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H van Baelen

Publications and source records attributed to H van Baelen.

10 recordsLinked to original sources
PubMed2001

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding.

OBJECTIVE: A novel assay was employed to study the free 1,25-dihydroxyvitamin D (1,25(OH)2D) concentrations in various populations with different levels of 1,25(OH)2D and vitamin D binding protein (DBP). DESIGN: In 12 healthy women before and after 3 months of oral estrogen/progestagen treatment, 10 pregnant women, and 16 patients with a nephrotic syndrome and normal renal function, the concentrations of total and free 1,25(OH)2D, DBP and albumin were assessed. METHODS: The total concentration of 1,25(OH)2D in serum was assessed using a radioreceptor assay. The free fraction of 1,25(OH)2D was measured using symmetric dialysis. DBP was assessed using single radial immunodiffusion. Serum albumin concentrations were measured on an automated analyzer. RESULTS: In healthy women, the concentrations of total 1,25(OH)2D, free 1,25(OH)2D and DBP were 132+/-19 pmol/l, 92+/-30 fmol/l and 5.59+/-0.43 micromol/l. After 3 months of estrogen/progestagen treatment, total 1,25(OH)2D and DBP levels rose significantly to 175+/-51 pmol/l and 8.32+/-1.59 micromol/l (P< or =0.05 and P< or =0.001); the free 1,25(OH)2D remained unchanged (105+/-39 fmol/l; not significant). Pregnant women had significantly higher levels of total 1,25(OH)2D and DBP (239+/-68 pmol/l and 11.32+/-1.77 micromol/l; both P</=0.001); the free 1,25(OH)2D level, however, was not different (104+/-27 fmol/l; not significant). Unexpectedly, in patients with nephrotic syndrome, no lower DBP levels were found (5.36+/-0.84 micromol/l) relative to that in controls. Despite this, levels of both total (69+/-26 pmol/l, P< or =0.001) and free 1,25(OH)2D (53+/-28 fmol/l; P< or =0.001) were significantly lower than in controls. Albumin levels were lowered from 628+/-38 micromol/l to 300+/-84 micromol/l (P < or = 0.001). CONCLUSIONS: Higher estrogen levels result in higher DBP levels, with a parallel rise in total 1,25(OH)2D levels but without a change in the biologically active free fraction. The results in patients with nephrotic syndrome show that, with increasing glomerular protein leakage, the free 1,25(OH)2D concentration cannot be maintained.

Adult↗
PubMed1997

Comparison of 6-s-cis- and 6-s-trans-locked analogs of 1alpha,25-dihydroxyvitamin D3 indicates that the 6-s-cis conformation is preferred for rapid nongenomic biological responses and that neither 6-s-cis- nor 6-s-trans-locked analogs are preferred for genomic biological responses.

The hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] generates biological responses via both genomic and rapid, nongenomic mechanisms. The genomic responses utilize signal transduction pathways linked to a nuclear receptor (VDRnuc) for 1alpha,25(OH)2D3, while the rapid responses are believed to utilize other signal transduction pathways that may be linked to a putative membrane receptor for 1alpha,25(OH)2D3. The natural seco steroid is capable of facile rotation about its 6,7 single carbon bond, which permits generation of a continuum of potential ligand shapes extending from the 6-s-cis (steroid like) to the 6-s-trans (extended). To identify the shape of conformer(s) that can serve as agonists for the genomic and rapid biological responses, we measured multiple known agonist activities of two families of chemically synthesized analogs that were either locked in the 6-s-cis (6C) or 6-s-trans (6T) conformation. We found that 6T locked analogs were inactive or significantly less active than 1alpha,25(OH)2D3 in both rapid responses (transcaltachia in perfused chick intestine, 45Ca2+ influx in ROS 17/2.8 cells) and genomic (osteocalcin induction in MG-63 cells, differentiation of HL-60 cells, growth arrest of MCF-7 cells, promoter transfection in COS-7 cells) assays. In genomic assays, 6C locked analogs bound poorly to the VDRnuc and were significantly less effective than 1alpha,25(OH)2D3 in the same series of assays designed to measure genomic responses. In contrast, the 6C locked analogs were potent agonists of both rapid response pathways and had activities equivalent to the conformationally flexibile 1alpha,25(OH)2D3; this represents the first demonstration that 6-s-cis locked analogs can function as agonists for vitamin D responses.

Animals↗
PubMed1991

Vitamin D analogs with low affinity for the vitamin D binding protein: enhanced in vitro and decreased in vivo activity.

The affinity of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] and analogs with side-chain modifications [MC 903 or calcipotriol, MC 1147 or 24,24-dihomo-1 alpha,25-(OH)2D3 and 1,25-(OH)2-16ene-23yne-D3] for the vitamin D receptor and the serum vitamin D binding protein (DBP) were compared. The affinity of MC 903 for the receptor from chick and rat duodenum or from human peripheral blood mononuclear cells or HL-60 cells varied between 60 and 100% relative to the affinity of 1,25-(OH)2D3. The relative affinity of 1,25-(OH)2-16ene-23yne-D3 and MC 1147 varied for the same receptors between 45-70 and 3.5-25%, respectively. The relative affinity of MC 903 for human DBP was 30-fold decreased, whereas the two other analogs did not bind to DBP at all even in more than 1000-fold excess. The in vitro biologic activity of 1 alpha,25-(OH)2D3 on phytohemagglutinin-stimulated normal human lymphocyte proliferation was markedly inhibited by the addition of physiologic amounts of DBP to the cell culture medium. No such inhibition was observed when MC 903 or 1147 was evaluated similarly. DBP therefore reversed the rank order of the in vitro potency of these analogs. Intramuscular injections for 10 consecutive days to vitamin D-deficient chicks demonstrated a greater than or equal to 100-fold lower biologic activity of MC 903, MC 1147, and 1,25-(OH)2-16ene-23yne-D3 compared to that of 1 alpha,25-(OH)2D3 as evaluated by serum calcium and osteocalcin concentrations, as well as by duodenal calbindin D28K and bone calcium content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

The measurement of the vitamin D-binding protein in human serum.

The concentration of the vitamin D-binding protein was measured in human serum by single radial immunodiffusion. Normal serum concentrations were slightly higher in normal women than in normal men. No race-related difference was found between white people from Belgium and black people from Zaire. Lower concentrations were found in cord serum and in patients with cirrhosis of the liver. Increased serum levels were observed during pregnancy or during the intake of estro-progestogens. The serum level of the vitamin D-binding protein was not altered in various diseases of calcium metabolism (primary osteoporosis, primary and secondary hyperparathyroidism, rickets, osteomalacia or vitamin D intoxication). No correlation was found between serum levels of 25-hydroxy vitamin D and those of its binding protein. From these data the following conclusions can be drawn: 1) The serum concentration of the vitamin D-binding protein (about 6.10(-6)M) largely exceeds the normal serum concentration of 25-hydroxy vitamin D (about 4.10(-8)M), so that this protein is normally for less than 1% saturated, 2) Normal serum levels of the vitamin D-binding protein were observed in several diseases of calcium metabolism, and 3) The free concentration of 25-hydroxyvitamin D is not regulated at a constant level.

Adult↗
PubMed1977

Concentration of transcortin in the pregnant rat and its foetuses.

The concentration of transcortin in serum from foetal, neonatal, pregnant and lactating rats was measured by a single radial immunodiffusion method. A decrease in transcortin concentration in sera from foetuses and pregnant rats occurred starting on days 19 and 20 of pregnancy respectively. A more pronounced fall in transcortin concentration in foetal and maternal serum was observed after treating pregnant rats with dexamethasone. These results suggest that corticosterone may be responsible for the observed changes in transcortin concentration.

Age Factors↗
PubMed1976

The transport of vitamin D in the serum of primates.

"Transcalciferin" (the serum transport protein for cholecalciferol and related substances) of two New World monkeys, Cebus apella and Cebus albifrons, was found to be immunologically identical with the transcalciferin of other monkeys and partially with that of man. In contrast with the alpha-globulin mobility of the transcalciferin of other primates, the transcalciferin of cebus monkey has the electrophoretic mobility of albumin. Most of the serum 25-hydroxycholecalciferol was precipitable with isolated monospecific anti-(human transcalciferin) gamma-globulins but not with anti-(human albumin) gamma-globulins. These results indicate that the transport of 25-hydroxycholecalciferol in the cebus monkey is not due to albumin itself but to transcalciferin with the electrophoretic mobility of albumin. Similar variants of transcalciferin also exist in man.

Animals↗