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Biomedical subjects

M Garabedian

Publications and source records attributed to M Garabedian.

At least 109 records · Page 6Linked to original sources
PubMed1977

Phosphatase content of rat calvaria after in vivo administration of vitamin D3 metabolites.

The effects of acute or chronic administration of small doses (130 pmol) of 25-hydroxycholecalciferol, 24,25-dihydroxycholecalciferol, and 1,25-dihydroxycholecalciferol on rat calvaria acid and alkaline phosphatase activities were investigated in weanling male albino Wistar rats raised on a vitamin D-deficient, low-calcium diet. The results indicate that each of these active metabolites has a different effect on calvarial phosphatase activities. 25-hydroxycholecalciferol causes a significant increase, and 24,25-dihydroxycholecalciferol a decrease in the enzymatic activity. In animals treated with 1,25-dihydroxycholecalciferol these activities are lower after one injection, but after seven daily doses they are not different from those of ethanol-injected control rats. The observed changes do not seem to be related to changes in serum calcium and/or phosphorus concentrations.

Acid Phosphatase↗
PubMed1977

The effect of induced metabolic acidosis on vitamin D3 metabolism in rachitic chicks.

The metabolism of vitamin D3 was studied in 3-week-old, vitamin D deficient chicks, fed since hatching with a diet containing 3% ammonium chloride, 1% calcium, and 0.7% phosphorus. When kidney homogenates were incubated in vitro with [3H]25-(OH)D3, the production of 1,25-(OH)2D3 was reduced by 40% in acidotic birds. During in vivo experiments, after injection of [3H]D3 (1220 pM/bird), the level of 1,25-(OH)2D3 was also reduced in blood plasma, intestine, and tibiae in acidotic chicks as compared with the controls. As a large increase in plasma phosphate was found during acidosis, these results are discussed in relation to the possible role of phosphorus in the control of 1,25-(OH)2D3 synthesis.

Acidosis↗
PubMed1977

Long-term therapy with 1alpha-hydroxyvitamin D3 in children with 'pseudo-deficiency' rickets.

This investigation confirms that 1alpha-hydroxyvitamin D3 (1alpha-OHD3) is a potent drug for the treatment of patients with pseudo-deficiency rickets (Balsan et al., 1975a; Reade et al., 1975; Prader et al., 1976). 1alpha-OHD3 corrects their intestinal malabsorption of calcium and phosphorus, normalizes their serum calcium and phosphate concentrations and promotes healing of skeletal lesions. This study also shows differences in the needs for 1alpha-OHD3 of children with PDR. Three factors appear to be of importance: familial sensitivity, severity of chronic secondary hyperparathyroidism, and periods of increased growth velocity. Tolerance to long-term 1alpha-OHD3 therapy, at doses varying from 0.5 to 2 microgram/d is excellent. Surveillance of patients should include regular measurements of 24 h urinary excretion of calcium, since hypercalciuria is the first signal of overdosage.

Adolescent↗
PubMed1977

Binding of cholecalciferol metabolites to rat duodenal mucosa cytosol.

In vitro binding of 25-hydroxycholecalciferol (25-(OH)D3) and 1alpha,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in the duodenal mucosa cytosol of rachitic rats: both 25-(OH)D3 and 1,25-(OH)2D3 bind to a macromolecule (sedimentation coefficient 5.5 to 6 S in low or high ionic strength) with a high affinity (KD at 4 degrees C = 1.2 X 10-9M and 2 x 10-9M, respectively). In addition, it is concluded from competition and chase experiments that 25-(OH)D3 binding sites differ from that for 1,25-(OH)2D3.

Animals↗
PubMed1976

1,25-Dihydroxycholecalciferol effect on serum phosphorus homeostasis in rats.

It has recently been shown that 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) increases the serum phosphorus concentration of rats on a low-phosphorus diet. While studying the biological activity of 1,25(OH)2D3, we observed that under certain circumstances 1,25-(OH)2D3 would decrease the serum phosphorus concentration. The analysis of all data obtained in rat experiments during the past 3 years revealed highly significant linear correlations (P less than 0.001) between changes of serum phosphorus concentrations after the administration of 1,25-(OH)2-D3 (130 pmol/d for 1 or 5 days) and serum phosphorus or calcium levels in the animals before injection. Similar correlations could only be found with the higher dose of 25-hydroxycholecalciferol (130 pmol/d for 5 days). Another vitamin D3 metabolite, 24,25-dihydroxycholecalciferol, had no effect on serum phosphorus concentrations under our experimental conditions. The 1,25-(OH)2D3 effect on serum phosphorus concentration does not require the presence of circulating parathormone and/or calcitonin. We suggest that 1,25-(OH)2D3 might be an important factor in serum phosphorus homeostasis.

Animals↗
PubMed1975

Relationship of 25-hydroxyvitamin D3 side chain structure to biological activity.

27-nor-25-Hydroxyvitamin D3, 26,27-bisnor-25-hydroxyvitamin D3, and 22-27-hexanor-20-hydroxyvitamin D3 and the corresponding 5,6-trans isomers have been synthesized. All compounds were tested for their ability to induce intestinal calcium transport and bone calcium mobilization in normal and anephric rats. The 27-nor- and 26,27-bisnor-25-hydroxyvitamin D3 analog are capable of stimulating intestinal calcium transport and bone calcium mobilization in normal rats but are 10 to 100 times less active than 25-hydroxyvitamin D3. Although these analogs are inactive in anephric rats, their corresponding 5,6-trans isomer are capable of stimulating both intestine and bone activity in these animals. The 22-27-hexanor-20-hydroxyvitamin D3 and its corresponding 5,6-trans isomer are incapable of stimulating either intestinal calcium transport or bone calcium mobilization. These results suggest that minor alterations in the side chain significantly decrease the biopotency of 25-hydroxyvitamin D3. Since these analogs are biologically active in normal but not in anephric animals, it appears that the kidney 1alpha-hydroxylation is necessary for activity. Since 22-27-hexanor=20-hydroxyvitamin D3 and its corresponding 5,6-trans analog are biologically inactive, it is likely that at least part of the side chain is necessary for 25-hydroxyvitamin D3 to stimulate intestinal calcium transport and bone calcium mobilization.

Animals↗
PubMed1975

Pancreatography in the diagnosis of carcinoma of the pancreas.

Until recently the pancreas was regarded as one of the most diagnostically unapproachable organs. Tests of function were for the most part indirect, and results tended to be misleading. Endoscopic pancreatography has proved useful in the investigation of diseases of the pancreas and the biliary tree, and has become routine in several gastroenterology centers around the world. Experience with the procedure in patients with suspected carcinoma of the pancreas is reviewed.

Catheterization↗
PubMed1975

1,25-dihydroxyvitamin D3 and 1, alpha-hydroxyvitamin D3 in children: biologic and therapeutic effects in nutritional rickets and different types of vitamin D resistance.

This investigation confirms the high level of biologic activity and the similarity of the effects of small doses of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) and of its analog 1alpha-hydroxyvitamin D3 (1alpha-OH-D3) on children with nutritional rickets, "pseudodeficiency" rickets (PDR), hereditary hypophosphatemia, chronic idiopathic hypoparathyroidism, and chronic renal failure. It also shows that cystinotic patients may develop, at the end stage of the disease, a certain degree of resistance to 1,25-(OH)2-D3. The comparison of the therapeutic effects of long term oral administration of 1,25-(OH)2-D3 or 1alpha-OH-D3 to two D-deficient children and two sibs with PDR demonstrates differences in sensitivity. In the patients with nutritional rickets, 0.5 mug/24 hr of either drug corrects the biochemical abnormalities, initiates healing of skeletal lesions in 28 days, and cures the metaphyseal le lesions in 60 days of therapy. In contrast, it appears that doses of either drug that are curative in D deficiency rickets are only partly active in PDR. These observations indicate that the hypothesis of a deficit in 25-hydroxycholecalciferol 1alpha-hydroxylase in patients with PDR must await for confirmation more direct evidences, and that such a deficit, even if proven, may not account for all of the biochemical and skeletal alterations seen in patients with this inherited disorder.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1974

Metabolism of 25-hydroxyvitamin D3 in anephric rats: a new active metabolite.

After the injection of radioactive 25-hydroxyvitamin D(3) into rats given a normal diet, two metabolites can be detected on Sephadex LH-20 chromatography modified to reveal polar metabolites. The first is designated peak Va, which by means of periodate cleavage has been identified as 24,25-dihydroxyvitamin D(3). The second more polar metabolite has been designated peak X(1) and is only partially sensitive to periodate. This metabolite appears in serum, bone, intestine, and liver and does not chromatograph on any system like any of the previously identified metabolites. Nephrectomy, especially in the animals given large doses of 25-hydroxyvitamin D(3), does not abolish production of either peak Va or X(1), revealing that both metabolites can be made in extra-renal tissue. Peak X(1) has marked ability to elevate serum calcium of rats on a vitamin D-deficient, low calcium diet, but requires the presence of kidneys to carry out this function.

Animals↗
PubMed1974

Duodenitis.

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Adult↗
PubMed1973

Calcium-mobilizing effect of large doses of 25-hydroxycholecalciferol in anephric rats.

The effect of high doses of 25-hydroxycholecalciferol on plasma calcium concentration was studied in rats receiving a low-calcium normal vitamin D diet. In bilaterally nephrectomized animals, as in sham-operated controls, 62.5 nmol of 25-hyroxycholecalciferol did not produce a rise of plasma calcium concentration. In contrast, the administration of 125 or 625 nmol, doses 1,000-5,000 times the minimal active dose in D-deficient rats, was followed in both groups of animals by a significant increase of plasma calcium concentration. Removal of either parathyroids alone or parathyroid and thyroid glands did not suppress this effect. These data suggest that when large doses are used in vivo, the renal conversion of 25-hydroxycholecalciferol to more polar metabolites is not an obligatory step for its calcium-mobilizing action. The present study does not elucidate, however, the exact mechanism(s) of this effect.

Animals↗
PubMed1972

1,25-dihydroxycholecalciferol: metabolite of vitamin D3 active on bone in anephric rats.

Nephrectomy prevents completely the bone calcium mobilization response to 25-hydroxycholecalciferol. In contrast it does not prevent this response to 1,25-dihydroxycholecalciferol. Because it is known that the kidney is the site of 1,25-dihydroxycholecalciferol formation, these results provide evidence that 1,25-dihydroxycholecalciferol or a further metabolite thereof and not 25-hydroxycholecalciferol is the metabolically active form of vitamin D(3) responsible for bone calcium mobilization.

Animals↗