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Biomedical subjects

U Trechsel

Publications and source records attributed to U Trechsel.

At least 37 records · Page 2Linked to original sources
PubMed1986

[The regulation of bone remodeling].

The adult skeleton is subject to a remodeling process which must be tightly regulated to keep bone mass constant. Bone resorption and bone formation are coupled. After a brief review of the cellular mechanisms of bone remodeling, its regulation is discussed. Bone resorption is modulated by parathyroid hormone, 1,25-dihydroxyvitamin D and other hormones. Locally, agents such as prostaglandins and factors from the immune system are important. Bone formation is stimulated by insulin and somatomedin C (= insulin like growth factor 1) which mediates the effect of growth hormone. Other hormones and local factors also play a role.

Bone Development↗
PubMed1986

Reduced parathyroid hormone response to peroral phosphate in osteoporotic patients.

To determine whether PTH secretion can be stimulated in osteoporosis by peroral phosphate (1.5 g phosphorus), we have compared serum PTH and urinary cyclic AMP responses in 8 osteoporotic patients with vertebral compression fractures to those of 7 age-matched control subjects. While there was no statistically significant difference in the rise of serum phosphate and urinary phosphate excretion and in the fall of serumionized calcium concentrations, serum PTH and urinary cyclic AMP were increased in control subjects, but not in osteoporotic patients (osteoporotics vs. control group: PTH, p less than 0.01; cyclic AMP/glomerular filtrate, p less than 0.05). Moreover, plasma levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were the same in the 2 groups of subjects. Serum levels of the carboxyl-terminal flanking peptide (PDN-21) encoded by the calcitonin gene and cosecreted with calcitonin were similar in normal and osteoporotic subjects before and 3 min after 1-min intravenous calcium infusions (2 mg/kg body weight), and of calcitonin after the calcium infusions. We conclude that calcitonin and PDN-21 responses to intravenous calcium are the same in normal and osteoporotic subjects, whereas stimulation of PTH secretion by peroral phosphate is impaired in some osteoporotic patients.

Administration, Oral↗
PubMed1985

Stimulation of interleukin 1 and 3 production by retinoic acid in vitro.

Retinoic acid and other retinoids stimulate or inhibit a number of immune responses, but their mechanism of action on immune cells is not fully understood. However, retinoids have been shown to inhibit interferon production, so they could act by influencing the production of lymphokines. Hence we have studied the effect of retinoic acid on the production of interleukins (ILs) 1 and 3 in vitro. Models for the production of ILs were the murine macrophage cell line P388D1 and human peripheral blood mononuclear cells for IL 1 and the murine WEHI-3 cell line for IL 3. Retinoic acid stimulated IL 1 release by P388D1 cells in a dose-related fashion, starting at 10(-9) M and maximally at 10(-8)-10(-6) M. With peripheral blood mononuclear cells a maximal stimulation of IL 1 release was observed with 10(-7) M-retinoic acid. IL 3 release by WEHI-3 cells was also stimulated by retinoic acid in a dose-related fashion. The maximal response was obtained with 10(-8) M-retinoic acid. These results show that retinoic acid, in physiological concentrations, exerts selective effects on interleukin production in vitro, and this stimulation of IL 1 and IL 3 release may explain some of the immunostimulatory effects of retinoids in vivo. Moreover, since IL 1 is known to influence connective tissues and bone, an increase in IL 1 might also explain some of the changes observed in these tissues in vitamin A poisoning and with high-dose retinoid therapy.

Animals↗
PubMed1985

Effect of bisphosphonates on production of interleukin 1-like activity by macrophages and its effect on rabbit chondrocytes.

Bisphosphonates are potent inhibitors of bone resorption, but their mode of action is still unknown. Since interleukin 1 (IL-1)-like activity has been shown to stimulate bone resorption in vitro, we have studied whether bisphosphonates inhibit either the production of IL-1-like activity or its effect on one type of connective tissue cell, chondrocytes. The production of IL-1-like activity was examined using rabbit peritoneal macrophages and the murine macrophage cell line P388D1, and the effect of IL-1-like activity was assessed by measuring the secretion of collagenase and prostaglandin E2 (PGE2) by rabbit chondrocytes. Production of IL-1-like activity was unaffected by bisphosphonates, whereas the effect of IL-1-like activity on collagenase and prostaglandin E2 secretion by rabbit chondrocytes was increased rather than inhibited by bisphosphonates. Finally, bisphosphonates increased DNA and cell number in chondrocyte cultures, but this effect was blocked when IL-1-like activity was added to the cultures. Thus, our results provide no evidence for a direct inhibitory effect of bisphosphonates on either the production of IL-1-like activity or the action of IL-1-like activity on chondrocytes.

Animals↗
PubMed1985

Influence of vitamin D3 metabolites on the production of interleukins 1,2 and 3.

We investigated the effect of vitamin D3 metabolites on the release of the three interleukins (IL) IL 1, IL 2 and IL 3 by mononuclear cells. Models for the production of these mediators were the release of IL 1 by the murine macrophage cell line P388D1, of IL2 by rat spleen cells, and of IL 3 by the murine WEHI-3 cell line. IL 1 production was significantly increased with 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) at 10(-10)M and above. 1,25(OH)2D3 did not stimulate cell proliferation as assessed with [methyl-3H]thymidine (3H-TdR) incorporation. 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and 25-hydroxyvitamin D3 (25(OH)D3) were about 1000 times less effective than 1,25(OH)2D3. IL 2 production, by cultured rat spleen cells stimulated with Concanavalin A, was decreased by increasing concentrations of 1,25(OH)2D3. The minimal effective dose varied between experiments and ranged from 10(-11) to 10(-8) M. Moreover, proliferation (3H-TdR incorporation) of mouse thymocytes treated with phytohemagglutinin and IL 1 was decreased in a dose-dependent fashion by 1,25(OH)2D3 starting at 10-11) M. This effect might be secondary to a decrease of endogenous IL 2 production. IL 3 release by WEHI-3 cells was significantly increased with 10(-11)-10(-9) M 1,25(OH)2D3, whereas higher concentrations were less effective or decreased IL 3 production. These results show that 1,25(OH)2D3 and, to a lesser extent, 24,25(OH)2D3 and 25(OH)D3 have selective effects on lymphokine production. It is tempting to speculate that the actions of 1,25(OH)2D3 on bone might in part be mediated by lymphokines. Moreover, we suggest that 1,25(OH)2D3 might not be an immunoregulator per se, but makes use of the immune system to exert its influence on one of its classical targets, namely the bone, and possibly on other connective tissues.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Suppression of parathyroid secretion after administration of WR-2721 in a patient with parathyroid carcinoma.

WR-2721 is an organic thiophosphate, known as a radioprotective agent, which also inhibits parathyroid hormone (PTH) secretion and reduces the plasma calcium level in euparathyroid animals and human subjects. In this study we present evidence that WR-2721 is also able to reduce an abnormal PTH secretion in a case of parathyroid carcinoma. The intravenous infusion of a single dose (750 mg/m2) of WR-2721 was followed within 3 h by a reduction in the plasma concentration of PTH by 60%, and of Ca by about 0.45 mmol/l. These changes were associated with a diminution in urinary cAMP excretion. Based on this observation it appears that WR-2721 merits further investigation as a possible agent for the medical treatment of hyperparathyroidism.

Amifostine↗
PubMed1985

Evidence for a particularly severe secondary hyperparathyroidism in analgesic abuse nephropathy.

Ca metabolism was compared in two groups of patients with chronic interstitial nephritis: in 21 patients (analgesic abuse nephropathy (AAN) group), nephropathy was due to exposure for 5-50 years (mean 21.1) to phenacetin-containing analgesics, whereas in 21 other patients (controls) it was due to exposure for 1-80 years (mean 21.4; NS) to other causes. Patients were followed for 2.5 +/- 0.6 and 1.6 +/- 0.6 years, respectively (mean +/- SEM; NS). Blood Ca, P, protein, creatinine, alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) as well as arterial acid-base status and urinary excretion rate of Ca, P and creatinine were determined serially. Results were included only when P was maintained between 0.7 and 1.9 mmol/l. The range of creatinine levels studied was 95-1,600 mumol/l. No differences were found between the two groups with respect to creatinine clearance, blood P, protein, arterial pH and bicarbonate, and urinary excretion rates of Ca and P. Mean plasma Ca was significantly lower, and PTH was significantly higher in the AAN group than in the control group; mean plasma alkaline phosphatase activity was also significantly higher in the AAN group. In both groups Ca was negatively correlated with creatinine, but the slope of the regression line was steeper in the AAN group than in controls. The degree of hypocalcemia was related to the increase in plasma PTH and alkaline phosphatase, but not to the plasma level of 25(OH)D or 1,25(OH)2D.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Influence of macrophage products on the release of plasminogen activator, collagenase, beta-glucuronidase and prostaglandin E2 by articular chondrocytes.

We describe the effects of products of mononuclear phagocytes on the secretory activity of chondrocytes. The primary confluent cultures of rabbit articular chondrocytes were exposed to standard medium alone or enriched with conditioned medium obtained from cultures of rabbit peritoneal macrophages, the mouse macrophage cell line P388D1 or human blood mononuclear cells. Four markers of release were assessed, the neutral proteinases plasminogen activator and collagenase, the acid hydrolase beta-glucuronidase and prostaglandin E2, and the kinetics of their changes were monitored. Chondrocytes that were cultured in standard medium secreted large amounts of plasminogen activator, some beta-glucuronidase, but no collagenase, and released only minor amounts of prostaglandin E2. The addition of conditioned medium from rabbit macrophages induced a rapid release of large quantities of prostaglandin E2 and an abundant secretion of collagenase, while abolishing or strongly decreasing plasminogen activator secretion. In addition, beta-glucuronidase secretion was markedly enhanced. The decrease in secretion of plasminogen activator appeared to reflect a diminished production, since no evidence was found for the generation of inhibitors or for an accelerated extracellular breakdown of the enzyme. Conditioned media of the mouse and human mononuclear cells influenced the secretory activities of rabbit articular chondrocytes in a similar way, suggesting that the factor (or factors) acting on chondrocytes is produced by a variety of macrophages, and that its action is not species-restricted. The time course and concentration-dependence of the effects observed indicate that the secretion of plasminogen activator and collagenase are influenced in a strictly reciprocal fashion by the macrophage products. The release of prostaglandin E2 paralleled that of collagenase.

Animals↗
PubMed1984

Interleukin 2-independent stimulation of rabbit chondrocyte collagenase and prostaglandin E2 production by an interleukin 1-like factor.

In the present study, interleukin 1 (IL 1)-containing media from different sources, namely a murine macrophage cell line (P388D1), rabbit peritoneal macrophages, and human peripheral blood mononuclear cells, were compared for their effect on thymocyte proliferation and on collagenase and PGE2 secretion by chondrocytes. A high correlation was found between the enhancement of thymocyte proliferation and the induction of collagenase and PGE2 secretion by chondrocytes. Furthermore, a highly purified IL 1-like factor, namely mononuclear cell factor (MCF) was also active on chondrocytes. The addition of highly purified IL 2 to rabbit chondrocytes had no effect on collagenase and PGE2 secretion induced by IL 1-containing media. Our findings suggest that the factor which induced collagenase and PGE2 secretion by rabbit chondrocytes was an IL 1-like factor. Thus, collagenase secretion by chondrocytes may be used as an IL 2-insensitive assay for the detection of IL 1-like factors.

Animals↗
PubMed1984

Lack of effects of 1,25- and 24,25-dihydroxy vitamin D on parathyroid hormone response to hypocalcemia in cattle.

Effects of 1,25(OH)2D3 or 24,25(OH)2D3 on plasma PTH were examined following induced hypocalcemia with EGTA. EGTA infusions caused an elevation of plasma PTH within 10 min. Sixty min after the start of EGTA infusions, 1,25(OH)2D3 or 24,25(OH)2D3 were IV administered. Transient (within 5 min) elevations in plasma PTH were observed in two of five animals following the administration of 1,25(OH)2D3 or of 24,25(OH)2D3. Neither secosterol had an effect on the induced elevations in plasma PTH during the remaining 60 min of the EGTA infusions. Twenty-two hr following 24,25(OH)2D3 administration, plasma PTH, ionized and total calcium, inorganic phosphate, and magnesium were normal, while plasma 24,25(OH)2D was elevated. The plasma PTH response to EGTA-induced hypocalcemia was not significantly altered from that observed prior to the administration of 24,25(OH)2D3. Animals, which were IV injected with 1,25(OH)2D3 received the same amount IM 60 min later. Twenty-two h following IM 1,25(OH)2D3, plasma 1,25(OH)2D, ionized and total calcium, and plasma inorganic phosphate were elevated. Plasma PTH and magnesium were lowered. The PTH response to EGTA-induced hypocalcemia was significantly reduced in these animals. A similar reduction in the PTH response to induced hypocalcemia was observed in animals receiving 7 hr IV infusions of calcium chloride. The findings suggest that the blunted response was, in part, the consequence of the preceding hypercalcemia. These results indicate that 1,25(OH)2D3 does not directly regulate plasma PTH secretion and that 24,25(OH)2D3 has no effect on plasma PTH during induced hypocalcemia in the bovine species.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Unilateral nephrectomy and 1,25-dihydroxyvitamin D3.

Several renal functions respond to nephron loss by a compensatory adaptation. Whether the production of 1,25(OH)2D3 also adapts to a renal mass reduction is still a matter of controversy. In the present study we have investigated in rats the influence of unilateral nephrectomy, in both the acute (48 hr) and chronic (2 to 6 weeks) state, on plasma 1,25(OH)2D3 level measured by competitive protein binding assay. In the acute state no difference in plasma 1,25(OH)2D3 level between sham-operated (SHAM) and unilateral-nephrectomized (UNI-NX) rats was found. The presence of the thyroparathyroid glands was not required for maintaining plasma 1,25(OH)2D3 at a normal level 48 hr after UNI-NX. In the chronic state in rats fed at 1.1% Ca diet, plasma 1,25(OH)2D3 (means +/- SEM) was 94 +/- 4 in SHAM and 98 +/- 8 pM in UNI-NX. In rats fed a 0.1% Ca diet it was 252 +/- 16 in SHAM and 239 +/- 20 pM in UNI-NX. Analysis of 3H-1,25(OH)2D3 plasma decay curve indicated that in UNI-NX under a high calcium diet the normalization of plasma 1,25(OH)2D3 appears to be entirely due to an increase in production, whereas under a low calcium diet part of it may also result from a moderate decrease in the elimination rate. In conclusion, this study indicates that unilateral nephrectomy does not affect the level of plasma 1,25(OH)2D3 even under a calcium restriction challenge. This compensatory adaptation appears to be independent of parathyroid hormone.

Animals↗
PubMed1983

Nature of calcemic effect of 1,25-dihydroxyvitamin D3 in experimental hypoparathyroidism.

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] treatment on the daily fluctuation of plasma calcium concentration ( [Ca]P1) in relation to the feeding-fasting alternation has been studied in vitamin D-replete sham-operated (sham) and thyroparathyroidectomized (TPTX) rats fed a normal Ca diet. 1,25(OH)2D3 was given (26 or 39 pmol/day) intraperitoneally either by single injection or constant infusion using osmotic minipumps. After 7 days of treatment [Ca]P1 was measured at 4-h intervals for 24 h. Pair-fed, sham and TPTX animals received the solvent vehicle intraperitoneally. The results show that in sham rats the very moderate daily fluctuation of [Ca]P1 was not accentuated by 1,25(OH)2D3. A marked fluctuation of [Ca]P1 in relation to the food intake was observed in untreated TPTX as compared with sham rats. In TPTX rats 1,25(OH)2D3 increased the fasting [Ca]P1. In contrast the rise in [Ca]P1 during feeding was not significantly accentuated by 1,25(OH)2D3. The daily fluctuation of [Ca]P1 was the same whether the dose of 1,25(OH)2D3 was given in one single injection or by constant infusion, suggesting that this hormone is not involved in the hour-to-hour regulation of [Ca]P1. In conclusion, in the absence of parathyroid glands, 1,25(OH)2D3 given in doses that stimulate intestinal calcium absorption has a much more pronounced effect on the fasting calcemia than on the rise in calcemia observed during the feeding period. These results suggest that the mobilization of calcium from bone could play an important role in the calcemic effect of 1,25(OH)2D3 when given in the hypoparathyroid state.

Animals↗
PubMed1983

Rapidity of plasma 1,25-dihydroxyvitamin D responses to hypo- and hypercalcemia in steers.

Experiments were designed to study the rapidity of changes in plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels in response to hypercalcemia and hypocalcemia induced by 10-h infusions of CaCl2 or EGTA in steers. In response to CaCl2 infusions, 1,25-(OH)2D was decreased within 4 h (P less than 0.05) and remained lower (P less than 0.05) than preinfusion concentrations for up to 14 h after termination of the infusions. PTH and inorganic phosphate (Pin) transiently decreased in response to the CaCl2 infusions, whereas total magnesium (Mg) continuously fell for up to 24 h after the start of the infusions. In response to infusions with EGTA, on the other hand, 1,25-(OH)2D continuously increased and was raised significantly (P less than 0.05) between 12 and 24 h after the start of the infusions. PTH increased within 2 h (P less than 0.05) and remained elevated (P less than 0.05) for up to 2 h after the end of the EGTA infusions, whereas Pin and Mg were not significantly changed. During and after 10-h control infusions of sodium chloride, the levels of 1,25-(OH)2D, PTH, Ca, Ca++, Pin, and Mg remained unaltered. In conclusion, plasma levels of 1,25-(OH)2D were lowered in response to hypercalcemia within 4 h and increased in response to hypocalcemia within 12 h. After termination of the infusions with CaCl2 or EGTA, levels of 1,25-(OH)2D remained decreased or elevated for at least 14 h, even though Ca, Ca++, and PTH levels were normalized. The slow changes in 1,25-(OH)2D contrast with the rapid responses of PTH to hyper- and hypocalcemia.

Animals↗
PubMed1983

Vitamin D replacement therapy in patients with the nephrotic syndrome.

The possibility to achieve and maintain normal plasma levels of 25-hydroxyvitamin D3 (25OHD3), with long-term vitamin D replacement therapy, has been evaluated in 9 patients with nephrotic syndrome. Plasma levels of 25OHD3 rose from 10.8 +/- 5.0 (SD) nmol/l to 29.5 +/- 11.1 (p less than 0.001) with a daily dose of 25 micrograms of vitamin D3 per os. Plasma levels of 1,25-dihydroxyvitamin D3 were low before treatment (39.5 +/- 22.7 pmol/l) and returned to the normal range under therapy in the patients without renal failure. Low levels of vitamin D metabolites in nephrotic syndrome can be normalized with long-term oral vitamin D replacement therapy.

Adult↗
PubMed1982

[Particularly severe calcium metabolic disorder in nephropathy from analgesic abuse].

Calcium (Ca) metabolism was compared in 2 groups of patients with chronic interstitial nephritis: in 21 patients (AAN-group) nephropathy was due to exposure for 5 to 50 years (mean 21.1) to phenacetin containing analgesics, whereas in 21 other patients (controls) it was due to exposure for 1 to 80 years (mean 21.4) (NS) to other causes. Patients were followed for 2.5 +/- 0.6 and 1.6 +/- 0.6 years respectively (mean +/- SEM) (NS). Blood Ca, P, protein, creatinine, alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), together with arterial acid-base status and urinary excretion rate of Ca, P and creatinine were measured serially. For each patient the results were averaged for 2 degrees of renal failure, i.e. for creatinine levels below and above 400 mumol/l (logarithmic mean). Results were included only when P was maintained between 0.7 and 1.9 mmol/l. The range of creatinine levels studied was 95 to 1600 mumol/l. No differences were found between the 2 groups with respect to creatinine clearance, blood, P, protein, arterial pH and urinary excretion rates of Ca and P. There was a trend for blood HCO3 to be lower in the AAN group. Mean plasma Ca was significantly lower, and PTH was significantly higher, in the AAN than in the control group at both degrees of renal failure; mean plasma alkaline phosphatase activity was also significantly higher in the AAN group, but at severe degrees of renal failure only. Significant correlations were observed between individual values of both Ca and PTH (r = -0.747) and PTH and alkaline phosphatase (r = 0.603). The degree of hypocalcemia and of hyperparathyroidism was not related to the plasma level of 25-OH-D. It is concluded that at comparable degrees and duration of renal failure patients with AAN, when compared with patients with interstitial nephritis of other origins, have lower blood Ca and consequently higher PTH levels and alkaline phosphatase activities, suggesting more severe osteodystrophy.

Adult↗
PubMed1982

[Primary hyperparathyroidism of the aged female: effect of estrogens on calcium metabolism].

Serum calcium, urinary calcium and a calcium loading test were evaluated twice in 5 elderly women with primary hyperparathyroidism, once not under and once under estrogen therapy. The treatment produced a significant lowering of blood calcium and normalization of urinary calcium excretion in the fasting state, per 24 h and after calcium load. Estrogen therapy might be useful in conservative treatment of asymptomatic hyperparathyroidism and in symptomatic cases where surgery is impossible.

Aged↗