New bone induction by demineralized bone matrix in immunosuppressed rats.

Subcutaneous implantation of demineralized bone matrix (DBM) initiates a sequence of developmental events which culminate in endochondral bone formation. To test the effects of T-cell deficiency on new bone formation, the morphology of DBM-induced bone was examined in rats thymectomized at three weeks of age and in thymectomized or nonthymectomized rats lethally irradiated and reconstituted with syngeneic bone marrow. At 24 days after implantation, bone induction in control rats was appropriate for their age, while thymectomized-irradiated-reconstituted rats and thymectomized rats had significantly more new bone and larger bone marrow space than the controls. In non-thymectomized, irradiated and reconstituted rats, bone induction occurred in only 25% of the animals, compared to 95% in other groups.     

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 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.     

Reversible reduction in bone blood flow in streptozotocin-diabetic rats

Summary Tibial growth and blood flow were both found to be markedly reduced in anaesthetised streptozotocin-diabetic rats compared to controls. Insulin treatment restored tibial growth to approximately control values and increased tibial blood flow to above control values. The observations are likely to be related to reduced bone turnover in uncontrolled diabetes.25 November 1986     

Granulocytosis induced in vivo by a mouse marrow stromal cell line,BMA1, which produces colony stimulating factor

Summary Nude mice were inoculated with BMA1 cells. These are cells which produce granulocyte-macrophage colony stimulating factor (GM-CSF); They are derived from mouse bone marrow stromal cells transfected with adenovirus 5 DNA. Progressive neutrophilia developed as the tumor grew, but disappeared quickly after local tumor excision. Media conditioned with tumor cells had GM-CSF but neither erythropoietin, nor burst-promoting activity. In all the tumors which developed, focal areas of bone formation were found among fibrosarcomatous tissues.     

Irradiation of the head by60Co opens the blood-brain barrier for drugs in rats

Summary The passage of 6 model drugs; acetylsalicylic acid, chloramphenicol, ethimizol, carbisocaine, heptacaine, and diazepam, through the blood-brain barrier, was determined in unirradiated control rats and in animals 1, 3, and 7 days after irradiation of the head only with a dose of 25 Gy from a⁶⁰Co source. The brain uptake index (BUI), which compares the uptake of the test substance with that of³H₂O 5 s after their injection into the common carotid artery, was significantly increased in comparison with unirradiated controls 7 days after irradiation, for all substances tested except for ethimizol. For acetylsalicylic acid and chloramphenicol it was also significantly increased in the other time intervals. The less lipophilic substances showed a greater relative increase of BUI than the more lipophilic ones.     

Critical period for induction of congenital hydrocephalus and dysplasia of subcommissural organ by prenatal X-irradiation in rats

Summary A single whole-body X-irradiation of pregnant Wistar rats at a dose of 1.05 Gy at 10.30, 12.30 and 14.30 h respectively, of gestational day 10 resulted in significantly high incidences of hydrocephalic offspring. No hydrocephalic offspring resulted from X-irradiation of pregnant rats with 1.05 Gy at 16.30 h whereas a dose of 1.22 Gy at 16.30 h resulted in a low but statistically significant incidence of hydrocephalus. Neither 1.05 Gy nor 1.22 Gy X-irradiation of pregnant rats at 18.30 h resulted in any hydrocephalic offspring. Dysplasia of the subcommissural organ was noticed in all the hydrocephalic brains histologically examined.