Biomedical subjects

M Garabedian

Publications and source records attributed to M Garabedian.

At least 37 records · Page 2Linked to original sources

PubMed1996

Evidence for a vitamin D paracrine system regulating maturation of developing rat lung epithelium.

Rat fetal lung is a target tissue for 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25 (OH)2 D3]. We have identified the cells that respond to the hormone and tested the hypothesis that the lung is also a source of 1 alpha,25(OH)2D3. We found that 1) at the end of pregnancy (days 20-21) alveolar type II cells (ATII) bore 1 alpha,25(OH)2D3 receptors and responded to the hormone. Incubating these cells with 10(-9) M 1 alpha,25(OH)2D3 for 48 h stimulated the synthesis (87.3 +/- 9.1%) and release (61.7 +/- 6.1%) of disaturated phosphatidylcholine; 2) EB-1213, a 1 alpha,25(OH)2D3 analogue with low calcemic activity, had similar effects on ATII; 3) neither fetal lung fibroblasts nor neonatal ATII (day 2 postpartum) expressed 1 alpha,25(OH)2D3 receptors; and 4) in contrast, fetal lung fibroblasts taken on days 19-22 of gestation converted [3H]25(OH)D3 to [3H]1 alpha,25(OH)2D3, whereas ATII and skin fibroblasts did not. These findings suggest that 1 alpha,25(OH)2D3 is a local mediator of epithelial-mesenchymal cell interactions in the developing rat lung and that 1 alpha,25(OH)2D3 or EB-1213 might be therapeutically useful in treating the respiratory distress syndrome of premature neonates.

Animals↗

PubMed1995

Influence of spontaneous calcium intake and physical exercise on the vertebral and femoral bone mineral density of children and adolescents.

Peak bone mass is determined mainly by genetic-ethnic factors, but environmental factors such as calcium intake and physical activity during childhood and adolescence could play a role. We have measured the bone mineral density (BMD) of 151 healthy children and adolescents, ages 7-15.3 years. Density was measured by dual X-ray absorptiometry (DXA) at two sites (lumbar verterbrae L1-L4 and the upper femur), and the data were analyzed in terms of the height, weight, sexual maturation, spontaneous calcium intake, and physical activity. Of the children, 57-71% had calcium intakes below 1000 mg/day. BMD increased with pubertal maturation from 0.68 +/- 0.08 to 0.92 +/- 0.09 g/cm2 (vertebral bone density, VBD) and from 0.87 +/- 0.10 to 1.03 +/- 0.09 g/cm2 (femoral bone density, FBD) between Tanner stage 1 and 5. Multiple regression analysis showed that body weight and Tanner stage were main determinants of bone density when expressed as g/cm2. The weekly duration of sports activity also influenced both the vertebral (p < 0.001) and femoral (p = 0.01) sites, especially in girls and during puberty. Dietary calcium appeared to be another independent determinant of BMD, especially before puberty, at the vertebral (p = 0.02) site. Most important, dietary calcium was found to be the main determinant of vertebral mineral density, when expressed as z score, in both sexes. Moreover, 93% of the 28 children with low vertebral z score values (below -1) and 84% of the 31 children with low femoral z score values (below -1) had dietary calcium intakes below 1000 mg/day.

Absorptiometry, Photon↗

PubMed1995

Markers of bone remodeling in the elderly subject: effects of vitamin D insufficiency and its correction.

The elderly subject is prone to both vitamin B insufficiency and calcium insufficiency due to a low calcium intake and calcium malabsorption. These two alterations may lead to secondary hyperparathyroidism, and thus to increased bone loss. We investigated 72 elderly subjects (16 men and 56 women) with vitamin D insufficiency and 25 healthy elderly women with normal vitamin D status, with respect to their indices of calcium metabolism and of bone remodeling: serum total alkaline phosphates (phosphatases), bone AP (BAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), urine hydroxyproline (HYP), and the 3-OH-pyridinium derivatives pyridinoline (PYD) and deoxypyridinoline (DPD), which are new markers of bone resorption. We then studied the modifications of these markers in the patients with vitamin D insufficiency at 3 months and 6 months after onset of a daily vitamin D and calcium supplementation. When compared with elderly subjects with normal vitamin D status, patients with vitamin D insufficiency had increased intact parathyroid hormone (iPTH) levels (60.1 +/- 10.2 vs 30.2 +/- 4.5, p < 0.001) and a high bone turnover as reflected by increased values of most serum and urine markers of bone remodeling. PYD and DPD levels were significantly correlated with all indices of bone turnover, unlike HYP, which showed no correlation with bone formation markers (AP, BAP, and BGP). A daily supplement of 800 IU vitamin D3 and 1 g of elemental calcium increased 25(OH)D levels and induced a dramatic decrease of iPTH levels; at 3 and 6 months, the mean iPTH level decreased by 50% (p < 0.0001), reaching the mean value of healthy vitamin D sufficient elderly women. All markers of bone turnover, except TRAP, decreased significantly at 3 and 6 months. The PYD/DPD ratio increased significantly at 3 and 6 months. The decrease of bone markers was more marked in patients with more severe hyperparathyroidism, the greatest variations being obtained with BAP (45%, p = 0.006) and DPD (43%, p = 0.036) levels. Most markers of bone remodeling are increased in elderly subjects with vitamin D insufficiently and vary with its correction. However, BAP and DPD are the most sensitive indicators of increased bone turnover due to secondary hyperparathyroidism.

Aged↗

PubMed1995

[Saccharomyces boulardii fungemia in a patient with severe burns].

A case of Saccharomyces boulardii fungaemia in a burn patient is reported. S. boulardii was administered in order to improve the digestive tolerance to enteral nutrition. After a surgical procedure, a sepsis syndrome occurred, with a white blood cell count increase, abdominal meteorism and respiratory insufficiency, associated with seven blood cultures positive to S. boulardii. Digestive translocation of the yeast seems to be the most likely origin of this fungaemia. Some fungaemias from S. boulardii have been published. However it is not usual to find such severe clinical features as in our case which leads us to reconsider the therapeutic use of S. boulardii in situations including a gastrointestinal tract suffering.

Adolescent↗

PubMed1995

Evaluation of a new solid formulation of calcium and vitamin D in institutionalized elderly subjects. A randomized comparative trial versus separate administration of both constituents.

Supplementation with 800 IU of vitamin D and 1 g of calcium each day is recommended in institutionalized elderly subjects to prevent secondary hyperparathyroidism and its adverse skeletal effects. An original formulation (IDEOS) combining vitamin D and calcium has been developed for use in this end. The aim of this study was to determine whether administration of this association, of which each tablet contains 500 mg calcium and 400 IU vitamin D3, produces the same beneficial effects on laboratory parameters as separate administration of both active agents. A multicenter randomized study was conducted in 91 elderly institutionalized subjects (mean age 83.1 years) who had vitamin D deficiency [25-(OH)D < 6 ng/ml] without severe renal failure. Subjects were randomly assigned to one of the two treatment groups. Treatment duration was six months. One group (G1, n = 46) received one tablet of the new formulation twice daily. The other (G2, n = 45) received 8 drops of vitamin D3 (800 IU/day) and one calcium carbonate 500 mg tablet twice daily. Blood tests were carried out at inclusion and after three and six months of treatment. In group G1, plasma 25-(OH)D levels increased from 2.6 ng/ml at inclusion to 14.6 ng/ml at month 6 (p < 0.001), and iPTH fell from 63.2 pg/ml at inclusion to 33.8 pg/ml at month 6 (p < 0.001). In group G2, 25-(OH)D rose from 2.8 ng/ml at inclusion to 13.5 ng/ml at month 6 (p < 0.001), and iPTH fell from 55.4 pg/ml at inclusion to 32.5 pg/ml at month 6 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Prevalence and biological consequences of vitamin D deficiency in elderly institutionalized subjects.

The prevalence of vitamin D deficiency was evaluated in a population of elderly institutionalized subjects in seven long-term geriatric care facilities in France (Amiens, Francheville, Ivry, Lille, Montpellier, Oissel and Villejuif). Residents whose functional capability was relatively good were entered into the study. There were 126 patients (99 females and 27 males) with a mean age +/- SD of 84 +/- 6.6 years. All subjects had been institutionalized for over six months and were capable of walking at least as far as the dining room. None had received vitamin D or other compounds known to affect the metabolism of phosphorus and calcium within six months before the study. Vitamin D status was evaluated by determining serum 25 hydroxyvitamin D (25 OH D) levels using a radiocompetition assay after extraction and chromatographic separation. Mean serum 25 OH D was 3.17 +/- 2.52 ng/ml (median 2.5). Eighty-five per cent of subjects had serum 25 OH D values of less than 5 ng/ml and 98% had values under 10 ng/ml, which is the cutoff usually taken to define vitamin D deficiency. Mean serum levels of intact parathyroid hormone were increased approximately two-fold as compared with values in healthy adults (70 +/- 39 pg/ml versus 33 +/- 12 pg/ml). Biochemical markers for bone formation (alkaline phosphatase, osteocalcin) and bone resorption (TRAP, hydroxyproline, pyridinoline) were all increased, with mean values 1.4-fold to 3.4-fold those seen in healthy adults. Serum 25 OH D levels were negatively correlated with serum intact parathyroid hormone levels (r = 0.41; p < 0.0001). Serum intact parathyroid hormone levels were positively correlated with alkaline phosphatase activity (r = 0.30; p < 0.001) and serum osteocalcin levels (r = 0.36; p < 0.0001) and negatively correlated with corrected serum calcium levels (r = -0.20; p < 0.02). Conclusion. Our data demonstrate that severe vitamin D deficiency is present in virtually all elderly institutionalized subjects and is accompanied with secondary hyperparathyroidism responsible for increases in markers of bone remodeling. Routine vitamin D supplementation is warranted in elderly institutionalized subjects.

Adult↗

PubMed1994

[Nutrition proteins and muscular catabolism in severely burnt patients. Comparative effects of small peptides or free amino acids].

The beneficial effects of high caloric and protein enteral diet on wound healing and prevention of infection in severely burned patients is well documented. However, the relative proportion of each nutrient and especially the form of nitrogen supply have not yet been clearly established. The aim of this study was to compare, in severely burned patients, the efficiency of a partial protein hydrolysate and free amino acid formula during a 15-day enteral feeding. Twenty burned patients ranging in age from 18 to 67 years with a mean burn size of 40 +/- 12% of total body surface area, of which 31 +/- 14% was deep dermal, were studied prospectively and randomised in two groups. Group A received the free amino acid diet which was obtained by hydrolysis of the protein hydrolysate given to Group B (60% small peptides). All diets contained a nitrogen source of similar amino acid composition. Nitrogen balance was measured daily and serum protein concentrations were determined on days 0, 4, 8, 11 and 15. Anthropometric parameters, urinary 3 methylhistidine/creatinine ratio and plasma amino acid concentration were assessed on days 0, 8 and 15. Daily and cumulative nitrogen balance at D15 did not differ between the two groups. In group A, the circulating visceral proteins increased at all times of the study without decrease of acute phase reactant, whereas only transthyretin and retinol binding protein increased at D11 and D15 with a significant decrease of C-reactive protein at the same time in the other group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Cultured circulating mononuclear cells from osteopetrotic infants express the osteoclast-associated vitronectin receptor and form multinucleated cells in response to 1,25-dihydroxyvitamin D3.

Malignant osteopetrosis is characterized by impaired osteoclast activity. Osteoclasts derive from hematopoietic stem cells. In osteopetrosis, marrow cavities fail to develop, resulting in extramedullary hematopoiesis and the presence of stem cells in the bloodstream. Resistance to 1,25-(OH)2D3 may be involved in the pathogenesis of the disease. Sensitivity to 1,25-(OH)2D3, calcitonin sensitivity, and expression of the osteoclast-associated vitronectin receptor (VR) was examined in cultures of circulating mononuclear cells of seven osteopetrotic infants (1.5-6 months old). Since peripheral blood from age-matched children contains few stem cells, umbilical cord blood was used as control. Mononucleated cells were isolated by the Ficoll-Hypaque method and cultured (10(6) cells per ml) in alpha-MEM containing 20% horse serum in presence or absence of added 1,25-(OH)2D3. VR was identified by immunochemical staining with MAb 23C6. 1,25-(OH)2D3 at 10(-8) M significantly stimulated the formation of multinucleated cells (MNC) in cultures from all osteopetrotic patients and cord blood samples. Cells from three of five patients responded to 10(-9) M 1,25-(OH)2D3, the minimal stimulatory concentration for cord blood. Salmon calcitonin (100 ng/ml) partially inhibited the 10(-8) M 1,25-(OH)2D3-induced MNC formation in cultures from three of six patients and in cultures of all cord blood samples. In both types of cultures mononuclear cells and MNC cross-reacted with MAb 23C6, and 1,25-(OH)2D3 concentration did not influence the number and percentage of these cells. This study does not support the hypothesis of 1,25-(OH)2D3 resistance in osteopetrotic infants and shows that mononuclear cells expressing VR, possibly osteoclast progenitors, develop in cultures of circulating mononuclear cells from these infants. 1,25-(OH)2D3 may not be closely involved in VR expression.

Bone Resorption↗

PubMed1993

Maturational changes induced by 1 alpha,25-dihydroxyvitamin D3 in type II cells from fetal rat lung explants.

Specific binding sites for 1 alpha,25 dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] localized to type II pneumocytes have been evidenced in fetal rat lung at the end of gestation, suggesting a role for vitamin D3 in the control of lung maturation. In this study, we describe the morphological changes that occur in lung explants from 18-day-old rat fetuses grown for 1 and 2 days in control conditions and in the presence of 1 alpha,25(OH)2D3 (10(-9) M) or dexamethasone (10(-7) M). Point counting and planimetric measurements on light and electron micrographs show that 1 alpha,25-(OH)2D3 1) dramatically decreases the mean glycogen content of type II cell profiles between days 1 and 2 of the culture, suggesting an acceleration of the glycogenolytic processes normally occurring at that stage and 2) does not change the intracellular osmiophilic lamellar body (OLB) content of cell profiles, but increases the amount of intraluminal surfactant by 126% when expressed as surfactant clusters surface area/section surface area and by 129% when expressed on a per cell basis, suggesting a stimulation of surfactant synthesis and secretion. By contrast, dexamethasone increases the mean intracellular OLB content of type II cell profiles by 306% and decreases the relative surface area of secreted material by 53 and 73%. In conclusion, 1 alpha,25(OH)2D3 accelerates the physiological maturation of fetal rat type II pneumocytes and could represent a key factor for the onset of normal lung function at birth.

Animals↗

PubMed1993

[Neonatal cardiac failure secondary to hypocalcemia caused by maternal vitamin D deficiency].

BACKGROUND: Heart failure is a rare manifestation of neonatal hypocalcemia. This paper describes such a case resulting from maternal vitamin D deficiency. CASE REPORT: A full-term boy, born in December after a normal pregnancy, was admitted at the age of 6 weeks because of dyspnea that appeared during suckling. Examination showed heart failure. Electrocardiogram showed that the corrected QT-interval was lengthened (0.54 s, normal < 0.45 s). Echocardiogram showed dilated, hypokinetic myocardiopathy. His serum calcium concentration was low (1.40 mmol/l) and phosphate was high (2.8 mmol/l); his alkaline phosphatase was 513 Ul/l. His blood PTH concentration was high (120 pg/ml) and his 25 (OH) D was low (5 ng/ml). The patient was given calcium (1 g/m2/day) and 1.25 (OH)2 D (2 micrograms/day orally). His serum calcium returned to normal within 4 days, and his cardiac abnormality was resolved within 3 months. His mother's blood 25 (OH) D concentration was very low (3 ng/ml), 6 weeks after birth. CONCLUSION: Neonatal hypocalcemia appears to have been compounded in this case by a maternal vitamin D deficiency. Hence, all pregnant women at risk of deficiency should be given vitamin D.

Calcium↗

PubMed1993

[Antenatal form of Bartter's syndrome].

Six cases of tubular disorder of antenatal onset responsible for biological manifestations characteristic of Bartter syndrome and severe hypercalciuria are reported. In all six cases, severe hydramnios occurred during pregnancy between the 26th and 28th week after the last menstrual period. All six patients were born prematurely; gestational age ranged from 20 to 35 weeks. Major polyuria with dehydration occurred immediately after birth. The amounts of water and sodium needed to compensate urinary losses ranged from 280 to 370 ml/kg/day and 25 to 43 mmol/kg/d, respectively, during the first two postnatal months. Decreased serum potassium levels and increased plasma levels of renin and aldosterone were seen in all six patients. Increased urinary excretion of calcium was evidenced during the first postnatal week in three cases. Urinary calcium excretion in the six patients ranged from 15 to 30 mg/kg/d. Nephrocalcinosis developed in all six patients and two patients developed urinary lithiasis. One patient died at one month of age from necrotizing enteropathy. The five remaining patients gradually developed severe growth failure with measurements between 4 and 5.5 SDs below the mean. These five patients had evidence of hyperparathyroidism including increased serum levels of parathyroid hormone (5/5), increased serum alkaline phosphatase activity (4/5), and roentgenographic bone changes (1/5). Ionized calcium assays performed in three of the five patients disclosed low values (range 1.25-1.47 mmol/l; mean = 1.35; normal values = 1.42-1.62), although total serum calcium levels were normal or high (range 2.16-2.98 mmol/l; mean 2.61; normal values = 2.45-2.65) probably as a result of chronic dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1992

Mineral metabolism in infants with malignant osteopetrosis: heterogeneity in plasma 1,25-dihydroxyvitamin D levels and bone histology.

A group of 16 infants, 2 weeks to 11 months old, with malignant osteopetrosis were investigated to examine their vitamin D metabolism and parathyroid function. Bone biopsies from 6 children were studied by light microscopic histomorphometry and by electron microscopy. Considerable heterogeneity existed among the patients with respect to the parameters reflecting mineral metabolism and with respect to the histological manifestations of the disease. The most constant findings were as follows. Immunoreactive parathyroid hormone (iPTH) was elevated in all children, except in 1 patient who had tubular acidosis, and plasma calcium was low or normal, suggesting skeletal resistance to PTH. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] was not constantly elevated and appeared to depend on plasma phosphorus, as both parameters were negatively correlated (r = 0.704, p less than 0.01). Osteoblast activity, as evaluated by circulating alkaline phosphatase and osteocalcin and osteoblast number, measured for 6 children by bone histology, were not increased, despite hyperparathyroidism, suggesting PTH resistance or defective osteoblasts. Osteoclasts could be detected in 5 of the 6 children who had a biopsy. Osteoclast number (5.7-13.3% of bone surface) was normal or mildly increased, and marrow spaces were relatively well developed in 4 patients, whereas 1 child had markedly increased osteoclast number (28.3% of bone surface) and reduced marrow cavities. These 5 children received transplants, and engraftment occurred in all, except in the "hyperosteoclastic" patient. Further studies are necessary to establish the prognostic significance of this histologic feature.

Alkaline Phosphatase↗

PubMed1992

Non-aluminic adynamic bone disease in non-dialyzed uremic patients: a new type of osteopathy due to overtreatment?

Adynamic bone disease, characterized by a low bone formation rate with normal or reduced amount of unmineralized osteoid, is supposed to be the consequence of aluminum intoxication in uremic patients. However, the emergence of adynamic bone disease has been recently reported in hemodialyzed patients in the total absence of aluminum overload. This study was aimed to assess whether such a histological pattern of adynamic bone disease was already present in uremic patients not yet on dialysis. Twenty-seven asymptomatic uremic patients (mean age +/- SD 43 +/- 10 years, mean creatinine clearance 19 +/- 3 ml/mm) were studied and bone biopsies were repeated in 16 of them after 18 +/- 10 months of treatment with oral calcium carbonate (1-3 g of elemental calcium/day) and calcidiol (21 +/- 14 micrograms/day). None of the patients received aluminum hydroxide, and the search for bone aluminum deposits was negative in all patients both before and after treatment. Two patients fulfilled the criteria of adynamic bone disease on their post-treatment biopsies. They originated from patients classified as having normal bone histology before treatment. Comparison with the other patients showed that they had comparable plasma C-terminal PTH but higher plasma creatinine than patients with normal bone histology and lower plasma C-terminal PTH than patients with osteitis fibrosa but comparable plasma creatinine. The plasma levels of 1,25(OH)2D reached values above normal after treatment in these two patients. It is suggested that adynamic bone disease not related to aluminum intoxication can develop in uremic patients independently of dialysis, and is favored by a relative hypoparathyroidism for the degree of renal failure, possibly induced by elevated plasma concentrations of calcitriol.

Adult↗

PubMed1990

[Ionized calcium. An essential parameter for the study of calcium metabolism].

Calcium ions in plasma are either free (ionized calcium) or bound to protein and small anions. Ionized calcium is the physiologically active fraction. Several factors have recently been combined to change the measurement of ionized calcium from a specialized to a routine test. Reliable instrumentation, easy to maintain, is now available with simultaneous pH measurement. This paper focuses on both the analytical consideration required to perform reliable laboratory measurements and the clinical situations where ionized calcium has proved to provide a substantially different clinical interpretation than the measurement of total calcium.

Adolescent↗

PubMed1990

1,25(OH)2D2 production by T lymphocytes and alveolar macrophages recovered by lavage from normocalcemic patients with tuberculosis.

To compare extra-renal 1,25(OH)2D3 production in different types of granulomatous disease, and to identify the cell types responsible, we have evaluated the conversion of 25(OH)D3 in 1,25(OH)2D3 by uncultured cells recovered by bronchoalveolar lavage and blood mononuclear cells from normocalcemic patients with sarcoidosis and tuberculosis. 1,25(OH)2D3 was produced both by lavage cells (12/12 tuberculosis patients, 2/6 sarcoidosis patients) and blood mononuclear cells (3/5 tuberculosis patients, 0/3 sarcoidosis patients) from patients but not controls, but significantly greater amounts were produced by lavage cells from tuberculosis patients than those of sarcoidosis patients (P less than 0.001). 1,25(OH)2D3 production by lavage cells from tuberculosis patients correlated with the number of CD8+ T lymphocytes present but not other cell types. T lymphocytes appeared to be an important source of 1,25(OH)2D3 production, since purified T lymphocytes from all patients with tuberculosis produced 1,25(OH)2D3, and 1,25(OH)2D3 production by these cells correlated closely with that produced by unseparated lavage cells. Because 1,25(OH)2D3 can improve the capacity of macrophages to kill mycobacteria, our results support the conclusion that macrophage-lymphocyte interactions, mediated at least in part by 1,25(OH)2D3, may be an important component of a successful antituberculous immune response.

Adult↗

PubMed1990

1,25-dihydroxyvitamin D3 receptors in rat lung during the perinatal period: regulation and immunohistochemical localization.

We have previously reported that in contrast to what has been described in adult lung, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has specific binding sites in rat fetal lung at the end of gestation, and it stimulates in vitro the phospholipid biosynthesis and surfactant release from fetal rat type II pneumocytes. In the present study an immunohistochemical technique using a rat monoclonal antibody (9A7 gamma) and binding studies were carried out on fresh lung tissues from fetal and newborn rats during the perinatal period to identify the cell(s) directly responsive to 1,25-(OH)2D3 in fetal lung and to look for a down-regulation of the 1,25-(OH)2D3 receptors in the perinatal period. We also searched for a regulation of 1,25-(OH)2D3 binding to fetal lung by 1,25-(OH)2D3 itself and by factors known to affect lung maturation or be involved in parturition. Our results suggest that 1) fetal type II pneumocytes are target cells for 1,25-(OH)2D3; 2) a physiological down-regulation of the 1,25-(OH)2D3 receptors in rat lung occurs in the perinatal period, starting a few hours before birth and lasting at least up to the fifth day of life; and 3) the capacity of rat fetal lung to bind 1,25-(OH)2D3 can be modulated in vitro by different hormones; a small inhibitory effect is observed with oxytocin (100 microU/ml), while PRL (10(-8) M), T4 (10(-6)-10(-10) M), 1,25-(OH)2D3 (10(-9)-10(-10) M), and, to a lesser extent, dexamethasone (10(-7) M) induce a 2- to 4-fold increase in the number of 1,25-(OH)2D3 receptors without altering the binding affinity of receptor for 1,25-(OH)2D3.

Animals↗

PubMed1990

[Vitamin D supplementation in institutionalized elderly. Effects of vitamin D3 (100,000 IU) orally administered every 3 months on serum levels of 25-hydroxyvitamin D].

A clinical trial carried out during the autumn/winter season in 46 institutionalized elderly subjects (35 women, 11 men) (group mean age = 83 +/- 2 years) revealed a severe deficiency in vitamin D in these subjects (25-hydroxyvitamin D level less than or equal to 3 ng/ml). After oral administration of 100,000 IU of vitamin D3, an increase in 25-hydroxyvitamin D levels above the 10 ng/ml threshold was observed and maintained for three months. A second dose, administered after 3 months, made it possible to sustain this level. No sign of toxicity was detected, notably no trace of hypercalcemia. In contrast, no change in the deficit (25-hydroxyvitamin D level less than or equal to 3 ng/ml) was seen in the placebo population. Three-monthly administration of the moderate dosage of 100,000 IU of vitamin D3 all year round would offer a simple, effective and risk-free system to counteract vitamin D deficiency in the elderly and of preventing the risk of osteomalacia, thus reducing the incidence of fractures.

Administration, Oral↗

PubMed1989

Stimulatory effect of 1,25-dihydroxyvitamin D3 on the glucose-6-phosphate dehydrogenase activity in the MCF-7 human breast cancer cell line.

Human breast cancer cell lines have been shown to possess high affinity receptors for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and their growth is inhibited by this steroid. The present study examines the effect of 1,25(OH)2D3 on the activity of glucose-6-phosphate dehydrogenase (G6PD) in cells of a human breast cancer cell line MCF-7. G6PD, an enzyme which controls the hexose monophosphate shunt, is elevated and sensitive to 17 beta-estradiol in breast tumors. G6PD activity was stimulated by 1,25(OH)2D3 in a dose-dependent manner at very low concentrations of steroid (10(-10)-10(-12) M). 1,25(OH)2D3 increased maximum velocity without modifying the affinity constant of the enzyme for glucose-6-phosphate.

Breast Neoplasms↗