Toll-like receptors regulate B cell cytokine production in patients with diabetes.

AIMS/HYPOTHESIS: Understanding cellular and molecular events in diabetes mellitus will identify new approaches for therapy. Immune system cells are important modulators of chronic inflammation in diabetes mellitus, but the role of B cells is not adequately studied. The aim of this work was to define the function of B cells in diabetes mellitus patients through focus on B cell responses to pattern recognition receptors. METHODS: We measured expression and function of Toll-like receptors (TLRs) on peripheral blood B cells from diabetes mellitus patients by flow cytometry and multiplexed cytokine analysis. We similarly analysed B cells from non-diabetic donors and periodontal disease patients as comparative cohorts. RESULTS: B cells from diabetes mellitus patients secrete multiple pro-inflammatory cytokines, and IL-8 production is significantly elevated in B cells from diabetic patients compared with those from non-diabetic individuals. These data, plus modest elevation of TLR surface expression, suggest B cell IL-8 hyperproduction is a cytokine-specific outcome of altered TLR function in B cells from diabetes mellitus patients. Altered TLR function is further evidenced by demonstration of an unexpected, albeit modest 'anti-inflammatory' function for TLR4. Importantly, B cells from diabetes mellitus patients fail to secrete IL-10, an anti-inflammatory cytokine implicated in inflammatory disease resolution, under a variety of TLR-stimulating conditions. Comparative analyses of B cells from patients with a second chronic inflammatory disease, periodontal disease, indicated that some alterations in B cell TLR function associate specifically with diabetes mellitus. CONCLUSIONS/INTERPRETATION: Altered TLR function in B cells from diabetes mellitus patients increases inflammation by two mechanisms: elevation of pro-inflammatory IL-8 and lack of anti-inflammatory/protective IL-10 production.

A microneurovascular study of the great saphenous vein in man and the possible implications for survival of venous flaps.

Cross sections (n = 372) of human long saphenous veins (n = 12) from unsalvageable fresh above knee amputation specimens brought to a trauma centre in a large metropolitan hospital were studied. The veins were harvested longitudinally with an amount of soft tissue equivalent to the diameter of the vein and sectioned at intervals of 5 mm. The sections were stained with haematoxylin and eosin for general study, Van Gieson for better delineation of different coats of the vessel wall and reticulin stain to differentiate between venules and arterioles. The vascular structures within the vein wall and its surrounds were analysed by using analySISpro via a CCD camera attached to a light microscope, with the help of a frame grabber card and image analysis software. Results show that the vein has vasa vasorum within its wall, a capillary network around it, arterioles, venules and the saphenous nerve and its branches with their vascular network a further distance apart. The relevance of the microsurgical anatomy of the saphenous vein and its soft tissue envelope in the survival of venous flaps is discussed.

An unusual case of orbital trauma with a large foreign body in the maxilla.

A case in which a broken handle of a scooter was found lodged in the right maxillary sinus and infratemporal fossa with an unusual route of entry through the orbital floor without any injury to the globe is reported.