In vivo stem cell tracking using scintigraphy in a canine model of DMD

One of the main challenges in cell therapy for muscle diseases is to efficiently target the muscle. To address this issue and achieve better understanding of in vivo cell fate, we evaluated the relevance of a non-invasive cell tracking method in the Golden Retriever Muscular Dystrophy (GRMD) model, a well-recognised model of Duchenne Muscular Dystrophy (DMD). Mesoangioblasts were directly labelled with 111In-oxine, and injected through one of the femoral arteries. The scintigraphy images obtained provided the first quantitative mapping of the immediate biodistribution of mesoangioblasts in a large animal model of DMD. The results revealed that cells were trapped by the first capillary filters: the injected limb and the lung. During the days following injection, radioactivity was redistributed to the liver. In vitro studies, performed with the same cells prepared for injecting the animal, revealed prominent cell death and 111In release. In vivo, cell death resulted in 111In release into the vasculature that was taken up by the liver, resulting in a non-specific and non-cell-bound radioactive signal. Indirect labelling methods would be an attractive alternative to track cells on the mid- and long-term

Adjuvant immunotherapy of feline injection-site sarcomas with the recombinant canarypox virus expressing feline interleukine-2 evaluated in a controlled monocentric clinical trial when used in association with surgery and brachytherapy

The objective of this randomised, controlled, parallel-group monocentric clinical trial was to assess the efficacy (at low and high dose) and the safety (at high dose) of a recombinant canarypox virus (ALVAC®) expressing feline interleukin 2 (IL-2). ALVAC IL-2 was administered to cats as an adjunct treatment of feline fibrosarcoma in complement to surgery and brachytherapy (reference treatment). Seventy-one cats with a first occurrence of feline fibrosarcoma were referred to the Veterinary Oncology Centre for post-surgical radiotherapy. They were randomly assigned to three treatment groups: reference treatment group (23 cats), ALVAC IL-2 low dose group (25 cats) and ALVAC IL-2 high dose group (23 cats). Two dosages of ALVAC IL-2 were used to assess both safety (high dose) and efficacy (high and low doses). The treatment consisted of six consecutive doses of ALVAC IL-2 administered subcutaneously at the tumour site on Day 0 (one day before brachytherapy treatment), Day 7, Day 14, Day 21, Day 35 and Day 49. All cats were evaluated for relapse (i.e. local tumour recurrence and/or metastasis) every three months for at least one year (ALVAC IL-2 high dose group) or two years (reference treatment and ALVAC IL-2 low dose groups) by complete physical examination and regular CT scans. ALVAC IL-2 treatment was well tolerated and adverse effects were limited to mild local reactions. ALVAC IL-2 treatment resulted in a significant longer median time to relapse (>730 days in the ALVAC IL-2 low dose group) than in the reference treatment group (287 days), and a significant reduction of the risk of relapse by 56% at one year (ALVAC IL-2 treatment groups versus reference treatment group) and 65% at two years (ALVAC IL-2 low dose treatment group versus reference treatment group)

Plasma ACTH precursors in cats with pituitary-dependent hyperadrenocorticism

Background : Diagnosis of pituitary-dependent hyperadrenocorticism (PDH) in cats is challenging because there is no specific diagnostic test. Hypothesis/Objective : The determination of plasma ACTH precursor (POMC and pro-ACTH) concentration might facilitate the diagnosis of PDH in cats. The aim of the study was to evaluate prospectively the plasma concentrations of ACTH precursors in a small cohort of cats with PDH and to estimate the value of this approach for diagnosis. Animals Four groups of cats were included: group 1 (cats with PDH), group 2 (cats with diabetes mellitus but not hyperadrenocorticism (HAC)), group 3 (cats with diabetes mellitus and confirmed acromegaly but not HAC), and group 4 (healthy cats). Methods : PDH diagnosis was based on clinical data, low-dose dexamethasone suppression test (LDDST), and adrenal and pituitary gland computed tomography (CT) scan. For groups 2, 3, and 4, hyperadrenocorticism was excluded by LDDST or urine cortisol:creatinine ratio (UCCR). An immunoluminometric assay was used to determine plasma concentrations of ACTH precursors in the 4 groups of cats. Results : Group 1 contained 9 cats (enlarged pituitary gland in 7/9). Plasma ACTH precursor concentrations ranged from 1010 similar to pmol/L with 8/9 concentrations =229 similar to pmol/L. Groups 2, 3, and 4 included 13, 7, and 13 cats, respectively. Plasma ACTH precursor concentrations ranged from <53 to 96 similar to pmol/L in group 2, <53 to 72 similar to pmol/L in group 3, and <53 to 99 similar to pmol/L in group 4. Conclusion and Clinical Importance : High plasma concentration of ACTH precursors in cats (>100 similar to pmol/L) is highly suggestive of PDH

Primary Hyperparathyroidism and Monoclonal Gammopathy in a Dog

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