Effect of halogenmethylenebisphosphonates on bone cells in culture and on bone resorption in vivo

Summary Dihalogenmethylenebisphosphonates increase alkaline phosphatase activity and fatty acid oxidation in calvaria cells in culture (Cl₂MBP>Br₂MBPF₂MBP). The monohalogen C1MBP and the non-halogenated analogues are less active on phosphatase and inactive on or inhibitory towards fatty acid oxidation. The three dihalogenbisphosphonates and C1MBP inhibit bone resorption in vivo, Cl₂MBP most strongly.Acknowledgments. We thank Miss M.-L. Aebersold, Miss J. Portenier, Mrs I. Tschudi and Mrs Ch. Marti for their skilled technical assistance. This work has been supported by the Swiss National Science Foundation (grant 3.937.82), by the Procter & Gamble Company, Cincinnati, USA, by the Istituto Gentili S.p.A., Pisa, Italy, and by the Ausbildungs- und Förderungsfonds der Arbeitsgemeinschaft für Osteosynthese (AO), Chur, Switzerland.     

Tetracyclines inhibit parathyroid hormone-induced bone resorption in organ culture

Several tetracyclines (minocycline, doxycycline, tetracycline), in levels approximating physiologic concentrations, were found to inhibit parathyroid hormone-induced bone resorption in organ culture; the specificity of this effect was demonstrated by comparison with other (non-tetracycline) types of antibiotics. The ability of tetracyclines to inhibit bone resorption is consistent with the recent proposal by Golub et al. that these antibiotics can inhibit mammalian collagenolytic enzymes by a mechanism unrelated to the drug's antibacterial efficacy, a property which could be therapeutically useful in diseases characterized by excessive collagen breakdown.     

Tetracyclines inhibit parathyroid hormone-induced bone resorption in organ culture

Summary Several tetracyclines (minocycline, doxycycline, tetracycline), in levels approximating physiologic concentrations, were found to inhibit parathyroid hormone-induced bone resorption in organ culture; the specificity of this effect was demonstrated by comparison with other (non-tetracycline) types of antibiotics. The ability of tetracyclines to inhibit bone resorption is consistent with the recent proposal by Golub et al². that these antibiotics can inhibit mammalian collagenolytic enzymes by a mechanism unrelated to the drug's antibacterial efficacy, a property which could be therapeutically useful in diseases characterized by excessive collagen breakdown.     

Effect of fatty acids on fetal rat bone in culture

Zusammenfassung Nachweis, dass Fettsäuren (Palmitin-, Stearin- und Ölsäuren) in sehr niedrigen Konzentrationen die Kalziumabgabe und die Knochenresorption in fötalen Ratten in vitro fördern.

---

---

The studies were supported by USPHS grant No. AM 11262. The albumin monomer was kindly supplied by Drs.J. Brand andL. Raisz.     

Genotoxic effects of dithane M-45 on the bone marrow cells of mice in vivo

Genotoxic effects of dithane M-45 were studied on the bone marrow cells of male albino mice (Lacca strain) in vivo. Different doses (30 mg, 40 mg and 300 mg/kg b.wt) of dithane M-45 were injected intraperitoneally and their effects were investigated after time intervals of 1, 2, 5 and 10 days. The chromosomal aberrations observed in the bone marrow cells of male mice after treatment with dithane M-45 were fragments, rings, dicentric chromosomes, terminal chromatid deletions, chromatid gaps and breaks. In addition to these chromosomal aberrations, physiological effects such as uneven stretching of chromatin material, end-to-end chromosomal associations, exchange configurations, clumping, stickiness and centromeric associations were also observed.     

Genotoxic effects of dithane M-45 on the bone marrow cells of mice in vivo

Summary Genotoxic effects of dithane M-45 were studied on the bone marrow cells of male albino mice (Lacca strain) in vivo. Different doses (30 mg, 40 mg and 300 mg/kg b.wt) of dithane M-45 were injected intraperitoneally and their effects were investigated after time intervals of 1, 2, 5 and 10 days. The chromosomal aberrations observed in the bone marrow cells of male mice after treatment with dithane M-45 were fragments, rings, dicentric chromosomes, terminal chromatid deletions, chromatid gaps and breaks. In addition to these chromosomal aberrations, physiological effects such as uneven stretching of chromatin material, end-to-end chromosomal associations, exchange configurations, clumping, stickiness and centromeric associations were also observed.     

Effect of pulsing electromagnetic fields on DNA synthesis in mammalian cells in culture

Summary DNA synthesis in Chinese hamster V79 cells was significantly enhanced when they were exposed to weak, pulsing electromagnetic fields generated by specific combinations of the pulse width (25s), frequency (10, 100 Hz) and magnetic intensity (2×10^–5 8×10^–5T). Conversely the DNA synthesis of cells in the fields at 4×10^–4 T was repressed to 80% of that in controls not exposed to the fields.This work was supported by Kaken Pharmaceutical Co., Ltd, Tokyo, Japan, and in part by a Grant-in-Aid from the Ministry of Education, Science and Culture of Japan and from the Foundation for Life Science Promotion Tokyo, Japan to I.K.     

Effect of pulsing electromagnetic fields on DNA synthesis in mammalian cells in culture

DNA synthesis in Chinese hamster V79 cells was significantly enhanced when they were exposed to weak, pulsing electromagnetic fields generated by specific combinations of the pulse width (25 microseconds), frequency (10, 100 Hz) and magnetic intensity (2 X 10(-5), 8 X 10(-5) T). Conversely the DNA synthesis of cells in the fields at 4 X 10(-4) T was repressed to 80% of that in controls not exposed to the fields.     

Effect of low density lipoprotein on proteoglycan synthesis by aorta cells in culture

Summary Increasing the content of human serum low density lipoprotein in the growth medium led to greater incorporation of³⁵S-sulfate into proteoglycan (mostly into dermatan sulfate) by primary aorta cells but did not affect similar incorporation by fibroblast cells. These results suggest a mechanism which can explain the increased deposition of lipid in aorta due to hyperlipidemia.Acknowledgements. This work was supported by a Fort Polk-American Heart Association-Louisiana, Inc. Research Award.     

Effect in vivo of norepinephrine on the membrane resistance of brown fat cells

Résumé La dépolarisation de la membrane des cellules adipeuses brunes, produite par l'administration in vivo de noradrénaline, est aussi accompagnée d'une augmentation de la perméabilité mesurée par une augmentation de la résistance membranaire.

---

---

Supported in part by research grant NASA No. NGR-05-004-035.     

Effect of Progesterone on the in vivo binding of estrogens by uterine cells

Summary Progesterone selectively inhibits estradiol upltake by the nuclei of the luminal epithelial cells but not by other uterine cells. This inhibition in estrogen binding parallels the inhibition by progesterone of some estrogenic responses in the luminal epithelial cells only.Acknowledgments. This work was supported by Grant No. 2015 From the Oficina Técnica de Desarrollo Cientifico y Creación Artística of the University of Chile.     

The effect of phytohemagglutinin in vivo on the mitotic activity of the bone marrow cells in young rats

Résumé Chez des rats (mâles et femelles) auxquels on a administré de la phytohémagglutinine P (Difco) par voie intrapéritonienne, l'activité mitotique dans les cellules de la moelle des os a été notablement plus grande à l'âge de trois et six semaines qu'à l'âge de douze semaines (par comparasion avec les animaux de contrôle).     

Induction of sister chromatid exchanges in vivo in bone marrow cells of AKR mice]

Induction of sister chromatid exchanges (SCEs) in bone-marrow cells of AKR Mice receiving in vivo four drugs well-known for their mutagenesis activity has been tested. A decreasing activity in SCE was shown by the drugs tested in the order cyclophosphamide, procarbazine, methylmethane sulfonate and diethylnitrosamine. This technique presents an encouraging method for testing the effect of chemical agents in vivo.     

Effect of calcitonin on glycosaminoglycan synthesis by embryo calf bone cells in vitro

Zusammenfassung Es wurde gefunden, dass rohe Calcitoninpräparate die Inkorporation von¹⁴C-Glucose in die Glycosaminoglycan-(GAG)-Synthese fördern. Unter denselben Zellkulturbedingungen wurde Calcitonin mit stark spezifischer Aktivität rasch inaktiviert und zeigte keine stimulierende Wirkung; wurde aber der Serumgehalt im Milieu stark eingeschränkt, so verursachte das Calcitonin (50 Einheiten/mg) eine hundertprozentige Erhöhung der¹⁴C-GAG-Synthese.     

Effect of low density lipoprotein on proteoglycan synthesis by aorta cells in culture.

Increasing the content of human serum low density lipoprotein in the growth medium led to greater incorporation of 35S-sulfate into proteoglycan (mostly into dermatan sulfate) by primary aorta cells but did not affect similar incorporation by fibroblast cells. These results suggest a mechanism which can explain the increased deposition of lipid in aorta due to hyperlipidemia.