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Biomedical subjects

M Garabedian

Publications and source records attributed to M Garabedian.

At least 73 records · Page 4Linked to original sources
PubMed1986

[Congenital hyperparathyroidism. 3 cases].

Hypotonia, neonatal respiratory distress with a chest wall deformity should arouse clinical suspicion to the diagnosis of primary hyperthyroidism. The most common signs at this age are hypercalcaemia, increased alkaline phosphatase, low TRPP and radiological changes especially in the hip. Radio-immunological assay of PTH and plasma concentrations of Vitamin D metabolites are important diagnostic aids but the interpretation of these results should take the clinical and familial context into consideration. Rapid bone structural changes, the resistance of the hypercalcaemia to usual therapeutic measures and the progression to rickets justify urgent surgical treatment. Nearly all cases are due to clear cell hyperplasia.

Alkaline Phosphatase↗
PubMed1985

Vitamin D metabolite effects on membrane potential and potassium intracellular activity in rabbit cartilage.

In rabbit cartilage growth plates, the membrane potential, Vm, and potassium intracellular activities, alpha iK, were determined in order to study the effects of long-term (48 h) and short-term (1-2 min) exposures to vitamin D metabolites. Results are as follows: (i) in proliferative cells, Vm was -55.6 +/- 0.2 mV, n = 30, and alpha ik = 50.8 +/- 4.2 mM, n = 22; (ii) in hypertrophic cells, Vm was -35.5 +/- 0.8 mV, n = 88, and alpha iK = 85.1 +/- 5.4 mM, n = 20; (iii) Vm (-44.0 +/- 1.0 mV, n = 33) and alpha iK (114.7 +/- 8.7 mM, n = 14) were increased in metatarsal hypertrophic cells incubated with 10(-10)M of 1,25(OH)2D3 but were unaffected by the presence of 24,25(OH)2D3; (iv) an hyperpolarization of Vm was observed after short-term exposure of the hypertrophic cells to 10(-10)M of 1,25(OH)2D3 (-2.2 +/- 0.2 mV, n = 34) and 24,25(OH)2D3 (-2.2 +/- 0.7 mV, n = 17) but not to 25(OH)D3 (+0.3 +/- 0.8 mV, n = 10).

24,25-Dihydroxyvitamin D 3↗
PubMed1985

[Circulating metabolites of vitamin D in 14 children with hypercalcemia].

Circulating vitamin D metabolite concentrations, i.e. 25-(OH)D, 24,25-(OH)2D, 1,25-(OH)2D have been assayed in 14 hypercalcemic children. Results are as follows: a) Children with vitamin D intoxication (n = 2) had elevated serum 25-(OH)D and 24,25-(OH)2D concentrations but their 1,25-(OH)2D concentrations were similar to those found in normocalcemic children (10-110 pg/ml); b) Children with familial idiopathic hypercalcemia and hypocalciuria (n = 5), children with hypercalcemia and either Bartter's syndrome (n = 1), hemangiomatosis (n = 1), osteopetrosis after medullary graft (n = 1), also had 1,25-(OH)2D concentrations in the normal range; c) In contrast, 1,25-(OH)2D were elevated (160-470 pg/ml) in the four children with severe idiopathic hypercalcemia and elfin facies.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Influence of biochemical and hormonal factors on the bone histomorphometric features of uraemic patients.

A multidimensional analysis was used to evaluate, the influence on bone histology of various biochemical and hormonal factors in 20 uraemic patients on chronic haemodialysis or haemofiltration. A positive relationship (p less than 0.1) was found between PTH and osteoclastic and osteoblastic surfaces but not with mineral apposition and bone formation rates. The mineral appositional rate which reflects the cellular activity of osteoblasts was positively related to D metabolites 25(OH)D3 and 1,25(OH)2D3 and to phosphate (p less than 0.1). Mineral appositional rate and bone formation rate were negatively related to bone aluminium (p less than 0.05). These data indicate that: 1) PTH simulates bone turnover but has no direct effect on the bone cellular activity of osteoblasts which is mainly dependent on D metabolites and phosphate; 2) mild aluminium overload not severe enough to cause osteomalacia decreases bone formation in uraemic patients. This study evaluates the role of various simultaneously measured biochemical and hormonal factors on bone histological parameters in uraemic patients.

Adult↗
PubMed1984

Involvement of 1,25-dihydroxycholecalciferol in the short- and long-term increase of intestinal calcium absorption in laying hens: stimulation by gonadal hormones is partly independent of 1,25-dihydroxycholecalciferol.

The short- and long-term effects of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and its interactions with sexual steroids on Ca absorption were studied in hens. A single injection of 375 ng 1,25(OH)2D3 did not increase intestinal calcium transport in D-repleted hens within 24 hr of administration. However, five daily injections of 1 alpha-(OH)D3(0.5 micrograms/kg), a low Ca intake, or oestrogen-testosterone (O.T) did increase calcium absorption in D-repleted immature pullets (measured by in vivo perfusion), mainly by increasing the diffusional component of Ca transport. O.T. further increased the stimulation by 1 alpha-(OH)D3 of calcium absorption and of duodenal CaBP concentration. At higher doses the stimulation by 1 alpha-(OH)D3 of calcium transport estimated by in situ ligated loop procedure was dose dependent and was not saturable at daily doses of less than 3 micrograms/kg. When Ca transport was stimulated by 2 micrograms/kg of 1 alpha-(OH)D3, an additional effect of O.T. was observed again without any increase in plasma levels of 1,25(OH)2D3. Both oestrogen and testosterone were necessary for this effect on Ca transport. This is evidence for an indirect effect on Ca transport, as both steroids are also necessary to induce medullary bone. It is concluded that O.T. increased intestinal absorption of calcium, first by stimulating 25(OH)D3 1 alpha-hydroxylase activity but also by another mechanism which is independent of 1,25(OH)2D3 metabolism.

Animals↗
PubMed1984

[Effects on muscular and general proteolysis in burn patients of a solution enriched with branched amino acids].

In order to assess the effects of a branched chain amino acid (BCAA) enriched solution on urinary nitrogen loss and muscle protein breakdown, 22 burnt patients were randomly divided into two groups immediately after hospital admission: 11 patients received a 22% BCAA amino acid solution, 11 patients received a 41% BCAA amino acid solution. Nitrogen intake was 0.2 g per day during the first 4 days in each group. Urinary total nitrogen, urinary creatinine and urinary 3,methylhistidine (3,MeHis) were measured for 4 days. Nitrogen balance, 3,MeHis/nitrogen ratio and 3,MeHis/creatinine ratio were calculated in each group. The two groups were compared using Student's test. Nitrogen, creatinine and 3,MeHis urinary excretion, and nitrogen balance were not significantly different in the two groups, except for urinary nitrogen on day 3 which was slightly higher in the 41% BCAA group. The 3,MeHis/nitrogen ratio on day 1, day 2 and during the whole study period, as well as the 3,MeHis/creatinine ratio on day 2, were significantly lower in the 41% BCAA group. These results were in agreement with a decrease in muscle/whole body urinary nitrogen excretion. However, no beneficial effect upon nitrogen loss or nitrogen balance was shown by using the 41% BCAA rich amino acid solution.

Adolescent↗
PubMed1984

[Hypophosphatemic rickets in premature infants independent of vitamin D].

The etiology and prevention of rickets in prematures infants are still controversial: insufficient storage or intake in minerals and/or vitamin D, immature vitamin D metabolism, necessitating early vitamin supplementation, for some associated with calcium and phosphate supplementation. The authors report a case of rickets which could be related to an immaturity of the tubular mechanisms of phosphate reabsorption, with a favourable outcome following an increase in calcium and phosphate intake.

Calcium↗
PubMed1983

Rickets and alopecia with resistance to 1,25-dihydroxyvitamin D: two different clinical courses with two different cellular defects.

UNLABELLED: Two unrelated patients, aged 22 months and 31 months, with alopecia and rickets resistant to 1,25-dihydroxyvitamin D (1,25-(OH)2D] (vitamin D-dependency type II) presented with similar biochemical and radiologic features. They were treated with large doses of vitamin D3 derivatives [25-hydroxyvitamin D3 (25-(OH)D3), 1,25-(OH)2D3, and 1 alpha-hydroxyvitamin D3] for 28 months and 6 yr, respectively. In both patients, serum 1,25-(OH)2D levels remained high (approximately 10- to 100-fold normal) during the different therapeutic regimens. Circulating 1,25-(OH)2D and 24,25-dihydroxyvitamin D levels at various stages of the disease suggested in these children disturbances in the regulation of 25-hydroxyvitamin D (25(OH)D) 1 alpha- and 24-hydroxylase systems. In one child, all therapeutic trials were unsuccessful. Studies of her cultured skin fibroblasts showed low capacity (10% normal) for saturable (presumably receptor mediated) nuclear uptake of tritiated 1,25-(OH)2D3; the uptake process of nucleus associated 1,25-(OH)2D3 was normal in apparent affinity for 1,25-(OH)2D3 and in sedimentation velocity of nucleus-associated hormone. In the second child, correction of biochemical abnormalities, healing of rickets, and catch-up growth were obtained during similar therapeutic trials up to the age of 6 yr when a relapse occurred. This relapse has persisted for 2 yr in spite of similar or higher circulating concentrations of 25-(OH)D and 1,25-(OH)2D than those obtained previously when she was responsive to therapy. In her cultured skin fibroblasts, saturable high affinity nuclear uptake of 1,25(OH)2D was unmeasurable. IN CONCLUSION: 1) distinct patterns of clinical response can occur in patients with the syndrome of vitamin D-dependency type II, and can be associated with differing abnormalities in interaction of 1,25-(OH)2D3 with cultured skin fibroblasts; 2) aggravation of the resistance to 1,25-(OH)2D3 may occur during long term therapy in some patients.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Evaluation of 25-hydroxyvitamin D and vitamin D binding protein losses in thirteen children on continuous ambulatory peritoneal dialysis.

Thirteen children, 6 females, 7 males, aged 2 to 13 years were studied. At the time of study they were on continuous ambulatory peritoneal dialysis (CAPD) for 1 to 22 months. 25-(OH)D loss in daily dialysate fluids represented 2 to 22 micrograms/day. A significant correlation was found between 25-(OH)D plasma concentration and 25-(OH)D dialysate concentration. 25-(OH)D clearance was correlated to 25-(OH)D binding protein clearance (p less than 0.001). These findings of important 25-(OH)D losses in the dialysate fluid of children on CAPD demonstrate the necessity of carefully adapted vitamin D intakes with such a treatment.

Adolescent↗
PubMed1982

Possible link between changes in plasma 24,25-dihydroxyvitamin D and healing of bone resorption in dialysis osteodystrophy.

Histomorphometric studies of bone biopsies were performed on 12 hemodialyzed patients before and after six months of treatment with 25-(OH) and 1 alpha-(OH) vitamin D3. Patients could be classified into three groups according to bone resorption: Group I with normal bone resorption; Group II with elevated initial bone resorption unresponsive to vitamin D treatment; group III with elevated initial bone resorption sensitive to vitamin D treatment. None of the patients had histological signs of osteomalacia. In Group I, plasma concentrations of 24,25-(OH)2D and the ratio of 24,25-(OH)2D to 25-(OH) D remained in the normal range throughout the study; in Group II these parameters were subnormal initially and did not increase above normal except in one case; in Group III, plasma concentrations of 24,25-(OH)2D were high before or at the beginning of vitamin D administration and normal at the time of the second biopsy and wide variations were observed in the ratio of 24,25-(OH)2D to 25-(OH)D. No difference was found between these last two groups with regard to the cumulative dose of vitamin D derivatives administered or the changes in plasma PTH, CT, calcium and phosphate. These observations suggest a specific regulation of plasma 24,25-(OH)2D concentrations in hemodialyzed patients and a possible link (independent of circulating PTH, CT, or phosphate) between this regulation and healing of bone resorption. However, no correlation was found between plasma 24,25-(OH)2D and either one of the simultaneously measured biochemical or histological parameters.

24,25-Dihydroxyvitamin D 3↗
PubMed1982

In vitro action of 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol on matrix organization and mineral distribution in rabbit growth plate.

Growth plates of 18-day-old rabbits were incubated in a protein-free synthetic medium, either without any additive, with 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] (10(-10) M), with 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] (10(-10) M and 10(-9) M), with both metabolites, or with the ethanol solvent alone. Cartilages, before and after 5 days of incubation, were studied by light and electron microscopy. The intracellular calcium distribution was analyzed by the potassium pyroantimonate method, and the calcium content was verified by x-ray microprobe analysis. When compared to nonincubated samples the cartilages incubated for 5 days without any additive as well as the cartilages incubated with the solvent alone showed excessive hydratation and hypertrophy of the chondrocytes, which had lost their columnar arrangement. The matrix and the cells were devoid of mineral. The ultrastructure of the cells was well preserved. These changes were largely prevented by the presence of both vitamin D3 metabolites. With regard to calcium distribution, 1,25-(OH)2D3 maintained calcium in mitochondria and crystals in matrix vesicles, whereas 24,25-(OH)2D3 only partly maintained mitochondrial mineral. In the chondrocytes incubated with this latter metabolite, small calcium granules were seen in the cytoplasm; most vesicles were devoid of crystals, and amorphous precipitates were seen in the matrix. These data demonstrate the in vitro influence of vitamin D3 metabolites on the organization and mineralization of the cartilage matrix and on the distribution of intracellular calcium in chondrocytes. Furthermore, they support the hypothesis that the in vitro action of 1,25-(OH)2D3 is different from that of 24,25-(OH)2D3 in that 1,25-(OH)2D3 may influence calcium storage in mitochondria and matrix vesicles, whereas 24,25-(OH)2D3 is likely to be involved in calcium transport and release.

24,25-Dihydroxyvitamin D 3↗
PubMed1982

In vitro formation of 25-hydroxyvitamin D3 metabolites in endometrium: dependence on the hormonal status of the rat.

Rat myometrial tissue and endometrial cells were incubated with labeled 25-hydroxyvitamin D3 ([3H-26,27] 25OHD3) for 70 min at 37 C, and the resulting metabolites were isolated by sequential Sephadex LH-20 chromatography and high performance liquid chromatography. Two peaks more polar than 25OHD3 were present on the Sephadex LH-20 chromatograms. One of these metabolites had an identical chromatographic behavior on three different HPLC systems and an identical sensitivity to periodate cleavage as biosynthetic [3H-26,27] 24,25-dihydroxyvitamin D3 ([3H-26,27]24,25-(OH)2D3]. The in vitro production of this putative 24,25-(OH)2D3 was significantly higher in castrated animals than in normal adult rats. Treatment of rats with 17 beta-estradiol and/or medroxyprogesterone acetate reversed the effect of ovariectomy on 25OHD3 conversion. The in vitro production of the putative 24,25-(OH)2D3 was low during the estrous cycle and the initial stage of pregnancy. A dramatic increase in its production was observed on days 12 and 14 of pregnancy. 25OHD3 conversion was higher in endometrium than in myometrium under every experimental condition tested. These results demonstrate the ability of rat uterine tissue to convert 25OHD3 into more polar derivatives in vitro, and show the influence of the hormonal status of the rat on this in vitro capacity.

24,25-Dihydroxyvitamin D 3↗