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Biomedical subjects

R Salvatori

Publications and source records attributed to R Salvatori.

29 records · Page 2Linked to original sources
PubMed1993

Gallium nitrate regulates rat osteoblast expression of osteocalcin protein and mRNA levels.

Gallium nitrate, a group IIIa metal salt, has been found to be clinically effective for the treatment of accelerated bone resorption in cancer-related hypercalcemia and Paget's disease. Here we report the effects of gallium nitrate on osteocalcin mRNA and protein levels on the rat osteoblast-like cell line ROS 17/2.8. Gallium nitrate reduced both constitutive and vitamin D3-stimulated osteocalcin protein levels in culture medium by one-half and osteocalcin mRNA levels to one-third to one-tenth of control. Gallium nitrate also inhibited vitamin D3 stimulation of osteocalcin and osteopontin mRNA levels but did not affect constitutive osteopontin mRNA levels. Among several different metals examined, gallium was unique in its ability to reduce osteocalcin mRNA levels without decreasing levels of other mRNAs synthesized by ROS 17/2.8 cells. The effects of gallium nitrate on osteocalcin mRNA and protein synthesis mimic those seen when ROS 17/2.8 cells are exposed to transforming growth factor beta 1 (TGF beta 1); however, TGF-beta 1 was not detected in gallium nitrate-treated ROS 17/2.8 cell media. Use of the RNA polymerase II inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole demonstrated that gallium nitrate did not alter the stability of osteocalcin mRNA. Transient transfection assays using the rat osteocalcin promoter linked to the bacterial reporter gene chloramphenicol acetyltransferase indicated that gallium nitrate blocked reporter gene expression stimulated by the osteocalcin promoter. This is the first reported effect of gallium nitrate on isolated osteoblast cells.

Animals↗
PubMed1993

Gallium nitrate increases type I collagen and fibronectin mRNA and collagen protein levels in bone and fibroblast cells.

Gallium is a Group IIIa transitional element with therapeutic efficacy in the treatment of metabolic bone disorders. Previously described antiresorptive effects of gallium on osteoclasts are not sufficient to account for the full range of effects of gallium on bone structure and metabolism. We have recently shown that gallium nitrate inhibits osteocalcin gene expression and the synthesis of osteocalcin protein, an osteoblast-specific bone matrix protein that is thought to serve as a signal to trigger osteoclastic resorption. Here we present evidence for an additional mechanism by which gallium may function to augment bone mass by altering matrix protein synthesis by osteoblastic and fibroblastic cells. Rat calvarial explants exposed to gallium nitrate for 48 h showed increased incorporation of 3H-proline into hydroxyproline and collagenase digestible protein. In addition, gallium treatment increased steady-state mRNA levels for fibronectin and type I procollagen chains in primary rat calvarial osteoblast-enriched cultures, the ROS 17/2.8 osteoblastic osteosarcoma line, and nontransformed human dermal fibroblasts. These findings suggest that the exposure of mesenchymally-derived cells to gallium results in an altered pattern of matrix protein synthesis that would favor increased bone formation.

Adult↗
PubMed1992

Anti-iodothyronine autoantibodies in a girl with hyperthyroidism due to pituitary resistance to thyroid hormones.

In the present study, we report the uncommon case of a 9.6-yr-old girl with circulating anti-T3 autoantibodies (T3-Ab) and hyperthyroidism due to inappropriate secretion of TSH (IST). The diagnosis of IST was based on the findings of normal TSH levels (2.4 mU/L) in the presence of high free T4 (28.2 pmol/L) and free T3 (FT3) levels, as measured by direct measurement methods based on "one-step" analog tracer (28.0 pmol/L) and "two-step" Lisophase (13.3 pmol/L) techniques. The discrepancy between the two measurements suggested a methodological interference due to T3-Ab in "one-step" technique, being the "two-step" methodology unaffected by the presence of such autoantibodies. T3-Ab were documented by high nonspecific binding of serum to labeled T3 (38.0% vs 4.3 +/- 2.1% in controls). The clinical picture of hyperthyroidism, the qualitatively normal TSH responses to TRH and T3 suppression tests, the normal pituitary imaging and the values of some parameters of peripheral thyroid hormone action compatible with hyperthyroidism indicated that the patient was affected by pituitary resistance to thyroid hormones (PRTH). Chronic treatment with dopaminergic agent bromocriptine (7.5 mg/day) did not cause TSH secretion to be suppressed, while the administration of thyroid hormone analog TRIAC (1.4 mg/day) inhibited TSH release (from 2.4 to 0.2 mU/L). As a consequence, circulating thyroid hormone levels normalized and euthyroidism was restored. During TRIAC administration, FT3 levels, measured by "one-step" analog tracer technique, gave spuriously high values due to the methodological interference of T3-Ab (15.2 vs 4.3 pmol/L as measured by "two-step" Lisophase technique).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1992

Prostaglandin E1 inhibits collagenase gene expression in rabbit synoviocytes and human fibroblasts.

Cartilage breakdown, as seen in inflammatory and degenerative joint diseases, can be mediated by proteolytic enzymes, such as the metalloproteinase collagenase, the only enzyme able to digest collagen at neutral pH. In vitro collagenase gene expression can be stimulated by the phorbol ester tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. We have investigated the effect of prostaglandin E1 (PGE1) on 12-O-tetradecanoyl-phorbol-13-acetate-stimulated collagenase mRNA levels in the rabbit synoviocyte cell line HIG-82. PGE1, but not PGE2 or PGF2 alpha, was able to selectively reduce collagenase mRNA levels in a dose-dependent fashion. PGE1 markedly increased intracellular levels of cAMP, while PGE2 and PGF2 alpha had little or no effect on cAMP production in the HIG-82 synoviocytes. Agents known to increase intracellular cAMP levels, such as the adenyl cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), mimicked the effect of PGE1, on collagenase mRNA levels. PGE1, forskolin, and IBMX also decreased collagenase mRNA levels in human skin fibroblasts, demonstrating that this observation was not unique to the HIG-82 cell line. Transient transfection experiments carried out in HIG-82 cells using a 1.2-kilobase portion of the 5'-flanking region of the human collagenase gene linked to the reporter gene luciferase demonstrated that PGE1, forskolin, and IBMX exert their inhibitory effect on the promoter region of the collagenase gene.

1-Methyl-3-isobutylxanthine↗
PubMed1991

The growth hormone response to pyridostigmine plus growth hormone releasing hormone is not influenced by pubertal maturation.

We have evaluated the effect of pubertal maturation on the GH response to growth hormone releasing hormone (GHRH), pyridostigmine (PD) and the combined administration of PD + GHRH in a group of short normal children. Fifteen were prepubertal (13 boys and 2 girls, age 5.0 - 12.5 yr), 10 were early pubertal (8 boys and 2 girls, age 11.5 - 16.9 yr in Tanner stage 2-3 of pubertal maturation), and 6 were late pubertal (6 boys and 2 girls, age 13.6 - 17.1 yr in Tanner stage 4-5 of pubertal maturation). All subjects were tested on three occasions with GHRH 1-29 (1 microgram/Kg iv), PD (60 mg po) and PD + GHRH (60 mg PD administered orally 60 min before GHRH). Peak GH levels after GHRH, PD, and PD + GHRH in the prepubertal children (16.0 +/- 2.8, 8.1 +/- 1.3 and 51.1 +/- 5.5 ng/ml, mean +/- SE, respectively) were not different from those observed in the early pubertal (18.4 +/- 2.1, 9.1 +/- 1.9 and 41.2 +/- 5.6 ng/ml, respectively) and in the late pubertal group (14.9 +/- 2.3, 13.1 +/- 2.4 and 42.6 +/- 2.9 ng/ml, respectively). Evaluation of the area under the curve (AUC) also showed no difference in the GH response to GHRH, PD and PD + GHRH between the three groups studied. These results confirm that the combination PD + GHRH is a powerful test to study the GH secretory capacity of the pituitary, and show that pubertal maturation has no effect on the GH response to this test.

Administration, Oral↗
PubMed1990

Pyridostigmine does not reverse dexamethasone-induced growth hormone inhibition.

Glucocorticoids inhibit the growth hormone (GH) response to a variety of stimuli, including GH-releasing hormone (GHRH) in vivo, but they increase GHRH-stimulated GH secretion when added, in vitro, to animal and human pituitary cells. This discrepancy has led to the hypothesis that glucocorticoids act in vivo by increasing somatostatin secretion from the hypothalamus. To examine this hypothesis, we used a cholinergic drug, pyridostigmine (PD), which reduces hypothalamic somatostatin secretion. Eight normal volunteers were studied. They underwent four tests: (1) GHRH test; (2) Dex + GHRH (GHRH test after treatment the night before, with dexamethasone (Dex)); (3) PD + GHRH; (4) Dex + PD + GHRH. Dex significantly inhibited the GH response to GHRH expressed as area under the GH/time curve (AUC, microgram/1/min) (mean +/- SEM = 895.2 +/- 196.6 vs 1970.9 +/- 600.1, P less than 0.05). PD significantly increased the AUC of GH secretion in PD + GHRH compared with GHRH alone (3541.2 +/- 571.3 vs 1970.9 +/- 600.1, P less than 0.01) but by no means restored completely the normal GH response to GHRH, when given to Dex-pretreated subjects. Furthermore, the mean AUC of Dex + PD + GHRH was significantly lower than that of PD + GHRH (1621.7 +/- 500.6 vs 3541.2 +/- 571.3, P less than 0.01), demonstrating that Dex continues to exert its inhibitory effect on GH secretion in the presence of PD. These results suggest that glucocorticoid-induced GH inhibition does not act solely through an increase in hypothalamic somatostatin secretion.

Adult↗
PubMedDate not supplied

Thyrotoxicosis due to metastatic papillary thyroid cancer in a patient with Graves' disease.

Thyrotoxicosis resulting from functional thyroid cancer metastases is extremely rare, and is mostly caused by follicular cancer. The lesions causing thyrotoxicosis are usually bulky and extensive. We report here a patient with Graves' disease and concomitant papillary thyroid cancer who developed metastases causing symptomatic thyrotoxicosis. His serum titers of thyroid stimulating Ig (TSIs) were elevated. We believe that TSIs were responsible for thyrotoxicosis by stimulating hormonogenesis in the metastatic lesions.

Aged↗