RESUMO
Using a rat fracture model, we investigated the effects of a decrease in serum levels of thyroid hormone on the fracture-repair process. Rats were divided into the following groups: (a) controls, (b) those treated with methimazole for the duration of the experiment, and (c) those treated with methimazole and L-thyroxine, receiving both for the same duration. Three weeks after the initiation of pharmacologic treatment, closed femoral fractures were produced. The formation of cartilage tissue in the fracture callus in all rats was not obviously different on day 7 after fracture. In the rats treated with methimazole, differentiation from proliferating to hypertrophic chondrocytes in the fracture callus was less advanced and vascular invasion was clearly inhibited on day 12. Gene expression of alkaline phosphatase and osteocalcin in the callus was significantly lower in these rats than in the controls on days 10, 12, and 14. The mechanical properties of the fracture callus were also significantly weaker in these animals than in the controls on day 21, resulting in impaired fracture repair. These results demonstrate that hypothyroidism inhibits endochondral ossification, resulting in an impaired fracture-repair process. L-thyroxine replacement in the rats treated with methimazole caused the impaired repair process to revert to normal. These results indicate that thyroid hormone is one of the critical systemic factors for fracture repair.
Assuntos
Cartilagem/fisiologia , Consolidação da Fratura , Hipotireoidismo/fisiopatologia , Osteogênese , Fosfatase Alcalina/genética , Animais , Fenômenos Biomecânicos , Expressão Gênica , Masculino , Metimazol/farmacologia , Pró-Colágeno/genética , Ratos , Ratos Long-Evans , Tiroxina/farmacologiaRESUMO
Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic-committed progenitor cells (CFU-M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU-M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU-M in vitro. In-vivo and in-vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.
Assuntos
Megacariócitos/citologia , Inibidores da Agregação Plaquetária/farmacologia , Quinazolinas/farmacologia , Adulto , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Divisão Celular , Sobrevivência Celular , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Feminino , Humanos , Masculino , Megacariócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Células-TroncoRESUMO
The authors have developed a murine monoclonal antibody, RC-82.4, against an antigen expressed by a human erythroleukemia cell line OCI-MIR. The antibody reacts with an antigen expressed by proerythroblasts, normoblasts, and some reticulocytes but not expressed in erythrocytes, granulocytes, monocytes, megakaryocytes, plasma cells, or lymphocytes. The authors have established an immunocytochemical method for studying bone marrow smears with RC-82.4. By studying bone marrow smears from 11 patients with M-6 erythroleukemia and 104 patients with various other hematologic and nonhematologic malignancies, the authors have found that RC-82.4 has great sensitivity and specificity in recognizing erythroid differentiation in blasts. The authors have used RC-82.4 and antihemoglobin antibodies to identify erythroblasts in acute and secondary acquired cases of erythroleukemia that would have been unclassifiable by morphologic and all other conventional cytochemical and immunocytochemical criteria.