Interruption of inflammatory pathways may provide a novel approach to the therapy of atherosclerosis. Recently, we and others have implicated the immune mediator dyad CD40͞CD40L (CD40 ligand), which is expressed on endothelial and smooth muscle cells, macrophages, and T lymphocytes within human atherosclerotic lesions, in aspects of atherogenesis and the acute coronary syndromes, including regulation of matrix metalloproteinases, procoagulant activity, cytokines, etc. In vivo, interruption of CD40 signaling reduced the initiation and early phases of atheroma formation in hypercholesterolemic mice. However, whether interruption of CD40 signaling can retard the progression or even regress established lesions remains unknown. We report here that anti-CD40L antibody treatment of randomly assigned low-density lipoprotein receptor-deficient mice during the second half of a 26-week regimen of high-cholesterol diet did not regress, but did significantly reduce further evolution of established atherosclerotic lesions within the aortic arch and particularly the thoracic and abdominal aorta, as compared with control treatment (application of rat-IgG or saline; 13 weeks, continued high-cholesterol diet). In addition to limiting lesion progression, anti-CD40L treatment changed the composition of atheroma in manners thought to favor plaque stability, e.g., reduced relative content of macrophages and lipid, as well as increased relative content of smooth muscle cells and collagen. These data implicate CD40͞CD40L as crucial mediators not only in the initial events of atherogenesis but also during the evolution of established atheroma. This study lends further support to the importance of this specific inflammatory signaling pathway in atherosclerosis and its complications.

The incidence of an initial medial elbow injury was 22.1%. Age, number of throws per day, thoracic kyphosis angle, and elbow extension deficit are newly discovered risk factors related to physical function. Improvement of the posture and early detection of a silent elbow extension deficit may prevent a medial elbow injury.

These results indicate that the experimental allergic rhinitis established in the present study can be a valuable model for analyzing the pathogenesis of the disease and developing new therapeutic drugs.

A prevention program aiming to improve physical function can prevent medial elbow injury in youth baseball players.

ABSTRACT-In the majority of the models of experimental allergic rhinitis, antigen challenge has been performed by single topical instillation or perfusion with the solution. The present study was performed to establish a good model using Japanese cedar pollen, which is able to repeatedly induce allergy restricted to the upper airway. Guinea pigs sensitized with the pollen extracts were subjected to quantitative and repeated inhaling of the pollen with a devised apparatus. Following the respective challenges, the nasal cavity was washed with a new technique: Washing with physiologic saline was performed from one nostril to the other one, the latter of which was kept under slightly reduced pressure. When the animal was subjected to cedar pollen inhalation, almost all the pollens inhaled were located in the upper airway. At the 5th inhalation, nasal cavity lavage revealed that both albumin leakage and histamine release into the nasal cavity were in creased at maximum levels in 1 hr (respectively 2 mg and 3 ng/animal); and at the same time, a considerable number of leukocytes, especially eosinophils, were found migrating into the nasal cavity for at least 10 hr. The present methods can permit various analyses of allergic rhinitis and the assessment of drugs without sacrificing the animal over the long term.

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In CAI, altered subtalar internal rotation occurs with increased talocrural anterior translation and reduced talocrural internal rotation during weightbearing ankle internal rotation in plantarflexion. These results suggest that altered subtalar mechanics may contribute to CAI symptoms.

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