Search PubMed⌕ Search

Biomedical subjects

M Garabedian

Publications and source records attributed to M Garabedian.

At least 55 records · Page 3Linked to original sources
PubMed1989

Corticosteroid-induced changes in the responsiveness of human osteoblast-like cells to parathyroid hormone.

We investigated the in vitro effect of corticosteroids on the responsiveness of human cells of osteoblast lineage to parathyroid hormone (PTH). Prior to corticosteroid treatment, the cells demonstrated only a small increase in cAMP production and no measurable change in transmembrane potential in response to PTH. Exposure of cells to dexamethasone resulted in a 5-fold increase in PTH-induced cAMP production and in measurable PTH-induced membrane depolarization in all cells studied. The effect of corticosteroids on cAMP production was specific for PTH (not seen with PGE1 or forskolin), occurred in a time- and dose-dependent fashion and in the absence of cell proliferation. Most of the cells were of osteoblast lineage as determined by the presence of alkaline phosphatase activity and BGP secretion. These findings further support the idea that corticosteroids increase the sensitivity of cells of osteoblast lineage to PTH, perhaps by transforming cells which initially have a low responsiveness to PTH to a state of high responsiveness.

Adolescent↗
PubMed1989

Evidence for extrarenal production of 1,25-dihydroxyvitamin during physiological bone growth: in vivo and in vitro production by deer antler cells.

The development of deer antler follows a pattern similar to that described for mammalian endochondral ossification and has been proposed as a suitable model for studies of bone growth. We investigated seasonal changes in the plasma concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D] and calcium and the activity of alkaline phosphatase in relation to the antler cycle during 1 yr in 4 captive roe deer and measured these biological parameters in 27 wild roe deer during their antler cycle. A significant elevation of 1,25-(OH)2D in peripheral plasma, with no parallel increase in the concentration of its precursor 25-hydroxyvitamin D, was observed to accompany the rapid growth phase of the antler cycle in captive (P less than 0.001) and wild (P less than 0.025) deer. During the same phase there was a gradient in levels of 1,25-(OH)2D in antler vs. jugular blood (P less than 0.01). In addition, velvet cells in culture proved to have the ability to convert 25-hydroxyvitamin D3 into a more polar derivative, which was indistinguishable from true 1,25-(OH)2D3 with regard to its chromatographic properties, its UV absorbance at 254 nm, and its ability to bind to the 1,25-(OH)2D3 receptors present in chick intestinal cytosol. These in vivo and in vitro results strongly suggest that local production of 1,25-(OH)2D by the antler cells does occur in vivo and may contribute to the increase in plasma 1,25-(OH)2D during bone growth.

Alkaline Phosphatase↗
PubMed1989

[Prophylaxis of vitamin D deficiency in hypothyroidism in the newborn infant].

This study deals with the relationship between the occurrence of hypercalcemia and the administration of prophylactic doses of vitamin D in children with hypothyroidism, before and during L-thyroxine (LT4) treatment. The goal of the study was to determine the dosage of vitamin D necessary to prevent rickets without inducing hypercalcemia. There was a 23% prevalence of hypercalcemia at the time of the diagnosis of hypothyroidism by screening whereas it was 21% in the children who were not given vitamin D during the first 3 months of LT4 treatment. This figure was significantly higher in those who were given vitamin D during the first 3 months of treatment and reached 70%. However, one of the 19 children not given vitamin D presented with biological signs evoking vitamin D deficiency. In conclusion, in hypothyroid infants, vitamin D should be administered carefully during the first 6 months of treatment and restricted to children at risk for developing vitamin D deficiency.

Calcifediol↗
PubMed1989

Cells bearing granulocyte-macrophage and T lymphocyte antigens in the rat uterus before and during ovum implantation.

There is little detailed information on the distribution of granulocytes-macrophages and lymphocytes at the pre- and peri-implantation period of the embryo in the uterus. Using two monoclonal antibodies (MAS-099C and MRC-OX41) we found that cells labelled with antibodies specific to either T lymphocytes and thymocytes or granulocytes-macrophages were present in the endometrium and myometrium before ovum implantation. Both types of labelled cells appeared to migrate from the uterine lumen to the deep endometrium, where their number peaked on day 4. At the early implantation period (days 5 to 7), there was a total lack of labelled cells around the conceptus. Specific changes before ovum implantation in the distribution or activation state of T lymphocytes and granulocyte macrophages may favour early embryo acceptance.

Animals↗
PubMed1989

[Deficiency rickets: the current situation in France and Algeria].

Persisting vitamin D deficiency rickets in France results from the climatic, environmental and geographic situation of this country. Although systematic administration of vitamin D supplements to infants greatly reduced the prevalence of rickets among infants, clinical and/or biological signs of vitamin D deficiency are still found in children and adolescents, mainly during the winter and in populations vulnerable for economic, cultural or religious reasons. Signs of vitamin D deficiency are also found, during the winter-spring seasons, in pregnant women and their newborns living in urban areas. Such vitamin D deficiencies could be overcome by vitamin D supplementation to susceptible populations. In Algeria, vitamin D deficiency rickets present a continuing public health problem. The persisting high incidence of rickets among children appears to result mainly from economic and cultural factors. Vitamin D supplementation and health education are mandatory to reduce the prevalence of vitamin D deficiency among pregnant women and the occurrence of vitamin D deficiency rickets in infants, whether breast-fed or not.

Algeria↗
PubMed1988

Calcium-dependent metabolism of 25-hydroxycholecalciferol in silver eel tissues.

We investigated the in vitro metabolism of [26,27-3H]-25-(OH)D3 in different eel tissues. After incubation with [3H]-25-(OH)D3, tissues were extracted with methanol-chloroform and chromatographed on Sephadex LH 20 columns. Two derivatives less polar than 25-(OH)D3 were detected, the first one being sensitive to KOH treatment. Three peaks more polar than 25-(OH)D3 were also found: peak I migrated close to the 24,25-(OH)2D3 area and was quantitatively the most important, but the presence of 24,25-(OH)2D3 could not be demonstrated; peak II migrated in the 1,25-(OH)2D3 region; and peak III had an elution position twice that of peak II. After 6-h incubation of tissues isolated from control eels, peak I was found in all tissues including intestine and gills. It was highest in pituitary gland and brain and lowest in ovaries and muscle. It was not significantly modified 20 days after ablation of the corpuscules of Stannius. In contrast, in vivo daily calcium chloride injection was followed 24 hr later by a significant increase in the [3H]-25-(OH)D3 conversion into peak I in gills, intestine, and the spinal cord and by an inhibition of this conversion in pituitary gland, skin, and muscle. The inhibition was found in all tissues after five daily calcium injections. Calcium injection had no effect on the in vitro metabolite synthesis by the corpuscules of Stannius. These results suggest that vitamin D is not metabolized in the same way in eel as in mammals and that this metabolism could in part be calcium dependent.

Animals↗
PubMed1988

Vitamin D metabolism in tuberculosis. Production of 1,25(OH)2D3 by cells recovered by bronchoalveolar lavage and the role of this metabolite in calcium homeostasis.

To investigate the extrarenal production of 1,25(OH)2D3 in tuberculosis, we extensively evaluated a patient with tuberculosis, hypercalcemia, and an elevated plasma concentration of 1,25(OH)2D3. Fresh total cells and cultured alveolar macrophages obtained by bronchoalveolar lavage were demonstrated to synthesize 1,25(OH)2D3 prior to and after nine months of successful antituberculous therapy. The continued capacity to produce 1,25(OH)2D3 was associated with a persistent lymphocytic alveolitis in this patient. This extrarenal production of 1,25(OH)2D3 probably contributed to the increased levels of plasma 1,25(OH)2D observed in our patient. Nevertheless, a close correlation between plasma 1,25(OH)2D and serum calcium was not observed. These findings suggest that although extrarenal production of 1,25(OH)2D3 occurs in tuberculosis, it need not be a predominant factor producing the abnormalities in calcium homeostasis observed in such patients.

Adult↗
PubMed1988

Congenital adrenal hyperplasia associated with hyperphosphatemic rickets.

The authors describe a boy with precocious puberty due to adrenal hyperplasia associated with rickets, hypocalcemia, hyperphosphatemia, elevated PTH and alkaline phosphatase levels, and concentrations of 25-OH-D and 1,25-(OH)2D at the upper limit or above normal range. Treatment with hydrocortisone for 9 months did not normalize hypocalcemia and hyperphosphatemia. The addition of 1,25-(OH)2D3 (0.5-2 micrograms/day) to the corticoid treatment for 1 year was followed by a progressive normalization of plasma calcium, phosphorus, PTH and alkaline phosphatase concentrations with improvement of the osteomalacia on bone biopsy.

Adrenal Hyperplasia, Congenital↗
PubMed1988

Thyroid and parathyroid-independent increase in plasma 1,25-dihydroxyvitamin D during late pregnancy in the rat.

The effect of thyroparathyroidectomy (TPTX) on the plasma concentrations of the vitamin D metabolites (25-(OH)D, 24,25-(OH)2D and 1,25-(OH)2D) has been studied in pregnant rats and their fetuses during the last quarter of gestation. Maternal and fetal vitamin D metabolites were not significantly affected by TPTX. A significant increase in plasma 1,25-(OH)2D concentrations was observed in both TPTX and control mothers and fetuses from days 19 to 21. Fetal and maternal plasma 25-(OH)D were positively correlated in both control and TPTX groups. Such a correlation was also found for 24,25-(OH)2D in the two groups. In contrast, a positive correlation between maternal and fetal plasma concentrations of 1,25-(OH)2D was found in TPTX but not in control rats. These data suggest that major alterations in calcium metabolism, such as that produced by maternal TPTX, are insufficient to affect the changes in maternal and fetal plasma 1,25-(OH)2D during late pregnancy significantly. They also suggest that parathyroid hormone, thyroxine, and/or calcitonin may control a possible placental transfer of 1,25-(OH)2D in the rat.

24,25-Dihydroxyvitamin D 3↗
PubMed1988

[Administration of a single dose of 100,000 U.I. of vitamin D3 in the pregnant woman in winter. The effect on blood calcium level of the newborn infant].

Serum levels of 25-hydroxyvitamin D [25-(OH)D], calcium, phosphate and alkaline phosphatase activity were measured between December and July in 110 pregnant women during the last trimester of pregnancy, and in their infants on the fifth day of life. This study showed a fall, during spring, below 6 ng/ml, of the maternal 25-(OH)D concentration at the time of delivery, and a fall of the 25-(OH)D and calcium concentrations in newborns. The existence of a positive correlation between calcium and 25-(OH)D levels in the newborns suggests that the low calcium concentrations found in the infants born in spring is related to a vitamin D deficiency of the infant and therefore of the mother. The administration of a single low dose of vitamin D3 (100,000 I.U.) on the sixth or seventh month of pregnancy allowed to prevent the seasonal fall in serum calcium and 25-(OH)D concentrations. This dosage appears therefore to be sufficient to reduce the risk of vitamin D deficiency of the newborn and the occurrence of neonatal hypocalcemia.

Adult↗
PubMed1987

[Extrarenal synthesis of calcitriol in sarcoidosis].

Mean plasma calcitriol was significantly increased in a patient with sarcoidosis and hypercalcemia without elevation of PTH. Recent studies provided evidence for an extrarenal production of calcitriol. To investigate this possibility, the conversion of calcidiol by a sarcoid lymph node homogenate was studied. After 2-hour incubation, a product was present in the incubation, which comigrated with synthetic calcitriol on two high performance liquid chromatography systems, was detected by ultraviolet absorption spectrometry and was bound with high affinity by the chick intestinal receptor for calcitriol. These results provide further evidence for an extrarenal synthesis of calcitriol, contributing to the excessive amounts of this metabolite found in the plasma of patients with sarcoidosis.

Adult↗
PubMed1986

Mechanisms of 1,25(OH)2D3-induced rapid changes of membrane potential in proximal tubule: role of Ca2+-dependent K+ channels.

Eleven different secosteroids or steroids (10(-10) to 10(-8) M) were acutely and reversibly introduced in solutions delivered to the lumen of single proximal tubules of the amphibian Necturus kidney while recording basolateral cell membrane potential Vm. Seven of these molecules (1,25(OH)2D3, 25(OH)D3, 24,25(OH)2D3, 5,6-trans-25(OH)D3, 19-diol-cholesterol, estradiol and testosterone) resulted in changes of Vm (delta Vm) occurring in a few seconds, the largest delta Vm being observed with 1,25(OH)2D3, +6.5 +/- 0.75 mV (n = 19); these seven (seco)steroids, but not the four inactive sterols (vitamin D3, cholesterol, 1 alpha D3 and aldosterone) possess a hydroxyl group on at least one carbon of the C17 to C25 lateral chain of the sterol ring. The delta Vm effect was present in Na+-free or Cl-free media, but it was abolished in HCO3-free media. Depolarization of cell membrane potential by addition of glucose, 11 mM, in luminal perfusion fluid abolished the 1,25(OH)2D3-evoked delta Vm effect, suggesting dependence of the latter on the absolute value of membrane potential. Barium, a blocking agent of K+ conductances, suppressed the 1,25(OH)2D3-evoked delta Vm effect, even when the proper effects of barium of cell membrane potential were canceled by current clamp. Pretreatment with quinine, a putative blocker of Ca2+-dependent K+ channels also abolished the 1,25(OH)2D3-evoked depolarization. Such observations are consistent with the presence of Ca2+-dependent K+ channels at the apical cell membrane of the proximal tubule, these channels being inactivated by 1,25(OH)2D3 and probably by other (seco)steroids.

Animals↗
PubMed1986

Hypercalcemia in infants with congenital hypothyroidism and its relation to vitamin D and thyroid hormones.

The circulating concentrations of calcium, phosphorus, and vitamin D metabolites were measured in 25 infants (fifteen to 30 days of age) with congenital hypothyroidism before treatment or during the first 6 months of thyroxine therapy. Five of the children before treatment and four during the early 3 months of treatment had mild hypercalcemia (10.8 to 12.4 mg/dl). Hypercalcemia before treatment did not appear to be related to the vitamin D status of the infant nor to an alteration in vitamin D metabolism, but to the presence of a residual thyroid secretion. In contrast, hypercalcemia during thyroxine therapy was related to vitamin D supplementation, even though the serum calcium concentration could not be correlated with the circulating concentration of any of the vitamin D metabolites assayed and obvious changes in vitamin D metabolism could not be demonstrated.

24,25-Dihydroxyvitamin D 3↗
PubMed1986

Response to parathyroid hormone and 1,25-dihydroxyvitamin D3 of bone-derived cells isolated from normal children and children with abnormalities in skeletal development.

In order to evaluate the role of intrinsic defects in osteoblast function in the pathogenesis of diseases of skeletal development, we developed techniques which permit the evaluation of the metabolic properties of bone-derived cells in vitro. Cells from control children demonstrated a variety of properties classically attributed to osteoblasts (presence of alkaline phosphatase positive cells and synthesis of bone gla protein) and responded to PTH (cAMP production) and to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) ([3H]25-hydroxyvitamin D3 conversion into [3H]24,25-dihydroxyvitamin D3 and bone gla protein secretion). Using these techniques we evaluated the function of cultured bone cells from patients with three rare diseases of skeletal development. Cells from a patient with rickets resistant to 1,25(OH)2D3 were resistant to 1,25(OH)2D3 but responded normally to PTH. Cells from a patient with acroosteolysis with osteoporosis responded normally to PTH and 1,25(OH)2D3. Cells from a patient with hyperphosphatasia with osteoectasia responded normally to 1,25(OH)2D3 but did not respond to PTH. The results demonstrate that bone cell cultures can provide information about the role of osteoblast dysfunction in such diseases.

Alkaline Phosphatase↗
PubMed1986

[Effect of dietary supply of calcium on thyroid function in rats].

To determine if calcium had a goitrogenic effect on the thyroid function in rats, weanling rats were fed, for three weeks, a diet containing either 0.5 microgram or 0.04 microgram iodine per gram of diet, or an adequate (0.47%) or an excessive (2%) amount of calcium. With an adequate iodine diet, the calcium load did not induce an increase in the weight of the thyroid or a decrease in serum thyroid hormone concentration. However, the rats given a calcium load had a lighter body weight and a lower iodine content in the thyroid tissue; they also had a higher thyroxine (T4) content in the liver and kidney tissues than the rats receiving an adequate calcium diet. With a low iodine diet, the calcium load brought out a decrease in growth and a lower serum triiodothyronine (T3) concentration and liver and kidney T3 contents. These changes suggest that the calcium load might have acted on the thyroid function through an inhibition of T4-T3 conversion in the serum as well as in liver and kidney tissues.

Animals↗