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D Baylink

Publications and source records attributed to D Baylink.

At least 19 recordsLinked to original sources
PubMed1994

Pharmacokinetic profile of a new fluoride preparation: sustained-release monofluorophosphate.

The pharmacokinetic profiles of a sustained-release monofluorophosphate (MFP-SR) preparation (76 mg) and of plain MFP (76 mg) were compared in six osteoporotic females. These studies were performed in a randomized, crossover, double-blind design to select a preparation that would result in therapeutic serum levels while avoiding high serum peak values. Following a single dose of 76 mg MFP-SR, the serum fluoride levels remained within the accepted therapeutic range (5-10 microM/liter) for 24 hours. In contrast, following a single dose of 76 mg plain MFP, serum fluoride levels exhibited a wide circadian fluctuation and serum levels approximately threefold higher than those of the MFP-SR preparation (9.5 +/- 1.6 vs 3.5 +/- 0.8 microM/liter, P < 0.005). Compared with plain MFP, the sustained-release MFP had a significantly lower peak concentration (Cmax MFP-SR: 10.6 +/- 3 vs CmaxMFP: 18.9 +/- 5 microM/liter, P < 0.005) and a significantly longer absorption lag time (TmaxMFP-SR 7.3 +/- 1.6 vs TmaxMFP: 3.0 +/- 0.6 h, P < 0.05). Twenty-four-hour urinary fluoride excretion after ingestion of plain or SR fluoride was significantly increased from pretreatment values documenting absorption with either MFP formulation. Our results show that the use of sustained-release MFP preparation that we tested prevents the development of high peak levels associated with the use of plain MFP preparations. Furthermore, a single dose of MFP-SR resulted in serum fluoride levels within the accepted range of 5-10 microM/liter for 24 hours.

Aged↗
PubMed1993

Peripheral monocyte culture supernatants of menopausal women can induce bone resorption: involvement of cytokines.

Increased bone resorption is a mechanism contributing to bone loss in the postmenopausal period. Cytokines are involved in osteoclastic differentiation and, therefore, may play a role in the regulation of bone resorption. Several previous works showed the implication of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the modulation of bone remodeling. This study determines the concomitant production of the three cytokines and tests the bone-resorbing activity of peripheral monocyte supernatants. Four groups of women were studied: premenopausal women (n = 13; mean age, 47 +/- 0.9 yr), untreated postmenopausal women (n = 21; mean age, 52 +/- 0.6 yr), postmenopausal women treated with estrogens (n = 14; mean age, 54.2 +/- 1.1 yr), or postmenopausal women treated with ethanehydroxydiphosphonate (n = 12; mean age, 53.2 +/- 2 yr). Assignment to clinical groups was verified by plasma FSH and estradiol determinations. Lumbar spine bone mineral density was significantly higher in the premenopausal women group than in the three postmenopausal groups. Peripheral blood monocytes were cultured for 48 h with 20% autologous plasma, and after stimulation with lipopolysaccharides. IL-1, IL-6, and TNF alpha levels were measured by RIA in the monocyte surpernatants. The three cytokines were highly correlated to each other, IL-1 with IL-6 (r = 0.76; P < 0.001), IL-1 with TNF alpha (r = 0.89; P < 0.001), and IL-6 with TNF alpha (r = 0.89; P < 0.001). The mean levels of the three cytokines could not be compared because of the variations in the values. However, a trend toward lower levels in the three cytokines was noted in estrogen-treated women compared to the untreated postmenopausals. The bone-resorbing activity of monocyte supernatants, assessed by fetal long bone-resorbing assay, increased in untreated postmenopausal compared to that in premenopausal women (1.22 +/- 0.08 vs. 0.87 +/- 0.11; P < 0.05). In estrogen-treated patients, this activity decreased to premenopausal levels (0.89 +/- 0.04 vs. 0.87 +/- 0.11; P = NS). The resorbing activity was correlated to IL-1 (r = 0.28; P = 0.03), IL-6 (r = 0.52; P < 0.01), and TNF alpha (r = 0.48; P < 0.01). The addition of cytokine inhibitors and IL-1 receptor antagonist and TNF alpha antibodies to the supernatant bone culture medium induced a significant decrease in the calcium release. Those data show the involvement of several cytokines in the bone resorption process after estrogen deficiency.

Bone Resorption↗
PubMed1990

Studies of the mechanism by which androgens enhance mitogenesis and differentiation in bone cells.

Recently, we reported a direct effect of androgens on murine and human bone cells to stimulate bone cell proliferation and differentiation. To test whether this effect of androgenic steroids might be mediated by growth factors, we measured relative concentrations of insulin-like growth factor-I and -II (IGF-I and IGF-II) and transforming growth factor-beta (TGF beta) in the conditioned medium from androgen-treated murine calvarial cell cultures. Only the concentration of TGF beta was increased. Consistent with the increased secretion of TGF beta in the mouse calvarial cell system, we observed an increased expression of TGF beta mRNA in a normal human osteoblastic cell system. We also determined whether androgens alter the response to growth factors. We found that dihydrotestosterone (DHT) treatment enhanced the mitogenic effects of fibroblast growth factor (FGF) and IGF-II but not those of IGF-I. The enhanced effect of FGF and IGF-II after DHT pretreatment was not affected by addition of TGF beta-blocking antibodies or by changing the culture medium. This indicated that in addition to increased release of TGF beta, another mechanism might be involved in the action of DHT on human and murine bone cells. Thus, we investigated the binding of human IGF-II to human osteoblastic cells and observed an increase in IGF-II binding after DHT treatment. Our results are consistent with a mechanism of action of androgens on bone cells that involves the induction of TGF beta and, in addition, may sensitize the cells to show an enhanced response to FGF and IGF-II, possibly by changing the receptor binding of mitogenic growth factors.

Androgens↗
PubMed1989

Characterization of the receptor for insulin-like growth factor II in bone cells.

We have previously shown that insulin-like growth factor II (IGF-II) is produced by bone cells and that IGF-II stimulates cell proliferation and collagen synthesis in bone cells. We now extend these in vitro findings by demonstrating specific IGF-II binding to bone cells derived from newborn mouse calvaria and embryonic chick calvaria. The kinetics of [125I] IGF-II binding in embryonic chick calvaria cells showed time and temperature dependence. Scatchard analysis of [125I]IGF-II binding to chick calvaria cells showed an apparent Kd of 1.4 x 10(-10) M, with a calculated receptor site concentration of 40,000/cell. The specificity characteristics showed that IGF-II was significantly more potent than IGF-I or insulin in displacing IGF-II tracer. Competition for binding of [125I]IGF-II by unlabeled IGF-II showed a dose-dependent displacement between 0.5 and 25 ng/ml. Fifty percent displacement of [125I]IGF-II binding to chick and mouse calvarial cells was achieved at 1-2 ng/ml; 90% of specific binding of [125I]IGF-II was displaceable in the presence of 125 ng/ml of unlabeled IGF-II. IGF-I showed less than 5% cross reactivity for displacement of [125I]IGF-II binding to chick and mouse bone cells. Type II receptor inhibitory antibodies, R-II-PAB1 inhibited the binding of [125I]IGF-II to mouse bone cells and H-35 rat hepatoma cells (which contain type II but not type I receptors) in a dose-dependent manner. R-II-PAB1 also inhibited basal cell proliferation as well as IGF-II-, IGF-I-, and fibroblast growth factor (FGF)-induced cell proliferation in mouse bone cells. In chick calvaria bone cells and TE89 human osteosarcoma cells, R-II-PABI inhibited neither binding of [125I]IGF-II nor IGF-II-induced cell proliferation. These results together with our findings that IGF-II increased chick bone cell proliferation in the presence of maximal doses of IGF-I suggest that at least part of the mitogenic action of IGF-II is mediated through type II rather than type I receptors in bone cells.

Animals↗
PubMed1989

Transforming growth factor beta mediates the estrogen induced inhibition of UMR106 cell growth.

A mitogenic response to transforming growth factor beta (TGF) occurred in the UMR106 cells cultured in serum-free medium and exposed serially to estradiol and TGF. This mitogenic response was lost when insulin was removed from the medium. TGF inhibited growth and increased the alkaline phosphatase content in the UMR106 cells cultured in medium lacking insulin. Prior exposure of the cells to estradiol enhanced this response. Monoclonal antibodies against TGF blocked the estradiol induced inhibition of growth after a two day incubation in medium devoid of insulin.

Alkaline Phosphatase↗
PubMed1986

Chemical and biological characterization of low-molecular-weight human skeletal growth factor.

Skeletal growth factor (SGF) activity was extracted from human bone matrix by demineralization and purified under dissociative conditions using hydroxyapatite, HPLC gel-filtration and HPLC reverse-phase chromatography. Human SGF thus purified was characterized chemically and biologically. Purified human SGF stimulated chick embryo bone cell proliferation at picomolar concentrations (half maximum at 2-3 ng/ml) and had little or no activity on other cell types tested (mouse 3T3 and normal rat kidney fibroblasts, embryonic chick intestinal and human placental cells). Human SGF did not displace 125I-labeled epidermal growth factor binding to normal rat kidney cells and did not stimulate normal rat kidney cell colony formation in soft agar. Human SGF activity was sensitive to trypsin, chymotrypsin, papain, dithiothreitol and performic acid but was resistant to heat (upto 70 degrees C), pH (3-10), cyanogen bromide, alkaline phosphatase and neuraminidase and did not bind jack bean concanavalin A or kidney bean lectin. From our chemical and biological studies it appears that human SGF is different from other known polypeptide growth factors: epidermal growth factor, fibroblast growth factor, insulin, insulin-like growth factor-I, platelet-derived growth factor and transforming growth factor.

Animals↗
PubMed1984

Bone-derived factors active on bone cells.

Effects of systemic calcium regulating hormones have been studied extensively, yet mechanisms of bone volume regulation at the local level are poorly understood. Our laboratory has reported evidence for two locally mediated processes of bone volume regulation which function independently of systemic control: (1) coupling of bone formation and resorption and (2) repletion of resorbed bone. These local regulatory mechanisms have been shown to occur in vivo and in vitro. We have reported that embryonic chick tibiae in culture, stimulated to resorb, release a factor in the serum-free culture medium that stimulates bone cell proliferation and bone matrix formation in vitro. We have postulated that this factor could be involved in the coupling mechanism. Subsequently, a similar factor which stimulates bone cell proliferation, collagen synthesis and bone formation in vitro was extracted from embryonic and adult bones. The factor partially purified from human bone, designated as human skeletal growth factor, has molecular weight, heat sensitivity and biological activity similar to the factor found in bone conditioned medium. Many other biologically active factors have also been extracted from bone cells or demineralized bone by different laboratories. Their actions on bone cells range from chemotactic to mitogenic. These recently discovered bone factors emphasize that there is important regulation of bone metabolism at the local level.

Animals↗
PubMed1984

A correction: inhibitory activity in the conditioned medium of embryonic chick bones is due to thymidine.

Earlier studies from this laboratory suggested that embryonic chick bones in organ culture released into the culture medium a specific inhibitor of bone cell proliferation as defined by inhibition of [3H]TdR incorporation into DNA. Dialysis and membrane ultrafiltration experiments suggested that the inhibitory substance (IS) had a molecular weight between 6000 and 14,000. However, subsequent studies on the purification of IS have revealed that the inhibitory activity in bone-conditioned medium is of lower molecular weight and has several properties in common with thymidine (TdR): (1) IS coeluted with [3H]TdR upon gel filtration chromatography on Sephadex G-10. (2) IS bound to charcoal but not to cation or anion exchange resins. (3) Bone-conditioned medium decreased incorporation of [3H]TdR into the free [3H]TdR pool of cells in monolayer culture. (4) Conditioned medium inhibited [3H]TdR incorporation into [3H]thymidine monophosphate in a reaction catalyzed by thymidine kinase. The equivalent concentration of TdR in conditioned medium as estimated by thymidine kinase assay was sufficient to account for the reduction in [3H]TdR incorporation into bone cell DNA. No evidence was found for a specific inhibitor of bone cell proliferation other than TdR. Hence we conclude that the inhibitory effect of IS is due to dilution of [3H]TdR by nonradioactive TdR. Furthermore, media conditioned by several tumor cell lines also contained a low-molecular-weight component which inhibited [3H]TdR incorporation. The results suggest that organ- and cell-conditioned media can contain significant concentrations of TdR which can artifactually inhibit [3H]TdR incorporation in cell proliferation assays.

Animals↗
PubMed1982

Coupling factor.

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Animals↗
PubMed1982

[Different radiological, histomorphometrical and biochemical findings in two cases of adult osteopetrosis (author's transl)].

Morphokinetic measurements after tetracycline labeling were performed on bone specimens of the iliac crest in a 30-year-old man and a 38-year-old women. On radiographs, the osteopetrosis (=marble bone disease Albers-Schönberg) was characterized by an almost homogenous osteosclerosis in the man and by variable zones of high and normal density in the woman. Histologically, the man revealed increased rates of bone formation and mineralisation as signs of hyperactivity of the osteoblasts accompanied, biochemically, by an elevation of serum alkaline phosphatase and a high urinary output of hydroxyproline. In the woman increased resorbing bone seams, and elevation of serum acid phosphatase and a slightly lowered urinary output of hydroxyproline were apparent as signs of an osteoclastic deficiency. The cause of osteopetrosis has been generally ascribed to decreased bone resorption. This study shows that the accumulation of bone mass in osteopetrosis may be due also to increased bone formation and that by pathomechanism, probably, two forms of osteopetrosis in the adult may be differentiated.

Acid Phosphatase↗
PubMed1973

Inhibition of bone matrix formation, mineralization, and resorption in thyroparathyroidectomized rats.

In previous work we found that vitamin D-deficient and also calcium-deficient rats developed hypocalcemia and an impairment of bone formation and mineralization. The present study of thyroparathyroidectomized (TPTX) rats was undertaken to determine the effect of hypocalcemia without secondary hyperparathyroidism. TPTX rats fed a normal diet developed hypocalcemia and hyperphosphatemia in association with impairment of osteoblastic bone matrix formation and of mineralization of newly formed matrix. The serum calcium x phosphorus product was not decreased. The decreased formation was largely due to a reduction in matrix apposition indicating decreased synthetic activity of individual ostcoblasts. In contrast to the above results, when TPTX rats were fed a high-calcium diet to prevent hypocalcemia, no impairment of either formation or mineralization was found. From the results of these two experiments, it is reasonably certain that hypocalcemia was responsible for the inhibition of formation and mineralization. Moreover, based on the magnitude of the changes in serum calcium and bone parameters in TPTX rats, hypocalcemia could have accounted for the inhibition of formation and mineralization in calcium-deficient as well as vitamin D-deficient rats. In TPTX rats the mineralization defect was manifested by decreases in both the rate of osteoid maturation (indicating a delayed onset of mineralization) and the rate of mineralization. A strong correlation (r = 0.95, P < 0.001) was observed between these two rates suggesting a tight coupling of these two aspects of mineralization.TPTX rats also had lower bone resorption rates and higher serum phosphorus levels than sham-operated animals when the normal calcium diet was fed but not when the high-calcium diet was fed. Thus the inhibition of bone resorption in TPTX rats was at least partially prevented by correction of hyperphosphatemia. This is consistent with previous work showing an inverse relationship between serum phosphorus and bone resorption. Accordingly, the depression of bone resorption in TPTX rats was probably due to hyperphosphatemia as well as to hypoparathyroidism.

Animals↗