This study quantified and compared the transduction efficiencies of adenoviral (Ad), Arg-Gly-Asp (RGD)-modified Ad, adenoassociated viral serotype 2 (AAV2), and self-complementary AAV2 (scAAV2) vectors within full-thickness osteoarthritic (OA) and unaffected canine cartilage explants in vitro. Intraarticular administration of Ad and scAAV2 vectors was performed to determine the ability of these vectors to transduce unaffected guinea pig cartilage in vivo. Following explant exposure to vector treatment or control, the onset and surface distribution of reporter gene expression was monitored daily with fluorescent microscopy. At termination, explants were divided: one half was digested for analysis using flow cytometry; the remaining portion was used for histology and immunohistochemistry (IHC). Intact articular joints were collected for real-time RT-PCR and IHC to detect reporter gene expression following injection of selected vectors. Ad vector transduced focal areas along the perimeters of explants; the remaining vectors transduced chondrocytes across 100% of the surface. Greater mean transduction efficiencies were found with both AAV2 vectors as compared to the Ad vector (p 0.026). Ad and Ad-RGD vectors transduced only superficial chondrocytes of OA and unaffected cartilage. Uniform reporter gene expression from AAV2 and scAAV2 was detected in the tangential and transitional zones of OA cartilage, but not deeper zones. AAV2 and scAAV2 vectors achieved partial and fullthickness transduction of unaffected cartilage. In vivo work revealed that scAAV2 vector, but not Ad vector, transduced deeper zones of cartilage and menisci. This study demonstrates that AAV2 and scAAV2 are reliable vectors for use in cartilage in vitro and in vivo. ß
Objective—To determine frequency of antimicrobial drug (AMD) use in dogs within 12 months prior to admission to a veterinary teaching hospital. Design—Owner survey and medical records review. Animals—435 dogs admitted to a veterinary teaching hospital. Procedures—Demographic characteristics and information regarding AMD use in dogs were obtained from medical records and results of surveys completed by owners of dogs. Results—242 (55.6%) dogs received at least 1 AMD within 12 months prior to hospital admission; 125 (51.7%) of these dogs had a disease of the integument at the time of admission. β-Lactam AMDs were used more frequently than AMDs of any other class (176/242 [72.7%] dogs). Three hundred sixty-eight dogs had a medical problem at the time of hospital admission; 225 (61.1%) of these dogs had received at least 1 AMD within 12 months prior to hospital admission. Dogs referred by a veterinarian to the hospital were 2.39 times as likely to have received at least 1 AMD within 30 days prior to hospital admission as were dogs admitted without a referral. Conclusions and Clinical Relevance—Results indicated AMDs were frequently administered to dogs prior to admission to the teaching hospital. Use of AMDs in animals could be a risk factor for coselection and spread of multidrug-resistant pathogens, and colonization or infection of dogs with such pathogens could have a negative impact on the health of other animals and humans.
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