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Biomedical subjects

J C Robin

Publications and source records attributed to J C Robin.

At least 19 recordsLinked to original sources

Benzo(B)thiophene-2-carboxylic acid: calcium uptake and cyclic AMP production in isolated bone cells.

The purpose of the present study was to investigate the mechanism of action on bone of Benzo(B)Thiophene-2-Carboxylic Acid (BL-5583). BL-5583, at a dose range of 0.01-100 micrograms/ml, inhibited spontaneous as well as A23187 and PTH-induced bone resorption in tissue culture. This compound also decreased calcium uptake in both osteoclastic and osteoblastic enriched bone cell populations obtained by sequential collagenase digestion of 1-2 day newborn rat calvariae. The decrease occurred after a 5 min. incubation with 45Ca and BL-5583. The effective dose range was 0.01-100 micrograms/ml. No effect on leucine incorporation or lactic acid production by bone cells was observed. BL-5583 also induced a transient decrease in calcium uptake in skin cells isolated from fetal rats by collagenase digestion, suggesting a lack of tissue specificity for this compound. No effect on cyclic AMP in isolated bone cells was observed with the same dose range that produced a calcium effect.

Animals

Study of antiosteoporotic agents in tissue culture.

Cultures of osteoblast-like cells were established from calvariae of Sprague-Dawley rats. Pentoxifylline increased cAMP levels and calcium uptake in these cultures. However, calcium uptake increased at lower levels than required to increase cAMP levels. Thus, it is likely that cAMP unrelated mechanisms are also involved in these phenomena.

Animals

Studies on the pathophysiology and therapy of osteoporosis.

Etiologic and pathologic factors in clinical osteoporosis are reviewed. Techniques were developed to determine total skeletal calcium content with in vivo neutron activation analysis and to induce osteoporosis (in about three months) with low calcium diet, corticosteroid or heparin treatment in experimental animals. Genetic influence was demonstrated: C3H/St (Ha) mice were more susceptible to osteoporosis by all three modalities than C57B1/6 (J) mice. Fluoride was ineffective in preventing osteoporosis induced by either of these three modalities. Heparin induced osteoporosis was prevented by conjugated estrogens, progestins or their combinations. Progestins were shown in other studies to inhibit estrogen induced metaplasia and neoplasia. Combining estrogens with progestin may result in an increased therapeutic index for the prevention of postmenopausal osteoporosis. Human and salmon calcitonin, Deca - Durabolin, an anabolic steroid, Mopidamole, a pyrimidopyrimidine derivative, Trental, a methylxanthine derivative, certain 2-thiophene carboxylic acid derivatives and imidazoquinazolines exhibited anti-osteoporotic effects.

Animals

Studies on osteoporosis X. Effect of estrogen-progestin combination on heparin-induced osteoporosis.

Neutron activation analysis was employed to determine total body calcium in C3H/St(Ha) female mice. As 99% of body calcium is in bone, loss of calcium was used as an index of bone loss (osteoporosis). Heparin (500 U/kg b.i.d. caused bone loss in 3 months. Premarin (2 mg/kg q.d.) or norethindrone (40 mg/kg q.d.) alone prevented this osteoporosis. A Premarin-norethindrone combination (2 mg - 10 mg q.d. respectively) appeared to be somewhat more effective than either agent alone, but this difference was not significant at the 5% level. Combinations of estrogen and progestins may prevent metabolic bone disease at the same time reducing the danger of estrogen induced neoplasia.

Animals

Studies on osteoporoses. XI. Effects of a methylxanthine derivative. A preliminary report.

Heparin (500 U/kg s.c. B.I.D.) induced significant osteoporosis in C3H/St(Ha) female mice after 3 months of treatment. Pentoxifylline (12 mg/kg i.m. B.I.D.) prevented this experimental osteoporosis. Osteoporosis was measured by in vivo neutron activation analysis and results were confirmed by atomic absorption spectroscopy. Pentoxifylline (0.1-100 microgram/ml) increased calcium uptake and cAMP production in osteoblast-like bone cells isolated from fetal Sprague-Dawley rats. Theoretical implications for osteoblast control of bone resorption are discussed.

Animals

Studies on osteoporosis VII. Effect of 17 beta-hydroxy-4-estren-3-one 17-decanoate on experimental osteoporosis.

Total body neutron activation analysis was employed to measure total calcium in C3H/St (Ha) female mice. Ninety-nine percent of total body calcium is in bone and loss of calcium was used as an index of osteoporosis. Heparin (500 U/kg B.I.D.) treatment for three months resulted in significant osteoporosis. 17 beta-Hydroxy-4-estren-3-one 17-decanoate 1.5 mg/kg or 4 mg/kg twice monthly prevented this heparin accelerated osteoporosis. The results suggest that 17 beta-hydroxy-4-estren-3-one 17-decanoate may be capable of preventing bone loss and partially increasing bone mass in patients exposed to osteoporosis inducing regimens.

Animals

Prostacyclin: effects on cyclic AMP in bone cells.

Prostacyclin (PGI2) increased cyclic AMP in specific rat bone cell populations obtained by sequential collagenase digestion of calvariae. An osteoclastic population, characterized by high acid phosphatase levels and the ability to resorb bone in vitro, was more sensitive as reflected by responses to lower doses of PGI2 (2.3 x 10(-8)M) as well as greater responses to higher doses (3.5 x 10(-4)) of PGI2 than the other populations isolated. The osteoblastic populations, characterized by high alkaline phosphatase levels and the inability to resorb devitalized bone did not respond significantly to PGI2 at doses less than 10(-4)M and increases in cAMP were smaller. Then results suggest a differential effect of PGI2 on osteoclasts and osteoblasts which may be involved in the mode of action of endogenously produced PGI2 in bone.

Animals

Studies on osteoporoses. VIII. Effect of estrogen on steroid induced osteoporosis.

Neutron activation analysis was employed to determine total body calcium in 5-8 month and 15-18 month old C3H/St(Ha) and C57/BL6 (JACOBS) female mice. Ninety-nine percent of calcium is in bone and loss of calcium was used as an index of osteoporosis. Prednisolone (50 mg/kg q.d.) treatment for three months resulted in significant osteoporosis in the C3H/St(Ha) mice of both age groups but did not cause significant bone loss in the C57/BL6 (JACOBS) mice of either age group. Premarin (20 mg/kg q.d.) failed to prevent steroid accelerated osteoporosis.

Adrenal Cortex Hormones

Studies on osteoporoses. XII. Effect of imidazoquinazolinones on experimental osteoporosis. A preliminary report.

In vivo neutron activation analysis was employed to determine total body calcium content in C3H/St(Ha) female mice. Ninety-nine percent of calcium is in bone and loss of calcium was used as an index of osteoporosis. Heparin (500 U/kg b.i.d.) treatment for three months resulted in significant osteoporosis. BL3459 and BL4160 (6 mg/kg i.m. q.d.) prevented this heparin induced osteoporosis. BL4160 appeared to be more effective than BL3459 in this regard but the difference was not statistically significant.

Animals

Studies on osteoporosis VI. Effect of human and salmon calcitonin on experimental osteoporosis.

Neutron activation analysis was employed to determine total body calcium in C3H/St (Ha) female mice. Ninty-nine percent of total body calcium is in bone and loss of calcium was used as an index of osteoporosis. Heparin (500 U/kg B.I.D.) treatment for three months resulted in significant osteoporosis. Both human and salmon calcitonin (4 MRC U/Kg B.I.D.) prevented heparin induced osteoporosis. The results suggest that calcitonin may prevent pathological fractures in patients on anticoagulants and other osteoporosis inducing regimens.

Animals

Studies on osteoporosis. IX. Effect of fluoride on steroid induced osteoporosis.

Neutron activation analysis was employed to determine total body calcium in 5-8 month and 15-18 month old C3H/St(Ha) and C57/BL6 (JACOBS) female mice. Ninety-nine percent of calcium is in bone and loss of calcium was used as an index of osteoporosis. Prednisolone (50 mg/kg q.d.) treatment for three months resulted in significant osteoporosis in the C3H/St(Ha) mice of both age groups but did not cause significant bone loss in the C57/BL6 (JACOBS) mice of either age group. Fluoride (75 PPM) failed to prevent osteoporosis in both strains and both age groups.

Adrenal Cortex Hormones

Studies on osteoporosis. V. Comparison of methods of evaluation of osteoporosis and study of chromosome changes induced by neutron activation.

In vivo activation analysis was compared with ashing and atomic absorption spectrophotometry for the determination of total skeletal calcium content in mice. The results were close to identical. The possible mutagenic-carcinogenic effect of repeated exposure to whole body neutron irradiation was studied by chromosome analysis. Under the conditions of these experiments, no significant chromosome changes were seen.

Activation Analysis

Studies on osteoporosis III. Effect of estrogens and fluoride.

Total skeletal calcium levels were determined in female mice with the aid of whole body neutron activation analysis. Three months treatment with heparin produced significant osteoporosis in C3-H/St(Ha) mice but not in C57/BL6 (J) mice. Treatment with a conjugated natural estrogen preparation (Premarin) prevented heparin accelerated osteoporosis, but high level fluoride in the drinking water had no preventive effect. In some experiments there was a suggestion of a deleterious effect of fluoride.

Animals

Studies on osteoporosis IV. Effect of benzo[b]thiophene-2- and dibenzothiophene-4-carboxylic acid on heparin accelerated osteoporosis.

Total skeletal calcium was determined in female mice with the aid of whole body neutron activation analysis. Three months treatment with heaprin produced significant osteoporosis in C3-H/St(Ha) mice but not in C57/BL6(J) mice. This was more pronounced in the younger (5-8 months) than in the older (15-18 months) animals. Two 2-thiophene carboxylic acid derivatives showed significant osteoporosis preventive activity.

Animals

Studies on osteoporosis. II. Effect of estrogens and fluoride on experimental osteoporosis. A preliminary report.

Total skeletal calcium level was determined in female mice with the aid of whole body neutron activation analysis. Three months treatment with heparin produced significant osteoporosis in C3H/St(Ha) mice of 3--5 months of age. Treatment with a conjugated natural estrogen preparation (Premarin) prevented this phenomenon but high level fluoride in the drinking water failed to show preventive activity.

Animals

Studies on osteoporosis I. Experimental models. Effect of age, sex, genetic background, diet, steroid and heparin treatment on calcium metabolism of mice.

C3H/St(Ha) and C57Bl/6(J) mice of both sexes and various ages were exposed to whole body neutron irradiation. The 49Ca generated (half life 8.8 minutes) was immediately determined in a whole body counter. Total body calcium content was calculated. It was assumed that 99% of this represented skeletal calcium. In females, significant decrease in calcium content occurred after 23 months of age. In C3H/St(Ha) mice, low calcium diet, heparin (500 i.u./Kg. b.i.d.) and prednisolone (50 mg/Kg) treatment accelerated calcium loss and produced significant decrease in 3 months. C57Bl/6(J) mice were less susceptible to the latter drugs.

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