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Hypoglycaemia caused by malignant tumours other than insulinoma is referred to as non-islet cell tumour hypoglycaemia (NICTH), which may be caused by hepatocellular carcinoma (HCC) and leiomyosarcoma (LMS) in veterinary medicine. However, the pathogenetic mechanism of NICTH remains unclear. Therefore, this study aimed to evaluate the gene-expression levels of glucoregulatory factors in canine HCC and LMS accompanied by hypoglycaemia.Four patients (three with HCC and one with LMS) exhibiting hypoglycemia were included in the hypoglycemic (H) group, whereas ten patients not exhibiting hypoglycemia were in the non-hypoglycaemia (NH) group. The preoperative and postoperative blood glucose and serum insulin-like growth factor-2 (IGF-2) levels, as well as the expression of genes involved regulating blood glucose levels were analysed.Compared with the NH group, the H group exhibited significantly decreased blood-glucose levels, which increased to normal values after surgery. Compared with the NH group, the H group exhibited significantly increased gene expression of insulin-like growth factor 1, IGF-2, and insulin-like growth factor binding protein 3 in the tumours. Conversely, expression of genes encoding glucoregulatory factors including insulin, gastric inhibitory polypeptide and glucagon was not observed. Serum IGF-2 levels were significantly higher in the H group compared with that in the control group (healthy dogs) and NH group. In two cases in the H group, serum IGF-2 levels decreased after tumour resection.These results suggest that NICTH development in dogs with HCC and LMS is mechanistically associated with IGF-2 overexpression and elevated serum IGF-2 levels.

Angiogenesis plays an important role in the proliferation and metastasis mechanisms of malignant tumors. Vascular endothelial growth factor (VEGF), a group of cytokines that contribute to angiogenesis and vasculogenesis. This study aimed to investigate the serum VEGF-A concentrations in dogs with various proliferative diseases. A total of 202 dogs that were histopathologically diagnosed with proliferative diseases were included in the study. Serum VEGF-A concentrations were measured using enzyme-linked immunosorbent assay. Median serum VEGF-A concentrations in dogs were as follows: healthy dogs, 4 pg/ml [0-21 pg/ml]; hepatocellular carcinoma, 30 pg/ml [0-158 pg/ml, P=0.001]; hepatocellular adenoma, 32 pg/ml [0-49 pg/ml, P=0.003]; hepatic nodular hyperplasia, 18 pg/ml [0-51 pg/ml, P=0.595]; adrenal pheochromocytoma, 32 pg/ml [0-187 pg/ml, P=0.001]; adrenocortical carcinoma, 32 pg/ml [3-161 pg/ml, P=0.002]; adrenocortical adenoma, 27 pg/ml [0-106 pg/ml, P=0.005]; colorectal adenocarcinoma, 36 pg/ml [0-75 pg/ml, P=0.002]; colorectal adenoma, 43 pg/ml [0-48 pg/ml, P=0.144]; inflammatory colorectal polyps, 37 pg/ml [0-111 pg/ml, P=0.001]; pulmonary adenocarcinoma, 35 pg/ml [4-107 pg/ml, P=0.002]; pulmonary histiocytic sarcoma, 35 pg/ml [0-131 pg/ml, P=0.016]; and follicular thyroid carcinoma, 35 pg/ml [0-106 pg/ml, P=0.009]. The serum VEGF-A concentrations were significantly higher in dogs with neoplastic lesions compared to healthy dogs, except for colorectal adenoma. High serum VEGF-A concentrations were observed in dogs with proliferative diseases. The present study suggests that angiogenesis-inhibiting therapy, which targets VEGF-A, may be useful for canine neoplastic diseases.

This study aimed to evaluate the outcomes and complications of triple-combination surgery consisting of thoracic duct ligation (TDL), partial pericardiectomy (PPC), and cisterna chyli ablation (CCA) for the treatment of idiopathic chylothorax in dogs. Eleven privately owned dogs with idiopathic chylothorax underwent the triple-combination surgery: TDL and PPC were performed in left recumbency, followed by CCA in dorsal recumbency. Of the 11 dogs, seven were Shiba, two were Afghan hounds, and one each was Borzoi and mixed-breed. TDL and PPC required two intercostal thoracotomies in five dogs, whereas they were performed through a single intercostal incision in the other dogs. None of the dogs showed major intraoperative complications. The median operation time was 190 min (range, 151-234 min). Nine dogs showed no pleural effusion after surgery without medical management. Another dog showed the disappearance of chylous effusion, followed by the pleural accumulation of modified transudate. However, the residual one dog in whom chylothorax did not improve postoperatively died 4 months after the combination surgery. The mortality rate at the conclusion of this study was 9.1%. Although the triple-combination surgery with TDL, PPC, and CCA was complex and required a prolonged operation time, the success rate of resolving chylothorax in our study was comparable to that of open surgery as previously reported. Therefore, this study suggests that such triple-combination surgery can become one of the therapeutic options for the management of canine idiopathic chylothorax.

OBJECTIVE To evaluate the clinical impact on quantitative analysis of contrast-enhanced ultrasound (CEUS) on single extrahepatic portosystemic shunt (PSS) in dogs. ANIMALS 21 client-owned dogs with single extrahepatic PSS and 5 healthy Beagles. PROCEDURES In all dogs, CEUS was performed to calculate the rising time (RT), rising rate (RR), and portal vein-to-hepatic parenchyma transit time (ΔHP-PV) from the time-intensity curve obtained in the hepatic parenchyma and portal vein. All dogs in the PSS group underwent preoperative CT angiography (CTA) and surgery. The CEUS variables in the PSS group were compared with those in the healthy dogs (control group) and were analyzed for shunt types and grades of intrahepatic portal venous branches based on CTA findings, intraoperative portal pressure, and surgical procedures. RESULTS All 3 CEUS variables showed no significant differences between the PSS and control groups. The RT and ΔHP-PV in the left gastrophrenic shunt group were significantly longer than in the other shunt types. In the intrahepatic portal vascularity, the RT in grade 1 was significantly shorter than in grades 3 and 4, and the RR in grade 1 was significantly higher than in grade 4. The RT and ΔHP-PV were significantly correlated with portal pressure variables. The RT in dogs with partial ligation was significantly shorter than in dogs with complete ligation and percutaneous transvenous coil embolization. CLINICAL RELEVANCE Quantitative assessments of CEUS may be useful for estimating intrahepatic portal vascularity in dogs with single extrahepatic PSS.

OBJECTIVE To evaluate the hepatic CT perfusion (CTP) for determining the appropriate protocol for the dual-input maximum-slope model in dogs. ANIMALS 5 healthy dogs. PROCEDURES Each dog underwent CTP with different contrast medium administration protocols. Combinations of three different injected doses of iohexol (450, 600, and 750 mg/kg) and injection durations (5, 10, and 15 seconds) were used. The CT values at the aorta, portal vein, and hepatic parenchyma were measured to create a time–density curve, and CTP parameters were measured simultaneously on each hepatic lobe using a 320-row multidetector CT scanner. RESULTS The maximum peak enhancement at the aorta, portal vein, and hepatic parenchyma was greater with the 750-mg/kg dose than with the 450-mg/kg dose. With an injection duration of 15 seconds, the aortic enhancement peak was less, and the arrival time at the aortic enhancement peak was longer compared to that with a 5-second injection duration. The CTP parameters in the caudate process of the caudate lobe and left lateral lobe differed with different injection durations. The CTP parameters in the caudate process of the caudate lobe, left lateral lobe, and right lateral lobe differed with varying injected doses. CLINICAL RELEVANCE Our study demonstrated that rapid administration of the contrast medium was required for quantitative analysis of hepatic CTP in healthy dogs. The CTP parameters differed with respect to the contrast medium administration protocol, and it was necessary to administer the contrast medium within a fixed duration and at a fixed dose to evaluate CTP correctly.

OBJECTIVE To describe the clinical, diagnostic, and pathological features and postoperative prognosis of canine combined hepatocellular-cholangiocarcinoma (cHCC-CCA). ANIMALS 14 privately owned dogs that underwent surgical treatment. PROCEDURES The medical records, including signalment, clinical signs, blood test, urine analysis, computed tomography (CT) findings, intraoperative findings, and pathological findings, were retrospectively reviewed in the dogs with cHCC-CCA. RESULTS Of 306 dogs that underwent surgical removal of hepatic masses, 14 dogs (4.6%) were pathologically confirmed to have cHCC-CCA. Median age and body weight were 11.3 years and 7.3 kg, respectively. There were no specific clinicopathological findings for cHCC-CCA. CT revealed a massive hepatic mass in all dogs and the inclusion of cyst-like lesions within the mass in 13 dogs. Intrahepatic metastases were found at time of surgery in 2 dogs (14.3%). Of the residual 12 dogs, 1 dog showed postoperative formation of intrahepatic nodules suggestive of metastases and another had intrahepatic and pulmonary nodules and a forelimb skin mass, suggesting postoperative metastases. The median survival time of the patients with cHCC-CCA was 700 days (range, 10 to 869 days) after surgery. CLINICAL RELEVANCE To the authors’ knowledge, this is the first study to describe the clinical, diagnostic, and pathological features and postoperative prognosis of canine cHCC-CCA. The clinical and diagnostic features of canine cHCC-CCA might be more similar to those of HCC rather than to those of CCA, but the preoperative diagnosis differentiating between HCC and cHCC-CCA was challenging. Our study suggests that the postoperative prognosis of canine patients with cHCC-CCA is similar to that of dogs with HCC.

Secretogranin II (SgII) and III (SgIII) function within peptide hormone-producing cells and are involved in secretory granule formation. However, their function in active amine-producing cells is not fully understood. In this study, we analyzed the expression profiles of SgII and SgIII in canine adrenal medulla and pheochromocytomas by immunohistochemical staining. In normal adrenal tissues, the intensity of coexpression of these two secretogranins (Sgs) differed from each chromaffin cell, although a complete match was not observed. The coexpression of vesicular monoamine transporter 2 (VMAT2) with SgIII was similar to that with chromogranin A, but there was a subpopulation of VMAT2-expressing cells that were negative or hardly detectable for SgII. These results are the first to indicate that there are distinct expression patterns for SgII and SgIII in adrenal chromaffin cells. Furthermore, the expression of these two Sgs varied in intensity among pheochromocytomas and did not necessarily correlate with clinical plasma catecholamine levels in patients. However, compared with SgIII, the expression of SgII was shown to be strong at the single-cell level in some tumor tissues. These findings provide a fundamental understanding of the expression differences between SgII and SgIII in normal adrenal chromaffin cells and pheochromocytomas.

Objective The aim of this study was to determine the degree of bone deformities and hindlimb postural abnormalities in a standing position in awake Toy poodles with and without grade 2 medial patellar luxation (MPL) using high speed 320-row computed tomography (CT). Methods The limbs with grade 2 MPL (MPL-G2 group) and without any orthopaedic disorders (control group) were imaged in a standing position, without sedation or anaesthesia, using CT. In MPL-G2 group, images were obtained when the patella was luxated (G2-L group) and reduced (non-luxation, G2-NL group). Bone morphologies of the femur and tibia were quantified three-dimensionally. Hindlimb standing posture was evaluated by measuring femoral rotation and abduction angles, tibial rotation angle, metatarsal rotation angle, foot rotation angle, angle between the femoral anatomical axis and the mechanical axis of hindlimb and stifle joint line convergence angle. Results There were no significant differences in bone morphologic parameters between the MPL-G2 group (5 limbs) and the control group (6 limbs). In the G2-NL group, there were no significant hindlimb postural abnormalities. In contrast, in the G2-L group, significant hindlimb postural abnormalities including external rotation of femur, internal rotation of tibia and foot, external rotation of tarsal joint, large stifle joint convergence angle, genu varum and toe-in standing were observed. Conclusion Dogs with grade 2 MPL have no bone deformities but show abnormal standing posture when the patella is luxated.

OBJECTIVE To evaluate the clinical feasibility and usefulness of measuring shunt fraction (SF) and hepatic perfusion with CT in dogs with a single extrahepatic portosystemic shunt (EPSS). ANIMALS 36 client-owned dogs with EPSS. PROCEDURES Dogs with EPSS referred for treatment between February 2016 and May 2017 were eligible for the clinical trial. Shunt type, SF, and hepatic perfusion were determined in each dog with a 320-row multidetector CT scanner, and surgical treatment was performed by a single veterinary surgeon. Differences in results between dogs grouped according to age (< 3 years vs ≥ 3 years), shunt type, and subgroups (eg, clinical signs and surgical procedure) were analyzed, and correlations between the SF and hepatic perfusion variables were evaluated. RESULTS The median SF was higher in dogs < 3 years old (74.6%; n = 18) versus dogs ≥ 3 years old (35.1%; 18). Correlations were identified between SF and hepatic perfusion variables, and differences in results for SF and hepatic perfusion variables were detected between dogs grouped according to shunt type. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that CT-derived measurements of SF and hepatic perfusion variables in dogs with EPSS were feasible and could be useful (eg, estimating EPSS condition status and planning treatment) in clinical settings. In addition, our findings suggested that perfusion CT could be useful for distinguishing hemodynamic characteristics among different types of portosystemic shunts in dogs.

Objective The aim of this study was to evaluate the bone deformities of the distal femur of Toy Poodles with medial patellar luxation (MPL) using computed tomography. Methods Computed tomography data from 37 stifles of Toy Poodles (16 normal, 10 grade 2 MPL and 11 grade 4 MPL) were analysed. For trochlear morphology, sulcus angle, medial or lateral trochlear inclination and trochlear angle were compared. For condylar morphology, distance between the apex of the medial or lateral trochlear ridge and the most caudal point of the medial or lateral femoral condyle (MC or LC), the length of the cranial/middle (anterior) part (MC(a) or LC(a')) and caudal (posterior) part (MC(p) or LC(p')) of distal femur and medial or lateral condyle width (MCW or LCW) were measured, and the ratios of medial-to-lateral condyles and anterior–posterior parts were compared. Results Sulcus angle was significantly higher, and medial trochlear inclination was significantly lower in grade 4 MPL group than other groups. Lateral trochlear inclination was not significantly different among 3 groups. Trochlear angles at proximal trochlear groove were significantly lower in grade 4 MPL group than other groups. MC/LC, MC(a)/LC(a'), MC(a)/MC(p), and LC(a')/LC(p') were significantly lower in grade 4 MPL group than other groups; however, there were no significant differences in MC(p)/LC(p') and MCW/LCW among three groups. Conclusion Hypoplasia of the cranial and middle rather than caudal compartment of the distal femur was the primary morphological abnormality in Toy Poodles with grade 4 MPL.

Background Prostatic cancer is uncommon in dogs. Dogs with prostatic carcinoma have been reported to have a poor prognosis. Information regarding prognosis with various surgery options as well as prognosis with surgical vs. medical treatment is lacking. This retrospective study compares the outcomes of medical management to surgical treatment in dogs with prostatic adenocarcinoma and assesses the surgical outcomes of patients who underwent total prostatectomy (TP) and prostatocystectomy (TPC). The medical records of 41 dogs with prostatic adenocarcinoma, between February 2008 and June 2019, were reviewed for information on signalment, clinical signs in the initial evaluation, preoperative diagnostic imaging findings, treatment type (non-surgical or surgical), surgery type, postoperative complications, adjunctive medical therapy, and survival time. The dogs were divided into non-surgical (n = 12) or surgical (n = 29) groups. The surgical group was subdivided into the TP (n = 20) and TPC (n = 9) subgroups. Results Age was not significantly different between the surgical (median 13.1 years [8.4–15.4] years) and the non-surgical groups (median 10.8 [7.7–15.3] years). Body weight (BW) was also not significantly different between the surgical (median 6.8 kg [2.4–34.5 kg]) and non-surgical groups (median 6.4 kg [3.7–9.12 kg]). The overall median survival time (MST) from the initial evaluation was significantly longer in the surgical than in the non-surgical group (337 vs. 90.5 days). The postoperative MST was significantly longer in the TP group than in the TPC subgroup (510 vs. 83 days). As TPC was performed in cases of tumor progression, its postoperative complications were severe, resulting in a shorter MST. Ten (50%) and 6 patients (30%) in the TP subgroup postoperatively showed mild and severe urinary incontinence, respectively, whereas all patients in TPC subgroup did show severe incontinence. Conclusion Results of the study suggest that surgical treatment of prostatic carcinoma results in longer survival times over medical management alone. In particular, TP might be recommended for improving survival time and quality of life in canine prostatic adenocarcinoma that does not infiltrate the bladder. Early detection is key for a survival advantage with surgical treatment.

Osteoarthritis (OA) is one of the major causes of chronic pain in dogs. However, the pathogenesis of OA has not been fully understood in dogs. The objective of this study was to comprehensively investigate the mRNA expression levels of proinflammatory cytokines, inflammatory mediators, nerve growth factor and its receptor, and matrix metalloproteinases in the synovium of dogs with spontaneous OA as well as to elucidate their relationships with the severity of synovitis. Dogs that were diagnosed with stifle OA on the basis of radiographic findings were included, and the degree of synovitis was observed using stifle arthroscopy. The dogs were assigned to two different groups depending on their synovitis scores: the low-grade group (score of 1 or 2; n = 8) and high-grade group (score of 3 to 5; n = 18). The dogs showing no evidence of orthopedic disease were included in the control group (n = 6). Synovial tissue samples were collected from the sites at which synovitis scores were assessed using arthroscopy. Total RNA was extracted from the collected synovial tissue, and cDNA was synthesized. Subsequently, RT-qPCR were performed using canine-specific primer sets for IL1B, IL6, CXCL8, TNF, TGFB1, PTGS2, PTGES, MMP3, MMP13, NGF, NTRK1, and PTGER4. Expression levels of IL1B, IL6, CXCL8, and MMP13 were significantly higher in the high-grade group than in the control group. In addition, expression levels of IL1B, CXCL8, TNF, and PTGS2 were significantly higher in the high-grade group than in the low-grade group. Expression levels of IL1B, IL6, CXCL8, TNF, PTGS2, and PTGER4 showed significant positive correlation with synovitis score. In conclusion, all mRNA expression levels in the synovial membrane varied according to the degree of synovitis in dogs with spontaneous OA. Thus, this study may partially elucidate the pathogenesis of synovitis in dogs with spontaneous OA.

This study investigated the direct effects of non-steroidal anti-inflammatory drugs (NSAIDs) and atrial natriuretic peptide (ANP) on canine-derived vascular endothelial cells (VECs). VECs were isolated and cultured from canine arteries and veins. The mRNA expressions of vascular endothelial growth factor receptor 2, cyclooxygenase-2, and natriuretic peptide receptor 1 were detected in the cultured VECs. The viability of the cultured VECs was reduced in a dose-dependent manner by meloxicam, carprofen, and robenacoxib. By contrast, dose escalations of ANP had only marginal influence on the viability of cultured VECs. NSAIDs may potentially serve as not only analgesic agents against cancerous and perioperative pain but also as adjuvant anti-angiogenic drugs in dogs with malignant tumors.

Background Gallbladder agenesis (GBA) is extremely rare in dogs. Hypothesis/objectives To describe the history, clinical signs, diagnosis, treatment, and outcomes of dogs with GBA. Animals Seventeen client-owned dogs with GBA. Methods Medical records from 2006 through 2016 were retrospectively reviewed. Dogs were included when GBA was suspected on abdominal ultrasonography and confirmed by gross evaluation. Signalment, clinical signs, clinicopathological data, diagnostic imaging, histopathology, treatment, and outcome were recorded. Results Dogs were of 6 different breeds, and Chihuahuas (10 of 17) were most common. Median age at presentation was 1.9 (range, 0.7-7.4) years. Clinical signs included vomiting (5 of 17), anorexia (2 of 17), ascites (2 of 17), diarrhea (1 of 17), lethargy (1 of 17), and seizures (1 of 17). All dogs had increased serum activity of at least 1 liver enzyme, most commonly alanine aminotransferase (15 of 17). Fifteen dogs underwent computed tomography (CT) cholangiography; common bile duct (CBD) dilatation was confirmed in 12, without evidence of bile duct obstruction. Gross evaluation confirmed malformation of the liver lobes in 14 of 17 dogs and acquired portosystemic collaterals in 5 of 17. Ductal plate malformation was confirmed histologically in 16 of 17 dogs. During follow-up (range, 4-3,379 days), 16 of 17 dogs remained alive. Conclusions and clinical importance Dogs with GBA exhibit clinicopathological signs of hepatobiliary injury and hepatic histopathological changes consistent with a ductal plate abnormality. Computed tomography cholangiography was superior to ultrasound examination in identifying accompanying nonobstructive CBD distention. Computed tomography cholangiography combined with laparoscopic liver biopsy is the preferable approach to characterize the full disease spectrum accompanying GBA in dogs.

The prognosis of canine transitional cell carcinoma (TCC) of urinary bladder is generally poor because it is difficult to diagnose at early stages and conventional therapies, such as surgical resection and/or chemotherapy, are often not curative treatments. Based on our previous report that recombinant measles virus (rMV-SLAMblind) therapy could be a new treatment for canine mammary tumor, the applicability of rMV-SLAMblind in canine urinary bladder TCC was examined in this study. A canine TCC cell line was established from a TCC patient dog by transplanting a piece of the tumor mass into an immunodeficient mouse and then isolating the primary TCC cells from the grown tumor mass. The primary cultured cells, named TCC-NU1, express nectin-4, a receptor for rMV-SLAMblind infection. The rMV-SLAMblind infected TCC-NU1 cells, and dose-dependently showed cell cytotoxicity. Moreover, intratumoral administration of rMV-SLAMblind in a xenograft model bearing TCC-NU1 cells significantly suppressed the tumor growth reducing the endpoint mass of tumors in treated mice compared to control mice. These results suggest that virotherapy with rMV-SLAMblind be a new candidate therapy for canine TCC.

Brachycephalic airway syndrome (BAS) is a common disease in certain "flat-faced" dog breeds. This syndrome includes stenotic nares, elongated and thickened soft palate, laryngeal collapse, and tracheal hypoplasia. Pharyngeal collapse is also commonly observed, but it is unclear if laryngopharynx motions are merely sequelae or actually contribute to BAS respiratory symptoms. Laryngopharynx motion was imaged using dynamic four-dimensional computed tomography (4D-CT) during spontaneous respiration in four dogs with different BAS types. Dynamic 4D-CT showed laryngopharynx motion in the following order during inspiration: pharyngeal collapse, contraction, and laryngospasm. We concluded that dynamic 4D-CT is a highly-detailed diagnostic approach for detecting laryngopharynx motion. Pharyngeal contraction during inspiration appears to contribute toward the worsening of clinical respiratory signs of BAS.

We investigated the utility of triple-phase helical computed tomography (CT) in differentiating between benign and malignant splenic masses in dogs. Forty-two dogs with primary splenic masses underwent triple-phase helical CT scanning (before administration of contrast, and in the arterial phase, portal venous phase, and delayed phase) prior to splenectomy. Tissue specimens were sent for pathological diagnosis; these included hematomas (n=14), nodular hyperplasias (n=12), hemangiosarcomas (n=11), and undifferentiated sarcomas (n=5). The CT findings were compared with the histological findings. Nodular hyperplasia significantly displayed a homogeneous normal enhancement pattern in all phases. Hemangiosarcoma displayed 2 significant contrast-enhancement patterns, including a homogeneous pattern of poor enhancement in all phases, and a heterogeneous remarkable enhancement pattern in the arterial and portal venous phases. Hematoma and undifferentiated sarcoma displayed a heterogeneous normal enhancement pattern in all phases. The contrast-enhanced volumetric ratios of hematoma tended to be greater than those of undifferentiated sarcoma. Our study demonstrated that the characteristic findings on triple-phase helical CT could be useful for the preoperative differentiation of hematoma, nodular hyperplasia, hemangiosarcoma, and undifferentiated sarcoma in dogs. Triple-phase helical CT may be a useful diagnostic tool in dogs with splenic masses.

We investigated the in vitro differentiation of canine bone marrow stromal cells (BMSCs) into voltage- and glutamate-responsive neuron-like cells. BMSCs were obtained from the bone marrow of healthy beagle dogs. Canine BMSCs were incubated with the basal medium for neurons containing recombinant human basic fibroblast growth factor (bFGF; 100 ng/ml). The viability of the bFGF-treated cells was assessed by a trypan blue exclusion assay, and the morphology was monitored. Real-time RT-PCR was performed to evaluate mRNA expression of neuronal, neural stem cell and glial markers. Western blotting and immunocytochemical analysis for the neuronal markers were performed to evaluate the protein expression and localization. The Ca(2+) mobilization of the cells was evaluated using the Ca(2+) indicator Fluo3 to monitor Ca(2+) influx. To investigate the mechanism of bFGF-induced neuronal differentiation, the fibroblast growth factor receptor inhibitor, the phosphoinositide 3-kinase inhibitor or the Akt inhibitor was tested. The bFGF treatment resulted in the maintenance of the viability of canine BMSCs for 10 days, in the expression of neuronal marker mRNAs and proteins and in the manifestation of neuron-like morphology. Furthermore, in the bFGF-treated BMSCs, a high concentration of KCl and L-glutamate induced an increase in intracellular Ca(2+) levels. Each inhibitor significantly attenuated the bFGF-induced increase in neuronal marker mRNA expression. These results suggest that bFGF contributes to the differentiation of canine BMSCs into voltage- and glutamate-responsive neuron-like cells and may lead to the development of new cell-based treatments for neuronal diseases.

Nineteen cases of histiocytic sarcomas in Pembroke Welsh Corgi were examined histopathologically. Focal or multiple masses were detected in the lung or in regional lymph nodes, or in both lung and nodes. All neoplastic lesions had common histological features characterized by the proliferation of pleomorphic histiocytic cells combined with various inflammatory cells. Most of the pleomorphic neoplastic cells were immunopositive for human leukocyte antigen (HLA)-DR and Iba-1. The median survival time for all dogs was 133 days. In the present study, several prognostic factors, such as gender, age, single or multiple lesions, lymph node involvement at the time of diagnosis, surgical resection status and additional chemotherapy, were examined, although none of these factors approached statistical significance. Histiocytic sarcoma must be considered in the differential diagnosis of dogs with pulmonary masses, especially in the canine breed.

We investigated the cell viability, proliferative capacity and neuronal differentiation potential of canine bone marrow stromal cells (BMSCs) after cryopreservation. BMSCs were cryopreserved using cryoprotectant solutions with 10% DMSO and 10% FBS (DF group) or without DMSO and FBS (DF-free group); fresh BMSCs were used as a control. The cell viability and proliferative capacity of BMSCs were similar in the DF-free and control groups, while those in the DF group were lower. In all groups, BMSCs differentiated into neuron-like cells that stained positive against neuron markers, and the mRNA expression levels of neuron markers increased after neuronal induction. In conclusion, cryopreservation with DF-free cryoprotectant solution did not diminish the cell viability, proliferative capacity or neuronal differentiation potential of canine BMSCs.

The purpose of this study was to evaluate the gene expression of growth factors and growth factor receptors of primary hepatic masses, including hepatocellular carcinoma (HCC) and nodular hyperplasia (NH), in dogs. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to measure the expression of 18 genes in 18 HCCs, 10 NHs, 11 surrounding non-cancerous liver tissues and 4 healthy control liver tissues. Platelet-derived growth factor-B (PDGF-B), transforming growth factor-α, epidermal growth factor receptor, epidermal growth factor and hepatocyte growth factor were found to be differentially expressed in HCC compared with NH and the surrounding non-cancerous and healthy control liver tissues. PDGF-B is suggested to have the potential to become a valuable ancillary target for the treatment of canine HCC.

Objective—To investigate the in vitro differentiation of canine bone marrow stromal cells (BMSCs) into functional, mature neurons. Sample—Bone marrow from 6 adult dogs. Procedures—BMSCs were isolated from bone marrow and chemically induced to develop into neurons. The morphology of the BMSCs during neuronal induction was monitored, and immunocytochemical analyses for neuron markers were performed after the induction. Real-time PCR methods were used to evaluate the mRNA expression levels of markers for neural stem or progenitor cells, neurons, and ion channels, and western blotting was used to assess the expression of neuronal proteins before and after neuronal induction. The electrophysiological properties of the neuron-like cells induced from canine BMSCs were evaluated with fluorescent dye to monitor Ca2+ influx. Results—Canine BMSCs developed a neuron-like morphology after neuronal induction. Immunocytochemical analysis revealed that these neuron-like cells were positive for neuron markers. After induction, the cells’ mRNA expression levels of almost all neuron and ion channel markers increased, and the protein expression levels of nestin and neurofilament-L increased significantly. However, the neuron-like cells derived from canine BMSCs did not have the Ca2+ influx characteristic of spiking neurons. Conclusions and Clinical Relevance—Although canine BMSCs had neuron-like morphological and biochemical properties after induction, they did not develop the electrophysiological characteristics of neurons. Thus, these results have suggested that canine BMSCs could have the capacity to differentiate into a neuronal lineage, but the differentiation protocol used may have been insufficient to induce development into functional neurons.

A 13-year-old female Labrador Retriever presented with chronic regurgitation. Radiography and computed tomography (CT) revealed nodules in the caudal esophagus. Upper gastrointestinal endoscopy followed by histopathological examination revealed esophageal granulomas caused by Spirocerca lupi. The infection was treated with milbemycin oxime. The therapy was successful, and a remarkable reduction in granulomas was observed. This case report describes the diagnostic imaging findings and treatment outcome of a dog with S. lupi infection in Japan.

The prevalences of displacement and deformity of the medial and lateral fabellae in dogs were investigated. This was a retrospective epidemiologic study. Radiographs of canine stifle joints (1022 limbs, 534 dogs) were obtained. The images were taken at the Nihon University Animal Medical Center and three private animal hospitals from January 2003 to July 2012. The position and morphology of the medial or lateral fabella were evaluated on the radiographs. The prevalence of displacement of the medial and lateral fabellae was 1.7% and 0.3%, respectively. The prevalence of deformity of the medial and lateral fabellae was 6.9% and 4.6%, respectively. Aplasia or hypoplasia of the fabella was detected more frequently in the medial fabella. On the other hand, a bipartite or multipartite fabella was observed more frequently in the lateral fabella. Nearly all cases of displacement or deformity of the fabella occurred in dogs weighing less than 10 kg. Abnormalities of the fabella were observed in the medial and lateral fabella. We found that abnormal fabellae were closely associated with medial patellar luxation and to a lesser extent with cranial cruciate ligament rupture. No clinical signs were associated with an abnormality of the fabella, with the exception of two dogs with traumatic avulsion of the lateral head of the gastrocnemius muscle.

A 13-year-old neutered female Shih Tzu was referred for investigation of a cranial abdominal mass. Investigations including conventional radiography, abdominal ultrasonography and computed tomography confirmed the mass in the caudate lobe of the liver. As a collateral vein originating from the caudal vena cava (CVC) communicated with the azygos vein, the CVC was ligated and transected cranial to the right renal vein and cranial to the mass under temporary occlusion of the thoracic descending aorta and posthepatic CVC. The mass combined with the CVC was excised. The mass was confirmed as hepatocellular carcinoma (HCC). This report describes the first case with successful en bloc resection of a large HCC involving the CVC in a dog.

The purposes of this study were to determine the tissue distribution of canine adrenomedullin (AM) and to determine whether increased canine AM mRNA expression is associated with congestive heart failure (CHF) due to mitral regurgitation (MR). Canine AM mRNA expression was detectable in various normal tissues, including cardiovascular tissues. In addition, the AM mRNA expression in the left atrium of dogs with MR was significantly higher than that in normal subjects. In conclusion, AM is a potential neurohumoral factor in dogs with CHF due to MR.

Objective—To investigate the relationship between myocardial performance index (MPI; also known as the Tei index) and cardiac function in anesthetized cats administered dobutamine. Animals—6 adult cats. Procedures—Cats were anesthetized by administration of propofol (6 mg/kg, IV), and anesthesia was maintained by administration of isoflurane. Heart rate and systolic arterial pressure (SAP) were monitored. Stroke volume, cardiac output, and aortic blood flow (ABF) were measured by use of transesophageal ultrasonography. Left ventricular fractional shortening (LVFS), mitral E-wave velocity-to-A-wave velocity (E:A) ratio, and ejection time were measured by use of transthoracic echocardiography. Dobutamine was administrated via a cephalic vein at rates of 2.5, 5.0, and 10 μg/kg/min. Results—Heart rate, SAP, cardiac output, and ABF increased with dobutamine administration, whereas stroke volume significantly decreased. The LVFS significantly increased, and the E:A ratio significantly decreased. Total isovolumic time and the MPI significantly decreased. The MPI was negatively correlated (r = −0.63) with LVFS. Conversely, the MPI was positively correlated with the E:A ratio (r = 0.47), stroke volume (r = 0.66), and total isovolumic time (r = 0.95). However, the MPI was not significantly correlated with heart rate, SAP, cardiac output, or ABF. Conclusion and Clinical Relevance—Analysis suggested that the MPI provides a sensitive clinical assessment of cardiac response to medication in cats, which may be similar to the usefulness of the MPI reported in humans.