Preliminary safety and imaging efficacy of the near-infrared fluorescent contrast agent DA364 during fluorescence-guided surgery in dogs with spontaneous superficial tumors.

Tumor-targeting contrast agents may facilitate resection of solid neoplasms during fluorescence-guided surgery. Preliminary safety and imaging efficacy of the near-infrared fluorescent probe DA364 were evaluated during surgical resection of spontaneous solid tumors in 24 dogs. Intra-operative imaging was performed in situ and on excised specimens to evaluate fluorescence intensities of tumor and adjacent tissues. After standard-of-care tumor resection, the wound bed was imaged again, and additional tissue was excised if residual fluorescence was detected. DA364 was well tolerated after intravenous administration. The median tumor-to-background ratio in situ for mammary tumors, mast cell tumors and sarcomas was 1.8 (range 1.2-3.9), 2.2 (range 1.0-5.6), and 4.2 (range 2.0-4.3), respectively. Qualitative intra-operative tumor identification was feasible in half of the cases. Remaining fluorescence was detected in four wound beds that contained residual disease, and in11 tumor-free wound beds, confirmed by histopathology. Overall, DA364 did not raise safety concerns and showed accumulation in different types of spontaneous tumors, showing potential to pinpoint residual disease. Larger clinical trials are necessary to select accurate dosing and imaging protocols for specific indications to evaluate the sensitivity and specificity of the agent.

Chronic Model of Inflammatory Bowel Disease in IL-10-/- Transgenic Mice: Evaluation with Ultrasound Molecular Imaging.

Objective: Acute mouse models of inflammatory bowel disease (IBD) fail to mirror the chronic nature of IBD in patients. We sought to develop a chronic mouse IBD model for assessing long-term anti-inflammatory effects with ultrasound molecular imaging (USMI) by using dual P- and E-selectin targeted microbubbles (MBSelectin). Materials and Methods: Interleukin 10 deficient (IL-10-/- on a C57BL/6 genetic background; n=55) and FVB (n=16) mice were used. In IL-10-/-mice, various experimental regimens including piroxicam, 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sulfate sodium (DSS), respectively were used for promoting colitis; colitis was induced with DSS in FVB mice. Using clinical and small animal ultrasound scanners, evolution of inflammation in proximal, middle and distal colon, was monitored with USMI by using MBSelectin at multiple time points. Imaged colon segments were analyzed ex vivo for inflammatory changes on H&E staining and for P-selectin expression on immunofluorescence staining. Results: Sustained colitis was not detected with USMI in IL-10-/- or FVB mice with various experimental regimens. USMI signals either gradually decreased after the colitis enhancing/inducing drug/agents were discontinued, or the mortality rate of mice was high. Inflammation was observed on H&E staining in IL-10-/- mice with piroxicam promotion, while stable overexpression of P-selectin was not found on immunofluorescence staining in the same mice. Conclusion: Sustained colitis in IL-10-/- mice induced with piroxicam, TNBS or DSS, and in FVB mice induced with DSS, was not detected with USMI using MBSelectin, and this was verified by immunofluorescence staining for inflammation marker P-selectin. Thus, these models may not be appropriate for long-term monitoring of chronic colitis and subsequent treatment response with dual-selectin targeted USMI.

Scleral and corneal xanthomatous inflammation in a gray mouse lemur (Microcebus murinus).

Bilateral multifocal corneal opacity was detected in a 4.5-year-old male captive gray mouse lemur (Microcebus murinus) without other clinical ocular changes. Histopathological examination revealed a severe diffuse granulomatous scleritis and focal keratitis with intralesional cholesterol, consistent with xanthomatous inflammation. This is the first report of xanthomatous inflammation in a gray mouse lemur. This condition may be the result of systemic factors (lipid metabolism disorders) and/or local predisposing factors such as hemorrhage or inflammation. The pathogenesis in this case could not be fully determined. Further studies on lemurs are required for a better understanding of their lipid metabolism, as well as for diagnosing and evaluating the incidence of xanthomatous inflammation in these species.

Jaagsiekte sheep retrovirus infection of lung slice cultures.

BACKGROUND: Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible neoplastic disease of sheep. OPA is an economically important veterinary disease and is also a valuable naturally occurring animal model of human lung cancer, with which it shares a similar histological appearance and the activation of common cell signaling pathways. Interestingly, the JSRV Env protein is directly oncogenic and capable of driving cellular transformation in vivo and in vitro. Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo. RESULTS: We describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo. Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA. CONCLUSIONS: We conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

Type II atresia ani associated with rectovaginal fistula in a male pseudohermaphrodite kitten.

A combination of gastrointestinal and urogenital congenital abnormalities was diagnosed and surgically treated in a kitten. Physical examination, exploratory laparotomy, castration, histological examination, and cytogenetic karyotyping were utilized to determine the true gender of the kitten. The kitten was confirmed to be a male (38 XY) pseudohermaphrodite with Type II atresia ani and rectovaginal fistula.

Atrésie anale associée à une fistule recto-vaginale chez un chaton male pseudohermaphrodite. Une combinaison d'anomalies congénitales gastro-intestinales et uro-génitales a été diagnostiquée et traitée chirurgicalement chez un chaton. L'examen clinique, une laparotomie exploratrice, la castration avec examen histologique des testicules ainsi qu'un caryotypage ont été réalisés pour déterminer le véritable sexe de l'animal. Il a été confirmé que le chaton était un male (38 XY) pseudohermaphrodite avec atrésie anale de Type II et fistule rectovaginale.(Traduit par les auteurs).

Skin fragility syndrome in a cat with multicentric follicular lymphoma.

An 11-year-old, spayed female domestic shorthair cat was presented for a right flank wound. On clinical examination, a single non-painful skin tear lesion with irregular edges was detected. During the examination, star-shaped cigarette paper-like skin lesions appeared spontaneously. An abdominal mass was also palpated. Feline skin fragility syndrome (FSFS) was suspected and a multicentric lymphoma was diagnosed by fine needle aspiration. The cat's condition declined and it died spontaneously. Post-mortem examination confirmed the diagnosis of lymphoma. Neoplastic lymphocytes were not observed in the skin. Histological analysis of the skin was consistent with the morphological aspects of FSFS. A possible direct link between the two conditions remains a matter of speculation, but this case report provides the first description of FSFS associated with multicentric follicular lymphoma. Thus, multicentric follicular lymphoma should be considered as a differential diagnosis in cats presenting with FSFS.