+ and D− rats. It suggests, but does not prove, that the hormone may act via an action independent of genomic nuclear activation.

25-Hydroxycholecalciferol-binding protein: Partial purification from rat duodenal mucosa cells

Abstract The 25-hydroxycholecalciferol-binding protein has been partially purified (purification factor: 37) from rat duodenal cytosol, using chromatographic procedures on gel and ionic exchange resin. This partially purified protein bound 25-hydroxycholecalciferol with high affinity (KD = 5.7 × 10−9M) and low binding capacity (23 × 10−12 mole/mg of protein. Using a rabbit antiserum obtained against such partially purified protein, we demonstrated that 25-hydroxycholecalciferol cytosolic binder and 25-hydroxycholecalciferol plasmatic binding share common antigenic sites.

Measles virus and Guillain-Barré syndrome during long-term hemodialysis

In a black man, recently receiving long-term hemodialysis, a severe, rapidly progressive polyradiculoneuritis (Guillain-Barre syndrome) developed. Routine virologic study revealed a high antimeasles virus antibody titer (1:1280 by hemagglutination-inhibition) which progressively decreased. There was no clinical evidence of measles. Discussed here is the possible relationship between the Guillain-Barre syndrome and clinically inapparent measles associated with and perhaps modified by the uremic state.

Nuclear uptake of cholecalciferol metabolites in rat duodenal mucosa.

Abstract 1α, 25-Dihydroxycholecalciferol (1,25-(OH) 2 D 3 ) and 25-hydroxycholecalciferol (25-(OH)D 3 ) nuclear uptake was in vitro studied in duodenal mucosa cells from vitamin D-deficient rats. Both 1,25-(OH) 2 D 3 and 25-(OH)D 3 were found in association with purified nuclei. However a saturable maximal uptake (1.4 pmol/mg DNA) was demonstrated only for 1,25-(OH) 2 D 3 . This 1,25-(OH) 2 D 3 nuclear uptake is specific as it is not altered by the presence of either 25-(OH)D 3 or 1α-hydroxycholecalciferol.

Direct in Vitro Effects of 1,25 (OH) 2 Vitamin D3 on Phosphate Transport in Isolated Enterocytes from Normal or Vitamin D Deficient Rats

1,25 dihydroxy vitamin D3 (1,25(OH)2 D3), the main active metabolite of vitamin D3, stimulates intestinal phosphate (Pi) absorption (1). Pi transport across the enterocyte appears to involve at least three steps (2): 1) Pi entry across the luminal brush border membrane into the enterocyte, a secondary active or facilitated process requiring energy provided by the sodium (Na+) gradient, 2) Pi transport from the mucosal to the serosal side of the cell, 3) Pi extrusion of the enterocyte into the extracellular space across the basolateral membrane. It has been proposed that 1,25(OH)2 D3 could act by altering the rate of Na+ dependent mucosal entry of Pi into the cell. However, the precise mechanism by which the hormone enhances intestinal Pi transport is still controversial.

Plasma vitamin D metabolites in a patient with sporadic hypophosphataemic osteomalacia (adult-onset type).

Abstract. Sporadic hypophosphataemic osteomalacia (adult‐onset type) was demonstrated in a 40‐year‐old man on the basis of severe osteomalacia, hypophos‐phataemia, hyperphosphaturia and glycinuria. Plasma immunoreactive parathyroid hormone (iPTH) concentration was 9‐3 ng prot./ml (normal range: 4–8 ng prot./ml). Plasma 25‐hydroxy‐vitamin D and 24, 25‐dihydroxy‐vitamin D concentrations were 11 and 2–4 ng/ml respectively. Basal lα, 25‐dihydroxy‐vitamin D concentrations were slightly elevated (116 and 96 pg/ml) and increased to 240 pg/ml after 3 days on a low‐phosphorus diet. The patient was put on oral treatment with 25‐hydroxycholecalciferol (100 μ per day) and phosphorus (1500 mg per day). On the 4th month on treatment, a clinical improvement was apparent. Plasma 25(OH) D was 44 ng/ml, plasma l,25 (OH)2D was 256 pg/ml. However, plasma phosphorus remained low (0.77 mmol/l). On the 9th month of treatment a radiological improvement was evident despite a persistent hypophosphataemia (0.68 mmol/I). These facts suggest in our patient the existence of a vitamin D‐independent renal phosphorus leak.