Objectives The intestinal mucosal barrier is important to protect the body from the large numbers of microbes that inhabit the intestines and the molecules they release. Intestinal barrier function is impaired in humans with cystic fibrosis (CF), including reduced activity of the lipopolysaccharide detoxifying enzyme intestinal alkaline phosphatase (IAP) and increased permeability. The objective of this study was to determine the suitability of using the CF mouse to investigate intestinal barrier function, and whether interventions that are beneficial for the CF mouse intestinal phenotype (antibiotics or laxative) would improve barrier function. Also tested were the effects of exogenous IAP administration. Methods The Cftrtm1UNC mouse was used. IAP expression (encoded by the murine Akp3 gene) was measured by qRT-PCR and enzyme activity. Intestinal permeability was assessed by measuring rhodamine dextran plasma levels following gavage. Results CF mice had 40% Akp3 mRNA expression and 30% IAP enzyme activity, as compared to wild type mice. Oral antibiotics and laxative treatments normalized Akp3 expression and IAP enzyme activity in the CF intestine. CF mice had a 5-fold greater transfer of rhodamine dextran from gut lumen to blood. Antibiotic and laxative treatments reduced intestinal permeability in CF mice. Administration of exogenous purified IAP to CF mice reduced intestinal permeability to WT levels and also reduced small intestinal bacterial overgrowth by more than 80%. Conclusions The CF mouse intestine has impaired mucosal barrier function, similar to human CF. Interventions that improve other aspects of the CF intestinal phenotype (antibiotics and laxative) also increased IAP activity and decreased intestinal permeability in CF mice. Exogenous IAP improved permeability and strongly reduced bacterial overgrowth in CF mice, suggesting this may be a useful therapy for CF.
Background Cercopithifilaria bainae is a tick‐vectored filarioid nematode associated with erythematous dermatitis in dogs. It has not been reported previously in the United States. Hypothesis/Objective To describe clinical, histological and parasitological diagnosis and treatment of C. bainae in a dog. Animals An 11‐month‐old golden retriever/standard poodle mixed breed dog from Florida (USA). Methods and materials The dog had no travel history within or outside the United States, was presented with a one month history of annular erythematous plaques on the head and ulcers on the medial canthi. Lesions were unresponsive to antibiotic treatment. Results Histopathological evaluation of skin biopsies revealed an eosinophilic to lymphohistiocytic perivascular dermatitis with multiple microgranulomas and rare 5–10 μm diameter microfilariae within microgranulomas. Microfilarial morphology was consistent with C. bainae. PCR and sequencing of 18S rRNA and mitochondrial cytochrome oxidase subunit I genes confirmed the nematodes as C. bainae. The dog was treated with a commercial spot‐on containing imidacloprid and moxidectin, and clinical resolution occurred. Conclusions and clinical importance To the best of the authors’ knowledge, this is the first report of C. bainae in a dog in the United States and the first description of dermatological lesions caused primarily by C. bainae.
Background -The value of susceptibility tests for the selection of topical otological antimicrobial agents is unclear. Laboratories test antibiotic concentrations substantially lower than concentrations supplied in topical formulations. Additionally, microbiological consensus statements are not available for topical antimicrobials.Hypothesis/Objectives -The primary aim of this study was to measure the minimum inhibitory (MIC) and bactericidal (MBC) concentrations of enrofloxacin, gentamicin, marbofloxacin, neomycin, orbifloxacin, polymyxin B and silver sulfadiazine (SSD) from concentrations available in otological formulations (COF) to 1:59,000 dilution. The secondary aim was to evaluate the effect of Tris-EDTA in conjunction with these antimicrobial agents.Methods and materials -Twenty resistant clinical isolates [Staphylococcus pseudintermedius (n = 10) and Pseudomonas aeruginosa (n = 10)] were tested by broth microdilution using a concentrated inoculum (3.75 9 10 7 cfu/mL).Results -Concentrations available in otological formulations were at least 269 greater than the MICs for S. pseudintermedius and P. aeruginosa. COFs of polymyxin B and SSD were 279 greater than the MBCs for P. aeruginosa, whereas all other antimicrobial COFs were equal to or less than the MBCs for both organisms. Tris-EDTA significantly reduced the MICs of all antimicrobials, except with SSD for P. aeruginosa, and it significantly increased the MIC of SSD for S. pseudintermedius.Conclusions and clinical importance -Further studies are warranted to validate the present results in vivo. COFs are inhibitory and less likely bactericidal, with few exceptions, against resistant strains of these organisms. Tris-EDTA may be advantageous for P. aeruginosa whereas no additional benefit is afforded against S. pseudintermedius. Susceptibility tests may not be useful for the selection of topical otological antimicrobial agents.
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