Transgenic expression of murine chemokine decoy receptor D6 by islets reveals the role of inflammatory CC chemokines in the development of autoimmune diabetes in NOD mice.

AIMS/HYPOTHESIS: Autoimmune diabetes results from a progressive destruction of insulin-producing beta cells in the pancreatic islets by chemokine-attracted lymphocytes. Because islet cells in NOD mice produce chemokines during the development of autoimmune diabetes, we investigated the role of inflammatory CC chemokines in disease progression in these mice. METHODS: We generated a transgenic NOD mouse model that overproduces the inflammatory CC chemokine decoy receptor D6 in pancreatic islets. RESULTS: The frequency of diabetes and insulitis scores of transgenic mice were decreased significantly, compared with non-transgenic control littermates. Transgenic expression of D6 (also known as Ccbp2) did not affect systemic lymphocyte development or alter: (1) the T cell subsets such as T helper (Th)1, Th2 and T regulatory cells; or (2) antigen-presenting cells such as dendritic cells or macrophages. The percentages and numbers of T and B lymphocytes were decreased significantly in the pancreas. Activation status, autoantigen-specific proliferation and diabetogenicity of lymphocytes were also markedly reduced. CONCLUSIONS/INTERPRETATION: Inflammatory CC chemokines play a critical role in the development of autoimmune diabetes. Transgenic expression of D6 in pancreatic islets of NOD mice reduced this pathogenic process by suppressing activation of autoreactive lymphocytes and by reducing migration of lymphocytes to the pancreas.

Experimental osteoarthritis induced by surgical realignment of the patella in BALB/c mice.

The patellofemoral joint is an important source of symptoms in osteoarthritis of the knee. We have used a newly designed surgical model of patellar strengthening to induce osteoarthritis in BALB/c mice and to establish markers by investigating the relationship between osteoarthritis and synovial levels of matrix metalloproteinases (MMPs). Osteoarthritis was induced by using this microsurgical technique under direct vision without involving the cavity of the knee. Degeneration of cartilage was assessed by the Mankin score and synovial tissue was used to determine the mRNA expression levels of MMPs. Irrigation fluid from the knee was used to measure the concentrations of MMP-3 and MMP-9. Analysis of cartilage degeneration was correlated with the levels of expression of MMP. After operation the patellofemoral joint showed evidence of mild osteoarthritis at eight weeks and further degenerative changes by 12 weeks. The level of synovial MMP-9 mRNA correlated with the Mankin score at eight weeks, but not at 12 weeks. The levels of MMP-2, MMP-3 and MMP-14 mRNA correlated with the Mankin score at 12 weeks. An increase in MMP-3 was observed from four weeks up to 16 weeks. MMP-9 was notably increased at eight weeks, but the concentration at 16 weeks had decreased to the level observed at four weeks. Our observations suggest that MMP-2, MMP-3 and MMP-14 could be used as markers of the progression of osteoarthritic change.

Difference in time to x ray with similar time to treatment decision leads to differences in waiting times of patients with hip fracture in a crowded emergency department.

OBJECTIVE: Crowding of patients is common in emergency departments. The number of hip fracture patients not regarded as urgent builds up and patients wait for treatment. In this paper, we present the causes of waiting time and provide some suggestions to improve patient flow in emergency departments. METHODS: We undertook a retrospective review of emergency department records. Included in this study were 112 hip fracture patients seen between January 2005 and January 2007 at an urban, academically affiliated trauma centre. We recorded time to admission, to x ray, and to a definitive treatment decision. Patients were divided into two groups based on time to x ray of < or = 5 min, or > 5 min. RESULTS: There was no difference in the time between taking the x ray and the definitive decision on treatment in the two groups. CONCLUSIONS: We may reduce total waiting time for hip fracture patients by taking an x ray during triage. There are many patients in crowded emergency departments whose symptoms of hip contusion and hip pain, and with a clear history of a fall, are known at admission. Taking an x ray during triage when a patient presents with a typical history and symptoms can reduce total waiting time. We hope that further evaluation could confirm this point.