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Biomedical subjects

L V Avioli

Publications and source records attributed to L V Avioli.

At least 19 recordsLinked to original sources
PubMed1992

Lateral dual-energy radiography: artifact error from rib and pelvic bone.

A lateral projection of the lumbar spine with dual-energy radiography (DER) may be a more sensitive tool for the detection of vertebral demineralization than the standard anterior-posterior (AP) DER measurement. The lateral view allows measurement of the vertebral body and selective measurement of the central trabecular compartment, excluding the majority of the cortical envelope and posterior vertebral elements. The lateral DER typically contains L2-4 in the region of interest. The present study was designed to investigate the frequency and bone mineral content (BMC) contribution of rib to the L2 vertebral body BMC measurement in a lateral view DER scan. In addition, the frequency of pelvic overlap of L4 was evaluated. All patients were scanned in the supine position. Abdominal CT images of L2 were examined in 20 women aged 28-82 years to determine the frequency of rib and pelvic interference. QCT images of L2 also were examined in an additional 35 women aged 20-82 years to further investigate the frequency of rib overlap and to calculate the potential contribution of rib superimposition to the L2 BMC in a lateral projection. Pelvic overlap of L4 occurred in 15% of the 20 cases reviewed. Rib overlapped the L2 vertebral body in 100% of the L2 images. The expected contribution of rib BMC to L2 BMC in a lateral DER scan was 10.4% on average. There was no relationship between the percentage of rib BMC contribution and age and relatively poor correlations between rib BMC and that of either the vertebral body or the central trabecular compartment of L2. We conclude that supine positioning allows routine inclusion of L3 and L4 in a lateral lumbar scan. Results also suggest that L2 should be excluded from DER scans on patients scanned in either the lateral decubitus or supine position.

Adult↗
PubMed1992

Characterization of osteoblast-like cells from normal adult rat femoral trabecular bone.

Osteoblast-like cell cultures have been established from the trabecular surfaces of normal adult rat femoral trabecular bone. The cultured cells responded to stimulation by parathyroid hormone (rPTH), with a rise in intracellular cAMP in excess of 25-fold while failing to respond to incubation with sCT. Furthermore, the osteoblast-like cells exhibited a high level of alkaline phosphatase expression, both histochemically and biochemically. Incubations with 1,25(OH)2 vitamin D3 increased the alkaline phosphatase activity by 50% and stimulated bone Gla-protein (BGP) synthesis. When the cell layers were supplemented with both 50 micrograms/ml ascorbic acid and 10 mM beta-glycerophosphate and allowed to grow past confluency for 3 weeks, they formed calcified ridges and multilayered nodules. Confirmation of the mineralization of an extracellular matrix was made by von Kossa staining. This simple isolation technique now facilitates the availability of normal adult rat osteoblastic cells for investigation of bone and mineral metabolism.

Alkaline Phosphatase↗
PubMed1992

Regulation of ornithine decarboxylase by parathyroid hormone in osteoblastic cell systems.

Parathyroid hormone (PTH) has been shown to induce osteoblastic activity via a complex signal transduction process which is mediated either by cAMP or cytosolic calcium ([Ca2+]i), or a combination thereof. One of the PTH functions in osteoblasts is the induction of ornithine decarboxylase (ODC) activity. We have analyzed the second messengers involved in this process. 8-Bromo cAMP, a cAMP derivative, enhanced ODC activity in UMR106-01 osteoblastic cell system. The calcium ionophore A23187 and the protein kinase stimulator phorbol-12-myristate 13-acetate did not alter ODC activity. ODC activity was increased by bPTH-(1-34), PGE1, and PGE2 which stimulated both cAMP and [Ca2+]i. In contrast, PTH-(2-34), propionyl bPTH-(2-34), bPTH-(3-34), bPTH-(7-34), and PGF2 alpha, which only enhanced [Ca2+]i but not cAMP, had no effect on ODC activity. Thus, the stimulation of ODC in UMR106 cells by PTH appeared to be mediated primarily via the cAMP signal transduction pathway, and the mere increase in intracellular calcium could not account for the stimulation of ODC activity. ODC mRNA level was found to be increased by PTH treatment. Therefore, translation of ODC may be stimulated by PTH. Moreover, PTH also stimulated ODC antizyme activity, suggesting that the ODC degradation rate was increased.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Successful treatment of low turnover osteoporosis resulting from prolonged reserpine therapy with intermittent calcitonin and phosphate therapy.

Coherence therapy, popularly known by the acronym ADFR (Activate, Depress, Free, Repeat), was designed to increase bone mass in osteopenic patients. Accordingly, we report a case of a hypogonadal male with histologically proven low bone turnover osteoporosis and a progressive vertebral fracture syndrome, who responded favorably to ADFR treatment with the use of salmon calcitonin and inorganic phosphate. Dramatic increments in bone mass were observed during a 68-month period of therapy. Serial quantitative computerized tomography demonstrated a 146% increase from baseline in bone mineral density for the first 30 months of treatment, and dual energy radiography yielded a 36.5% increase for the subsequent 31-68 months. Furthermore, no episode of fracture occurred since coherence therapy was initiated.

Adult↗
PubMed1992

Effect of estrogen and calcitonin on vertebral bone density and vertebral height in osteoporotic women.

Estrogen and calcitonin increase bone density of osteoporotic women, particularly on the axial skeleton. To verify whether the effect of these drugs might in part be biased by spurious increases in bone density due to radiologically irrelevant microfractures, and consequent subtle decreases in vertebral height, we followed the changes in vertebral bone density (VBD), assessed by quantitative computed tomography, in relation to vertebral height (VH) in 60 osteoporotic women. VH was measured as the sum of anterior, central and posterior heights of L1-L3 vertebral bodies on lateral radiographs. Patients received either salmon calcitonin (sCT: 50 IU subcutaneously three times per week, n = 18), hormonal replacement therapy (HRT: conjugated estrogen 0.625 mg/day, days 1-25, plus medroxyprogesterone acetate 10 mg/day, days 16-25 of each month; n = 21) or calcium alone (Ca: 1000 mg/day, n = 21). After 1 year, VBD increased in the HRT group (+5.0 +/- 1.9%, p = 0.010), did not change significantly in the sCT group (+3.3 +/- 2.3%, p = 0.167), and decreased by 6.1 +/- 1.0% (p less than 0.001) in the Ca group. By analysis of variance, the changes induced by HRT and sCT were significantly different from those observed in the Ca group (F = 7.982, p less than 0.001). VH decreased slightly in all three subsets of patients (-0.9 +/- 0.5% in sCT, -1.5 +/- 0.3% in HRT, -0.1 +/- 0.5% in Ca), but these changes were not significantly different between groups (F = 2.545, p = 0.081).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Estrogen status and heredity are major determinants of premenopausal bone mass.

To analyze their relative effects on premenopausal bone mass, we have studied the impact of lifelong estrogen exposure, assessed by an estrogen score (ES; computed on age at menarche, average length of menstrual cycles since menarche, and use of birth control pills), heredity, and some environmental factors on vertebral bone density (VBD), of 63 premenopausal women (age, 19-40 yr). Compared with women with normal bone density (Z score > -1), subjects with low VBD (Z score < -1) had significantly lower ES (15.1 +/- 3.9 vs. 18.7 +/- 2.4, P = 0.001), higher age at menarche (13.8 +/- 1.7 vs. 12.6 +/- 1.4 yr, P = 0.005), and lower serum estradiol (46.9 +/- 37 vs. 86.6 +/- 57 pg/ml, P = 0.023) and estrone levels (107.4 +/- 60 vs. 178.8 +/- 9.0 pg/ml, P = 0.05). Likewise, women in the lowest quartile for VBD had significantly lower ES (15.3 +/- 4.5 vs. 18.1 +/- 2.7, P = 0.006) and higher age at menarche (13.9 +/- 1.9 vs. 12.8 +/- .4, P = 0.02) than those in the upper three quartiles. A higher proportion of subjects with irregular menses (52 vs. 23%, P = 0.03) and a positive family history of osteoporosis (86 vs. 61%, P = 0.04) was found in the low VBD group compared with subjects with normal VBD. VBD correlated positively with ES (r = 0.44, P = < 0.001) and negatively with age at menarche (r = -0.30, P = 0.03) by simple linear regression, whereas no correlation was found between VBD and age, body mass index, parity, lactation, physical activity, sunlight exposure, and dietary calcium and vitamin D intakes. The correlation between VBD and ES improved after correcting for the effect of all the other variables by partial correlation analysis (Pearson partial r = 0.57, P = < 0.01), which also disclosed a significant contribution of dietary calcium to VBD. However, ES was the only significant independent determinant of VBD, by stepwise multiple regression analysis (R2 = 0.24). Therefore, premenopausal estrogen exposure, and possibly genetic predisposition, rather than environmental factors, are the major determinants for the development of peak bone mass before menopause.

Adult↗
PubMed1992

Structure-function relationship of parathyroid hormone: activation of phospholipase-C, protein kinase-A and -C in osteosarcoma cells.

Recent evidence indicates that after PTh interaction with its receptor, both protein kinase-A (PKA) and protein kinase-C (PKC) are activated. To investigate the relationship between PTH structure and protein kinase stimulation, we have analyzed the effects of synthetic PTH fragments on PKA and PKC in the rat osteogenic sarcoma cells, UMR 106-01. Activation of PKA by 10(-7) M bovine (b) PTH-(1-34) was maximal (2.7-fold of control) at 5 min and remained elevated 15 min after hormone exposure. bPTH-(2-34), at equimolar doses, also stimulated PKA, but with a lower potency (1.4-fold of control), whereas propionyl bPTH-(2-34) [pbPTH-(2-34)], bPTH-(3-34), [Tyr34]bPTH-(7-34) amide [bPTH-(7-34)], and bPTH-(30-34) were ineffective. On the other hand, translocation of PKC activity from the cytosol to the membrane after exposure to bPTH-(1-34) was transient, with a peak at 1 min (1.9-fold of control), and returned to basal levels after 5 min. Other fragments, bPTH-(2-34), pbPTH-(2-34), bPTH-(3-34), and bPTH-(7-34), were also active on PKC, with relative potencies of 81%, 67%, 62%, and 51% of bPTH-(1-34), respectively, whereas bPTH-(30-34) was inactive. bPTH-(1-34), bPTH-(2-34), pbPTH-(2-34), and bPTH-(3-34) also induced inositol 1,4,5-trisphosphate production, with a potency order of 1.6-, 1.6-, 1.5-, and 1.6-fold over the control value, respectively, thus indicating activation of phospholipase-C. Neither bPTH-(7-34) nor bPTH-(30-34) caused a statistically significant increase in inositol 1,4,5-trisphosphate production. These results demonstrate that PTH signal transduction through the two different pathways can be dissociated; while activation of the cAMP/PKA system requires amino acids 1 and 2, the phospholipase-C/PKC system is coupled to a longer domain of the hormone's N-terminus.

Animals↗
PubMed1992

Heterogeneous intracellular free calcium responses to parathyroid hormone correlate with morphology and receptor distribution in osteogenic sarcoma cells.

The osteogenic sarcoma cell line UMR 106-01 exhibits heterogeneous morphology and hormone response in subconfluent monolayer cultures. In these studies we have explored the correlation between morphological profiles and patterns of cytosolic calcium [Ca2+]i response to PTH and other agonists in single UMR 106-01 cells loaded with the Ca(2+)-sensitive fluorescent indicator, fura-2. Realtime recording of [Ca2+]i revealed that PTH (10(-7) M) produced a transient [Ca2+]i rise in 19% of the cells studied. [Ca2+]i transients were also induced by prostaglandins E2 and F2 alpha, and fetal bovine serum, but with different response frequencies (20%, 12%, and 58%, respectively). Spatial resolution of changes in [Ca2+]i by video image analysis revealed that the response to PTH was more frequent in large polygonal cells with long cytoplasmic processes and less common in smaller cells growing in clusters, whereas there was no clear subtype specificity for the effects of epidermal growth factor and fetal bovine serum on [Ca2+]i. Autoradiographic analysis of cell monolayers demonstrated a higher density of PTH-binding sites on cells with cytoplasmic extensions, whereas epidermal growth factor-binding sites were largely on colony-forming cells. Thus, the [Ca2+]i response to hormonal stimulation is heterogeneous within UMR 106-01 cell populations and within single cells, and it correlates with receptor density. This suggests that osteoblastic cells respond to PTH by activation of changes in [Ca2+]i only at certain specific steps during osteoblast development or stages of the cell cycle.

Animals↗
PubMed1992

Osteoporosis syndromes: patient selection for calcitonin therapy.

Synthetic calcitonin-salmon is a treatment option for older patients with postmenopausal osteoporotic syndromes. Some clinical trials reveal a simple suppression of annual bone-loss rates with calcitonin therapy, whereas others show significant dose-related increases in vertebral and long-bone mass. Response is greater in patients with high-turnover (type I) osteoporosis than in those with the low/normal (type II) form. Candidates for calcitonin-salmon therapy include older women with established vertebral fractures, those who are osteopenic by bone mass analysis, and those in need of preventive therapy because of an accumulation of risk factors.

Aged↗
PubMed1992

Bone maturation and resorption by peritoneal macrophages in noninsulin-dependent streptozocin-induced diabetes in the rat.

The existence of osteopenia in noninsulin-dependent diabetes mellitus (NIDDM) is controversial. In this regard rats with a diabetic condition that simulates NIDDM have normal bone mineral content. However, normal total mineral content in bones does not preclude abnormalities in more delicate functions in bones of rats with NIDDM (specifically, bone maturation and response of bone matrix to resorptive activity). To evaluate these functions, bone maturation was studied in tibias from 14-week old male and female rats with streptozocin-induced NIDDM and controls. The ability of macrophages to resorb bone was studied in bone particles that were obtained from femors of male rats with NIDDM and controls. The diabetic rats had the overt NIDDM condition for 8 weeks at the time of the study. We found that bone maturation/mineralization remained intact in the diabetic rats and that response of the bone particles that were obtained from their femors to the resorptive activity of macrophages was similar to that of the bone particles that were obtained from controls. These data suggest that in the rat, a diabetic condition that simulates NIDDM does not alter the physiologic functions of the bone matrix.

Analysis of Variance↗
PubMed1991

Regulation of skeletal remodeling by parathyroid hormone.

PTH is responsible for the maintenance of calcium homeostasis and normocalcemia. Secretion of PTH is stimulated or suppressed by perturbations in the serum calcium level. The calciotropic effects of PTH are mediated primarily by bone, where PTH-stimulated remodeling may release calcium to the extracellular fluid, and by the kidneys, where calcium reabsorption and phosphate excretion are increased. The effects of PTH in bone are bipolar: including regulation of multiple cell types, especially, both osteoblasts and osteoclasts, and stimulating both bone formation (anabolic effects) and bone resorption (catabolic) effects. The purpose of this review is to discuss the available data regarding PTH-regulated bone remodeling, the role of second messengers produced by polyphosphoinositide hydrolysis, the possible role of G proteins in regulating this reaction, and the biologic effects of activating this system. Greater insight into the complexities of parathyroid hormone-regulated bone remodeling are still required.

Animals↗
PubMed1991

Dissociation of second messenger activation by parathyroid hormone fragments in osteosarcoma cells.

PTH activates multiple second messengers in its target cells, but the level at which the hormonal signal splits into different pathways is still unknown. To achieve insights on this issue, we have studied the structure-function relationship of PTH by analyzing the effects of bovine PTH-(1-34) [bPTH-(1-34)] and PTH fragments truncated at the N-terminus on the intracellular calcium concentration [( Ca2+]i) and cAMP production in the rat osteogenic sarcoma cell line UMR 106-01. [Ca2+]i was measured in single cells using fura-2. When exposed to 10(-7) M bPTH-(1-34), 20% of the cells responded with a transient increase in [Ca2+]i of variable amplitude. Equimolar doses of bPTH-(2-34), propionyl bPTH-(2-34) [(pbPTH-(2-34)], and bPTH-(3-34) also transiently increased [Ca2+]i, whereas both [tyrosine34]bPTH-(7-34) amide [bPTH-(7-34)] and bPTH-(30-34) were ineffective. The amplitude of the [Ca2+] i transients was dose-dependent, with threshold concentrations of 10(-10) M for bPTH-(1-34) and bPTH-(2-34), and 10(-9) M for bPTH-(3-34). The response rate to the active peptides ranged between 10-30%, without a clear dose-relatedness. A second addition of 10(-7) M bPTH-(1-34) to cells prestimulated with equimolar doses of bPTH-(2-34), pbPTH-(2-34), or bPTH-(3-34) produced another transient, whereas after exposure to 10(-7) M bPTH-(1-34), the cells were completely desensitized to a second homologous stimulation, suggesting that the binding affinity of the truncated peptides for the PTH receptor is lower than that of the intact bPTH-(1-34) fragment. In addition, both bPTH-(1-34) and bPTH-(2-34) dose-dependently stimulated cAMP production, but the former was more potent (ED50 = 10(-9) vs. 10(-7) M, respectively). On the contrary, pbPTH-(2-34), bPTH-(3-34), and bPTH-(7-34) had no effect on cAMP. Pretreating the cells with pertussis toxin to enhance cAMP responses via inhibition of Gi potentiated the effect of bPTH-(1-34) and bPTH-(2-34) and disclosed weak but detectable agonist action of pbPTH-(2-34). These results indicate that specific domains of the PTH molecule are linked to activation of different second messenger pathways; while the first two amino acids are indispensable for activating the cAMP system, generation of the [Ca2+]i signal appears to involve a longer domain, including the amino acid residue in position 3.

Animals↗