Some major challenges faced in current bone substitutes are infection and poor bone regeneration capacity. Skeletal diseases, the associated postoperative infections, and the risk of bone regeneration failure are increasing because of the increase in the global aging population. We have developed materials for bone regeneration that were based on octacalcium phosphate (OCP), which is a highly biocompatible major inorganic component of immature bones, using the ionic insertion method. Herein, we developed functional OCP blocks by introducing silica and Ag in the OCP crystal structure and evaluated their bone regeneration capacity. Similar to OCPs containing only Ag, Ag-substituted OCP-silica blocks (OCP-silica:Ag blocks) exhibited crucial contact antimicrobial activity against Staphylococcus aureus. The bone regeneration capacity of OCP-silica:Ag blocks implanted into bone defects created in rabbit femurs was comparable with that of OCP-silica blocks, with a remarkably higher bone attachment. In particular, they exhibited a critical cortical bone regeneration, which was not observed when OCP-silica blocks were used. These results reveal that, unlike the Ag phosphate coating on the surface of carbonate apatite introduced in previous studies, the Ag addition to OCP crystals introduces antibacterial properties and enhances the OCP bone regeneration capacity.

This study aimed to determine the incidence of emesis in dogs receiving a low dose of intravenous medetomidine. Anesthetic records of dogs that received ≤3 µg/kg medetomidine intravenously before anesthesia induction were retrospectively reviewed. Data included demographics, doses, and the presence of emesis, retching, sialorrhea, or lip licking. A total of 155 cases met the criteria. The administered dose of medetomidine was 3.0 (0.5-3.0) µg/kg (median [range]). Emesis occurred in 3 of 155 dogs (1.9%), while retching, sialorrhea, and lip licking occurred in two, two, and five dogs, respectively. The incidence of emesis observed in dogs receiving low-dose (≤3 µg/kg) intravenous medetomidine was lower than that reported in studies using higher doses.

Two dogs with patent ductus arteriosus and severe pulmonary hypertension were presented to our veterinary teaching hospital. In both dogs, sildenafil was initiated to treat pulmonary hypertension, and surgery was supposed to be scheduled after dose titration. Although no obvious improvement in pulmonary hypertension was observed, no dog had polycythaemia or an increased haematocrit level. The dogs underwent ductal occlusion, and treatment with beraprost sodium was subsequently initiated. Thereafter, severe pulmonary hypertension dramatically improved. No dog showed any clinical sign of right heart failure or adverse drug reaction postoperatively, thereby demonstrating the successful treatment of two dogs with patent ductus arteriosus and severe pulmonary hypertension, using sildenafil and beraprost sodium.

Background:Canine thymoma (CT) is the most common neoplastic disease of the cranial intrathoracic cavity. Reports of video-assisted thoracoscopic surgery-thymectomy (VATS-T) in dogs are increasing, but the surgical indication criteria remain unclear. This report highlights the value of a new criterion called the thymoma volume to cranial intrathoracic volume ratio (T/CI ratio) for evaluating the feasibility of VATS-T. Case Description:A neutered 9-year-old Papillon weighing 3.5 kg had a mass of approximately 20 mm in the cranial intrathoracic cavity. The dog was in good general condition and had no clinical symptoms. Computed tomography revealed a solitary mass with clear boundaries and weak contrast enhancement. The T/CI ratio obtained from CT examination was 2.4%. The dog underwent thoracoscopic tumor resection. Pathological examination revealed that the tumor was a thymoma. The dog was discharged without any postoperative complications. The T/CI ratios obtained from CT data of dogs of the same breed and weight, which ranged from 1.1% to 4.1%, were calculated based on previous reports that measured the volume of thymomas. Conclusion:The T/CI ratio may serve as a new objective criterion for evaluating the relationship between cranial intrathoracic volume and thymoma volume for VATS-T, regardless of dog body size. Although this case demonstrates a promising correlation between the CT-based T/CI ratio and the feasibility of VATS-T, the findings are limited to a single case. Further studies involving a larger number of patients are necessary to validate this observation.

Propofol is a potential injectable anesthetic agent used in total intravenous anesthesia. However, the sparing effect of fentanyl and medetomidine on the required propofol dose in dogs remains unclear. We aimed to investigate the effect of fentanyl constant-rate infusion (CRI) with or without medetomidine on the minimum infusion rate of propofol required to prevent motor movement (MIRNM) in dogs. Six healthy purpose-bred dogs were anesthetized on three occasions with propofol alone (loading dose [LD], 8 mg/kg to effect; initial infusion rate [IR], 0.70 mg/kg/min); propofol (LD, 6 mg/kg to effect; IR, 0.35 mg/kg/min) and fentanyl (LD, 2 µg/kg; IR, 0.10 µg/kg/min); or propofol (LD, 4 mg/kg to effect; IR, 0.25 mg/kg/min), fentanyl (LD, 2 µg/kg; IR, 0.10 µg/kg/min), and medetomidine (LD, 2 µg/kg; IR, 0.5 µg/kg/hr) under controlled ventilation. The MIRNM was determined by observing the response to a noxious electrical stimulus. Heart rate, blood pressure, and blood gas analyses were performed at 1, 2, 3, and 4 hr after initiating CRI. The MIRNM (mean [range]) was significantly lower in the propofol-fentanyl-medetomidine group (0.16 [0.10-0.27] mg/kg/min) than that in the propofol-alone group (0.63 [0.47-0.82] mg/kg/min) (P=0.0004). Fentanyl combined with medetomidine did not significantly decrease the mean arterial pressure in dogs receiving propofol CRI 1-3 hr after initiating CRI compared with propofol CRI alone (P>0.9999, P=0.1536, and P=0.0596, respectively), despite inducing a significantly lower heart rate.

Background: Lung tumors in dogs, significantly primary paragangliomas, are rare and have not been reported. This report describes a dog with a lung tumor diagnosed as a primary paraganglioma. Case Description: A 12-year-old spayed French bulldog presented with a left-sided pulmonary mass. The dog was in good general condition and had no clinical symptoms. Computed tomography (CT) revealed a pulmonary mass near the bifurcation of the posterior lobe bronchus of the left lung. The mass showed a strong contrast enhancement effect that was subsequently attenuated. The dog underwent Surgery to remove the mass from the left lung. Abnormal hypertension was observed during surgery, and hypertensive crisis was suspected. Based on the histopathology and preoperative and postoperative urinary metanephrine and normetanephrine levels, the dog was diagnosed with primary paraganglioma of the lung. Although the CT scan showed findings suggestive of the development of a neuroendocrine tumor, it was difficult to suspect the development of a paraganglioma. Conclusion: The possibility of catecholamine-producing tumors should be considered when we encounter a lung tumor with no clinical symptoms and a neuroendocrine tumor-like contrast enhancement pattern on a CT scan.

Rapid bone regeneration is crucial for restoring alveolar bone and oral functions following periodontal diseases. However, the development of effective biomedical materials for this purpose remains insufficient. While bone autografts can enhance bone regeneration, they are invasive to healthy areas. Specifically, for alveolar bone regeneration, the implanted material must possess adequate mechanical strength. Moreover, local administration is preferred for older adults, who are a primary target population, to maintain their quality of life. We developed a silica-substituted carbonate apatite (CO3Ap–silica) block as newly bone substitute with a bone growth factor, featuring the major inorganic component of mature bone to enhance bone regeneration. CO3Ap–silica block stimulated the bone remodeling process at the implantation site and demonstrated significantly better bone regeneration compared to currently used carbonate apatite substitutes. Therefore, this new material is expected to advance technologies for restoring occlusal function after periodontal disease.

Previously, assembling and developing a compatible bone remodeling process had been a dogma for bone substitute fabrication. However, considering patients who use such bone substitutes, such as elderly people, the major problem is poor bone remodeling, which has been a significant disadvantage limiting active intervention. Therefore, in this study, we introduced a new concept for bone substitutes, namely, a continuous up-regulating bone remodeling process using implanted materials for a rapid curing process. Using an ionic insertion method, inorganic silica, and a viability-controlled factor for bone remodeling, we fabricated octacalcium phosphate (OCP) with silica (OCP-silica) blocks as bone substitutes. The fabricated OCP-silica blocks consisted of hieratical silica and OCP structures at an atomic scale. In vivo experimental results indicated that these OCP-silica blocks enhanced bone remodeling and almost completely replaced all bone tissues in only 3 months compared with existing bone replacement-type bone substitutes.

Canine pulmonary adenocarcinoma (PAC) resembles human lung tumors in never-smokers, but it is rarer than human pulmonary adenocarcinoma. Therefore, research on canine PAC is challenging. In the present study, we successfully established various novel canine PAC cell lines from a single lesion in a dog, including two parent cell lines and fourteen cloned cell lines, and characterized their cellular properties in vitro. Several of these cell lines showed epithelial–mesenchymal transition (EMT)-like and/or cancer stem cell (CSCs)-like phenotypes. We additionally assessed the sensitivity of the cells to vinorelbine in vitro. Three clonal lines, two of which showed EMT- and CSC-like phenotypes, were resistant to vinorelbine. Furthermore, we evaluated the expression and activation status of EGFR, HER2, and Ras signaling factors. The findings indicated that the cell lines we established preserved the expression and activation of these factors to varying extents. These novel canine PAC cell lines can be utilized in future research for understanding the pathogenesis and development of treatments for canine PAC.

Abstract A 5‐year‐old, castrated, male domestic short‐haired cat presented with neurological deficits in the pelvic limbs, back pain and dysuria. Magnetic resonance imaging showed a mass lesion caudal to the L4 vertebrae. In addition, suspected haemorrhage was observed at the cranial aspect of the mass. There was no evidence to support the presence of extravertebral intrusion or vertebral body, osteolysis. Dorsal laminectomy and durotomy were performed to debulk the intraspinal mass. Histopathological and immunohistochemical assessment revealed a primitive neuroectodermal tumour (PNET). To our knowledge, this is the first report to describe the clinical and pathological features and imaging diagnosis of intraspinal PNET without extraspinal invasion in a cat.

This study aimed to investigate the effects of intravenous pimobendan on cardiovascular function and to determine the appropriate dose for clinical usage in cats. Six purpose-bred cats received one of the following treatments: intravenous pimobendan at a single dose of 0.075 mg/kg (low dose [LD] group), 0.15 mg/kg (middle dose [MD] group), 0.3 mg/kg (high dose [HD] group), or saline at 0.1 mL/kg (placebo group). Echocardiography and blood pressure measurements were performed before and 5, 15, 30, 45, and 60 minute after drug administration for each treatment. In the MD and HD groups, the fractional shortening, peak systolic velocity, cardiac output, and heart rate increased significantly. There were no significant differences in blood pressure among the groups. Intravenous pimobendan at 0.15-0.3 mg/kg increased the fractional shortening, peak systolic velocity, cardiac output in healthy cats.

Canine pulmonary adenocarcinoma (PAC) resembles human lung tumors in never-smokers, but it is rarer than human pulmonary adenocarcinoma. Therefore, research on canine PAC is challenging. In the present study, we successfully established various novel canine PAC cell lines from a single lesion in a dog, including two parent cell lines and fourteen cloned cell lines, and characterized their cellular properties in vitro . Several of these cell lines showed epithelial–mesenchymal transition (EMT)-like and/or cancer stem cell (CSCs)-like phenotypes. We additionally assessed the sensitivity of the cells to vinorelbine in vitro . Three clonal lines, two of which showed EMT- and CSC-like phenotypes, were resistant to vinorelbine. These novel canine PAC cell lines can be utilized in future research for understanding the pathogenesis and development of treatments for canine PAC.

This study aimed to determine the characteristics and reference values of each vertebra in the cervicothoracic region by performing diffusion tensor imaging (DTI) scans and analyzing DTI parameters in normal Beagle dogs. In five adult Beagles under anesthetic maintenance, DTI was performed using a 1.5-T magnetic resonance imaging (MRI) scanner. Axial DTI was performed using three overlapping slabs to cover the cervical and thoracic spinal cords. After post-processing, DTI parameters were calculated along the entire spinal cord. Among DTI parameters, fractional anisotropy, relative anisotropy, and axonal diffusivity significantly decreased in the caudal direction. However, the apparent diffusion coefficient, radial diffusivity, and mean diffusivity values were not significantly correlated with vertebral levels. We provide evidence for the existence of segment-dependent DTI parameters in the canine cervical spinal cord. Therefore, comparisons of DTI parameters between lesions at different vertebral levels should be avoided unless normative data are available. Furthermore, the DTI data obtained in this study may contribute to the development of a clinical reference for spinal cord evaluation in dogs using DTI parameters.

Cancers utilize a variety of molecules to escape host immune responses. Better understanding the immune environment surrounding cancer may facilitate application of innovative cancer immunotherapies, such as immune checkpoint inhibitors, to dogs as well as humans. In this study, we screened the expression of 20 immune regulatory molecules in diverse canine tumors (n = 59). Quantitative RT-PCR (qPCR) analysis revealed that some immune regulatory molecules, such as LGALS9 (coding Galectin-9) and CD48, were expressed in most canine tumors, but other molecules, such as CD274 (coding PD-L1), IL4I1, PVR, TNFSF18, ICOSLG, and TNFSF4, were rarely expressed. NECTIN2 was highly expressed in epithelial tumors but was low in non-epithelial tumors. In contrast, VSIR and CD200 expressions were low in epithelial tumors but high in non-epithelial tumors. Interestingly, several tumors expressed distinctive immunoregulatory factors. Hepatocellular carcinomas expressed FGL1, mast cell tumors expressed PDCD1LG2 (coding PD-L2), transitional cell carcinomas expressed VTCN1 (coding B7x), and lymphomas and squamous cell carcinomas expressed CD70. Consistent with qPCR results, immunofluorescence staining confirmed that hepatocellular carcinomas expressed FGL-1 protein. Thus, this study reveals the expression profile of immunoregulatory molecules in canine tumors and opens the door to better understanding the relationship between canine tumors and host immunity.

Distress affects animal welfare and scientific data validity. There is a lack of reports on the effects of multimodal analgesic approaches in mice. In this study, under the hypothesis that a multimodal analgesic protocol using buprenorphine with meloxicam has analgesic effects, we evaluated the effects of a multimodal analgesic protocol using buprenorphine with meloxicam on the well-being of mice during analgesic administration by changing the dosage of meloxicam. A total of 42 Slc:ICR male mice were categorized into nonsurgical and surgical groups (7 mice per group) and treated with an anesthetic (isoflurane) and analgesics (buprenorphine ± meloxicam). Analgesics were administered for 48 h after treatment. Buprenorphine (subcutaneous; 0.1 mg/kg/8 h) and meloxicam (subcutaneous; 0, 2.5, or 5 mg/kg/24 h) were administered twice. Body weight, food intake, nest consolidation score, and latency to burrow were evaluated. A significant decrease in food intake was observed 24 h after treatment, while a significant increase was observed 48 h post-treatment in all groups. Body weight showed a decreasing trend but was not significantly reduced. Furthermore, stomach, duodenum, and jejunum tissues showed no morphological abnormalities. Significant differences in burrow diving scores and the latency to burrow were observed between some groups, but these were not regarded as a consequence of the surgery and/or the meloxicam dose. When buprenorphine and meloxicam were combined, administering up to 5 mg/kg/day of meloxicam for 48 h to male mice after abdominal surgery had no significant negative effects on any tested parameters. In conclusion, a multimodal analgesic protocol of buprenorphine with meloxicam is among the options for increasing well-being in mice following abdominal surgery.

Abstract A 3‐year‐old neutered male golden retriever administered zonisamide for the treatment of seizures showed lethargy and had normal anion gap metabolic acidosis with hypokalaemia, hyperchloremia, and alkaline urine. The serum zonisamide concentration was close to the upper limit, which raised a suspicion of adverse effects of zonisamide. This is the first report showing that the fractional excretion of bicarbonate after compensation for the plasma bicarbonate concentration by a sodium bicarbonate infusion was approximately 5%, indicating distal renal tubular acidosis (RTA). The serum zonisamide concentration decreased, and adverse effects were abated by reducing the zonisamide dosage. Diagnostic therapy with bicarbonate served as a means of compensating for bicarbonate deficiency and contributed to the clinical diagnosis of the condition in zonisamide‐associated RTA in dogs.

In this study, Ag-substituted octacalcium phosphate (OCP) blocks exhibiting contact antibacterial ability were fabricated from precursor dicalcium dihydrate anhydrate blocks via immersion in both Ag+- and Na+-containing ammonium phosphate weak basic buffer solutions. The diametral tensile strength (DTS) value of the Ag-substituted blocks was similar to 2.5 MPa, which is sufficient for them to be used as a bone substitute material. Although the Ag contents of the Ag-substituted OCP blocks (0.17 +/- 0.01 at%) were much lower than those of Ag-substituted OCP powders (1.72 +/- 0.18 at%) prepared using Ag solutions with the same Ag concentration (20 mmol/L), the Ag-substituted OCP blocks exhibited excellent contact antibacterial activities toward various pathogens. In vivo implanting in bone defects evaluations indicated that the biocompatibility of the Ag-substituted OCP blocks was excellent and similar to that of the OCP blocks without Ag.

In humans, peri-anesthesia anxiety reportedly increases the anesthetic requirements for anesthesia induction. However, no studies have been conducted on cats regarding the effects of anxiety on anesthesia induction or anesthetic-mediated physiological changes. Therefore, we intended to investigate the effect of pre-anesthesia anxiety in healthy cats on the propofol dose required for anesthesia induction, and its impact on behavioral and physiological evaluations. The cats were placed in either a calm (CAL) or tense (ANX) environment. We performed physiological and behavioral evaluations before and after each environmental acclimatization period. Anesthesia was induced using propofol. We recorded the total dose of propofol administered for each clinical sign observed during anesthesia induction. The post-acclimatization behavioral evaluation score was significantly higher in the ANX group than the pre-acclimatization score. However, there was no significant difference in the propofol dose required for each clinical sign in the ANX or CAL groups. There were also no significant differences in the physiological evaluations between the ANX and CAL groups. Therefore, pre-anesthesia anxiety felt by cats did not affect propofol-mediated anesthesia induction.