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Biomedical subjects

M Garabedian

Publications and source records attributed to M Garabedian.

At least 91 records · Page 5Linked to original sources

Changes in plasma 1,25 and 24,25-dihydroxyvitamin D after renal transplantation in children.

The purpose of this investigation is to analyze changes in plasma 1,25-(OH)2D and 24,25-(OH)2D after successful renal transplantation in 20 children and young adults. Studies were performed on 8 subjects between the 1st and 10th month and on 12 others between the 20th and 30th to 36th month. Samples were assayed for plasma and urinary calcium, inorganic phosphate, creatinine, plasma bicarbonate, immunoreactive parathyroid hormone, 25-(OH)D, 24,25-(OH)2D, and 1,25-(OH)2D concentrations. Results showed the following: (1) All subjects had normal or high plasma levels of dihydroxyvitamin D metabolites. (2) In subjects with normal GFR's there was a significant inverse correlation between plasma 1,25-(OH)2D concentrations and tubular reabsorption of phosphorus. (3) These correlations were not found in subjects with subnormal creatinine clearances (50 to 100 ml/min/1.73 m2) even though plasma 1,25-(OH)2D concentrations in these subjects were similar to those with normal creatinine clearances. (4) In subjects with subnormal creatinine clearances, an increase in plasma 1,25-(OH)2D concentrations to very high levels was observed during the first months following renal transplantation.

24,25-Dihydroxyvitamin D 3↗

Plasma levels of vitamin D metabolites in the bovine species during the perinatal period.

Plasma vitamin D metabolites (25-OH D; 24,25-(OH)2D and 1,25-(OH)2D) were measured simultaneously in the blood plasma samples of young cows and their calves. Four of the calves were chronically catheterized in utero at least 2 weeks before the expected time of parturition. No significant hypocalcaemia occurred in the dams at calving. Plasma vitamin D metabolites showed no significant variations for 2 weeks before and 4 days after calving. But rapid changes in plasma 1,25-(OH)2D concentrations were observed in one calf during the first 48 postnatal hours. Before birth, the maternal and foetal concentrations of either 1,25-(OH)2D or 24,25-(OH)2D were positively correlated. 25-(OH) D (13 ng/ml), 24,25-(OH)2D (1 ng/ml) and 1,25-(OH)2D (76 pg/ml) were detected in one foetal plasma collected 35 days before term.

24,25-Dihydroxyvitamin D 3↗

Vitamin D3 metabolite injections to thyroparathyroidectomized pregnant rats: effects on calcium-binding proteins of maternal duodenum and of fetoplacental unit.

Fetomaternal relationships with respect to vitamin D metabolism were investigated in thyroparathyroidectomized (TPTX) pregnant rats, with or without treatment with different vitamin D3 metabolites. Calcium-binding protein (CaBP) in maternal duodenum was used as an index of 1,25-(OH)2D3 status of the mother. Pregnant rats were TPTX on day 12.5 and CaBP was measured on 21.5 days of gestation by RIA in maternal duodenal mucosa and in the fetoplacental unit (placenta, fetal membranes, and fetal intestine). In the duodenum of TPTX mothers, the CaBP concentration was reduced by 50%. This fall was associated with a decrease of 1,25-(OH)2D in maternal plasma. CaBP in maternal duodenum increased by the administration of 1,25-(OH)2D3 or 1,24,25-(OH)3D3. In contrast, 24,25-(OH)2D3 injections to TPTX mothers were ineffective. In both placenta and fetal membranes, CaBPs decreased by 20% in TPTX mothers and were normalized only in 1.25-(OH)2D3-treated TPTX mothers. In the fetal intestine, CaBP variations paralleled those of maternal duodenal CaBP. The data indicate that plasma levels of 1,25-(OH)2D in TPTX pregnant rats are partly under the control of maternal parathyroid glands, and they support that even in pregnancy, the CaBP concentration in maternal duodenum may well reflect the 1,25-(OH)2D status of the mother. The CaBP synthesis in placenta and fetal membranes are vitamin D-dependent, and their regulation differs from that of intestinal CaBP. It app]ears that 1 alpha-hydroxylase activities of the fetoplacental unit (placenta and fetal kidney) are blunted in TPTX animals and that CaBP synthesis in the fetus depends on the presence of 1 alpha-hydroxylated vitamin D3 metabolites in the mother.

24,25-Dihydroxyvitamin D 3↗

[Measurements of plasma concentrations of active vitamin D metabolites in children: interest and limit (author's transl)].

This study of the three main vitamin D metabolites namely 25-(OH) D, 24, 25-(OH) 2D and 1, 25-(OH) 2D includes (1) a summary of the usual assay techniques, (2) a discussion about the concentrations and the role of these metabolites during the neonatal and childhood periods, (3) a report of the results obtained during the past seven years in our laboratory with comments on the interest and limits of these assays for the diagnosis of different types of rickets.

24,25-Dihydroxyvitamin D 3↗

[Serum concentrations of vitamin D metabolites in idiopathic juvenile osteoporosis (author's transl)].

This report concerns a 13 year old girl with the clinical and radiological features of mild idiopathic juvenile osteoporosis. In this patient, no alteration was detected in serum calcium (total + ionized) and phosphorus concentration, serum alkaline phosphatase activity, nor in urinary calcium and phosphorus excretions. Plasma concentrations of cortisol were normal during daytime and sleep. Circulating immunoreactive parathyroid hormone was normal or low. The serum 25-(OH)D and 24,25-(OH)2D concentrations were below the normal range, and the 1,25-(OH)2D concentrations were above the normal range (720 pmol/l) at the beginning of the investigation. All vitamin D metabolites concentrations returned to normal values at the time of radiological recovery and after calcium and 25-(OH)D3 supplementation. A possible relationship between alterations of bone and of circulating vitamin D metabolites is discussed.

Adolescent↗

[Enteral nutrition by tube in burn patients].

The authors report a year's experience off artificial feeding (A.F.) in the Regional Burns Centre of Marseille. 28 patients have benefited from an A.F. of longer than 10 days. It consisted of four cases of parenteral feeding, six cases of enteric feeding and eighteen cases of combined parenteral and enteric feeding. The efficiency of the techniques of A.F. is demonstrated by the results: a weight loss greater than 10% was observed in only three patients. However, the phenomena of digestive intolerance in this type of patient is a significant limiting factor in tubal feeding.

Adolescent↗

Plasma 1,25(OH)2D3 and iPTH in transplanted adults with persisting hypophosphataemia.

Hypophosphataemia is a common finding among kidney transplanted patients [1,2]. In a previous study in kidney transplanted children with plasma creatinine below 1.1mg/dl, we demonstrated [3] a negative correlation between plasma phosphorus and 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), the renal hormonal form of vitamin D. No such correlation was apparent in children with minimal increase in plasma creatinine. The aim of the present investigation carried out in hypophosphataemic transplanted adults was two-fold: 1) to determine whether hypophosphataemia results from persisting hyperparathyroidism or from a renal phosphorus leak, or both, and 2) to study the relation between plasma phosphorus, iPTH and 1,25(OH)2D3 in these patients.

Adult↗

Metabolic and cellular activity of vitamin D.

Most of the effects of vitamin D on calcium and phosphorus homeostasis result from an increase in intestinal absorption of calcium and phosphorus and from bone mobilization. These effects are due to 1,25(OH)2D3, one of the renal vitamin D metabolites. Besides ionic mobilization, vitamin D may exert additional effects on bone which depend on metabolites other than 1,25(OH)2D3. Kidneys, parathyroid glands and muscle are probably target organs for vitamin D. The metabolite(s) responsible for these actions remain unknown.

Animals↗

Vitamin D and cartilage. I. In vitro metabolism of 25-hydroxycholecalciferol by cartilage.

In the present work, the capacity of cartilage to metabolize 25-hydroxycholecalciferol was investigated. Cartilage preparations from growth plate, articular surface, rib, scapula, and ear were isolated from 3-week-old normal rabbits and chickens. Each tissue was separately incubated with tritiated 25-hydroxycholecalciferol (, x 10(-9) M) for 1-24 h. Incubations of kidney and muscle were performed simultaneously for comparison. Similarly, cultured chondrocytes isolated from rabbit growth plate and articular cartilage were incubated for 1 or 20 h in medium free of fetal calf serum. After methanol-chloroform extraction of tissues, cells, and their respective media, chloroform phases were chromatographed on Sephadex LH-20 columns. The results show that kidney and cartilage are able to convert 25-hydroxycholecalciferol into a derivative which migrates in the 24,25-dihydroxycholecalciferol region. Cartilage tissue previously boiled is unable to metabolize 25-hydroxycholecalciferol. The conversion of 25-hydroxycholecalciferol occurs with all types of cartilage and is also observed in incubations of cultured chondrocytes. In the latter, the polar 25-hydroxycholecalciferol derivative is detected as early as 1 h after addition of 25-hydroxycholecalciferol. Two findings suggest that the polar derivative of 25-hydroxycholecalciferol produced by cartilage is 24,25-dihydroxycholecalciferol: 1) the cartilage derivative and 24,25-dihydroxycholecalciferol (synthetic and biosynthetic) comigrate during Sephadex LH-20 and high liquid pressure chromatography; and 2) both the cartilage derivative and 24,25-dihydroxycholecalciferol are sensitive to periodate treatment.

Animals↗

[Effects of the main derivatives of vitmain D in 3 siblings with "pseudo-deficiency" rickets].

Three siblings, respectively 20, 16 and 12 years old, presented with hypocalcemic vitamin D resistant rickets (Prader's type). Their clinical history included several periods of spontaneous cessation of therapy, with severe relapses. Since 1973, treatment was strictly observed, allowing to test the therapeutic effects of 25 OH D3, 1-25 (OH) 2 D3 and 1-alpha (OH) D3. The clinical effects are reported as well as biochemical data. Among them, an inactive form of hyperparathyroidism is emphasized, which may resemble some cases of pseudohypoparathyroidism. Simultaneous resistance to exogenous PTE was also demonstraded.

Adolescent↗

The in vitro production and activity of 24, 25-dihydroxycholecalciferol in cartilage and calvarium.

Previously reported results from our laboratory have indicated that 24, 25-dihydroxycholecalciferol can be formed in vitro during incubations of cartilage tissue or cartilage cells with 25-hydroxycholecalcified. They have also demonstrated the high potency of this dihydroxymetabolite of vitamin D3 in stimulating in vitro the sulfate incorporation into proteoglycans of cartilage cells in culture and in decreasing in vitro the parathyroid hormone action on rat calvarium phosphatases activities. The present report shows that 24, 25-)OH)2 D3 can also be produced during rat calvarium incubations with 25-hydroxycholecalciferol and that therefore calvarium as well as cartilage might be both a site of formation and a site of action for 24, 25-(OH)2 D3. The review of recent experimental and clinical investigations strongly suggests that this metabolite has a physiological significance and may be specifically active on some parameters of bone mineralization. Further studies on the cartilage and calvarium abilities to convert 25-hydroxycholecalciferol into 24, 25-(OH)2 D3 shows that this transformation occurs in the mitochondrial fraction but that it does not seem modified by factors known to control the 25-hydroxycholecalciferol metabolism in the kidney. Finally the analysis of experimental and clinical results published so far does not yet bring enough information to understand the significance of this extrarenal metabolism of 25-hydroxycholecalciferol.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗