Extracellular cyclic adenosine monophosphate‐dependent protein kinase A autoantibody and C‐reactive protein as serum biomarkers for diagnosis of cancer in dogs

Protein kinase A, a cyclic adenosine monophosphate (AMP)‐dependent enzyme, normally exists within mammalian cells; however, in cancer cells, it can leak out and be found in the serum. Extracellular cyclic AMP‐dependent protein kinase A (ECPKA) has been determined to increase in the serum of cancer‐bearing dogs. However, there have been no reports in the veterinary literature on serum ECPKA autoantibody (ECPKA‐Ab) expression in dogs with cancer. The aim of this study was to evaluate ECPKA‐Ab and C‐reactive protein (CRP) as serum biomarkers for cancer in dogs. ECPKA‐Ab and CRP levels were detected by an enzyme‐linked immunosorbent assay in serum samples from dogs with malignant tumours (n = 167), benign tumours (n = 42), or non‐tumour disease (n = 155) and from healthy control dogs (n = 123). ECPKA‐Ab and CRP levels were significantly higher in the dogs with malignant tumours than in those with benign tumours or non‐tumour diseases, as well as in the healthy controls (P < 0.001, Kruskal‐Wallis test). There was a significant positive correlation between the neoplastic index, which was developed using ECPKA‐Ab and CRP levels, and the presence of cancer in dogs (P < 0.001); the area under the receiver‐operating characteristic curve was estimated to be >0.85 (P < 0.001). In conclusion, ECPKA‐Ab is a potential serum biomarker for a broad spectrum of cancers. Combined measurement of CRP and ECPKA‐Ab levels in serum improves the sensitivity and accuracy of a diagnosis of cancer in dogs.     

Zinc Oxide Therapy Increases Prevalence and Persistence of Methicillin‐Resistant Staphylococcus aureus in Pigs: A Randomized Controlled Trial

There is concern that therapeutic use of zinc oxide (ZnO) in swine production may select for methicillin‐resistant Staphylococcus aureus (MRSA) due to co‐location of the zinc resistance gene (czrC) and methicillin resistance gene (mecA) within the staphylococcal cassette chromosome mec (SCCmec). The objective of this investigation was to determine whether MRSA carriage in pigs is influenced by exposure to therapeutic doses of in‐feed ZnO (3000 mg/kg) when compared to the recommended dietary levels (100 mg/kg). A randomized controlled trial was completed using 110 pigs that were naturally colonized with czrC‐positive MRSA. The pigs were followed from birth to weaning (21 d), at which point they were randomized into 8 pens and exposed to either a control feed (100 mg ZnO/kg feed; n = 49 pigs) or a treatment feed (3000 mg ZnO/kg feed; n = 50 pigs); neither feed contained additional antimicrobials. MRSA carriage was monitored weekly in each group for 4 weeks post‐weaning. The prevalence of MRSA was significantly higher in the treatment group at 1‐week (OR = 18.1; P < 0.01) and 2 weeks (OR = 3.01; P = 0.01) post‐weaning when compared to the control group, but there was no difference later in the nursery phase. Persistent MRSA carriage (testing positive ≥2 times post‐weaning) was observed in 2% (1/49) of control pigs and 22% (11/50) of treated pigs (P < 0.01). All MRSA isolates (spa types t034 and t3075) carried czrC and showed uniform resistance to zinc. These findings demonstrate that the prevalence and persistence of MRSA in nursery pigs can be affected by high levels of in‐feed ZnO in the absence of antibiotics.     

Evaluation of serum haptoglobin and C‐reactive protein in dogs with mammary tumors

Background: In veterinary medicine, there is increasing interest in measuring acute phase proteins as a tool in the diagnosis and monitoring of neoplastic diseases. Although mammary neoplasms are the most common type of cancer in dogs, acute phase proteins have not been extensively evaluated in dogs with mammary tumors. Objectives: The aim of this study was to evaluate serum haptoglobin (Hp) and C‐reactive protein (CRP) concentrations in the dogs with mammary tumors and assess their potential association with malignancy. Methods: A retrospective study of dogs with mammary tumors was performed. Serum concentrations of CRP and Hp were determined in healthy control dogs (n=20) and dogs with mammary tumors before surgery (n=41). Mammary tumors were grouped as carcinomas (n=24), fibrosarcoma (n=1), malignant mixed tumors (n=7), benign mixed tumors (n=6), and adenomas (n=3). CRP and Hp concentrations were compared in dogs with different tumor types and were also compared based on tumor size, lymph node infiltration, skin ulceration, fixation to underlying tissue, and time between tumor identification and removal. Results: Hp concentration was significantly (P<.043) higher in dogs with mammary tumors (median 2.03 g/L, range 0.09–2.94 g/L) compared with controls (1.38 g/L, range 0.08–3.00 g/L), but the range of values overlapped considerably. CRP concentration was higher in dogs with carcinomas (4.70 mg/L, range 0.63–128.96 mg/L) vs controls (2.11 mg/L, range 0.25–6.57 mg/L) (P=.0008) and in dogs with ulcerated skin (14.8 mg/L, range 5.7–128.9 mg/L, n=3) compared with those without ulceration (2.4 mg/L, range 0.11–30.3 mg/L, n=38) (P=.048). Conclusions: Serum Hp and CRP do not appear to have value in diagnosing or predicting malignancy of mammary tumors in dogs. Higher CRP concentrations in dogs with mammary carcinoma suggest a role for inflammation in this tumor type.     

Serum 25‐hydroxyvitamin D concentrations in dogs – correlation with health and cancer risk

25‐hydroxyvitamin D (25(OH)D) is important in bone health as well as many diseases including cancer. Supplementation may increase responsiveness of cancer cells to chemotherapy. Serum 25(OH)D, intact parathyroid hormone (iPTH) and canine C‐reactive protein (c‐CRP) were measured in healthy dogs and dogs with haemoabdomen. Regression analysis determined optimal 25(OH)D concentrations. In healthy dogs (n = 282), mean iPTH concentrations correlated inversely (r² = 0.88, P < 0.001) to 25(OH)D concentrations. Variation in both iPTH and c‐CRP plateaued at 25(OH)D concentrations of 100–120 ng mL^?1. Haemoabdomen dogs (n = 63, 43 malignant and 20 benign) had 25(OH)D concentrations ranging from 19.4 to >150 ng mL^?1. Relative risk of cancer increased with decreasing 25(OH)D concentrations [RR = 3.9 for 25(OH)D below 40 ng mL^?1 (P = 0.0001)]. Serum 25(OH)D concentrations in dogs vary widely, and are influenced by dietary VitD content. Serum vitD measurement can identify dogs for which supplementation may improve health and response to cancer therapy.     

A Retrospective Study of Multi‐agent Chemotherapy including either Cyclophosphamide or Lomustine as Initial Therapy for Canine High‐grade T‐cell Lymphoma (2011‐2017)

Multi‐agent chemotherapy (vincristine, epirubicin and prednisolone) including either cyclophosphamide (CEOP) or lomustine (LEOP) was given as first‐line chemotherapy to treatment‐naïve canine lymphoma patients with measurable, high grade T‐cell lymphoma (HGTCL). All patients responded to either CEOP or LEOP. Toxicity was typical of multi‐agent chemotherapy protocols and 25% of dogs receiving lomustine exhibited mild‐to‐moderate ALT elevation and 29% grade 3 or 4 neutropenia. Median progression‐free survival (100 versus 269 days) and overall survival (155 versus 327 days) were significantly higher in patients receiving LEOP compared to CEOP. Overall survival was improved for patients receiving LEOP compared to those receiving CEOP followed by lomustine‐based rescue therapy. The results of this retrospective study support further evaluation of lomustine as part of first‐line, multi‐agent therapy for patients with HGTCL.     

Comparison of Efficacy of Long‐term Oral Treatment with Telmisartan and Benazepril in Cats with Chronic Kidney Disease

Background

The efficacy and benefits of telmisartan in cats with chronic kidney disease (CKD) have not previously been reported.

Hypothesis

Long‐term treatment of cats with CKD using telmisartan decreases urine protein‐to‐creatinine ratio (UP/C) similar to benazepril.

Animals

Two‐hundred and twenty‐four client‐owned adult cats with CKD.

Methods

Prospective, multicenter, controlled, randomized, parallel group, blinded clinical trial with noninferiority design. Cats were allocated in a 1 : 1 ratio to either telmisartan (1 mg/kg; n = 112) or benazepril (0.5–1.0 mg/kg; n = 112) PO q24 h. The primary endpoint was prospectively defined as the change in proteinuria (benazepril:telmisartan) based on a log transformed weighted average of UP/C change from baseline (AUC 0→t/t) as a percentage compared using a confidence interval (CI) approach. Changes of UP/C from baseline were assessed on all study days and corrected for multiple comparisons.

Results

Telmisartan proved noninferior to benazepril in controlling proteinuria (CI, −0.035 to 0.268). At Day 180, UP/C compared to baseline in the telmisartan group was significantly lower (−0.05 ± 0.31; P = .016), whereas in the benazepril group the change (−0.02 ± 0.48) was not statistically significant (P = .136). Similar results were obtained at all assessment points with significant decrease in UP/C occurring with telmisartan but not benazepril.

Conclusion and Clinical Importance

Both telmisartan and benazepril were well tolerated and safe. Telmisartan proved to be noninferior to benazepril and significantly decreased proteinuria relative to baseline at all assessment points whereas benazepril did not.     

A Brucellosis Disease Control Strategy for the Kakheti Region of the Country of Georgia: An Agent‐Based Model

Brucellosis has been reported in livestock and humans in the country of Georgia with Brucella melitensis as the most common species causing disease. Georgia lacked sufficient data to assess effectiveness of the various potential control measures utilizing a reliable population‐based simulation model of animal‐to‐human transmission of this infection. Therefore, an agent‐based model was built using data from previous studies to evaluate the effect of an animal‐level infection control programme on human incidence and sheep flock and cattle herd prevalence of brucellosis in the Kakheti region of Georgia. This model simulated the patterns of interaction of human–animal workers, sheep flocks and cattle herds with various infection control measures and returned population‐based data. The model simulates the use of control measures needed for herd and flock prevalence to fall below 2%. As per the model output, shepherds had the greatest disease reduction as a result of the infection control programme. Cattle had the greatest influence on the incidence of human disease. Control strategies should include all susceptible animal species, sheep and cattle, identify the species of brucellosis present in the cattle population and should be conducted at the municipality level. This approach can be considered as a model to other countries and regions when assessment of control strategies is needed but data are scattered.     

A between‐experiment analysis of relationships linking dietary protein intake and post‐weaning diarrhea in weanling pigs under conditions of experimental infection with an enterotoxigenic strain of Escherichia coli

Numerous experiments have demonstrated that feeding a lower protein diet decreases protein fermentation in the gastrointestinal tract (GIT) and reduces the incidence of post‐weaning diarrhea (PWD). However, there is a lack of holistic evidence underpinning the relationship between feeding a lower protein diet and PWD in relation to physiological responses and protein fermentation in the GIT. The scope of this article, therefore, will: (i) focus on the impact of dietary protein levels on selected indices of GIT health in weaned pigs without and with experimental infection with an enterotoxigenic strain of Escherichia coli; and (ii) attempt to conduct regression analysis to examine the relationships between dietary‐origin protein intake, nitrogen fermentation indices, fecal consistency and the incidence of PWD. We used datasets generated from a series of four intensive experiments in weaned pigs. The collective results derived from these datasets indicate that restriction of daily protein intake to less than 60 g through feeding a lower protein diet for as little as 7 days after weaning reduced the incidence of PWD commensurate with a reduction in protein fermentation indices.     

A new insight into cystatin C contained in milk basic protein to bone metabolism: Effects on osteoclasts and osteoblastic MC3T3‐E1 cells in vitro

A milk protein fraction possessing alkaline isoelectric points (milk basic protein [MBP]) improves bone metabolism in vivo, and it inhibits bone resorption by osteoclasts and promotes mouse osteoblastic MC3T3‐E1 cells proliferation in vitro. Cystatin C (CysC) is a component of MBP and shows bone resorption inhibitory activity. Therefore, it is likely that MBP with higher CysC content improves bone metabolism more effectively. In this study, we prepared MBP with low and high contents of CysC and compared its effects on bone metabolism with standard MBP in vitro. Our results showed that the CysC content in MBP was positively related to not only bone resorption inhibitory activity but also MC3T3‐E1 cells proliferative activity. Furthermore, purified CysC stimulated MC3T3‐E1 cells proliferation. These results indicate that CysC contributes to promotion of MC3T3‐E1 cells proliferation, and MBP with higher CysC content shows enhanced bone resorption inhibitory activity and MC3T3‐E1 cells proliferative activity. CysC is considered an important factor in the effect on bone metabolism of MBP.