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Biomedical subjects

D T Baran

Publications and source records attributed to D T Baran.

At least 37 records · Page 2Linked to original sources
PubMed1995

1 alpha,25-Dihydroxyvitamin D3 rapidly alters phospholipid metabolism in the nuclear envelope of osteoblasts.

1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) has been shown to increase cytosolic calcium and inositol triphosphate levels in rat osteosarcoma cells (ROS 17/2.8) and to increase nuclear calcium in these cells. To determine the mechanism(s) of 1 alpha,25-(OH)2D3-induced changes in nuclear calcium, the effect of the hormone on phospholipid metabolism in isolated osteoblast nuclei was assessed. 1 alpha,25(OH)2D3, 20 nM, increased inositol triphosphate levels in the nuclei after 5 min of treatment. The biologically inactive epimer, 1 beta,25-(OH)2D3, had no significant effect on inositol triphosphate levels. ATP, 1 mM, also increased inositol triphosphate levels in the isolated nuclei after 5 min. 1 alpha,25-(OH)2D3, 20 nM, increased calcium in the isolated nuclei in the presence but not in the absence of extranuclear calcium within 5 min. Nuclear calcium was also increased within 5 min by ATP, 1 mM, and inositol triphosphate, 1 mM. The effect of ATP on nuclear calcium was not additive with 1 alpha,25-(OH)2D3, suggesting that these two agents increase nuclear calcium in these osteoblast-like cells by similar mechanisms. In summary, 1 alpha,25-(OH)2D3 and ATP rapidly increase inositol triphosphate levels in nuclei isolated from ROS 17/2.8 cells. The hormone, the nucleotide, and the inositol phospholipid increase nuclear calcium. Thus, the 1 alpha,25-(OH)2D3 and ATP effects on nuclear calcium may be mediated by changes in phospholipid metabolism in the nuclei of these osteoblast-like cells.

Adenosine Triphosphate↗
PubMed1995

Bone mineral density changes in the forearm after immobilization.

This study determined the early natural history of disuse osteoporosis in the ulna and radius. Six women and 2 men (mean age, 48.5 years; range, 35-60 years) having surgery on their wrists or hands had bone mineral density determined by single energy xray absorptiometry at 4 sites of the distal radius and ulna before operation, at cast removal (mean, 4.9 weeks after surgery), and after an average of 4.7 weeks of remobilization and hand therapy. A control group of 4 men and 4 women (mean age, 35.6 years; range, 24-46 years) had bone mineral density measurements of both forearms taken initially and again 5 weeks later. The patients had significant loss in bone mineral density at the ulna and distal sites of the forearm after 4.9 weeks of immobilization. Loss of bone mineral density continued at all 4 sites even after 4.7 weeks of remobilization and hand therapy. Bone mineral density increased significantly at the ultradistal radius of the contralateral forearm (which was not operated on) after 4.9 weeks, but this gain was no longer significant after 4.7 weeks of remobilization of the surgically treated forearm, suggesting that increased activity of the nonimmobilized forearm increased bone mineral density at certain sites. No changes in bone mineral density were seen in the control group. Immobilization of the forearm after hand or wrist surgery significantly decreases bone mass in the distal radius and ulna.

Adult↗
PubMed1994

Nongenomic actions of the steroid hormone 1 alpha,25-dihydroxyvitamin D3.

Recent studies indicate that the vitamin D hormone, 1 alpha,25-dihydroxyvitamin D3 exerts rapid effects (seconds to minutes) in a variety of cell types. These rapid nongenomic actions in osteoblasts include effects on membrane voltage-gated calcium channels, phospholipase C activity, and the sodium/hydrogen antiport. Since the rapid effects occur in osteoblasts that lack the nuclear vitamin D receptor, it is postulated that the nongenomic responses to the hormone reflect interaction with a separate, membrane localized signalling system. Preliminary studies demonstrate the presence of a receptor on the membranes of osteoblasts that lack the nuclear vitamin D receptor. This membrane receptor recognizes 1 alpha,25-dihydroxyvitamin D3 and its inaction 1 beta epimer, but not 25-hydroxyvitamin D3. These rapid nongenomic actions generated by interaction with the membrane receptor modulate the effects of the hormone on gene transcription. Thus, the rapid nongenomic pathway may play a regulatory function in modulating the genomic pathways affected by 1 alpha,25-dihydroxyvitamin D3.

Animals↗
PubMed1994

Binding characteristics of a membrane receptor that recognizes 1 alpha,25-dihydroxyvitamin D3 and its epimer, 1 beta,25-dihydroxyvitamin D3.

The steroid hormone 1 alpha,25-dihydroxyvitamin D3 has been shown to exert rapid effects (15 s to 5 min) in osteoblasts. These effects occur in osteoblast-like cells lacking the nuclear vitamin D receptor, ROS 24/1, suggesting that a separate signalling system mediates the rapid actions. These non-genomic actions include rapid activation of phospholipase C and opening of calcium channels, pointing to a membrane localization of this signalling system. Previous studies have shown that the 1 beta epimer of 1 alpha,25-dihydroxyvitamin D3 can block these rapid actions, indicating that the 1 beta epimer may bind to the receptor responsible for the rapid actions in a competitive manner. We have assessed the displacement of 3H-1 alpha,25-dihydroxyvitamin D3 by vitamin D compounds, as well as the apparent dissociation constant of 1 alpha,25-dihydroxyvitamin D3 and its 1 beta epimer for the membrane receptor in membrane preparations from ROS 24/1 cells. Increasing concentrations of 1 alpha,25-dihydroxyvitamin D3, 7.25 nM to 725 nM, displaced 3H-1 alpha,25-dihydroxyvitamin D3 from the membranes with 725 nM of the hormone displacing 40-49% of the radioactivity. Similarly, 1 beta,25-dihydroxyvitamin D3, 7.25 nM and 72.5 nM, displaced 1 alpha,25-dihydroxyvitamin D3 binding while 25-hydroxyvitamin D3, 72.5 nM and 725 nM, did not. The apparent dissociation constant (KD) for 1 alpha,25-dihydroxyvitamin D3 was determined from displacement of 3H-1 alpha,25-dihydroxyvitamin D3 yielding a value of 8.1 x 10(-7) M by Scatchard analysis. The KD for the 1 beta epimer determined from displacement of 3H-1 beta,25-dihydroxyvitamin D3 was 4.8 x 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Single X-ray absorptiometry of the forearm: precision, correlation, and reference data.

The performance of a single X-ray absorptiometry (SXA) device incorporating an X-ray tube as a photon source was evaluated with respect to precision in vivo and in vitro, scan time, image quality, and correlation with an existing dual energy X-ray absorptiometry (DXA) device. SXA precision in vivo, expressed as a coefficient of variation (CV), was 0.66% for bone mineral content (BMC) and 1.05% for bone mineral density (BMD). Precision in vitro, based on 78 BMC measurements of a forearm phantom over 195 days, was 0.53%. Correlation with DXA at the 8 mm distal forearm site was high (r = 0.97 for BMC and r = 0.96 for BMD). A preliminary SXA reference database composed of 151 healthy Caucasian American women was developed to facilitate the interpretation of patient measurements. SXA scan time was 4 minutes and delivered a radiation exposure of 1.68 mrem. SXA image quality and spatial resolution were superior to SPA and comparable to DXA.

Absorptiometry, Photon↗
PubMed1994

Bone mineral density in the femur and lumbar vertebrae decreases after twelve weeks of diabetes in spontaneously diabetic-prone BB/Worcester rats.

The accumulated data indicate that bone mineral density (BMD) is decreased in humans with insulin-dependent diabetes mellitus. The purpose of this study was to prospectively determine sequential lumbar and femoral BMD utilizing dual energy X-ray absorptiometry in rats that spontaneously become diabetic to determine if weight and blood glucose control would prevent the diabetes-related bone mass changes. BMD of the lumbar spine and femur was measured prior to the onset of diabetes and at 3-week intervals after the diagnosis of diabetes for 12 weeks in 14 diabetes-prone BB/Wor rats (DP) and eight diabetes-resistant BB/Wor control rats (DR). At 12 weeks, the lumbar (0.238 +/- 0.013 vs 0.262 +/- 0.007 g/cm2, P < 0.001) and femoral (0.313 +/- 0.013 vs 0.343 +/- 0.013 g/cm2, P < 0.001) BMD were significantly lower in the DP rats despite significantly greater body weights (387 +/- 26 vs 329 +/- 46 g, P < 0.001) and plasma glucose levels of only 178 mg/dl. There was no difference in plasma values of calcium, phosphorus, osteocalcin, or tartrate-resistant acid phosphatase between groups or differences in osteoblast numbers in histologic sections. There was a significant (P < 0.001) decrease in plasma creatinine in the diabetic animals. The results indicate that in this animal model of type I diabetes, spine and femoral BMD do not increase comparable to control despite weight and blood glucose control. This would suggest that the diabetic condition itself affects bone mass in the absence of weight loss and poor blood glucose control.

Absorptiometry, Photon↗
PubMed1994

Responsiveness of gene expression markers of osteoblastic and osteoclastic activity to calcitonin in the appendicular and axial skeleton of the rat in vivo.

We have previously shown that calcitonin (CT), an inhibitor of bone resorption, increases vertebral, but not femoral bone density in the rat. To address the physiologic responses associated with these effects on bone mineral density (BMD), we assessed mRNA transcripts reflecting activities of osteoblasts (type I collagen, osteocalcin, osteopontin, and alkaline phosphatase), osteoclasts [tartrate-resistant acid phosphatase (TRAP)], and cell proliferation (histone H4) in the spine and femur of these rats. CT increased spine BMD while increasing type I collagen and decreasing TRAP and histone mRNAs. In the femur, where CT had no effect on BMD, it decreased type I collagen and histone H4 mRNA but did not affect TRAP. CT had no effect on the gene expression of osteocalcin, osteopontin, or alkaline phosphatase at either site. The results indicate that selective alterations in gene expression, as reflected by steady state mRNA levels, are consistent with the changes observed by BMD measurement, and can more clearly define the specific contribution from osteoblast and osteoclast activity. This study demonstrates a heterogeneity in response of the axial and appendicular skeleton to CT, reflected by alterations in gene expression that provide a basis for understanding the observed BMD responses to various pharmacologic interventions.

Acid Phosphatase↗
PubMed1994

Magnitude and determinants of premenopausal bone loss.

Bone loss prior to menopause may contribute to a woman's risk for fracture due to osteoporosis later in life. Most, but not all, longitudinal and cross-sectional studies suggest that bone mass decreases prior to menopause. This bone loss may be prevented by calcium supplementation. Heredity, exercise and menstrual status also have an impact on bone mass. Prevention of bone loss prior to menopause will allow women to enter menopause with a greater bone mass reducing their risk of subsequent fracture.

Adult↗
PubMed1994

Rapid actions of 1 alpha-25-dihydroxyvitamin D3 physiologic role.

The steroid hormone, 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-[OH]2D3), has been shown to exert actions on cells within seconds. The rapidity of these effects has led to the speculation that they reflect nongenomic actions of the hormone which involve interaction with membrane receptors. Moreover, these rapid effects appear to modulate the actions of the hormone on gene transcription, suggesting that the physiologic role of the rapid actions may involve the regulation of hormone induced gene activation.

Animals↗
PubMed1994

Osteoporosis: monitoring techniques and alternate therapies. Calcitonin, fluoride, bisphosphonates, vitamin D.

The woman at greatest risk for developing osteoporosis is of Northern-European heritage, petite, a smoker, and sedentary. She has a family history of osteoporosis, has a lifelong history of low dietary calcium intake, and has undergone an early menopause or an oophorectomy. This article reviews the epidemiology, pathophysiology, differential diagnosis and classification, monitoring techniques, and alternate therapy of osteoporosis.

Biomarkers↗
PubMed1993

1 alpha,25-Dihydroxyvitamin D3 rapidly increases nuclear calcium levels in rat osteosarcoma cells.

1 alpha,25-Dihydroxyvitamin D3 increases intracellular calcium in rat osteoblast-like cells that possess the classic receptor (ROS 17/2.8) as well as those that lack the classic receptor (ROS 24/1), indicating that a separate signalling system mediates this rapid nongenomic action. To determine the intracellular sites of this calcium increase, cytosolic and nuclear fluorescence (340 nm/380 nm ratio) were measured in Fura 2AM loaded ROS 17/2.8 cells using digital microscopy. Within 5 min, cytosolic fluorescence increased by 29% (P < 0.05) and nuclear fluorescence by 30% (P < 0.01) after exposure to 1 alpha,25-dihydroxyvitamin D3 (20 nM). This effect was blocked by the inactive epimer 1 beta,25-dihydroxyvitamin D3. In an individual cell, cytosolic and nuclear fluorescence increased gradually after 1, 3, and 5 min exposure to vitamin D. Nuclei were then isolated from ROS 17/2.8 cells to directly measure the hormone's effect on nuclear calcium. The calcium content of Fura 2AM loaded nuclei was not affected by increasing the calcium concentration in the incubation buffer from 50 nM to 200 nM. After 5 min, 1 alpha,25-dihydroxyvitamin D3, 20 nM, increased the calcium of isolated nuclei in medium containing 50 nM calcium and 200 nM calcium. 1 beta,25-dihydroxyvitamin D3, 20 nM, had no effect on nuclear calcium but blocked the 1 alpha,25-dihydroxyvitamin D3 induced rise in the isolated nuclei. The results indicate that the nuclear membrane of the ROS 17/2.8 cells contain calcium permeability barriers and transport systems that are sensitive to and specific for 1 alpha,25-dihydroxyvitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of gallium nitrate in vitro and in normal rats.

Gallium nitrate (GN) is an inhibitor of bone resorption and thereby may result in a change in coupled bone formation. In the present investigation the effects of GN on bone formation were studied in the rat osteosarcoma (ROS) 17/2.8 cell line and normal diploid rat osteoblasts (ROB) in vitro and the femur of rats treated in vivo, measuring mRNA levels for two osteoblast parameters, type I collagen, a marker of matrix formation, and osteocalcin, a bone specific protein and also histone H4, a marker of cell proliferation. GN, at 50 microM for 3 h, increased type I collagen mRNA levels by 132% in ROS 17/2.8 cells and by 122% in proliferating ROB cells. Osteocalcin (OC) mRNA levels were decreased by 61% in ROS 17/2.8 cells and by 97% in differentiated ROB cells. These changes occurred in the absence of any effects on cell proliferation. Seventy-day-old female rats were then treated with GN, 0.5 mg/kg/day, for 3 weeks. As previously reported, GN decreased serum calcium levels, but had no effect on lumbar or femoral bone density. In contrast to the in vitro effects, GN had no effect on type I collagen steady-state mRNA levels in the femur; however, it decreased OC steady-state mRNA levels in the femur by 58%. These results suggest that GN has similar in vitro effects in transformed and normal osteoblasts, while the collagen-stimulatory effects observed in vitro cannot be extrapolated to in vivo models. The consistent inhibition of osteocalcin in vitro and in vivo suggests a more specific target for GN that may relate to its effects in inhibiting bone resorption in normal rats.

Animals↗
PubMed1993

1 alpha,25-dihydroxyvitamin D3-induced changes in intracellular pH in osteoblast-like cells modulate gene expression.

1 alpha,25-Dihydroxyvitamin D3 exerts rapid nongenomic effects on rat osteoblast-like cells independent of the classic nuclear receptor. These effects include changes in phospholipid metabolism and cell calcium. Intracellular calcium itself has been proposed to regulate intracellular pH in osteoblast cell lines. The purpose of this study was to determine the effect of 1 alpha,25-dihydroxyvitamin D3 on intracellular pH, the relationship of changes in calcium to changes in pH, and the role of pH changes in genomic activation. 1 alpha,25-Dihydroxyvitamin D3 increased intracellular pH within 10 min in rat osteoblast-like cells, an effect that was inhibited by removal of extracellular sodium and by the biologically inactive epimer 1 beta,25-dihydroxyvitamin D3. The hormone increased intracellular calcium in Quin 2 loaded cells in the presence and absence of extracellular sodium. The 1 alpha,25-dihydroxyvitamin D3-induced increments in osteocalcin and osteopontin mRNA levels were abolished in sodium-free medium. The results indicate that 1 alpha,25-dihydroxyvitamin D3-induced increments in cellular calcium precede cell alkalinization and that these changes in intracellular pH may modulate steady-state mRNA levels of genes induced by vitamin D.

Aminoquinolines↗
PubMed1993

Na+/H+ exchange and PLA2 activity act interdependently to mediate the rapid effects of 1 alpha, 25-dihydroxyvitamin D3.

1 alpha, 25-Dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) has been shown to rapidly increase cytosolic calcium in freshly isolated and cultured rat hepatocytes. The rise in cytosolic calcium is dependent on phospholipase A2 (PLA2) activation and cell alkalinization through the Na+/H+ antiport system. To further characterize the rapid effects of 1 alpha, 25-(OH)2D3, cultured hepatocytes were treated with inhibitors of PLA2 and the Na+/H+ antiport system. 1 alpha, 25-(OH)2D3 treatment caused a 31-66% increase in [32P]lysophosphatidylinositol (LPI) and a 0.04 increase in pH within 5 minutes. Inhibition of the Na+/H+ antiport system with amiloride or removal of extracellular sodium abolished the 1 alpha, 25-(OH)2D3 rise in LPI. Inhibition of PLA2 with bromophenacylbromide also blocked the 1 alpha, 25-(OH)2D3-induced rise in [32P]LPI and cytosolic alkalinization in response to 1 alpha, 25-(OH)2D3. The data indicate that 1 alpha, 25-(OH)2D3 rapidly increases the activity of PLA2 and the Na+/H+ antiport system. The production of LPI is dependent on PLA2 activation and cell alkalinization through the Na+/H+ antiport system. It appears that the two events are interdependent in hepatocytes.

Acetophenones↗
PubMed1993

Etidronate inhibits the thyroid hormone-induced bone loss in rats assessed by bone mineral density and messenger ribonucleic acid markers of osteoblast and osteoclast function.

TSH-suppressive doses of thyroid hormone are associated with bone loss. We have previously reported that L-T4 decreases femoral, but not vertebral bone mineral density (BMD) in rats. As bisphosphonates are able to decrease bone resorption, especially in high bone turnover states, we investigated the potential effects of etidronate disodium (EHDP) on L-T4-induced bone loss in the rat model by assessing BMD and gene expression of osteoblast (osteocalcin, osteopontin, type I collagen, and alkaline phosphatase), osteoclast (tartrate-resistant acid phosphatase), and cell growth (histone) markers in the skeleton. L-T4 administered for 20 days decreased BMD in the femur, but had no effect on the lumbar spine. EHDP alone had no effect on femoral or vertebral BMD, but did prevent the L-T4-induced bone loss in the femur. L-T4 increased mRNA levels of alkaline phosphatase, tartrate-resistant acid phosphatase, and histone H4 in the femur, but not in the vertebrae. EHDP, which alone had no effect on gene expression in the femur or vertebrae, inhibited the effect of L-T4 on mRNA markers in the femur. The results demonstrate that EHDP can prevent the L-T4-induced decrease in femoral BMD in rats that is associated with the prevention of changes in mRNA markers of osteoclast and osteoblast function. EHDP and other bisphosphonate compounds may be useful in the prevention of thyroid hormone-induced bone loss in humans.

Animals↗
PubMed1992

Excessive L-thyroxine therapy decreases femoral bone mineral densities in the male rat: effect of hypogonadism and calcitonin.

Excess thyroid hormone decreases bone mineral density (BMD), a potential problem in managing patients with differentiated thyroid carcinoma and nontoxic goiter who require lifelong TSH-suppressive doses of thyroid hormone. We studied the effect of thyroid hormone excess on vertebral and femoral BMD and the role of hypogonadism in modulating this effect in a rat model. The potential role of calcitonin (CT) in preventing thyroid hormone-associated bone loss was also investigated. A total of 40 male Sprague-Dawley rats were divided into four groups. Groups 1 and 2 were orchidectomized (ORX); groups 3 and 4 were sham operated (SO). Groups 1 and 3 received 20 micrograms intraperitoneal L-thyroxine (L-T4) per 100 g body weight daily for 3 weeks; groups 2 and 4 received vehicle IP. Another 40 rats were divided into four groups. Groups 1 and 2 received L-T4, and groups 1 and 3 received CT, 2.5 U per 100 g body weight, subcutaneously (SC) daily for 3 weeks. BMD of the L4 and 5 and the right femur were measured by dual-energy x-ray absorptiometry at baseline and at the end of the study. Orchidectomy decreased femoral (P < 0.05) but not lumbar BMD. The administration of excess L-T4 decreased femoral (cortical) BMD in both SO (P < 0.05) and ORX rats (P < 0.05) without affecting lumbar (trabecular) BMD. CT increased lumbar BMD in both vehicle (P < 0.001) and L-T4-treated rats (P < 0.001). However, CT did not affect femoral BMD in vehicle-treated rats and did not prevent the L-T4-induced femoral bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗