Macrocyclic lactone toxicity due to abamectin in farm dogs without the ABCB1 gene mutation

Abstract

CASE HISTORY: A 5-year-old entire female Huntaway from a sheep and beef farm was one of four dogs that developed clinical signs including hypersalivation, depression, blindness and ataxia after the death of another dog. A 4-year-old female Huntaway farm dog from a second farm was observed to be sitting down more often than usual on the day after being fed part of a calf carcass that had been treated with an abamectin pour-on.

CLINICAL FINDINGS: The first dog was ataxic and depressed but did respond to sound. The second dog presented with an acute onset of blindness, mydriasis, absence of a menace response, hypersalivation, gait abnormalities (e.g. high stepping gait and ataxia), and depression. Other presenting signs included muscle tremors, dehydration and difficulty eating. No abnormalities were detected from routine haematology and biochemistry. Analysis of samples of plasma from both dogs revealed concentrations of abamectin of 0.149 mg/L and 0.260 mg/L for the first and second dogs, respectively. Buccal swabs taken from the first dog for DNA testing for the ABCB1 gene mutation, gave a negative result.

DIAGNOSIS: In addition to the presenting signs which suggested a toxicosis, both dogs had measurable concentrations of abamectin in plasma confirming exposure.

CLINICAL RELEVANCE: Farm dogs exposed to concentrated pour-on products containing abamectin have been poisoned and recover or die. The product labels do not carry any warnings as to the risk of poisoning to dogs. This paper discusses two incidents affecting six farm dogs, but the authors are aware of more toxicoses in farm dogs exposed to abamectin.     

Failure of young goats to acquire resistance to Haemonchus contortus

Two experiments were carried out to investigate the acquisition by goats of resistance to Haemonchus contortus. In Experiment 1, five Saanen wethers reared worm-free and averaging 51/2 months of age at the start of the experiment, were dosed with 200 H. contortus infective larvae three times per week for 10 weeks (approximately 23 infective larvae/kg mean initial liveweight/week) and then given anthelmintic treatment. Each goat and an equal number of worm-free controls were then challenged with 10,000 infective larvae. Post mortem worm counts were carried out 30 days later. In Experiment 2, eight worm-free Saanen wethers, 14 months old at the start of the experiment, were dosed with 825 infective larvae per week for 14 weeks (approximately 23 infective larvae/kg mean initial liveweight/week) except for one week when only 300 larvae were given and one week when no larvae were given. After anthelmintic treatment, each received, together with seven worm-free control animals, a challenge dose of 15,000 infective larvae. Post-mortem worm counts were carried out 28 days later. There were no significant dii- ferences in post-mortem worm counts between previously infected and uninfected groups in either experiment. In both experiments, serum pepsinogen values rose significantly as a result of infection but there was no significant (p>0.5) correlation between worm counts and pepsinogen values on the day of slaughter.     

秦汉时期官方蓄犬现象研究

秦汉时期,官方蓄犬非常普遍。按正史记载及律令要求,此种现象既是选择偏好,也是制度使然,从朝廷中央到地方郡县、边关烽燧莫不如此。与之相应的是官方也为之配备专门的馆舍和官员。对这些犬只的管理,秦汉律令从数量、饲养环境、体型大小等角度都有限制。它们满足了各级官府治理鼠患、祭祀驱邪、娱乐狩猎、警戒防盗、肉食供给等多方面的需要。另外,此时文武官员对皇帝常以"犬马"自称,这种现象或许也与官方蓄犬浸染有关。     

Correlation between the histopathological diagnosis by AgNOR count and AgNOR area in canine mammary tumors

Background: Mammary tumors are the most common type of tumor in female dogs. The histopathological diagnosis is usually made by a hematoxylin-eosin (HE) staining of the tumor, which then requires a pathologist's judgment for assessment of malignancy. The purpose of this study was to investigate an alternative silver staining of some argyrophilic nucleolar organizer regions (AgNOR) for improving the diagnostic accuracy with mammary tumors.
Hypothesis: There is a correlation between the histopathological diagnosis by AgNOR count and AgNOR area in canine mammary tumors.
Animals: Seventy-three canine mammary tumors from 33 female dogs.
Materials and Methods: The AgNOR staining was evaluated retrospectively in 73 canine mammary tumors with a parallel HE staining as a "Gold Standard." Both a quantitative manual counting method and a qualitative computerized morphometric method were tested.
Result: The result from both methods indicated a clinically relevant difference in the mean values of the AgNOR in the following 4 categories: malignant, benign, hyperplastic, and normal mammary tissue. The counting method was superior, with 89% of the cases given a correct diagnosis of a malignant or a nonmalignant canine mammary tumor. The 2 methods were then compared to test their ability to classify the tumors correctly. Again, the counting method was the most reliable method, with a sensitivity of 80% and a specificity of 76% when the upper 50% of the AgNOR counts were presumed malignant.
Conclusion and Clinical Importance: The results indicated that an AgNOR test could be an aid to pathologists as a prognostic indicator or to assist them in deciding between a benign or a malignant diagnosis in questionable cases.     

Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma

Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T‐lymphocyte (CD3), FOXP3+ cell, B‐lymphocyte (Pax‐5), and CD204+ macrophage infiltration. We found that T‐lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T‐ and B‐lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti‐tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.     

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.