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Biomedical subjects

L V Avioli

Publications and source records attributed to L V Avioli.

At least 181 records · Page 10Linked to original sources
PubMed1984

Acute, but not chronic, metabolic acidosis disturbs 25-hydroxyvitamin D3 metabolism.

Previous studies in vitamin D deficient animals showing that acidosis may impair the production of 1,25(OH)2D3 are in conflict with studies in humans which have not shown convincing disturbances of 25OHD3 metabolism during acidosis. We have investigated the effect on renal 25OHD3 1- and 24-hydroxylase of acid loading for periods of 24 hr to 21 days. Acid loading resulted in immediate and sustained decrements in arterial pH and bicarbonate and increments in blood-ionized calcium. Acute (24-hr) acid loading decreased 1- and increased 24-hydroxylase activity. After 6 days of acid loading, no effect on 1- hydroxylase activity was observed and that on 24-hydroxylase activity was reduced. By 21 days the effect of acidosis on 24-hydroxylase activity was no longer observed. The results show that acidosis disturbs 25OHD3 metabolism in the physiological vitamin D and calcium replete state as well as in the vitamin D deficient state, but only acutely. Our data are consistent with studies in humans and suggest that, while short-term disturbances of 25OHD3 metabolism occur early in acidosis, they are transient and may not be causally related to the development of metabolic bone disease during chronic acidosis.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1984

Calcium and osteoporosis.

It has become increasingly apparent that the pathogenesis of osteoporosis is complex, poorly understood, and ill-defined. Calcium deficiency and/or calcium malabsorption and the homeostatic response to this biological insult may ultimately prove to be one of the pivotal factors in conditioning or modulating the skeletal response to senescence. Until we know more about the prevention and potential reversibility of age-related changes in bone cell function, hormonal secretion and metabolism, and dietary patterns that prove deleterious to skeletal health, clinicians will be confronted with an ever-increasing population of aging, fracture-prone, osteoporotic patients. Because calcium supplements improve the calcium balance of perimenopausal and postmenopausal women and because improvements in calcium balance can be correlated with increased skeletal mass, it appears desirable to focus our efforts on diets and/or calcium supplements that guarantee an adequate supply of this essential mineral. Because calcium replacement may simply retard bone resorption and may not restore bone already lost by the fracture-prone, osteoporotic female, dietary analyses and appropriate modification of calcium intakes should be made at least in the third and fourth decades of life, with the goal of retarding the inexorable loss of skeletal tissue as early as possible.

Adrenal Cortex Hormones↗
PubMed1984

Effect of histamine H2-receptor blockade on parathyroid status in normal and uraemic man.

Reports of parathyroid suppression during cimetidine therapy suggest that prolonged therapy with H2 antagonists may, by inducing relative hypoparathyroidism, compromise skeletal homeostasis and that under appropriate circumstances, these drugs may serve as a new modality in treating hyperparathyroidism. Using three different region-specific immunoassays, we have been unable to show an effect of cimetidine (1,800 mg/day) on parathyroid hormone concentration, or on urinary cyclic adenosine monophosphate and renal threshold phosphate concentration in 4 normal subjects. Ranitidine given for 8 weeks to 4 haemodialysed patients likewise failed to decrease parathyroid hormone concentration. H2 antagonists appear not to alter parathyroid status in either normal subjects or in uraemics and therefore are unlikely to influence skeletal metabolism in either instance.

Adult↗
PubMed1984

Abnormal regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase activity by calcium and calcitonin in renal cortex from hypophosphatemic (Hyp) mice.

25-Hydroxyvitamin D3-1 alpha-hydroxylase activity was assayed in primary serum-free monolayer tissue culture of renal cortical cells from hypophosphatemic (Hyp) mice and normal litter mates. Morphological and growth characteristics of cells from the two genotypes were indistinguishable. Basal enzyme activity was not significantly different in either type of cell over a wide range of substrate concentration. The enzyme from both genotypes was stimulated by PTH and suppressed by increased phosphate concentration in the culture medium. Whereas 1 alpha-hydroxylase activity in cells from normal mice was increased in low calcium medium and suppressed in high calcium medium, the enzyme in cells from Hyp mice was not altered by similar changes in the medium calcium concentration. Salmon calcitonin caused a significant increase in 1 alpha-hydroxylase in cells from normal mice, but did not stimulate enzyme activity in cells from Hyp mice. These studies indicate that control of 1 alpha-hydroxylase activity is abnormal in renal cortical cells from Hyp mice. Impaired control of this enzyme could result in the inappropriately low circulating concentrations of 1,25-dihydroxyvitamin D3 that have been observed in humans with hypophosphatemic rickets and in the relatively low activity of 1 alpha-hydroxylase in renal cortical homogenates of Hyp mice compared to that in normal mice on a low phosphate diet.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1984

Inhibition of calcitonin secretion by exogenous calcitonin in the rat.

The effect of synthetic salmon calcitonin (CT) on calcium- and pentagastrin-stimulated plasma CT was investigated in male Sprague-Dawley rats. Plasma samples were obtained before and 3 and 6 min after calcium (1 mg/100 g BW, iv) or pentagastrin (5 micrograms/100 g BW, iv) infusion. Although salmon CT at the dose of 0.4 MRC U/100 g BW administered 15 min before either the calcium or pentagastrin infusion did not influence circulating endogenous CT levels, salmon CT in doses of 4 and 20 U/100 g BW administered 15 min before the injection of secretogogues significantly reduced the response of CT to either calcium or pentagastrin without significantly changing plasma calcium levels from those of control animals. Salmon CT (20 U/100 g BW) given 5 min before pentagastrin infusion again significantly suppressed the response of plasma CT to this stimulus. Similarly, salmon CT administered chronically in a dose of 2 U/100 g BW for 28 days significantly reduced the response of CT to the calcium infusion. These data suggest that in the rat, at least pharmacological dosage of CT modulates the production and/or secretion of glandular CT itself.

Animals↗
PubMed1984

Impaired insulin action in rats with non-insulin-dependent diabetes.

Studies were performed to test the hypothesis that impaired insulin action occurs as an acquired phenomenon in the streptozocin (STZ)-treated, non-insulin-dependent (NIDDM) diabetic rat model. A number of methods were used to evaluate impaired carbohydrate tolerance in these animals. Plasma glucose and insulin levels were measured at 6 and 14 wk of age, and insulin glucose tolerance tests were performed at 4 and 5 wk of age (before overt hyperglycemia ensues), and at 8 and 14 wk of age (after the animals manifest overt diabetes). The STZ-treated rats had higher plasma glucose levels than those of control animals (P less than 0.001) at 6 and 14 wk of age, while their plasma insulin values were decreased to levels 73% of the controls (1.7 ng/ml versus 2.3 ng/ml, P less than 0.04). Glucose disappearance rates after high (0.35 U/kg) and low (0.175 U/kg) insulin challenge were reduced in the experimental diabetic animals at all ages with both insulin doses. The data suggest that these animals have an early and progressive acquired impairment in insulin action, most compatible with a defect in cellular biologic response to insulin. The possibility that this abnormality is secondary to insulin deficiency is raised.

Animals↗
PubMed1984

Alternate calcitonin and etidronate disodium therapy for Paget's bone disease.

The efficacy of salmon calcitonin and etidronate disodium was compared in the therapy of Paget's bone disease in 37 patients. Nineteen patients received etidronate for six months with a mean alkaline phosphatase reduction to 53% of initial values. Bone scintophotographs improved in 12 and were unchanged in seven. Symptoms improved in 11 subjects, were unchanged in seven, and worsened in one. Twelve of these patients were then treated with calcitonin for six months with continued improvement in alkaline phosphatase values to 36% of initial values. All bone scintophotographs improved compared with initial studies. Seven patients continued to improve symptomatically; five described no change. Eighteen individuals were treated initially with calcitonin for six months. During therapy, the alkaline phosphatase level fell to 76% of initial values. Bone scintophotographs were worse in two patients, did not change in seven, and improved in nine. Eleven patients reported improvement in symptoms and seven reported no change. Seventeen of these patients were then treated with etidronate for six months with a decrease in alkaline phosphatase levels to 64% of initial values. Compared with initial tests, bone scintophotographs were worse in three with no change in five and improvement in nine. Symptomatically, three patients reported improvement; four noted no change, and ten reported increasing pain. Although the reason for the poor response to initial calcitonin therapy and/or subsequent etidronate therapy is not apparent, we have concluded that patients fare better when treated with an etidronate calcitonin sequence when compared with those treated with a calcitonin/etidronate sequence.

Aged↗
PubMed1983

Matrix sialoprotein of developing bone.

Using nondegradative isolation procedures, we purified and characterized a glycoprotein from fetal calf bone that is rich in sialic acid. This bone sialoprotein (BSP) has an apparent Mr = 70,000-80,000 and stains with Alcian blue and Stains All on sodium dodecyl sulfate gels but does not stain with Coomassie blue without prior treatment with neuraminidase. This glycoprotein contains 50% protein, 12% sialic acid, 7% glucosamine, and 6% galactosamine. Fetal calf BSP is rich in glutamate (19%), aspartate (15.4%), and glycine (11.8%) but, in contrast to osteonectin and the bone proteoglycan, has relatively low amounts of leucine (4.3%). Antisera raised against fetal calf BSP localized the glycoprotein by indirect immunofluorescence to developing bone trabeculae with an overall tissue distribution identical with that of osteonectin. On competition enzyme-linked immunosorbent assay analysis, BSP was 11.5% (+/-2.4%, S.E.) of mineral-bound (guanidine-EDTA-soluble) calf bone protein. Immunoreplicas (Western blots) of calf bone extracts suggest that more than 95% of the antigenicity resided in the Mr = 70,000-80,000 region with the remaining cross-reactivity in Alcian blue positive, Mr = approximately 20,000 and approximately 30,000 bands. Brief treatment of the Mr = 70,000-80,000 species with trypsin produced lower molecular weight, Alcian blue-staining products of similar size. No BSP was detected in guanidine extracts of various soft or unmineralized connective tissues, but dentin contained small amounts (0.4%) of the protein. Rat and fetal human bone were also observed to contain a sialoprotein with similar properties and a certain degree of cross-reactivity with the bovine BSP.

Amino Acids↗
PubMed1983

Basic and clinical evaluation of the measurement of bone resonant frequency.

A new computerized apparatus was constructed to measure the resonant frequency of human ulna in vivo with high sensitivity and reproducibility. Experimental studies using aluminum bar and dried human bone revealed the importance of the ulna being positioned parallel to the radius, approximately 90 degree flexion of the elbow joint, and minimal muscle activity in order to demonstrate maximum resonant frequency of ulna. Measurement of bone resonance in monkeys in vivo and after removal of the bone in vitro showed good agreement. Product of F (maximum resonant frequency in Hz) and L (ulnar length in cm), FL, indicating the speed of propagation of sound wave through the ulna, showed a significant positive correlation with bone mineral content/bone width (BM/BW) measured by Norland-Cameron apparatus and age-bound decline in both sexes. Patients with osteomalacia and primary hyperparathyroid bone disease tended to have higher FL values than expected from BM/BW. Two-dimensional display of FL and BM/BW thus appears to be useful in distinguishing osteoporosis from osteomalacia better than the use of BM/BW alone.

Adolescent↗
PubMed1983

Vitamin D metabolism in the chronic streptozotocin-induced diabetic rat.

Alterations in circulating vitamin D3 metabolites have been documented in both experimental and human diabetes mellitus. Using a recirculating hepatic perfusion system and in vitro kidney mitochondrial assays, we studied vitamin D3 hydroxylation in control and insulin-deficient rats 6 weeks after the induction of streptozotocin-diabetes. Vitamin D3-25-hydroxylase activity, assessed by hepatic conversion of [3H]vitamin D3 to [3H]25-hydroxyvitamin D3 during a 4-h perfusion, was similar in diabetic and control animals. The hepatic degradation of 25-hydroxyvitamin D3 to more polar metabolites was also normal, as was glucuronide conjugation and biliary excretion of vitamin D3 metabolites. The chronic insulin-deficient state resulted in a significantly (P less than 0.01) decreased 1 alpha-hydroxylase activity and enhanced (P less than 0.001) renal 24-hydroxylase activity. These alterations in vitamin D metabolism may relate to the deranged mineral homeostasis and skeletal morphology observed in rats and humans with chronic insulin deficiency.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1983

The duodenal 1 alpha,25-dihydroxyvitamin D3 receptor in rats with experimentally induced diabetes.

Studies in the rat with streptozotocin-induced diabetes of short and long duration revealed decreased circulating 1 alpha,25-dihydroxyvitamin D [1,25-(OH)2D] levels and an intact 1,25-(OH)2D3 duodenal cytosolic receptor with a sedimentation coefficient of 3.3S. Whereas no significant alterations in the equilibrium dissociation constant (Kd) were observed in the diabetic animals, the number of 1,25-(OH)2D3-binding sites was increased in the animals with short term (235 +/- 48 vs. 100 +/- 15 fmol/mg protein) and long term (521 +/- 60 vs. 119 +/- 15 fmol/mg protein) diabetes. The data are consistent with the hypothesis that alterations in intestinal calcium absorption previously observed in the diabetic state are due, at least in part, to dynamic relationships between circulating 1,25-(OH)2D concentrations and the number of intestinal 1,25(OH)2D3-binding sites.

Animals↗
PubMed1983

Use of oral calcium loading to characterize the hypercalciuria of young insulin-dependent diabetics.

To investigate the pathogenesis of the alterations in bone and mineral metabolism that are found in young insulin-dependent diabetics (IDDs), we performed a standard oral calcium load in 26 IDDs, 7-18 yr of age, and in 17 normal children, 9-18 yr of age. Eighty-five percent of the IDDs had second metacarpal cortical bone widths below the mean for matched controls. Calcium excretion in the IDDs fell along a continuous spectrum, ranging from normal to values consistent with renal hypercalciuria. Immunoreactive PTH was significantly (P less than 0.03) lower in the IDDs compared to that in the controls, and 24,25-dihydroxyvitamin D was significantly elevated (P less than 0.001). We were not able to document a significantly lower concentration of 1,25-dihydroxyvitamin D in the IDDs. Serum calcium, phosphate, and PRL levels were normal, as were creatinine (Cr) clearance and 24-hr urinary cortisol excretion. There was no apparent correlation between the fasting and postload urinary Ca to Cr and glucose to Cr concentration ratios. The accumulated data suggest that in many young IDDs, there is a component of intestinal calcium hyperabsorption which results in appropriate feedback responses by the parathyroid gland and vitamin D metabolic pathway(s). This imbalance between circulating PTH and vitamin D metabolites could result in defective bone remodeling and decreased cortical thickness.

Adolescent↗