A model of cortical bone repair has been established for use in mice. The cortical defect consisted of a hole drilled through the entire diameter of the tibial diaphysis. The hematoma that initially filled the drill site was invaded by cells of mesenchymal appearance within 5 days of injury. Trabeculae of mineralized woven bone were present throughout the drill site by day 9. A reaction in the periosteum adjacent to the drill site, consisting of both new bone and cartilage formation, preceded deposition of bone tissue in the drill site. New woven bone was modeled to restore the marrow cavity to normal by 4 weeks after injury, and almost normal cortical structure was achieved by 6 weeks after injury. Immunohistochemical studies indicated that type III collagen was expressed within the drill site by day 5, reached a peak at day 7, and was diminished by day 9. In contrast, type I collagen was first detectable in the drill site at day 7, and staining was more intense by day 9. Osteopontin expression in the drill site coincided with the process of mineralization of new bone in this location. The model of bone repair described here provides a method for inducing reproducible bone lesions in a readily identifiable location in mice. It will be useful in the investigation of bone cell function in mouse strains that have been subjected to genetic manipulation.

Protease-activated receptor (PAR)-1, a G-protein-coupled receptor activated by thrombin, mediates thrombin-induced proliferation of osteoblasts. The current study was undertaken to define the role of PAR-1 in bone repair. Holes were drilled transversely through the diaphysis of both tibiae of PAR-1-null and wildtype mice. Three days later, fewer cells had invaded the drill site from adjacent bone marrow in PAR-1-null mice than in wild-type mice, and a lower percentage of cells were labeled with [ 3 H]thymidine in PAR-1-null drill sites. More osteoclasts were also observed in the drill site of PAR-1-null mice than in wild-type mice 7 days after drilling. New mineralized bone area was less in the drill site and on the adjacent periosteal surface in PAR-1-null mice than in wildtype mice at day 9. From day 14, no obvious differences could be seen between PAR-1-null and wild-type tibiae. In vitro thrombin caused a dose-dependent increase in proliferation of bone marrow stromal cells isolated from wild-type mice but not PAR-1-null mice. Thrombin stimulated survival of bone marrow stromal cells from both wild-type and PAR-1-null mice, but it did not affect bone marrow stromal cell migration in either wild-type or PAR-1-null cells Thrombin is a serine protease, which plays a central role in blood coagulation through its cleavage of fibrinogen, but also exerts specific receptor-mediated effects on cell function. Three thrombin receptors have been identified, protease-activated receptors (PARs)-1, -3, and -4, which are members of the seven transmembrane domain Gprotein-coupled receptor family. 1,2 Protease-activated receptor-1 is expressed by osteoblasts (bone-forming cells), and mediates thrombin-induced proliferation of these cells. [3][4][5] Thrombin also stimulates osteoclastic bone resorption in vitro. 6,7 Thrombin is generated during tissue injury, and PAR-1 activation appears to be involved in pathological processes including inflammation and wound healing. 8 -10 For example, when thrombin or a PAR-1-activating peptide is applied to incisional skin wounds in rats, wound healing is accelerated. 11 Because both osteoblast proliferation and bone resorption are important components of the process of bone repair, we hypothesized that thrombin, through PAR-1, may participate in this process. The current study was undertaken to investigate this hypothesis, using mice with a targeted disruption of the PAR-1 gene. 12 Fifty percent of these mice die at about day 9.5 of gestation, and the remainder survive to become apparently normal adults. Embryonic death of PAR-1-null mice can be prevented by targeted expression of PAR-1 in endothelial cells. 13 Although PAR-1 is expressed by platelets and mediates platelet aggregation in humans, PAR-1 is not expressed by mouse platelets, and therefore is not required for normal blood coagulation in this species. 14 A number of models of bone repair have been established for use in mice, including an unstabilized fracture model, stabilized fracture models involving internal or external fi...

In 6 years snake bite was diagnosed in 41 cats, with an average age of 20 months. The commonest presenting signs were dilated pupils, absence of the pupillary light reflex, depression and generalised muscle weakness. Other frequent findings were vomiting, dyspnoea, hindlimb ataxia and complete flaccid paralysis. Thirty-seven cases (90%) occurred in the 6 warmer months of the year. Tiger snakes were positively identified in 7 cases. A recovery rate of 89% was obtained in cases receiving 3000 units Tiger snake antivenene, fluid therapy and nursing. Cases presenting with a complete flaccid paralysis and sub-normal temperatures were poor prognostic risks.

Summary A foal with primary severe combined immunodeficiency, diagnosed within the first two weeks of life, was maintained with its dam in semi‐isolation. The foal received continuous prophylactic antibiotic therapy, plasma from a sibling hyperimmunised with equine adenovirus vaccine, and intensive general nursing care. A full sibling female was selected as a bone marrow donor on the basis of red blood cell cross‐matching and mixed lymphocyte reactions. Cyclophosphamide was given before two bone marrow transfusions at 35 and 73 days of age. To prevent graft versus host disease graft versus host disease the foal was maintained on methotrexate therapy. Reconstitution was not achieved nor were there signs of graft versus host disease. The foal died suddenly four days after the second bone marrow transfer when 77 days old. It had remained clinically free of any life threatening infectious disease and at necropsy a remarkable degree of freedom from infectious disease was confirmed. The most notable necropsy findings were bilateral nephrosis and myocardial degeneration and fibrosis. The likely cause of death was an electrolyte imbalance, particularly hypokalaemia, which secondarily affected the myocardium. Renal toxicity caused by the cytotoxic drugs, especially cyclophosphamide, may have contributed to the electrolyte imbalance. Résumé Un foal atteint d'une sévère immunodéficience primaire combinée, diagnostiquée au cours des deux premières semaines de la vie, fut confiné avec sa mère dans un demi isolement. Le foal reçut une antibiothérapie prophylactique continue, du plasma prélevé sur un parent d'un type sanguin voisin hyperimmuniséà l'aide d'un adenovirus vaccinal équin et bénificia de soins attentifs. Une femelle très proche sur le plan immunitaire fut utilisée comme donneur de moelle osseuse, après avoir été identifié par des réactions croisées erythrocytaires et par des réactions lymphocytaires. Une administration de cyclophonamide précéda deux transfusions de moelle osseuse à 35 et à 73 jours. Pour prévenir une réaction antagoniste greffon‐hôte le foal fut maintenu sous traitement au méthotrexate. La reconstitution n'eut pas lieu. On ne constata point de signes cliniques de maladie immunitaire. Le foal mourut soudain quatre jours après le second transfert de moelle osseuse, âgé de 77 jours. Il était resté cliniquement indemne de maladie infectieuse grave. L'autopsie confirma cet état par l'absence de lésions imputables à une maladie infectieuse. Les constatations nécropsiques les plus remarquables furent une néphrose bilatérale, une dégénérescence myocardique. La cause probable de la mort fut un déséquilibre électrolytique, notamment une hypokaliémie qui affecta secondairement le myocarde. Une toxicité rénale engendrée par les médicaments cytotoxiques, en particulier le cyclo phosphamide peut avoir favorisé le déséquilibre électrolytique. Zusammenfassung Ein Fohlen mit schwerer primärer, kombinierter Immundefizienz (PSCID) — diagnostiziert innert der ersten zwei Lebenswochen — wurde mit seiner Mutter in Halbis...

No abstract