Allergic conjunctivitis and conjunctival provocation tests in atopic dogs.

INTRODUCTION: Canine atopic dermatitis (cAD) is a very common disease, but little is known about eye involvement. The conjunctival provocation test (CPT) is used in human to study the ocular response to allergenic stimuli and to evaluate anti-allergic therapy. To our knowledge it has not been used in dogs. OBJECTIVES: To evaluate the prevalence of ocular signs in a population of atopic dogs and relate these with clinical cAD scores; and the usefulness of CPT for dust mites in atopic dogs with itchy eyes. PROCEDURES: Sixty cAD patients were evaluated for (i) ocular signs of allergic conjunctivitis including conjunctival hyperemia, chemosis, epiphora, ocular discharge, pruritus and corneal involvement, graded 0 to 3 according to severity, and (2) cAD Extent and Severity Index (CADESI-03). Additionally, CPTs for Dermatophagoides farinae (n = 12) and Dermatophagoides pteronyssinus (n = 12) were performed in sensitized atopic dogs and 24 control dogs. RESULTS: Periocular and ocular signs of allergy were present in 60% (36/60) of cases. Conjunctival hyperemia (90%) was the most common sign. Severity of ocular signs was significantly correlated with eye pruritus (r(s)  = 0.690, P = <0.001) and skin lesions score for head region (r(s) = 0.261, P = 0.04). A highly significant difference (P < 0.001, Fisher test) was found in CPTs between the test and the control groups. CONCLUSION:  Allergic conjunctivitis signs associated with cAD seem under valuated so these patients would benefit from an ophthalmologic evaluation. Furthermore, we found CPT to be a reliable, easy to perform and safe test for the etiologic diagnosis of allergic conjunctivitis in the dog

Antimicrobial resistance (AMR) nanomachines: mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation

In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments

NALP inflammasomes: a central role in innate immunity.

Inflammasomes are cytoplasmic multiprotein complexes that mediate the maturation of the proinflammatory cytokines interleukin-1beta (IL-1beta), IL-18, and possibly IL-33 by controlling the activation of the inflammatory caspases-1 and -5. Assembly of inflammasomes depends on NOD-like receptor (NLR) family members such as NALPs, NAIP, and IPAF. Various microbial and endogenous stimuli activate different types of inflammasomes. This article focuses on the Pyrin domain containing NLRs, known as NALP proteins. Recent findings provide exciting insights into how these proteins might be activated and also provide evidence of the critical role of the NALP inflammasomes in innate immunity and inflammatory diseases