Macrophage migration inhibitory factor (MIF) is originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibits the random migration of macrophages. MIF is now recognized as a multipotent cytokine involved in the regulation of immune and inf lammatory responses. In rheumatoid arthritis (RA), MIF promotes inf lammatory responses by inducing proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating neutrophil chemotaxis, and regulating angiogenesis and osteoclast differentiation. Expression of MIF in synovial tissue and synovial fluid levels of MIF are elevated in RA patients. Specifically, MIF levels correlate with RA disease activity and high levels are associated with bone erosion. In animal models of RA, the genetic and therapeutic inhibition of MIF has been shown to control inflammation and bone destruction. Based on the role of MIF in RA pathogenesis, small molecular inhibitors targeting it or its receptor pathways could provide a new therapeutic option for RA patients.
ObjectiveTo compare the accuracy rates of non-guided vs. ultrasound-guided needle placement in four lower limb muscles (tibialis posterior, peroneus longus, and short and long heads of the biceps femoris).MethodsTwo electromyographers examined the four muscles in each of eight lower limbs from four fresh frozen cadavers. Each electromyographer injected an assigned dye into each targeted muscle in a lower limb twice (once without guidance, another under ultrasound guidance). Therefore, four injections were done in each muscle of one lower limb. All injections were performed by two electromyographers using 18 gauge 1.5 inch or 24 gauge 2.4 inch needles to place 0.5 mL of colored acryl solution into the target muscles. The third person was blinded to the injection technique and dissected the lower limbs and determined injection accuracy.ResultsA 71.9% accuracy rate was achieved by blind needle placement vs. 96.9% accuracy with ultrasound-guided needle placement (p=0.001). Blind needle placement accuracy ranged from 50% to 93.8%.ConclusionUltrasound guidance produced superior accuracy compared with that of blind needle placement in most muscles. Clinicians should consider ultrasound guidance to optimize needle placement in these muscles, particularly the tibialis posterior.
The leptin receptor-deficient db/db mouse is a rodent model of type 2 diabetes and obesity. Diabetes in db/db mice shows an age-dependent progression, with early insulin resistance followed by an insulin secretory defect resulting in profound hyperglycemia. However, there is insufficient data on agedependent changes of energy metabolism in db/db mice. We demonstrated an age-dependent decrease in the respiratory exchange ratio (RER), calculated by a ratio of VO2/VCO2, in db/db mice. The RER determined by indirect calorimetry, was 1.03 in db/db mice under 6 weeks of age, which were similar to those in heterozygote (db/+) and wild-type (+/+) mice. However, RER decreased from approximately 0.9 to 0.8 by 10 weeks of age and subsequently returned to approximately 0.9 at 22 weeks of age. The changes in RER were concurrent with the alterations in body weight and blood glucose level. However, other metabolic indicators such as glucose tolerance, changes in body fat mass, and urinary glucose levels, did not change with age. The results suggested that the energy source utilized in db/db mice changed with the age-related progression of diabetes.
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