RESUMO
OBJECTIVE: This study has two aims: 1. Validate a non-invasive malocclusion model of mouse temporomandibular joint (TMJ) osteoarthritis (OA) that we developed and 2. Confirm role of inflammation in TMJ OA by comparing the disease in the presence and absence of the receptor for advanced glycation end products (RAGE). DESIGN: The malocclusion procedure was performed on eight week old mice, either wild type (WT) or without RAGE. RESULTS: We observed TMJ OA at two weeks post-misalignment/malocclusion. The modified Mankin score used for the semi-quantitative assessment of OA showed an overall significantly higher score in mice with malocclusion compared to control mice at all times points (2, 4, 6 and 8 weeks). Mice with malocclusion showed a decrease in body weight by the first week after misalignment but returned to normal weight for their ages during the following weeks. The RAGE knock out (KO) mice had statistically lower modified Mankin scores compared to WT mice of the same age. The RAGE KO mice had statistically lower levels of Mmp-13 and HtrA1 but higher Tgf-ß1, as measured by immunohistochemistry, compared to WT mice at eight weeks post malocclusion. CONCLUSIONS: We demonstrate an inexpensive, efficient, highly reproducible and non-invasive model of mouse TMJ OA. The mechanical nature of the malocclusion resembles the natural development of TMJ OA in humans, making this an ideal model in future studies that aim to elucidate the pathogenesis of the disease leading to the discovery of a treatment. The RAGE plays a role in mouse TMJ OA.
Assuntos
Má Oclusão/patologia , Osteoartrite/patologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Articulação Temporomandibular/patologia , Animais , Mau Alinhamento Ósseo , Cartilagem Articular/patologia , Condrócitos/patologia , Modelos Animais de Doenças , Produtos Finais de Glicação Avançada/metabolismo , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Imuno-Histoquímica , Má Oclusão/fisiopatologia , Metaloproteinase 13 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fios Ortodônticos , Osteoartrite/fisiopatologia , Serina Endopeptidases/metabolismo , Transtornos da Articulação Temporomandibular/patologia , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Type II diabetes is caused by a failure of the pancreatic beta-cells to compensate for insulin resistance leading to hyperglycaemia. There is evidence for an essential role of an increased beta-cell apoptosis in type II diabetes. High glucose concentrations induce IL-1beta production in human beta-cells, Fas expression and concomitant apoptosis owing to a constitutive expression of FasL. FASL and FAS map to loci linked to type II diabetes and estimates of insulin resistance, respectively. We have tested two functional promoter polymorphisms, FAS-670 G>A and FASL-844C>T as well as a microsatellite in the 3' UTR of FASL for association to type II diabetes in 549 type II diabetic patients and 525 normal-glucose-tolerant (NGT) control subjects. Furthermore, we have tested these polymorphisms for association to estimates of beta-cell function and insulin resistance in NGT subjects. We found significant association to type II diabetes for the allele distribution of the FASL microsatellite (P-value 0.02, Bonferroni corrected). The FAS-670G>A was associated with homeostasis model assessment insulin resistance index and body mass index (P-values 0.02 and 0.02). We conclude that polymorphisms of FASL and FAS associate with type II diabetes and estimates of insulin resistance in Danish white subjects.
Assuntos
Diabetes Mellitus Tipo 2/genética , Resistência à Insulina/genética , Glicoproteínas de Membrana/genética , Repetições de Microssatélites , Receptores do Fator de Necrose Tumoral/genética , Fatores de Necrose Tumoral/genética , Regiões 3' não Traduzidas/genética , Adulto , Idoso , Apoptose , Dinamarca , Proteína Ligante Fas , Feminino , Humanos , Células Secretoras de Insulina/citologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Característica Quantitativa Herdável , Receptor fasRESUMO
To maintain the patency of a peripherally inserted central catheter (PICC) line, it has been common practice to use 100 units of heparin as a flush. In this study, it was hypothesized that 10 units of heparin would maintain the patency of the PICC line as effectively as 100 units. To test this hypothesis, 46 patients who had PICC lines placed were retrospectively identified. Twenty patients received 100 units of heparin and had a PICC indwelling time ranging from 4 to 52 days (mean = 12 days) for a total of 314 indwelling days. Twenty-six patients received 10 units of heparin and had PICC indwelling time ranging from 2 to 54 days (mean = 11 days) for a total of 440 indwelling days. In two patients who received 100 units of heparin, PICC lines clotted after 2 days and 16 days, respectively. In four patients who received 10 units of heparin, PICC lines clotted after 5, 9, 29, and 36 days, respectively. Given the fact that this study was retrospective and uncontrolled, a statistical analysis was inappropriate; however, as a descriptive study, there appears to be evidence to support the original hypothesis. A controlled, blinded study must be performed to test the hypothesis statistically.