Inhibition of PAF-induced eosinophil accumulation in pulmonary airways of guinea pigs by anti-asthma drugs

Intraperitoneal (i.p.) injection of platelet activating factor (PAF) in guinea pigs caused a dose-related increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). The prevalence of eosinophils in BALF had significantly increased within 1 hr of i.p. injection of PAF (10 micrograms/animal) and was maximal after 24 hr. Subcutaneous osmotic mini-pumps were used to administer drugs for 5 days prior to i.p. injection of PAF (10 micrograms/animal) and for the subsequent 24 hr. The percentage increase of eosinophils in BALF, due to PAF, was inhibited in animals treated with dexamethasone, aminophylline, cromoglycate, tranilast or ketotifen, but not in animals treated with oxatomide, azelastine, amlexanox, ibudilast or AA-861. These results suggest that inhibition of pulmonary eosinophilia may be a necessary property of prophylactic anti-asthma drugs and provide indirect evidence favoring a role for PAF in eosinophilia of asthma.     

Outbreak of serogroup C meningococcal disease caused by a variant of Neisseria meningitidis serotype 2a ET-15 in a community of men who have sex with men

We describe an outbreak, in a community of men who have sex with men, of serogroup C meningococcal disease caused by a genetic variant of the serotype 2a ET-15 Neisseria meningitidis characterized by a point mutation in the gene coding for the serotype 2a antigen. A microbiological characterization of the outbreak strain is presented in this report.     

Loss of epithelial integrity resulting from E-cadherin dysfunction predisposes airway epithelial cells to adenoviral infection

Epithelial intercellular adhesion is fundamental to the formation of the airway epithelial protective barrier. In this respect, cadherins are important because these adhesion molecules regulate formation and maintenance of epithelial intercellular junctions. To study the importance of airway epithelial integrity in determining susceptibility to virus infection, we used a replication-incompetent adenovirus, RAd35, and an E-cadherin specific function-blocking antibody, SHE78-7, to disrupt intercellular contacts in human bronchial epithelial cell line 16HBE14o- and primary bronchial epithelial cells. After exposure of 16HBE14o- cell cultures to SHE78-7, disruption of the transepithelial permeability barrier was indicated by a loss of transepithelial electrical resistance and an associated increase of mannitol, inulin, and dextran paracellular flux. Subsequent exposure of SHE78-7-treated cell cultures to RAd35 showed a remarkable increase in adenoviral infection as assessed by beta-galactosidase reporter gene expression. In cultures exposed to SHE78-7, disruption of E-cadherin function resulted in infection equivalent to that in control cultures using 16-fold lower viral titers. These studies show that manipulation of E-cadherin function provides a specific means of altering epithelial integrity that in turn determines resistance of airway epithelia to adenoviral infection.     

Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness

Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects’ blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4⁺ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4⁺ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4⁺ T cell immune responsiveness.     

Molekulare Mechanismen der Embryoimplantation im Endometrium

Human Reproduction is a very complex and surprisingly inefficient process. The embryo development and the generation of a receptive endometrium needs an exact timing and synchronization. Understanding the factors involved in preimplantation embryo development and embryo-maternal interaction and implantation is crucial for improving success rates in reproductive medicine. The purpose of the present review is to describe briefly the function of adhesion- and hormonal factors, cytokines, growth factors and metalloproteinases. A better understanding of the molecular mechanisms of implantation will be responsible for the improvement of clinical and therapeutical management of sterility, infertility and contraception.     

Multimodal imaging in photic retinopathy

Letter to the Editor