Treatment of Canine Leishmaniasis with Meglumine Antimoniate: A Clinical Study of Tolerability and Efficacy.

Antimoniate therapy, in association with allopurinol, is one of the first-line treatments of canine leishmaniasis (CanL). This study evaluates the potential adverse effects associated with aNm in the treatment of CanL through both a retrospective analysis and a long-term prospective study also aimed to investigate its efficacy. The retrospective study reviewed records of 87 dogs with CanL with at least one follow-up available during or at the end of therapy with aNm (Glucantime®) at a dose of 50 mg/kg administered subcutaneously twice a day in association with allopurinol. In total, 29.8% of dogs showed adverse effects during treatment as local reactions at the injection site (n = 6), severe systemic reaction to pain (originating from the inoculation site) with depression and anorexia (n = 4), systemic disease due to renal function worsening (n = 4), acute pancreatitis (n = 1), diarrhea (n = 5), vomiting (n = 3) and severe idiosyncratic skin reactions (n = 3). Of these dogs, 13 (14.9%) required treatment suspension. The prospective study included 16 dogs, selected among the LeishVet stages II and III CKD IRIS stage 1 (International Renal Interest Society staging of canine Chronic Kidney Disease) and treated with the same aNm plus allopurinol protocol as in the retrospective study and observed for 360 days; 2 dogs were excluded for severe reactions at the injection site. Mild and transient adverse events were reported in the other 4 dogs. The criteria used to evaluate the efficacy of treatment with aNm were as follows: a reduction in the clinical score and improvement and/or normalization of laboratory parameters, negativization of PCR on the bone marrow samples and disease-free interval time. The proportion of reduction in the clinical score reached 91.9% at D180. No animals showed clinical laboratory relapse during the whole study duration and interestingly, the PCR results showed complete negativity between D0 and D60 in 78.5% of animals. Veterinarians must be vigilant regarding the potentially serious adverse effects associated with aNm and promptly stop drug administration if unexpected clinical manifestations occur. On the other hand, they should not discard its use for CanL treatment since it is confirmed that aNm in association with allopurinol is highly effective in controlling CanL.

Generation of Insulin-Producing Cells from Canine Bone Marrow-Derived Mesenchymal Stem Cells: A Preliminary Study.

Cell-based therapy using insulin-producing cells (IPCs) is anticipated as an alternative treatment option to insulin injection or pancreatic islet transplantation for the treatment of diabetes mellitus in both human and veterinary medicine. Several protocols were reported for the differentiation of mesenchymal stem cells (MSCs) into IPCs; to date, glucose-responsive IPCs have only been obtained from canine adipose tissue-derived MSCs (cAD-MSCs), but not from canine bone marrow-derived MSCs (cBM-MSCs). Therefore, this study aims to generate in vitro glucose-responsive IPCs from cBM-MSCs using two differentiation protocols: a two-step protocol using trichostatin (TSA) and a three-step protocol using mercaptoethanol to induce pancreatic and duodenal homeobox gene 1 (PDX-1) expression. A single experiment was carried out for each protocol. BM-MSCs from one dog were successfully cultured and expanded. Cells exposed to the two-step protocol appeared rarely grouped to form small clusters; gene expression analysis showed a slight increase in PDX-1 and insulin expression, but no insulin protein production nor secretion in the culture medium was detected either under basal conditions or following glucose stimulation. Conversely, cells exposed to the three-step protocol under a 3D culture system formed colony-like structures; insulin gene expression was upregulated compared to undifferentiated control and IPCs colonies secreted insulin in the culture medium, although insulin secretion was not enhanced by high-glucose culture conditions. The single experiment results suggest that the three-step differentiation protocol could generate IPCs from cBM-MSCs; however, further experiments are needed to confirm these data. The ability of IPCs from cBM- MSCs to produce insulin, described here for the first time, is a preliminary interesting result. Nevertheless, the IPCs' unresponsiveness to glucose, if confirmed, would affect its clinical application. Further studies are necessary to establish a differentiation protocol in this perspective.

Acute onset of hypertensive encephalopathy in a dog with right adrenal pheochromocytoma and neoplastic invasion of the caudal vena cava: Case report and review of the literature.

Background: Canine pheochromocytomas (PCCs) are rare tumors of the adrenal medulla. Clinical signs are often vague, resulting in intermittent catecholamine over secretion or neoplastic invasion of adjacent structures. Case Description: A 12-year-old Epagneul Breton dog with a 1-year history of chronic kidney disease, was examined for acute onset of severe neurological signs. Based on clinical and instrumental data, hypertensive encephalopathy was suspected. Cardiac and abdominal ultrasound were performed. Severe hypertensive cardiopathy and a right adrenal gland mass with invasion of the caudal vena cava were diagnosed. Computed tomography imaging confirmed the suspect of invasive malignant neoplasia. Emergency pharmacological therapy was started to reduce systemic pressure, improve clinical signs, and stabilize the dog in view of surgical resolution. After initial improvement, patient conditions abruptly worsened, and euthanasia was elected. Histology examination confirmed a right adrenal PCC, with caval invasion. Conclusion: To the authors' conclusions, acute hypertensive encephalopathy is a peculiar manifestation of PCCs. Ultrasound is a useful, and rapid test to suspect PCC as it can detect adrenal alterations, caval invasion, metastasis, and cardiac sequelae consistent with the condition. PCC can mimic multiple affections, and be misinterpreted, especially when a concurrent disease has already been diagnosed. Veterinarians need to be aware that comorbidities could mask clinical signs and delay diagnosis. Furthermore, this clinical case reminds us to include PCC also in the differential diagnosis of dogs with an acute onset of severe neurological signs.

Clinical insights to address canine strongyloidosis in daily practice.

Canine strongyloidosis by Strongyloides stercoralis is a parasitic disease emerging in Europe, which represents both a veterinary clinical issue and a public health challenge because of the zoonotic potential. The disease, not yet frequent in Europe, could induce severe clinical signs in dogs; thus, an early diagnosis and appropriate treatment are desirable. The aim of the present work is to retrospectively investigate the clinical and paraclinical findings in sick dogs naturally infected by S. stercoralis, with particular attention to ultrasound (US) changes at the gastrointestinal level. Twelve dogs were included in the study. The diagnosis was made by means of larval morphological identification on faecal samples and PCR. Most dogs presented with gastrointestinal signs; diarrhea and weight loss were the most common presenting complaint. Only one dog showed respiratory signs, associated to a parasitic cutaneous nodule. Hypoproteinaemia, anaemia, leucocytosis and an increase in alpha2-globulin fraction at serum protein electrophoresis were common (>50%) but not constant findings. The most reported US picture was a fluid-filled, distended, atonic small intestine mostly associated with altered wall layering, while the wall thickness commonly associated with chronic enteritis was only rarely reported. These changes, associated with other clinical and paraclinical alterations, could increase the suspicion of canine strongyloidosis and may direct clinicians to include strongyloidosis in the differential diagnosis of dogs with diarrhea. The histological examination at the intestinal level, available in five dogs, revealed the presence of parasites from the full-thickness biopsy, but not from the endoscopic biopsy. The critical points of diagnosis in clinical practice are also discussed.

Strongyloidiasis in humans and dogs in Southern Italy: an observational study.

Strongyloidiasis is a clinical issue both in humans and in dogs. Moreover, there are concerns about its zoonotic potential. We aimed to explore Strongyloides stercoralis epidemiology in Southern Italy in humans and dogs sharing the same environment in three different settings: (1) kennels (group K); (2) livestock farms (group L) and (3) agricultural farms (group A). For humans, a commercial ELISA test was used for screening. RT-PCR on faecal samples was done for people testing positive or equivocal at serology. On dog's faecal samples, Baermann test and RT-PCR were performed. A total of 145 dogs and 139 persons were tested. Based on faecal tests in dogs and serology in humans, a S. stercoralis positivity of 4.1% and 6.5% was revealed, respectively. The sites where cases were found were different for animals and humans. In dogs the highest positivity was in group K (6.7% against 2% and 0% in L and A). Differently, in humans the proportion of positive results was similar between the groups (p = 0.883). Fifty percent (3/6) of positive dogs were healthy; the other dogs presented weight loss and/or diarrhoea. ELISA-positive persons (n=9) were all in health, but abdominal pain (37.5%), urticaria (22.2%) and asthma (22.2%) were reported, resolving after treatment with oral ivermectin 200 µg/kg. RT-PCR performed on 13 human faecal samples resulted negative. These findings suggest that strongyloidiasis is present in humans and dogs in Southern Italy, and screening in larger cohorts would be needed for more accurate estimates.

Serum digoxin concentrations in dogs with atrial fibrillation under long term digoxin treatment.

Background: Atrial fibrillation (AF) is the most common arrhythmia in dogs, most frequently diagnosed as chronic AF associated with a structural heart disease. The therapeutic strategy, in these cases, is based on the heart rate control and digoxin is one of the most used drugs. Aim: The aim of this work was to study the serum digoxin concentration changes in dogs with AF under long-term treatment with digoxin. Furthermore, the remission of clinical signs and the correlation between digoxinemia and other clinical and laboratory variables were retrospectively evaluated. Methods: The prospective study was conducted on seven large breed dogs from the time of reaching the definitive digoxin dosage. Digoxinemia was determined at month: 1, 3, 6, 9, 12, then twice a year. A post hoc statistical analysis investigated the influence of selected clinical and laboratory variables on the risk to develop spikes in digoxinemia. Clinical data, heart rate, digoxin dosage (mg/m2), and digoxinemia (ng/ml) at all available follow-ups were retrospectively evaluated from the medical records of 17 further dogs and a linear regression analysis was performed on the whole data set. The relation between the time of remission of AF clinical signs and variables was also investigated. Results: An unexpected increase in digoxin serum concentration was recorded in three dogs after one year monitoring, in absence of digoxin dosage changes. No statistical significance of all the studied variables on the risk to develop spikes of digoxinemia was registered. Two dogs, reaching digoxinemia 4.46 and 5.24 ng/ml, showed symptoms that reversed after digoxin withdrawal. From retrospective data, 88% of dogs reached complete reverse of AF clinical signs in 2.1 months from digoxin treatment starting, regardless of digoxin initial dosage, digoxinemia, and heart rate. Conclusion: Digoxin in monotherapy remain a good option to treat AF in dogs, anyway digoxin toxicity could emerge during long-term therapy, similarly to what happen in human medicine. Life-threatening spikes of digoxinemia could occur, especially after 1-year treatment with digoxin. It is very important that practitioners be aware of this possibility and encourage the owners to monitor digoxinemia during long-term treatment to avoid dangerous and toxic effects.