A two-dose revaccination against tetanus is recommended for horses over 2 years old in Japan with no history of vaccination in the previous year. Here, the need for two-dose revaccination was evaluated in terms of antibody titers for each vaccine type, namely monovalent or multivalent. There was no difference in antibody titers between one- and two-dose regimens for up to 1 year, except at 8 weeks with the multivalent vaccine, and all horses had sufficient antibody titers for 1 year of tetanus prophylaxis. These results suggest that one-dose revaccination, regardless of the vaccine type, is as effective as two-dose in preventing tetanus for at least 1 year in horses not vaccinated in the previous year.

The present study assessed the financial viability of Peste des Petits Ruminants (PPR) vaccine Research & Development (R&D) investment in India and the Gross Technology Revenue (GTR) accrual to the different stakeholders. The Net Present Value (NPV), Internal Rate of Return (IRR) and Benefit Cost Ratio (BCR) of PPR vaccine development and administration were USD 16,326.6 million (INR 130,612 crore), USD 184,54.2 million (INR 147,633 crore) and USD 21,645.6 million (INR 173,164 crore); 162.2%, 167.6% and 169.7% and 43.3:1, 48.8:1 and 57.1:1, respectively under low, medium and high disease incidence scenarios. The estimated cumulative GTR accrued during 2001–02 to 2017–18 by the innovating public research institutions (Indian Council of Agricultural Research-Indian Veterinary Research Institute (ICAR-IVRI) and Tamil Nadu Veterinary and Animal Sciences University (TANUVAS)), private vaccine producers, public sector biologicals and government revenues in terms of taxes was USD 0.696 million (INR 5.568 crore) for ICAR-IVRI and USD 0.033 million (INR 0.26 crore) for TANUVAS; USD 5.00 million (INR 40 crore); USD 7.141 million (INR 57.1 crore) and USD 0.671 million (INR 5.36 crore), respectively. Overall, financial benefits of PPR vaccine development and administration to control PPR in India outweighs the investment in manifolds.

The abnormal or undesirable behaviors of owned dogs are not always considered problematic; it depends on the perception bias of their owners. To demonstrate the perception bias in dog owners’ attributes, 133 dog owners in Aomori (rural) and Tokyo (urban) were surveyed through questionnaires distributed via seven animal hospitals regarding the frequency of potentially problematic behaviors and their perceived difficulty with them. The interaction effects of the lived location (urban, rural), age (20s–50s, 60s or later), and sex (male, female) of the owners were evaluated through a hierarchical multiple regression model. The analyses of 115 responses demonstrated that the tendency of perception regarding the five major behaviors under consideration varied with these attributes. Our results indicated that owners living in Aomori undervalued destruction behaviors of their dogs both when family members were and were not at home, while they overvalued jumping on people. Senior owners tended to undervalue nuisance barking when family members were at home along with uncontrollable hyperactivity. Male owners also undervalued destructive behavior when family members were not home. The study concludes that perception bias due to dog owners’ attributes should be taken into account in epidemiological surveys and during medical interviews by veterinarians or other behavioral specialists. Further exhaustive investigation and exploration of the cultural background of these perception differences should be conducted.

Dogs with precursor-targeted immune-mediated anemia (PIMA) are commonly treated with immunosuppressive therapy, but information on predictors of treatment response and response time is limited. Therefore, we retrospectively investigated predictive factors that influenced the treatment response and duration required to observe a response in dogs with PIMA receiving continuous immunosuppressive therapies for more than 105 days. Of 50 client-owned dogs that developed PIMA, 27 were included in this study, of which 18 were responders and 9 were non-responders to immunosuppressive therapies. Sixteen of the 18 responders responded to treatment within 60 days and the remaining 2 responded at 93 and 126 days, respectively. We found that an erythroid-maturation ratio of <0.17 may be a useful predictor for treatment response. In addition, complications of immunosuppressive therapies were investigated further in 50 dogs. Pancreatitis (n=4) and pneumonia (3) occurred over the entire treatment period, and infections such as abscesses (3) tended to be more common in dogs on an extended period of immunosuppressive therapy. These findings may be helpful when planning for the initial treatment and may provide evidence for informed consent about potential comorbidities throughout the treatment course.

Adriamycin (ADR) is an effective chemotherapy drug for various cancers but has serious side effects. ADR-induced liver damage is a common problem during therapy, but the underlying mechanism remains to be fully understood. In contrast, ADR-induced glomerular damage is well studied in rodents, and sensitivity to ADR-induced nephropathy is because of the R2140C polymorphism of Prkdc gene. To investigate whether strain differences or sensitivity to ADR-induced liver damage are related to Prkdc polymorphism, this study compared the sensitivity to ADR-induced liver damage among C57BL/6J (B6J), B6-Prkdc^R2140C, and BALB/c mice. Although B6J exhibits resistance to ADR-induced liver injury, BALB/c and B6-Prkdc^R2140C are more susceptible to liver injury, which is exacerbated by the presence of R2140C mutation in PRKDC.

Transient receptor potential melastatin 4 (TRPM4) cation channels are expressed in prostate glands. However, the precise role of these channels in prostate contractility remains unclear. In this study, we examined whether TRPM4 channels were involved in adrenergic contractions in the mouse prostate gland. Adrenergic contractile responses elicited by noradrenaline or electrical field stimulation of the sympathetic nerve were isometrically recorded, and the effects of 9-phenanthrol, a specific TRPM4 channel inhibitor, on those contractile responses were investigated in mouse ventral prostate preparations. 9-phenanthrol (10 or 30 μM) inhibited noradrenaline- and sympathetic nerve-evoked contractions in a concentration-dependent manner. A similar inhibitory effect was observed with another TRPM4 channel inhibitor, 4-chloro-2-(2-(naphthalene-1-yloxy) acetamido) benzoic acid (NBA; 10 μM). Inhibition by 9-phenanthrol and NBA were much greater at lower noradrenaline concentrations and lower stimulus frequencies than those of higher concentrations or frequencies. However, 9-phenanthrol did not inhibit the noradrenaline-induced contractile response when the membrane potential was decreased to approximately 0 mV in the 140 mM K⁺ medium. Moreover, 9-phenanthrol does not affect noradrenaline-induced increases in spontaneous contractions of cardiac atrial preparation. This agent inhibited noradrenaline-induced contractions in the posterior aorta preparation. However, the inhibitory effect was significantly weaker than that observed in the prostate gland. These results suggest that TRPM4 channels are involved in adrenergic contractions in the mouse prostate gland, possibly through membrane depolarization by their opening; therefore, they might be potential candidates for treating benign prostatic hyperplasia.

The efficacy of orally administered drugs in cattle is thought to be slow because of the anatomical and physiological features of their forestomach. Thus, parenteral routes are mainly preferred to administer drugs. However, the effect of some drugs with unique physicochemical properties was promptly obtained even after oral administration in clinically ill cattle. Therefore, the present study aimed to investigate pharmacokinetically the usefulness of the oral route in cattle by comparing the oral pharmacokinetic properties of two sulfonamides with different physicochemical properties. Sulfadiazine (SDZ) and sulfamonomethoxine (SMM) were administered by intravenous and oral route to four female Holstein cows with a 4-weeks washout period. Blood samples were collected over time, and SDZ and SMM concentrations in plasma were analyzed by HPLC. Data obtained from the same animal after intravenous and oral administration were simultaneously analyzed with the one compartment model, and kinetic parameters were calculated. The T_max (mean ± SD) of SMM (2.75 ± 0.96 hr) was significantly achieved earlier than that of SDZ (5.00 ± 1.15 hr). Further, the mean absorption time of SMM (5.24 ± 0.69 hr) was significantly shorter than that of SDZ (5.92 ± 1.11 hr). Also, the half-life of absorption of SMM (3.91 ± 0.51 hr) was significantly shorter than that of SDZ (4.51 ± 0.82 hr). These data suggest that the absorption rates of highly unionized drugs (such as SMM) from the forestomach of cattle may be markedly higher than less unionized ones (such as SDZ).

Mechanistic/mammalian target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase that plays a major role in cell metabolism. Although mTORC1 inhibitors are known to exert immunosuppressive effects, their effects on immune cells are not fully understood. In the present study, we examined the involvement of mTORC1 in the differentiation and functions of macrophages using THP-1 cells, which are derived from human monocytic leukemia and differentiate into macrophage-like cells upon treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). We also examined the effects of two mTOR inhibitors, Torin 1 and rapamycin, on TPA-stimulated THP-1 cells. Although mTORC1 activation was observed upon TPA stimulation, mTOR inhibitors did not affect TPA-induced morphological changes or expression of the general macrophage marker, CD11b. In contrast, phagocytosis and fluid endocytosis were significantly impaired by the mTOR inhibitors. Endocytosis suppression was observed when mTOR inhibitors were added during differentiation, but not before or after differentiation, suggesting that endocytosis suppression altered the direction of differentiation. Furthermore, mTOR inhibitors altered the expression of M1/M2 polarization markers. These results suggest that the immunosuppressive effects of mTOR inhibitors may involve the suppression of macrophage endocytosis caused by abnormal cell differentiation.

In recent years, strategies targeting β-cell protection via autoimmune regulation have been suggested as novel and potent immunotherapeutic interventions against type 1 diabetes mellitus (T1D). Here, we investigated the potential of toceranib (TOC), a receptor-type tyrosine kinase (RTK) inhibitor used in veterinary practice, to ameliorate T1D. TOC reversed streptozotocin-induced T1D and improved the abnormalities in muscle and bone metabolism characteristic of T1D. Histopathological examination revealed that TOC significantly suppressed β-cell depletion and improved glycemic control with restoration of serum insulin levels. However, the effect of TOC on blood glucose levels and insulin secretion capacity is attenuated in chronic T1D, a more β-cell depleted state. These findings suggest that TOC improves glycemic control by ameliorating the streptozotocin-induced decrease in insulin secretory capacity. Finally, we examined the role of platelet-derived growth factor receptor (PDGFR) inhibition, a target of TOC, and found that inhibition of PDGFR reverses established T1D in mice. Our results show that TOC reverses T1D by preserving islet function via inhibition of RTK. The previously unrecognized pharmacological properties of TOC have been revealed, and these properties could lead to its application in the treatment of T1D in the veterinary field.

This report described the differentiation induction of canine oral mucosal melanoma (OMM) cells by resveratrol. Exposure of canine OMM cells to resveratrol (maximum dose: 50 μM and treatment period: 72 hr) induced differentiating features like melanocytes, and enhanced chemosensitivity against cisplatin, but alone had no influence on cell viability. Additionally, resveratrol significantly enhanced mRNA expression of key melanoma differentiation markers such as microphthalmia-associated transcription factor (MITF). Of several inhibitors against mitogen-activated protein kinase subtypes, only the c-Jun N-terminal kinase (JNK) inhibitor, SP600125, induced melanocyte-like morphological change and enhanced MITF mRNA expression. Furthermore, resveratrol also suppressed JNK activation in OMM cells by approximately 33%. Overall, these findings suggest that resveratrol induces differentiation in canine OMM cells, due to the inhibition of JNK signaling.

Oxidative stress is defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defense mechanisms of the body. An overproduction of ROS leads to lipid and protein oxidation, injuring the cells both in normal and pathological conditions. Rice bran protein hydrolysates (RBH) has potent antioxidant, anti-inflammatory, anti-angiotensin converting enzyme (ACE) and hypolipidemic effects. Little is known, however, about the effects of RBH in dogs. The present study evaluated the antioxidative, anti-ACE and metabolic effects of RBH in adult dogs. Eighteen adult dogs were divided into 2 groups: control (n=7) and RBH supplemented groups (n=11), received a diet with the same nutritional compositions. The RBH supplemented group was fed with RBH 500 mg/kg body weight (BW) mixed with food for 30 days. BW, blood glucose, lipid profiles, liver enzymes, electrocardiography (ECG), plasma ACE activity, oxidative stress and antioxidant biomarkers were determined on day 0 and day 30 of supplementation periods. Results showed that RBH decreased oxidative stress and increased antioxidant biomarkers by significantly reducing plasma malondialdehyde (MDA) and protein carbonyl, enhanced blood glutathione (GSH) and improved the GSH redox ratio. Moreover, decreased LDL-C and increased HDL-C levels were found after RBH supplementation whereas BW, blood glucose, liver enzymes, plasma ACE activity, plasma catalase (CAT) and superoxide dismutase (SOD) activity and cardiac function were not significantly changed. These results suggest that RBH may help to lower the risk of oxidative stress and dyslipidemia in adult dogs.

Diphtheria toxin-producing Corynebacterium ulcerans is a zoonotic pathogen that causes human diphtheria-like symptoms. After performing whole-genome analysis of the five isolates from sheltered cats in Osaka, Japan, we compared them with genome sequences of 25 strains of C. ulcerans from a public database. The five isolates from cats harbored 14 genes encoding possible virulence factors in diphtheria-toxin-producing C. ulcerans. These isolates also had diphtheria toxin gene-encoding prophage in their chromosome, although differences were found in other prophages possession. Whole-genome single-nucleotide polymorphism analysis showed that cats’ isolates belonged to ST337 branch, as were strains from Japanese human patients, with 41 or more single-nucleotide polymorphisms variations. High-resolution single-nucleotide polymorphism analysis of C. ulcerans was sufficient to distinguish cats’ isolates clearly as not different by conventional genotyping methods.

A 6-day-old male Japanese Black calf presented with a transverse fracture of the left calcaneus. In calcaneal fractures, traction of the gastrocnemius muscle causes substantial displacement of the proximal fracture fragment; therefore, external fixation alone is prone to failure of fusion or deformed fusion. Furthermore, internal fixation alone may result in refracture due to the high load on the implant. Therefore, internal and external fixation were used to treat the fracture. Bone fusion was observed on postoperative day 50; the wire was removed on postoperative day 90. Radiographic examination at 4 months postoperatively revealed that the bone had fused in normal alignment. Therefore, a good prognosis can be expected for calcaneal fractures treated with combined internal and external fixation.

The aims of this study were to evaluate metabolic profiles obtained at −14, 14, and 28 days in milk (DIM), and to identify potential predictive biomarkers of Holstein dairy cows with purulent vaginal discharge (PVD) at 28 DIM. The body condition score (BCS) and hematocrit (Hct) were evaluated, and a metabolic profile test (MPT) was performed at −14, 14, and 28 DIM using serum samples. Cows at 28 DIM were classified using a vaginoscopy and divided into groups of healthy cows (n=89) and cows with PVD (n=31). Albumin (Alb), total cholesterol (TCho), calcium (Ca) and, magnesium (Mg) levels were lower in cows with PVD than in healthy cows at 14 DIM. At 28 DIM, levels of Alb, TCho, Ca, blood urea nitrogen (BUN), Mg, and Hct were lower in cows with PVD. A multivariate stepwise logistic regression analysis showed that higher non-esterified fatty acids (NEFA; odds ratios; OR=4.47; P<0.01), lower Alb (OR=0.07; P<0.01) and lower TCho (OR=0.99; P=0.08) at 14 DIM, and lower Hct (OR=0.83; P=0.05), lower Alb (OR=0.12; P<0.01), and lower BUN (OR=0.74; P=0.02) at 28 DIM were significantly associated with PVD. In conclusion, serum Alb levels was a potential indicator associated with PVD, reflecting dietary protein deficiency preceding disease. Our findings suggest that MPT should be considered to monitor health status during the postpartum period for early diagnosis of PVD.