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U Trechsel

Publications and source records attributed to U Trechsel.

At least 55 records · Page 3Linked to original sources

Effects of products from macrophages, blood mononuclear cells and or retinol on collagenase secretion and collagen synthesis in chondrocyte culture.

Collagenase secretion was studied on cultures of rabbit articular chondrocytes. Differentiation of the cells was assessed by characterizing the type of 3H-labelled collagen produced during treatment with (1) conditioned media from rabbit peritoneal macrophages and human blood mononuclear cells, and (2) with retinol, a potent cartilage resorbing agent in tissue culture. Conditioned media stimulated collagenase secretion. Total collagen synthesis was reduced due to a decrease of synthesis of alpha 1 chains; the amount of alpha 2 chains synthesized was unchanged. This is thought to be due to a reduction in type II synthesis. Retinol did not stimulate collagenase secretion. Total collagen synthesis was reduced by retinol. alpha 2 chain synthesis, however, was significantly increased, suggesting a switch of collagen synthesis in favor of type I collagen, and therefore, dedifferentiation. These results demonstrate that dedifferentiation of chondrocytes with respect to collagen synthesis is not necessarily associated with a stimulation of collagenase secretion.

Animals↗

Increase of whole-body calcium and skeletal mass in normal and osteoporotic adult rats treated with parathyroid hormone.

1. The effect of long-term administration of parathyroid hormone (PTH) on whole-body calcium and ash weight of individual bones has been studied in normal and osteoporotic adult female rats in order to examine whether such a treatment could induce a positive calcium balance. 2. Osteoporosis was induced by calcium restriction during pregnancy and lactation. Sequential measurements of whole-body calcium were made by neutron activation. 3. In non-osteoporotic intact and thyroparathyroidectomized rats a daily dose of 75 units of human PTH 1-34 given subcutaneously for 3 weeks increased whole-body calcium. 4. In osteoporotic animals 25-50 units of either bovine PTH 1-84 or human PTH 1-34 given subcutaneously twice daily for 6 weeks increased both whole-body calcium and ash weight of individual bones. Microradiographic examination of the tibiae indicates, however, that PTH administration does not result in the restoration of individual trabeculae lost during the development of osteoporosis. 5. The results show that PTH can enhance skeletal mass in both normal and osteoporotic rats. In osteoporotic animals the restoration of whole-body calcium and ash weight of individual bones is not accompanied by a return of the morphological structure of the tibia to normal.

Animals↗

Plasma levels of vitamin D metabolites in diphosphonate-treated rats.

1. Protein-binding assays have been used to measure plasma 1,25-dihydroxy-vitamin D [1,25-(OH)2D] as well as 25-hydroxy-vitamin D [25-(OH)D] in rats given 10 mg of phosphorus (P) day(-1) kg(-1) as ethane-1-hydroxy-1,1-diphosphonate (EHDP). 2. In control animals given a normal laboratory chow plasma 25-(OH)D and 1,25-(OH)2D were about 40 nmol/l and 300 pmol/l respectively. 3. EHDP produced a decrease of plasma 1,25-(OH)2D to below 50 pmol/l in 2 days. 4. Both in control and in EHDP-treated rats plasma 1,25-(OH)2D increased when dietary calcium (Ca) was restricted to 0.1%, or dietary P to 0.2%, indicating that the well-known stimulatory effect of Ca or P deprivation was at least partially effective in EHDP-treated rats. 5. In response to an increase of the oral supply of vitamin D3 to 65 nmol/day the plasma level of 25-(OH)D rose in both control and EHDP groups. Plasma 1,25-(OH)2D was not increased above the normal value in control rats. In EHDP-treated rats, however, plasma 1,25-(OH)2D rose to a level equal to that in controls, suggesting that the effect of EHDP on plasma 1,25-(OH)2D can be overcome at high precursor concentration.

25-Hydroxyvitamin D 2↗

Use of dermestid beetles for cleaning bones.

Various parts of the skeleton of normal and osteoporotic rats were compared with respect to their dry weight, ash weight, and calcium content when the bones were cleaned by Dermestes maculatus beetles or manually. Both techniques gave similar results. This was also true when whole body calcium measured by neutron activation and total skeletal calcium from bones cleaned by the beetles were compared. Thus dermestid beetles are useful as a technique to clean bones, especially for the parts of the skeleton which are difficult to dissect by hand.

Animals↗

Calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D.

The increase of plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) in response to Ca restriction has been suggested to be essentially mediated by parathyroid hormone (PTH). In this study, we have assessed the influence of variations in calcium intake on plasma 1,25(OH)2D in pair-fed sham-operated (sham) and in hypocalcemic hypoparathyroid rats after thyroparathyroidectomy (TPTX). In sham rats, plasma 1,25(OH)2D increased from 189 +/- 16 to 486 +/- 41 pM when dietary calcium was inreased from 1.2% Ca to 0.2% Ca. This increase was associated with an increase in plasma PTH level. In TPTX rats, plasma 1,25(OH)2D increased from 112 +/- 9 to 332 +/- 36 pM when dietary calcium was decreased. In this case, the increase was not associated with a rise in plasma PTH level nor with an increase in urinary cyclic AMP. When TPTX rats were infused chronically with PTH (60 U/day), plasma 1,25(OH)2D was 62 +/- 9 pM when the 1.2% Ca diet was given and 281 +/- 45 pM with the 0.2% Ca diet. These reults confirm that the thyroparathyroid glands influence plasma 1,25(OH)2D but they also provide evidence for a PTH-independent response of plasma 1,25(OH)2D to Ca restriction.

Animals↗

Perinatal parathyroid hormone, vitamin D metabolites, and calcitonin in man.

Plasma levels of calcium and of parathyroid hormone (PTH) were comparable in the mothers at delivery and in nonpregnant controls; magnesium was decreased (P < 0.001) in maternal blood; and phosphate (P < 0.001), 1,25-dihydroxyvitamin D (1,25(OH)2D) (P < 0.001), and calcitonin (CT) (P < 0.01) were raised. Cord levels of calcium (P < 0.01), magnesium (P < 0.05), and CT (P < 0.01) were higher, and PTH (P < 0.01) was lower than in the maternal blood. Levels of 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D lower in fetal than in maternal blood (P < 0.01) and significant linear correlations between the vitamin D metabolites examined in mothers and neonates (P < 0.001) are consistent with a diffusion barrier across the placenta and/or different affinities of binding proteins. Plasma levels of 25(OH)D and 24,25(OH)2D were significantly related (P < 0.01), suggesting precursor product type, relationships. Levels of 1,25(OH)2D higher in arterial than in venous umbilical blood (P = 0.06, sign test; P < 0.005, paired t test) suggest that the fetus participates in the synthesis of 1,25(OH)2D. Maternal PTH was significantly related to the arteriovenous difference of 1,25(OH)2D levels (P < 0.01) in cord blood, and it possibly enhances the synthesis of 1,25(OH)2D during the final stage of fetal development.

Adolescent↗

Effects of disodium dichloromethylene diphosphonate on Paget's disease of bone.

19 patients with Paget's disease were treated orally for 6 months with disodium dichloromethylene diphosphonate. 1600 mg/day (10 patients) significantly reduced urine hydroxyproline, serum alkaline phosphatase, urine calcium, and the number of pagetic bone osteoclasts. Tetracycline double labelling revealed undisturbed bone mineralisation. There was improvement on quantitative bone-scans and bone pain diminished. There was a transient increase in parathyroid hormone level in 13 of the 19 patients during treatment, which was associated with a high serum 1,25 (OH)2D3. No adverse clinical side-effects have been observed and biochemical remission has persisted for 9 months.

Administration, Oral↗

Regulation of the metabolism of 25-hydroxyvitamin D3 in primary cultures of chick kidney cells.

A primary chick kidney cell culture is described, capable of forming 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], and 1,24,25-trihydroxyvitamin D3 [1,24,25(OH)3D3] over several days. The apparent Km values were 0.125 microM for the 1-hydroxylase and 2.1 microM for the 24-hydroxylase. Exogenous 1,25(OH)2D3 decreased 1-hydroxylase and increased 24-hydroxylase within 4 h. 24,25(OH)2D3 produced similar effects, but only in the absence of fetal calf serum. R and S isomers of 1,24,25(OH)3D3 were about fives times less active than 1,25(OH)2D3. Bovine parathyroid hormone stimulated the 1- and reduced the 24-hydroxylase in 6 h, but this only occurred in cultures either previously treated with 1,25(OH)2D3 and EGTA to lower Ca to 0.8 mM or in cultures grown in the presence of 25-hydroxyvitamin D3 (25(OH)D3). Under the latter condition, the sensitivity to bovine parathyroid hormone was enhanced, 0.04 U/ml producing a maximum response. Synthetic aminoterminal tetratriacontapeptide (1-34) human parathyroid hormone was equally effective. In the absence of D metabolites, estradiol for 6 h produced a dose-dependent inhibition of the 1-hydroxylase, but no change in the 24-hydroxylase. Progesterone, testosterone, and corticosterone had no significant effect. In cultures grown in the presence of 25(OH)D3 no reproducible effects were obtained with either 1 microM estradiol or 1 microM testosterone, alone or in combination, but 5 microM corticosterone decreased the 1- and increased the 24-hydroxylase. Changes in Ca and P concentrations of the medium as well as addition of ethane-l-hydroxy-1, 1-diphosphate for 48 h did not affect any of the hydroxylase activities. The modulation of the hydroxylase activities by vitamin D3 metabolites and parathyroid hormone suggests that these factors regulate the renal hydroxylase by direct actions, whereas it would appear that ethane-1-hydroxy-1,1-diphosphate, Ca, P, and steroid may exert their influence indirectly.

Animals↗

Calcium absorption in diphosphonate-treated rats: effect of parathyroid function, dietary calcium and phosphorus.

1. The role of parathyroid hormone (PTH) and 1, 25-dihydroxy-cholecalciferol (1,25-(OH)2D3) in modulation of intestinal Ca absorption was studied in rats, using disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), which is known to reduce 1,25-(OH)2D3 formation. 2. EHDP decreased intestinal Ca absorption. This effect could be abolished by small amounts of 1,25-(OH)2D3, whereas even large doses of PTH were ineffective. EHDP also decreased Ca absorption in thyroparathyroidectomized (TPTX) rats. Therefore the effect of EHDP on 1,25-(OH)2D3 production is unlikely to be mediated through PTH. 3. The correction by PTH of the decreased Ca absorption in TPTX rats was inhibited by EHDP. Since EHDP inhibits formation of 1,25-(OH)2D3 the effect of PTH on Ca absorption is likely to be mediated through this vitamin D3 metabolite. 4. In normal rats both a low Ca and a low P diet stimulated Ca absorption. In EHDP-treated intact rats low Ca still stimulated Ca absorption, whereas the effect of low P abolished. This indicates that low Ca and low P diets affect Ca absorption through different mechanisms. 5. Intestinal adaptation to a low Ca diet was still observed in EHDP-treated TPTX rats. Thus, in the rat, intestinal adaptation to low Ca diet can occur without PTH.

Animals↗

Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats.

Disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) is known to inhibit the crystallization of calcium phosphate salts in vitro. Large doses of EHDP administered in vivo inhibit skeletal mineralization, decrease intestinal calcium absorption, and produce hypercalcemia. In the present study, EHDP or one of 13 other phosphonates were given to rats at 10 mg P/kg-day sc for 7 days in order to better define the nature of the relationship between bone mineralization, intestinal absorption, and plasma calcium in the regulation of calcium homeostasis. Each of the phosphonates which inhibited skeletal mineralization in vivo also inhibited crystallization in vitro, but the converse was not true. A very close correlation was found between inhibition of skeletal mineralization, decreased intestinal calcium absorption, and slight hypercalcemia. A dose-response study with two compounds also revealed the same close correlation. It is argued that the impairment of intestinal calcium absorption in phosphonate-treated rats may represent a secondary homeostatic response to the primary effect of the drugs on bone mineralization. This response may be mediated by an elevation of a fraction of plasma calcium.

Animals↗

A new device for ultrafiltration. The ultrafiltrability of calcium and inorganic phosphate in human serum.

The various problems concerning the ultrafiltration of blood serum are outlined, and a novel ultrafiltration device, which overcomes all these problems is presented. Its main advantages are the following: (1) The deposition of protein on the filter is prevented by producing a flow across the filter surface. (2) The pCO2 remains constant, since the fluid is not in contact with a gas space. (3) The minimum serum volume is only 0.4 ml (4) Six samples can be processed simultaneously. (5) All commercially available filter types can be used. The machine, tested by measuring the ultrafiltrability of calcium, inorganic phosphate, sodium and chloride in human serum, proved to be a reliable laboratory tool. The precision of the determinations were comparable to respective serum analyses. The ultrafiltrabilities obtained, without correction for water content of serum, were 55.6 +/- 2.9% for calcium, 88.3 +/- 5.0% for inorganic phosphate, 95 +/- 1.7% for sodium, and 103 +/- 0.7% for chloride (means +/- S.D.).

Adult↗

Stimulation of calcium absorption and apparent increased intestinal 1,25-dihydroxycholecalciferol in rats treated with low doses of ethane-1-hydroxy-1,1-diphosphonate.

1. Ligated intestinal segments from rats treated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at the daily dose of 16 mumol (identical to 1 mg of phosphorus)/kg subcutaneously for 7 days show an increased rate of calcium absorption. 2. This dose of EHDP enhances the intestinal accumulation of a vitamin D3 metabolite with the chromatographic characteristics of 1,25-dihydroxycholecalciferol.

Animals↗