ARTICLES response through the oral delivery of bacterial extracts. This procedure is a common practice in Europe to reduce the clinical symptoms, the incidence, the duration, and the severity of disease in patients suffering from recurrent respiratory infections. 11,12 According to the concept of " common mucosal immune system, " presentation of an antigen at one mucosal site leads to the stimulation of an immune response at a distant mucosal site. Similarly, oral treatment with bacterial extracts modulates both systemic and local immune responses. 13 However, the mechanisms underlying the immunostimulatory effect of these bacterial extracts via the gastrointestinal route remain unclear. Broncho-Vaxom (BV) is an endotoxin-low, lyophilized fractionated alkaline extract of the following eight bacterial strains: Haemophilus influenzae , Diplococcus pneumonia , Klebsiella pneumoniae , Klebsiella ozaenae , Staphylococcus aureus , Streptococcus pyogenes , Streptococcus viridans , and Neisseria catarrhalis. It has been widely used in children and adults suffering from repeated upper respiratory tract infections, 14-16 and it efficiently reduces both the frequency and the duration of the infections. 12 In the present report, we have investigated the effect of oral BV administration in the development of allergic airway inflammation. To this aim, BALB / c mice were treated with BV orally, and subsequently sensitized and challenged with the Leishmania homolog of receptors for activated c kinase (LACK) antigen 17 or with the commonly used OVA antigen. RESULTS Oral administration of BV protects mice from allergic airway inflammation

OBJECTIVECalcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy in the last decades, but its mechanisms of action are not elucidated. CaD is able to correct the excessive vascular permeability in the retina of diabetic patients and in experimental diabetes. We investigated the molecular and cellular mechanisms underlying the protective effects of CaD against the increase in blood–retinal barrier (BRB) permeability induced by diabetes.RESEARCH DESIGN AND METHODSWistar rats were divided into three groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with CaD. The BRB breakdown was evaluated using Evans blue. The content or distribution of tight junction proteins (occludin, claudin-5, and zonula occluden-1 [ZO-1]), intercellular adhesion molecule-1 (ICAM-1), and p38 mitogen-activated protein kinase (p38 MAPK) was evaluated by Western blotting and immunohistochemistry. Leukocyte adhesion was evaluated in retinal vessels and in vitro. Oxidative stress was evaluated by the detection of oxidized carbonyls and tyrosine nitration. NF-κB activation was measured by enzyme-linked immunosorbent assay.RESULTSDiabetes increased the BRB permeability and retinal thickness. Diabetes also decreased occludin and claudin-5 levels and altered the distribution of ZO-1 and occludin in retinal vessels. These changes were inhibited by CaD treatment. CaD also inhibited the increase in leukocyte adhesion to retinal vessels or endothelial cells and in ICAM-1 levels, induced by diabetes or elevated glucose. Moreover, CaD decreased oxidative stress and p38 MAPK and NF-κB activation caused by diabetes.CONCLUSIONSCaD prevents the BRB breakdown induced by diabetes, by restoring tight junction protein levels and organization and decreasing leukocyte adhesion to retinal vessels. The protective effects of CaD are likely to involve the inhibition of p38 MAPK and NF-κB activation, possibly through the inhibition of oxidative/nitrosative stress.

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The onset of type 1 diabetes in NOD mice is delayed by oral administration of a bacterial extract (OM-85) and can be completely prevented by its intraperitoneal administration. Optimal prevention is observed when starting treatment at 3 or 6 weeks of age, and some effect is still observed with treatment at 10 weeks of age. Using genetically deficient mice and cytokine-neutralizing monoclonal antibodies, we demonstrate here that the therapeutic effect does not involve T-helper type 2 cytokines (interleu- kin

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