One potential limitation of adenovirus (Ad)-based vectors for the gene therapy of cystic fibrosis (CF) and other genetic diseases is the transience of expression observed in most in vivo systems. In this study, the influence of various factors on persistence of transgene expression in the lung was investigated. In the absence of immune pressure, such as in the nude mouse, the genomic structure of the vector was found to be predominant in determining the persistence of expression; Ad vector constructs with an E1-E3+E4ORF6+ backbone encoding beta-galactosidase (beta-Gal) or the cystic fibrosis transmembrane conductance regulator (CFTR) produced declining levels of expression while an Ad/CMV beta Gal vector with an E1-E3+E4+ backbone gave rise to sustained, long-term reporter gene expression. The ability of the latter vector to persist was in turn limited in part by the presence of cytotoxic T lymphocytes (CTLs). Adoptive transfer experiments indicated that CTLs directed against either viral proteins or the beta-Gal reporter gene product were able to reduce expression in nude C57BL/6 mice stably expressing beta-Gal from the E4+ vector. Finally, the specificity and strength of the CTL response elicited by Ad vector was found to vary considerably depending on mouse strain haplotype. These results indicate that persistence of transgene expression in a given system is determined by the interplay between several factors including genomic structure of the vector, host background, and immune response.

Background. Obesity has reached epidemic proportions in dogs and, as in humans, cost of care has increased due to associated comorbidities. In humans, asymptomatic urinary tract infections (UTI) may be more prevalent in the obese. Asymptomatic bacteriuria (AB) is the term used when UTI are asymptomatic. We hypothesized that morbidly obese dogs are similarly more likely to have asymptomatic bacteriuria than lean, overweight, and moderately obese dogs.Methods. A retrospective study was undertaken to explore a possible association between obesity and asymptomatic bacteriuria. Records from lean, overweight, and obese dogs receiving both a dual energy absorptiometry (DXA) scan and urine culture were included.Results. Six positive urine cultures were identified among 46 dogs fulfilling search criteria. All six positive cultures were found in dogs with body fat percentage of >45%. In dogs with body fat percentage of <45%, there were no positive urine cultures.Discussion. There was an increased prevalence of asymptomatic bacteriuria in the morbidly obese dogs in this study compared to those that were lean, overweight, or moderately obese. Whether antibiotic therapy is necessary in such cases is still being debated, but because asymptomatic bacteriuria may be associated with ascending infections, uroliths, or other complications, the data reported herein support the screening of obese patients for bacteriuria.

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The effect of probiotic therapy in chronic kidney disease (CKD) in cats is poorly defined, but gaining in popularity. However, cat owners often prefer to administer probiotics by combining them with food, rather than administering capsules intact, as is prescribed by the manufacturer. The efficacy of such non-recommended administration is unknown. In this double-blinded, controlled clinical trial, 10 cats with naturally-occurring CKD were randomized to receive either a probiotic-prebiotic combination (synbiotic) or psyllium husk (prebiotic only) for 2 months. Medications were sprinkled and mixed into food or given as a slurry. Blood urea nitrogen (BUN) and creatinine were measured twice prior to administration of medication, and then monthly for 2 months during the medication administration. Owners and clinicians were masked as to treatment. The maximal percentage change in BUN and creatinine was calculated for each cat. No differences in percentage change were detected between groups (P=0.8 for both BUN and creatinine). The synbiotic supplement used in this study, when applied to food or administered as a slurry fails to reduce azotemia in cats with CKD. Therefore, owners should not administer this synbiotic in this manner.