STARRY SKY HEPATIC ULTRASONOGRAPHIC PATTERN IN HORSES

The starry sky hepatic pattern is an unusual ultrasonographic appearance of equine liver characterized by numerous small, hyperechoic foci, some of which cast an acoustic shadow, distributed randomly throughout the hepatic parenchyma. Our objectives were to describe the signalment, clinical signs, clinicopathological findings, primary disease process, and ultrasonographic findings of horses with this ultrasonographic pattern, as well as determine the associated gross and histologic changes. The starry sky pattern was identified in 18 adult horses of mixed gender and breed. The horses had various clinical signs, with weight loss and anorexia reported most commonly. Liver size and parenchymal echogenicity were normal in most horses. The hyperechoic foci frequently caused acoustic shadowing. Biliary dilation was noted rarely. The ultrasonographic pattern was the result of numerous fibrosing hepatic granulomas in all horses evaluated histologically. γ‐Glutamyltransferase was the most commonly elevated hepatic enzyme, though it was increased in fewer than half the horses. Fifteen horses had an additional disease that was identified as the apparent cause of clinical signs. Three horses had primary hepatic disease while 12 had diseases of other body systems. Therefore, the starry sky ultrasonographic pattern is likely incidental in most horses and not clinically significant. Improved recognition of this pattern and further investigation of affected horses may help refine the etiology and clinical significance of the granulomas.     

GROSS AND HISTOPATHOLOGIC CORRELATION OF LOW‐FIELD MAGNETIC RESONANCE IMAGING FINDINGS IN THE STIFLE OF ASYMPTOMATIC HORSES

With the recent introduction of a 0.25T rotating MRI system, clinical evaluation of the equine stifle joint is now possible in the average equine athlete. A recent publication described common abnormalities of horses with stifle lameness detected with a low‐field MRI system; however, postmortem corroboration of the lesions detected was not possible. Therefore, our objective was to compare postmortem findings with low‐field MRI findings in equine cadaver stifle joints. Ten fresh cadaver stifle joints from horses without clinical signs of stifle disease were evaluated using low‐field MRI, gross dissection, and histopathology. In eight stifles, either the lateral or medial cranial meniscotibial ligament had an irregular shape, fiber separation, or moderate abnormal signal intensity (SI) on all sequences. In five stifles, the medial femoral condyle had articular cartilage fibrillation with or without an osteochondral defect over the weight bearing surface of the medial femoral condyle. All stifles had abnormal SI on all sequences within the patellar ligaments that corresponded with adipose tissue infiltrating between the collagen bundles. Other abnormalities identified included articular cartilage fibrillation of the tibial condyles in three stifles, and articular cartilage fibrillation with chondral defects in the patella in three stifles. All abnormalities detected with low‐field MRI were corroborated by gross dissection. Findings from the current study supported the use of low‐field MRI for detection of stifle joint lesions in horses and demonstrated that some stifle joint pathologies may be subclinical in horses.     

Evaluation of the carryover effect of antibiotic,bee pollen and propolis on growth performance,carcass traits and splenic and hepatic histology of growing rabbits

Sixty‐four nulliparous female rabbits were distributed among eight groups (eight animals/group). Group one was the unsupplemented control group; the other seven groups were supplemented with zinc bacitracin (ZnB) at 100 mg, or bee pollen (BP) and/or propolis (Pro) at 150 and 300 mg in a capsulated form, three times a week, day after day, continuously all over the experimental period. The experiment was run for eight parties; at each parity, 28 kids of each doe group (a total of 224 rabbits) were divided into two subgroups weaned, respectively, at 24 and 30 days of age. Thus, for each parity, there were 16 groups (eight does treatments × two weaning age, 14 rabbits per group). The growing rabbits fed the standard diets without supplements. The growth performance, the carcass traits, the liver and the spleen histology of rabbits were checked up to 90 days of age to find possible carryover effects of the supplements. The supplements had no significant effect on most of the growth performance at 90 days of age, but BP150 and BP+Pro300 increased the growth rate in comparison with ZnB group. The liver weight in the control, BP300 and Pro300 groups was higher than the ZnB one. The spleen weight was higher in the groups ZnB, BP150, Pro300 and BP+Pro300, followed by the control, BP300 and BP+Pro150 and thus Pro150. The heart % in the BP150 and Pro300 groups was higher than ZnB and BP+Pro150 groups. A lymphoid hyperplasia of splenic white pulp was observed in the BP+Pro groups, while propolis alone showed a mild activation of lymphobiosis. The Pro and BP groups showed the same picture of the control group exhibiting a hydropic degeneration of mostly hepatic cells, while the ZnB group exhibited adverse effect on the bile ducts featuring portal periductal inflammatory cells infiltration with epithelial hyperplasia reflecting chronic cholangitis.     

Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma

Immunotherapeutic strategies have shown promise for the treatment of canine osteosarcoma (cOSA). Very little is known about the immune microenvironment within cOSA, however, limiting our ability to identify potential immune targets and biomarkers of therapeutic response. We therefore prospectively assessed the disease‐free interval (DFI) and overall survival time (ST) of 30 dogs with cOSA treated with amputation and six doses of adjuvant carboplatin. We then quantified lymphocytic (CD3+, FOXP3+) and macrophage (CD204+) infiltrates within the primary tumours of this cohort using immunohistochemistry, and evaluated their association with outcome. Overall, the median DFI and ST were 392 and 455 days, respectively. The median number of CD3+ and FOXP3+ infiltrates were 45.8 cells/mm² (4.6‐607.6 cells/mm²) and 8.5 mm² (0‐163.1 cells/mm²), respectively. The median area of CD204+ macrophages was 4.7% (1.3%‐23.3%), and dogs with tumours containing greater than 4.7% CD204+ macrophages experienced a significantly longer DFI (P = 0.016). Interestingly, a significantly lower percentage of CD204+ macrophages was detected in cOSA arising from the proximal humerus compared to other appendicular bone locations (P = 0.016). Lymphocytic infiltrates did not appear to correlate with outcome in cOSA. Overall, our findings suggest that macrophages may play a role in inhibiting cOSA progression, as has been suggested in human osteosarcoma.     

Ultra‐frequent HRAS p.Q61R somatic mutation in canine acanthomatous ameloblastoma reveals pathogenic similarities with human ameloblastoma

Ameloblastoma is a locally aggressive odontogenic tumour that occurs in humans and dogs. Most ameloblastomas (AM) in humans harbour mutually‐exclusive driving mutations in BRAF, HRAS, KRAS, NRAS or FGFR2 that activate MAPK signalling, and in SMO that activates Hedgehog signalling. The remarkable clinical and histological similarities between canine acanthomatous ameloblastoma (CAA) and AM suggest they may harbour similar driving mutations. In this study, aimed at characterizing the mutational status of SMO, BRAF, HRAS, KRAS, NRAS and FGFR2 in CAA, we used RNA sequencing, Sanger sequencing and restriction fragment length polymorphism assays to demonstrate that 94% of CAA (n = 16) harbour a somatic HRAS p.Q61R mutation. The similarities in MAPK‐activating mutational profiles between CAA and AM implicate conserved molecular mechanisms of tumorigenesis, thus, qualifying the dog as a potentially useful model of disease. Given the relevance of RAS mutations in the pathogenesis of odontogenic tumours and other types of cancer, the results of this study are of comparative, translational, and veterinary value.     

Pharmacokinetics of sanguinarine,chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half‐life (t_1/2) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (C_max) of DHSA (2.49 ± 1.4 μg/L) was higher that of SA (1.89 ± 0.8 μg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h^?1·kg^?1) with a t_1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.     

Animal Biowarfare Research: Historical Perspective and Potential Future Attacks

A biological attack on livestock or poultry could result in the loss of valuable animals, costs related to the containment of outbreaks and the disposal of carcasses, lost trade and other economic effects involving suppliers, transporters, distributors and restaurants; however, it is not possible to secure all livestock, and livestock are much less well guarded than human targets. Thus, the vulnerability of the livestock industry to the introduction of biological agents varies for the following reasons: (i) the majority of lethal and contagious biological agents are environmentally resilient, endemic in foreign countries and harmless to humans, making it easier for terrorists to acquire, handle and deploy these pathogens, (ii) with animals concentrated in fewer production facilities and frequently transported between these facilities, a single pathogen introduction could cause widespread infection and (iii) the extent of human travel around the globe makes it difficult to exclude exotic animal diseases as possible biological agents. Historically, many governments have developed and planned to use biological agents for direct attacks on livestock or poultry. In the past, developed nations have actively developed biological weapons to target animals. The potential spectrum of bioterrorism ranges from isolated acts against individuals by individuals to tactical and strategic military attacks and state‐sponsored international terrorism intended to cause mass casualties in animals, humans or both. This review provides an overview of the past development and use of biological weapons and describes potential future attacks.