余戸 拓也

The object of this study is to evaluate the long-term outcome of hind limb weight-bearing function and progression of stifle osteoarthritis (OA) after tibial plateau leveling osteotomy (TPLO). Groups were classified by the degree of cranial cruciate ligament (CrCL) damage and presence or absence of medial meniscus damage as macroscopically evaluated during surgery. Weight-bearing function was assessed via the peak vertical force (PVF), and OA progression was assessed via the radiographic OA score (OAS) preoperatively and 1, 3, 6, 12, 18, 24, and 36 months postoperatively. In all stifles, PVF was significantly higher within 6 months postoperatively than preoperatively, and this high ratio was maintained for 36 months. The OAS was significantly higher 24 months postoperatively than preoperatively in stifles with a partial CrCL tear, and significantly increased at each timepoint after 3 months postoperatively in stifles with complete CrCL rupture. The OAS remained consistently lower in stifles with a partial CrCL tear and no treatment of the medial meniscus than in stifles with complete rupture. Thus, after TPLO, the weight-bearing function improved in the early postoperative period and was maintained for as long as 36 months. Although OA progressed over time after TPLO, the progression was more gradual in stifles with partial tears than in those with complete rupture. Canine patients would benefit from earlier surgical intervention through development of technology that enables early detection of ligament degeneration.

OBJECTIVES:  Dogs with patella alta reportedly have a shorter extensor mechanism than normal dogs. The present study aimed to measure the length of the extensor mechanism and to assess the effect of limb position on the quadriceps muscle length (QML)/femoral bone length (FL) ratio. STUDY DESIGN:  Three-dimensional computed tomography images were taken of 12 Beagle dogs. Each dog underwent computed tomographic imaging 24 times with different limb positions. The QML/FL was measured on each image, along with the hip flexion-extension, hip abduction-adduction and stifle flexion-extension angles. Multiple regression analysis was used to determine the effect of these angles on the QML/FL. RESULTS:  The QML/FL was increased with the hip extended (standardized partial regression coefficient 0.855 with linear plotting, 0.829 with log plotting) and with the stifle flexed (standardized partial regression coefficient 0.814 with linear plotting, 0.800 with log plotting). The partial regression coefficient of the hip abduction-adduction angle was small, indicating a small impact on the QML/FL. The 95% confidence range of the QML/FL with the hip extended and stifle flexed was 0.87 to 1.00 (mean ± standard deviation: 0.93 ± 0.03). CONCLUSION:  The QML/FL was more influenced by joint angles when the hip was flexed or the stifle was extended. Hence, these positions should be avoided when evaluating the QML/FL so that the QML is less altered by slight positioning disparities.

The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH-secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Double-immunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 ± 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 ± 5.2%) and somatotroph cells (94.7 ± 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was

The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH-secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Doubleimmunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 +/- 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 +/- 5.2%) and somatotroph cells (94.7 +/- 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was also significantly reduced in the thyrotroph cells of the surrounding normal pituitary tissue obtained from the resected ACTH-secreting pituitary adenoma (8.3 +/- 7.9%) compared with that in normal canine pituitary (P < 0.001). BMP4 has been reported to be expressed in corticotroph cells in the human pituitary gland. Therefore, the results of this study reveal a difference in the cellular pattern of BMP4-positive staining in the pituitary gland between humans and dogs and further revealed the pattern of BMPRII-positive staining in the dog pituitary gland. These species-specific differences regarding BMP4 should be considered when using dogs as an animal model for Cushing's disease. (C) 2015 Elsevier Inc. All rights reserved.

Eyes are supplied O-2 through the cornea and vessels of the retina and iris, which are tissues characterized by aerobic metabolism. Meanwhile, there are no reports on the association between iris sphincter contraction and aerobic metabolism. In this paper, we studied the aforementioned association. Eyes from adult pigs of either sex were obtained from a local abattoir. A muscle strip was connected to a transducer to isometrically record the tension. O-2 consumption was measured using a Clark-type polarograph connected to a biological oxygen monitor. Creatine phosphate (PCr) and adenosine triphosphate (ATP) contents were measured in the muscle strips by high-performance liquid chromatography (HPLC). Iris sphincter muscles were measured in resting, contractile or hypoxic phases. Contraction was induced by hyperosmotic 65 mM KCl (H-65K(+)) or carbachol (CCh), and hypoxia was induced by aeration with N-2 instead of O-2 or by addition of sodium cyanide (NaCN). H-65K(+)- and CCh-induced muscle contraction, involved increasing O-2 consumption. Hypoxia and NaCN significantly decreased H-65K(+)- and CCh-induced muscle contraction and/or O-2 consumption and PCr contents. Our results suggest that the contractile behavior in porcine iris sphincter highly depends on mitogen oxidative metabolism.

OBJECTIVE To assess effects of vertebral distraction-fusion techniques at a treated segment (C5-C6) and an adjacent segment (C4-C5) of canine cervical vertebrae. SAMPLE Cervical vertebrae harvested from cadavers of 10 skeletally mature Beagles. PROCEDURES Three models (intact, titanium plate, and polymethylmethacrylate [PMMA]) for stabilization of the caudal region of the cervical vertebrae (C4 through C7) were applied to the C5-C6 vertebral segment sequentially on the same specimens. Biomechanical assessments with flexion-extension, lateral bending, and axial rotational tests were conducted after each procedure. Range of motion (ROM) for a torque load applied with a 6-axis material tester was measured at C4-5 and C5-6 and calculated by use of a 3-D video measurement system. RESULTS In both the plate and PMMA models, ROM significantly increased at C4-5 and significantly decreased at C5-6, compared with results for the intact model. The ROM at C5-6 was significantly lower for the plate model versus the PMMA model in lateral bending and for the PMMA model versus the plate model in axial rotation. Conversely, ROM at C4-5 was significantly higher in axial rotation for the PMMA model versus the plate model. No significant differences were identified in flexion-extension between the PMMA and plate models at either site. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study suggested that vertebral distraction and fusion of canine vertebrae can change the mechanical environment at, and may cause disorders in, the adjacent segment. Additionally, findings suggested that effects on the adjacent segment differed on the basis of the fusion method used.

Background: Large bone defects in canines usually require assistance to achieve healing. Implantation of osteoinductive factors can promote bone healing, while transplantation of osteoprogenitor cells can enhance bone regeneration. We hypothesized that implantation of an osteoinductive factor, recombinant human bone morphogenetic protein-2 (rhBMP-2), combined with osteoprogenitor cells, bone marrow-derived mesenchymal stromal cells (BMSCs), would synergistically promote bone healing. In this study, we examined the combined effects of Escherichia coli-derived rhBMP-2 and BMSCs on bone healing after implantation into canine ulnar defects. Results: Critical-sized osteoperiosteal segmental defects (2.5 cm) were created in the ulnae of healthy female beagle dogs, and implanted with combinations of E. coli-derived rhBMP-2 (560 or 140 mu g) and autologous BMSCs (10(7), 10(5), or 0 cells). In the present study, 18 forelimbs of nine healthy purpose-bred female beagles were used. All six treatment groups contained three forelimbs, and the animals were euthanized after 12 weeks. The control groups (560 and 140 mu g/0 cells) were cited from our previous study to reduce the number of experimental animals. Radiographically, the regenerated bone width was significantly increased in the 560 or 140 mu g with 10(7) and 10(5) cells groups compared with the 0 cells groups. By quantitative CT, the bone mineral density was higher in the 560 mu g with 10(7) and 10(5) cells groups, while non-uniformity of the bone mineral density was improved in the 560 mu g with 10(7) and 10(5) cells groups and 140 mu g/10(7) cells group. Mechanically, the maximum loads at failure were significantly higher in the 560 mu g with 10(7) and 10(5) cells groups. Histologically, the regenerated bone was well-developed and contained osteocyte-like cells marrow cavities, and vessels. However, the osteoclasts and osteoblasts were hardly observed. The osteocyte-like cell numbers were significantly higher in the 560 mu g with 10(7) and 10(5) cells and 140 mu g with 10(7) and 10(5) cells groups. Conclusions: Implantation of E. coli-derived rhBMP-2 and BMSCs led to significantly enhanced bone formation, with improved bone mineral density and reduced non-uniformity of the regenerated bone. Combined implantation of rhBMP-2 and BMSCs may be useful for promotion of bone healing in critical-sized defects in canines.

Intramedullary bone marrow-derived mononuclear cell (BM-MNC) transplantation has demonstrated neuroprotective effects in the chronic stage of spinal cord injury (SCI). However, no previous study has evaluated its effects in the acute stage, even though cell death occurs mainly within 1 week after injury in all neuronal cells. Moreover, the mechanism underlying these effects remains unclear. We aimed to investigate the survival of intramedullary transplanted allogeneic BM-MNCs and the production of growth factors after transplantation to clarify the therapeutic potential of intramedullary transplanted BM-MNCs and their protective effects in acute SCI. Sprague-Dawley rats were subjected to traumatic SCI and received intramedullary transplantation of EGFP BM-MNCs (n = 6), BM-MNCs (n = 10), or solvent (n = 10) immediately after injury. To evaluate the transplanted BMMNCs and their therapeutic effects, immunohistochemical evaluations were performed at 3 and 7 days post-injury (DPI). BM-MNCs were observed at the injected site at both 3 (683 +/- 83 cells/mm(2)) and 7 DPI (395 +/- 64 cells/mm(2)). The expression of hepatocyte growth factor was observed in approximately 20% transplanted BMMNCs. Some BM-MNCs also expressed monocyte chemotactic protein-1 or vascular endothelial growth factor. The demyelinated area and number of cleaved caspase-3-positive cells were significantly smaller in the BM-MNC-transplanted group at 3 DPI. Hindlimb locomotor function was significantly improved in the BM-MNCtransplanted group at 7 DPI. These results suggest that intramedullary transplantation of BM-MNCs is an efficient method for introducing a large number of growth factor-producing cells that can induce neuroprotective effects in the acute stage of SCI. (C) 2016 Elsevier Ltd. All rights reserved.

Objectives : The objectives of this study were to establish a magnetic resonance imaging-based classification system for canine hyperadrenocorticism according to pituitary gland extension, determine indications for trans-sphenoidal hypophysectomy, and clarify the prognosis for each disease grade. Methods : A 5-point classification system (Grades 1 to 5) was developed based on tumour extension in dorsal and cranio-caudal directions. Cases were then classified as Type A: no arterial circle of Willis or cavernous sinus involvement and Type B: cases in which these blood vessels were involved. Results : Medical records and magnetic resonance imaging data of 37 cases with hyperadrenocorticism were reviewed. Thirty-three cases underwent surgery 4 Grade 5 cases did not have appropriate indications for surgery, and other therapies were used. Complete resection was achieved for 3, 3, 22 and 1 Grade 1A, 2A, 3A and 3B cases, respectively. Resection was incomplete in 1, 1 and 2 Grade 3A, 3B and 4B cases, respectively. Remission was achieved in 29 cases. Recurrence occurred in 4 cases, all of which were classified as Grade 3. Clinical Significance : Dogs with Type A, Grade 1 to 3 hyperadrenocorticism had a good prognosis following trans-sphenoidal hypophysectomy. Grade 3B, 4 and 5 cases may not be suitable for this surgery.

Objective-To identify characteristics of chondrodystrophoid and nonchondrodystrophoid small-breed dogs with cervical intervertebral disk herniation (IVDH). Design-Retrospective case series. Animals-187 small-breed (<= 15 kg [33 lb]) dogs that underwent surgery because of cervical IVDH. Procedures-Medical records were reviewed for information on breed, sex, age, weight, location of affected intervertebral disks, duration and severity of neurologic signs, and recovery time. Results-55 of the 187 (29.4%) dogs were Beagles. The most frequently affected intervertebral disk was C2-3 (81/253 [32.0%]), and this was the more frequently affected intervertebral disk in dogs of several chondrodystrophoid breeds, including Beagles (29/66 [43.9%]), Dachshunds (13/37 [35.1%]), Shih Tzus (16/41 [39.0%]), and Pekingese (3/10 [30.0%]). However, caudal disks (C5-6 or C6-7) were more frequently affected in Yorkshire Terriers (13/24 [54.2%]) and Chihuahuas (9/13 [69%]). Shih Tzus and Yorkshire Terriers were significantly older at the time of surgery (mean +/- SD age, 9.6 +/- 2.3 years and 9.5 +/- 2.5 years, respectively) than were Pomeranians (6.2 +/- 2.3 years), and Yorkshire Terriers had a significantly higher number of affected disks (2.0 +/- 0.9) than did Dachshunds (1.1 +/- 0.3). Mean recovery time was significantly longer in Yorkshire Terriers (36.7 +/- 13.0 days) than in Beagles (16.5 +/- 17.1 days), Shih Tzus (17.8 +/- 14.5 days), or Chihuahuas (12.2 +/- 7.2 days). Conclusions and Clinical Relevance-Results suggested that there may be breed-specific differences in the characteristics of cervical IVDH in small-breed dogs.

Objective: To create a canine model of excessive tibial plateau angle (eTPA) and assess the chondroid metaplasia and extracellular matrix alteration in the cranial cruciate ligament. Methods: Seven mature female Beagles were included. Cylindrical osteotomy was performed bilaterally in the proximal tibia. The TPA was increased to approximately 40° in the left tibia (eTPA stifle) and left unchanged in the right tibia (control stifle). Exercise stress was started at three months postoperatively, and at 12 months postoperatively the dogs were euthanatized and the cranial cruciate ligaments were collected. The specimens were subjected to haematoxylin and eosin staining to assess the ligamentocyte morphology and immunostaining to assess the type I (COLI), type II (COLII), and type III (COLIII) collagen, and the sry-type HMG box 9 (SOX9) staining. Results: Macroscopic cranial cruciate ligament injury was absent in six dogs but present in the eTPA stifle of one dog, which was excluded from the analysis. The ligamentocyte density decreased and the percentage of round ligamentocytes increased in the eTPA stifles. The COLII, COLIII, and SOX9 staining increased significantly and COLI deposition decreased in the eTPA stifles compared to the control stifle. Clinical significance: The extracellular matrix changed, COLI deposition decreased, and COLIII and SOX9 staining increased in the cranial cruciate ligament of the eTPA stifles. SOX9 may contribute to COLII synthesis in the extracellular matrix of the cranial cruciate ligament in eTPA stifles, and eTPA may promote chondroid metaplasia and extra - cellular matrix alteration.

Degenerative cranial cruciate ligament (CCL) rupture is characterized histologically by degenerating extracellular matrix (ECM) and chondroid metaplasia. Here, we describe the progression of chondroid metaplasia and the changes in the expression of ECM components in canine CCL rupture (CCLR). CCLs from 26 stifle joints with CCLR (CCLR group) and normal CCLs from 12 young beagles (control group) were examined histologically and immunohistochemically for expression of type I (COLD, type II (COLII), type III collagen (COLIII) and Sry-type HMG box 9 (SOX9). Cell density and morphology of CCLs were quantified using hematoxylin eosin staining. The percentage of round cells was higher in the CCLR group than in controls. COLI-positive areas were seen extensively in the connecting fibers, but weakly represented in the cytoplasm of normal CCLs. In the CCLR group, there were fewer COLT-positive areas, but many COLT-positive cells. The percentages of COLII-, COLIII- and SOX9-positive cells were higher in the CCLR group than in controls. The number of spindle cells with perinuclear halo was high in the CCLR group, and most of these cells were SOX9-positive. Deposition of COLT, the main ECM component of ligaments, decreased with increased COLIII expression in degenerated CCL tissue, which shows that the deposition of the ECM is changed in CCLR. On the contrary, expression of SOX9 increased, which may contribute to the synthesis of cartilage matrix. The expression of COLII and SOX9 in ligamentocytes showed that these cells tend to differentiate into chondrocytes.

OBJECTIVE To determine whether thioredoxin (TRX)-1 can be used as a valid biomarker for oxidative stress in dogs. ANIMALS AND SAMPLES 10 Beagles and Madin-Darby canine kidney cells. PROCEDURES Madin-Darby canine kidney cells were used to verify antigen cross-reactivity between human and canine anti-TRX-antibodies. Dogs were assigned to receive 21% or 100% O-2 (5 dogs/group) via an artificial respirator during a 3-hour period of isoflurane anesthesia (starting at 0 hours). Blood and urine samples were collected before (baseline) and at 6, 12, 24, and 48 hours after commencement of inhalation anesthesia. Concentrations of TRX-1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in plasma and urine samples were analyzed; urine concentrations were reported as ratios against urine creatinine concentration. RESULTS Canine TRX-1 was recognized by monoclonal human anti-TRX-1 antibodies (clones of adult T-cell leukemia-derived factor [ADF]-11 and ADF21) by western blot analysis. Results of an ELISA indicated that plasma TRX-1 concentration and urine TRX-1-to-creatinine concentration ratio increased rapidly after the 3-hour period of hyperoxia with maximal peaks at 12 and 6 hours, respectively. Urine 8-OHdG-to-creatinine concentration ratio also increased significantly after hyperoxia induction. However, unlike the rapid increase in urine TRX-1-to-creatinine concentration ratio, maximal urine 8-OHdG-to-creatinine concentration ratio was attained at 48 hours after hyperoxia induction. These variables remained unchanged from baseline in the control group. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that human anti-TRX monoclonal antibodies cross-reacted with canine TRX, and plasma TRX-1 concentrations were rapidly increased in dogs following an oxidative stress challenge. Thus, TRX may be a valuable clinical biomarker for detecting oxidative stress more rapidly than 8-OHdG in dogs.

Currently, the most commonly used bioresorbable scaffold is made of beta-tricalcium phosphate (β-TCP) it is hoped that scaffolds made of a mixture of hydroxyapatite (HA) and poly-D/L-lactide (PDLLA) will be able to act as novel bioresorbable scaffolds. The aim of this study was to evaluate the utility of a HA/PDLLA scaffold compared to β-TCP, at a loading site. Dogs underwent surgery to replace a section of tibial bone with a bioresorbable scaffold. After the follow-up period, the scaffold was subjected to histological analysis. The HA/PDLLA scaffold showed similar bone formation and superior cell and tissue infiltration compared to the β-TCP scaffold, as seen after Villanueva Goldner staining. Moreover, silver staining and immunohistochemistry for Von Willebrand factor and cathepsin K demonstrated better cell infiltration in the HA/PDLLA scaffold. The fibrous tissue and cells that had infiltrated into the HA/PDLLA scaffold tested positive for collagen type I and RUNX2, respectively, indicating that the tissue and cells that had infiltrated into the HA/PDLLA scaffold had the potential to differentiate into bone. The HA/PDLLA scaffold is therefore likely to find clinical application as a new bioresorbable scaffold.

Currently, the most commonly used bioresorbable scaffold is made of beta-tricalcium phosphate (beta-TCP); it is hoped that scaffolds made of a mixture of hydroxyapatite (HA) and poly-D/L-lactide (PDLLA) will be able to act as novel bioresorbable scaffolds. The aim of this study was to evaluate the utility of a HA/PDLLA scaffold compared to beta-TCP, at a loading site. Dogs underwent surgery to replace a section of tibial bone with a bioresorbable scaffold. After the follow-up period, the scaffold was subjected to histological analysis. The HA/PDLLA scaffold showed similar bone formation and superior cell and tissue infiltration compared to the beta-TCP scaffold, as seen after Villanueva Goldner staining. Moreover, silver staining and immunohistochemistry for Von Willebrand factor and cathepsin K demonstrated better cell infiltration in the HA/PDLLA scaffold. The fibrous tissue and cells that had infiltrated into the HA/PDLLA scaffold tested positive for collagen type I and RUNX2, respectively, indicating that the tissue and cells that had infiltrated into the HA/PDLLA scaffold had the potential to differentiate into bone. The HA/PDLLA scaffold is therefore likely to find clinical application as a new bioresorbable scaffold.

Conjunctival epithelial and goblet cell P2Y2 nucleotide receptors regulate ion transport and secretory function. Diquafosol is a P2Y2 purinergic receptor agonist that stimulates secretion of aqueous tear components from conjunctival epithelial cells and secretion of mucin from conjunctival goblet cells. In humans suffering from keratoconjunctivitis sicca (dry eye), topical administration of diquafosol improves corneal epithelial integrity and stabilises the tear film. The aim of the present study was to investigate P2Y2 receptor expression and to determine the effect of topical administration of diquafosol on mucin and aqueous tear production in dogs. Canine conjunctival P2Y2 receptor expression was evaluated by Western blotting and immunohistochemical analysis. The effect of diquafosol on mucin secretion was evaluated by examining mucin-5 subtype AC (MUC5AC) concentration in tears. The effect of diquafosol on aqueous secretions was evaluated by performing the Schirmer tear test (STT) and phenol red thread test. Expression of the P2Y2 receptor was confirmed in canine bulbar and palpebral conjunctivae and receptors were identified at the conjunctival epithelial and goblet cell surface. Tear MUC5AC concentration significantly increased after administration of 3% diquafosol ophthalmic solution, although neither STT nor phenol red thread test values showed any significant change after diquafosol instillation. Topical ocular administration of 3% diquafosol might improve corneal epithelial disorders in dogs through stabilisation of the tear film, by virtue of an increase in MUC5AC secretion.

To understand the effects of silicon (Si) in the urine with respect to the formation of urinary stones, the distribution of Si in urine was observed. Urine samples from cats with urolithiasis (n=10) and healthy cats (n=15) were used. The concentration of Si in the cats with urolithiasis was significantly higher (P<0.001). A significant correlation (P<0.05) was observed between the concentration of Si and those of other elements, such as calcium, magnesium, phosphorus, potassium and iron, only in the urine of the healthy cats. The distribution of elements in the urine differed between the cats with urolithiasis and the healthy cats. The Si concentration and its relationship with other elements were suggested to be useful biomarkers for urolithiasis in cats.

Objective: The aim of this study was to investigate the biomechanical effects of cranial cruciate ligament (CrCL) transection on stifle stability at three different stifle joint flexion angles using a robotic system. Methods: This was an ex vivo biomechanical study. Stifles (n = 6) were collected from the cadavers of Beagles weighing 10.5-12.0 kg. Six stifle joints were dissected, potted, and secured to the manipulator arms of a robotic simulator. With the stifle joint angle maintained at either hyperextension (151°), 135° or 90°, stability was assessed by application of a 50 N load in either the cranial-caudal (CrCd test) or proximal-distal (PD test) directions. The stifle was given a cranialcaudal load of 50 N (CrCd test). A proximaldistal compression load of 50 N was then administered by the manipulator (proximal-distal test: PD test). The change in three-dimensional kinematics of the intact and the CrCLtransected stifles was compared between hyperextension, and 135° and 90° flexion for the CrCd and PD load conditions. A value of p &lt 0.05 was considered statistically significant. Results: The cranial tibial displacements in the PD tests of the CrCL-transected stifles at 135° (8.4 ± 1.2 mm) and at 90° (8.1 ± 1.9 mm) were significantly greater than the displacement at 151.5° (5.1 ± 1.6 mm) (p = 0.004 and p = 0.012 respectively). Clinical significance: The canine stifle exhibited the most instability when the stifle flexion angle was 135°. © Schattauer 2014.

Previously, the ability of interferon (IFN) to reinforce antitumor immune capacity has received much attention. In humans and mice, natural killer (NK) cells are activated by IFN, thereby reinforcing antitumor immunity. We investigated whether NK cytotoxic activity can be enhanced by recombinant canine interferon-gamma (rCaIFN-gamma) in dogs. First, we investigated the effects of various concentrations of and time exposures to IFN-gamma in the culture medium on the NK cytotoxic activity of peripheral blood lymphocyte (PBLs) extracted from healthy beagles. Time- and concentration-dependent enhancement of NK cytotoxic activity of PBLs was observed. We then investigated whether the NK cytotoxic activity of PBLs is enhanced 24 h after administration of rCaIFN-gamma (10,000 units/kg body weight) in healthy beagles. Our in vivo study confirmed that NK cytotoxic activity of PBLs was enhanced by this approach, suggesting that antitumor immunity was reinforced. In dogs, rCaIFN-gamma may be effective for bolstering antitumor immune capacity. (C) 2013 Elsevier Ltd. All rights reserved.

The aim of this study was to determine the efficacy of a colorimetric pupil light reflex (PLR) device (Melan-100 (R), U.S.A.) in dogs with sudden acquired retinal degeneration syndrome (SARDS; 16 cases), progressive retinal atrophy (PRA; 10 cases) and optic pathway disease (6 cases). The colorimetric device detected PLR abnormality in 32, 16 and 9 eyes with SARDS, PRA and optic pathway disease, respectively, whereas white light detected PLR abnormality in 18, 11 and 9 eyes with SARDS, PRA and optic pathway disease, respectively. SARDS dogs displayed miosis, while optic pathway disease dogs displayed mydriasis in a blue light examination. Thus, colorimetric PLR may be a useful method for determining whether electroretinography (ERG) or magnetic resonance imaging (MRI) should be performed for dogs with acute blindness.

The objectives of this study were to investigate the normal histological localization of aquaporin (AQP) 5 protein in the lacrimal and nictitating membrane glands and to compare this localization in healthy and keratoconjunctivitis sicca (KCS) dogs. Lacrimal and nictitating membrane glands of 5 healthy Beagles and nictitating membrane glands of 5 KCS dogs (3 Beagles and 2 mongrel dogs: 0-13 years) were used for the present study. The owners of the KCS dogs did not consent to perform biopsies of the lacrimal glands. The localization and distribution of AQP5 protein were investigated by an immunohistochemical technique. In immunohistochemical staining, AQP5 was localized in the apical site of acinar epithelial and ductal epithelial cells from both the lacrimal and nictitating membrane glands in healthy dogs. However, AQP5 was not detected in the 5 KCS dogs. These results for immunohistochemical AQP5 localization might correlate with the deficiency in tear secretion found in KCS dogs. © The Author(s) 2012.

To investigate influence of general anesthesia on immunological anti-tumor activity, the natural killer (NK) cytotoxic activity of peripheral lymphocytes (PBLs) was measured in 7 dogs anesthetized for 3 hr with isoflurane following propofol-induction (anesthesia group) and 6 dogs without anesthesia (control group). Blood samples were collected before (baseline) and 24, 120 and 192 hr after the anesthesia. The PBLs were isolated via centrifugation with Ficoll-Hypaque solution (density, 1.073), and adherent cells were removed. The NK cytotoxic activity of the isolated PBLs against canine thyroid cancer cells was detected by the colorimetric rose Bengal assay. Significant decrease in the NK cytotoxic activity was observed at 24 hr after the anesthesia, compared with the baseline values and the control group. The NK cytotoxic activities were recovered to the baseline values until 120 hr after the anesthesia. The general anesthesia with isoflurane following propofol-induction decreased the NK cytotoxic activities of PBLs in dogs. This finding has a clinical relevance to the risk of tumor recurrence or metastasis induced by the suppression of immunological anti-tumor activity after general anesthesia in dogs. The results further emphasized the importance of the need to evaluate immune suppression following general anesthesia in animals.

Intervertebral disc (IVD) degeneration greatly affects quality of life. The nucleus pulposus (NP) of chondrodystrophic dog breeds (CDBs) is similar to the human NP, because the cells disappear with age and are replaced by fibrochondrocyte-like cells. However, because IVD develops as early as within the first year of life, we used canines as a model to investigate in vitro the mechanisms underlying IVD degeneration. Specifically, we evaluated the potential of a three-dimensional (3D) culture of healthy NP as an in vitro model system to investigate the mechanisms of IVD degeneration. Agarose hydrogels were populated with healthy NP cells from beagles after performing magnetic resonance imaging, and mRNA expression profiles and pericellular extracellular matrix (ECM) protein distribution were determined. After 25 days of 3D culture, there was a tendency for redifferentiation into the native NP phenotype, and mRNA levels of Col2A1, COMP, and CK18 were not significantly different from those of freshly isolated cells. Our findings suggest that long-term 3D culture promoted chondrodystrophic NP redifferentiation through reconstruction of the pericellular microenvironment. Further, lipopolysaccharide (LPS) induced expression of TNF-alpha, MMP3, MMP13, VEGF, and PGES mRNA in the 3D cultures, creating a molecular milieu that mimics that of degenerated NP. These results suggest that this in vitro model represents a reliable and cost-effective tool for evaluating new therapies for disc degeneration.

Objectives: To evaluate the efficacy of cortical allograft and fibroblast growth factor 2 (FGF-2)-impregnated autogenous cancellous bone in nonunion fracture repair in dogs. Methods: From January 2000 to August 2010, seven dogs underwent cortical allograft and FGF-2-impregnated autogenous cancellous bone implantation for treatment of a femoral nonunion following fracture. Radiographic images were used to assess healing. Results: The average length of the implanted cortical allograft was 29.1 ± 4.4 mm. A significant improvement in the postoperative percentage of femoral shortening was observed with the experimental treatment, from 85.2 ± 8.2% to 95.0 ± 4.8%. Using radiographic scoring, we analysed the process of bone remodelling. At three months post-surgery, the proximal and distal fracture lines had begun to disappear, and a complete absence was observed after six months. Bacterial infection was detected in two of the seven cases. Clinical significance: The findings of our study suggest that the combination of cortical allografts with FGF-2 impregnated cancellous autograft may be useful in cases of diaphyseal fracture non-union. The disappearance of the fracture line in dogs with nonunion was recognized at the same phase as the report in which healing process of allograft was evaluated in the experimental ostectomy model using the normal dog. © Schattauer 2013.

Because bone morphogenetic protein 2 gene transfected Escherichia coli (E-BMP-2) produce recombinant human BMP-2 (rhBMP-2) more efficiently than mammalian cells (Chinese hamster ovary [CHO]-BMP-2), they may be a more cost-effective source of rhBMP-2 for clinical use. However, use of E-BMP-2 for regenerating long bones in large animals has not been reported. In the current study, we evaluated the healing efficacy of E-BMP-2 in a canine model. We created 2.5-cm critical-size segmental ulnar defects in test animals, then implanted E-BMP-2 and 700 mg of artificial bone (beta-tricalcium phosphate; beta-TCP) into the wounds. We examined the differential effects of 5 E-BMP-2 treatments (0, 35, 140, 560, and 2240 mu g) across 5 experimental groups (control, BMP35, BMP140, BMP560, and BMP2240). Radiography and computed tomography were used to observe the regeneration process. The groups in which higher doses of E-BMP-2 were administered (BMP560 and BMP2240) displayed more pronounced bone regeneration; the regenerated tissues connected to the host bone, and the cross-sectional areas of the regenerated bone were larger than those of the originals. The groups in which lower doses of E-BMP-2 were administered (BMP35 and BMP140) experienced relatively less bone regeneration; furthermore, the regenerated tissues failed to connect to the host bone. In these groups, the cross-sectional areas of the regenerated bone were equal to or smaller than those of the originals. No regeneration was observed in the control group. These findings suggest that, like CHO-BMP-2, E-BMP-2 can be used for the regeneration of large defects in long bones and that its clinical use might decrease the cost of bone regeneration treatments.

Objectives: Severe intervertebral disc herniation causes complete paraplegia and loss of pain sensation in canines. The prognosis is poor, even when decompression surgery is performed immediately after onset. Studies suggest that bone marrow-derived mononuclear cells will regenerate the injured spinal cord and restore neurologic function. This study was conducted to assess the clinical efficacy of bone marrow-derived mononuclear cell autotransplanting in severe cases of canine intervertebral disc herniation. Materials and Methods: Eighty-two dogs (miniature dachshunds) with severe thoracolumbar intervertebral disc herniation were used. All had intervertebral disc herniation accompanied by paraplegia and loss of pain perception. In 36 dogs, bone marrow-derived mononuclear cells were autotransplanted to the lesioned spinal cord immediately after decompression surgery. Bone marrow was collected from the proximal humerus and subjected to density gradient centrifugation to isolate the bone marrow-derived mononuclear cells. The remaining 46 dogs (receiving surgical treatment only) were assigned as controls. Therapeutic efficacy was compared based on the rate of ambulatory recovery. Results: Ambulatory recovery was observed in 88.9% and 56.5% of animals in the bone marrow-derived mononuclear cells and control groups, and a significant difference was found. No complications were found in bone marrow-derived mononuclear cells group. Conclusions: Bone marrow-derived mononuclear cell transplanting revealed a significant increase in the recovery rate and, as has been reported in rats and humans, bone marrow-derived mononuclear cell autotransplanting shows efficacy in canines as well.

Objective-To evaluate the role of the semitendinosus muscle in stabilization of the canine stifle joint. Sample-Left stifle joints collected from cadavers of 8 healthy Beagles. Procedures-Left hind limbs, including the pelvis, were collected. To mimic the tensile force of the quadriceps, gastrocnemius, and semitendinosus muscles, wires were placed under strain between the ends of each muscle. A sensor was used to measure the tensile force in each wire. Specimens were tested in the following sequence: cranial cruciate ligament (CrCL) intact, CrCL transected, released (tensile force of semitendinosus muscle was released in the CrCL-transected stifle joint), and readjusted (tensile force of semitendinosus muscle was reapplied in the CrCL-transected stifle joint). Specimens were loaded at 65.3% of body weight, and tensile force in the wires as well as the cranial tibial displacement were measured. Results-Tensile force for the CrCL-transected condition increased significantly, compared with that for the CrCL-intact condition. Mean +/- SD cranial tibial displacement for the CrCL transected condition was 2.1 +/- 1.3 mm, which increased to 72 +/- 2.3 mm after release of the tensile force in the semitendinosus muscle. Conclusions and Clinical Relevance-Results supported the contention that the semitendinosus muscle is an agonist of the CrCL in the stifle joint of dogs. Moreover, the quadriceps and gastrocnemius muscles may be antagonists of the CrCL. These findings suggested that the risk of CrCL rupture may be increased by diseases (such as cauda equina syndrome) associated with a decrease in activity of the semitendinosus muscle. (Am J Vet Res 2012;73:672-680)

The concentrations of elements in urine obtained from cats with urolithiasis were compared with those of healthy cats. The concentration of several elements, such as sodium (Na), phosphorus (P), sulfur (S), and potassium (K), in urine obtained from cats with urolithiasis was significantly higher than that of healthy cats. A significant correlation (p < 0.01) was found between the concentration of magnesium (Mg) and that of other elements, such as P (r = 0.8913), S (r = 0.6817), and K (r = 0.8391), in the urine obtained from healthy cats. A significant correlation (r = 0.7422, p < 0.05) was also obtained between the concentration of K and that of P in urine collected from cats with urolithiasis, but the slope of regression line was significantly different from that of the urine obtained from healthy cats. Other correlations observed in healthy cats were not obtained from cats with urolithiasis. However, a significant correlation between the concentration of magnesium (Mg) and that of calcium was obtained only from cats with urolithiasis. The results of the present study suggest that urinary concentrations of various elements in cats with urolithiasis are higher than those of healthy cats. Furthermore, the balance of elements in the urine of cats with urolithiasis was altered.

Objective To evaluate effects of long-term administration of carprofen on healing of a tibial osteotomy in dogs. Animals-12 healthy female Beagles. Procedures-A mid-diaphyseal transverse osteotomy (stabilized with an intramedullary pin) of the right tibia was performed in each dog. The carprofen group (n = 6 dogs) received carprofen (2.2 mg/kg, PO, q 12 h) for 120 days; the control group (6) received no treatment. Bone healing and change in callus area were assessed radiographically over time. Dogs were euthanized 120 days after surgery, and tibiae were evaluated biomechanically and histologically. Results-The osteotomy line was not evident in the control group on radiographs obtained 120 days after surgery. In contrast, the osteotomy line was still evident in the carprofen group. Callus area was significantly less in the carprofen group, compared with the area in the control group, at 20, 30, and 60 days after surgery. At 120 days after surgery, stiffness, elastic modulus, and flexural rigidity in the carprofen group were significantly lower than corresponding values in the control group. Furthermore, histologic evaluation revealed that the cartilage area within the callus in the carprofen group was significantly greater than that in the control group. Conclusions and Clinical Relevance-Long-term administration of carprofen appeared to inhibit bone healing in dogs that underwent tibial osteotomy. We recommend caution for carprofen administration when treating fractures that have delays in healing associated with a reduction in osteogenesis as well as fractures associated with diseases that predispose animals to delays of osseous repair. (Am J Vet Res 2011;72:634-641)

This study investigated the influence of dried okara-tempeh, the insoluble portion of soybeans fermented with ragi-tempeh, on fecal microbiota and metabolites in dogs. Three dried okara-tempehs (individual weight: approximately 5 g) were given daily to each of 6 beagle dogs for a period of 2 weeks. The concentrations of fecal short-chain fatty acids, pH, and microbiota were determined. During the intake of the dried okara-tempeh, the level of Bifidobacterium expressed as log(10) number (CFU)/g wet feces was increased significantly (p<0.05) from 6.4 +/- 0.9 (mean +/- SD) to 8.8 +/- 0.8, and the level of Bacillus was also increased significantly (p < 0.05) from 4.1 +/- 1.8 to 7.3 +/- 0.6. Moreover, fecal concentrations of total short-chain fatty acids, acetic acid and propionic acid also increased significantly (p < 0.05) from 146.7 +/- 15.9 mu mol/g wet feces to 198.8 +/- 24.6 mu mol/g wet feces, from 90.3 +/- 8.6 mu mol/g wet feces to 116.3 +/- 17.91 mu mol/g wet feces, and from 39.3 +/- 3.7 mu mol/g wet feces to 60.0 +/- 9.1 mu mol/g wet feces respectively on day 7 of dried okara-tempeh intake compared to pre-intake. Fecal pH decreased significantly (p < 0.05) from 6.2 +/- 0.3 to 5.6 +/- 0.2 during intake. The findings obtained by this study demonstrate that the intake of dried okara-tempeh was effective for improving the fecal environment in dogs and that okara, which is currently discarded, can be effectively utilized in dog feed.

Postoperative changes in endocrinological status and serum chemistry during the 4 years after transsphenoidal surgery (ISS) in 25 dogs with Cushing's disease were investigated in a prospective study. In all 25 dogs. Cushing's disease was diagnosed from resected pituitary tissues as a corticotroph adenoma in the anterior lobe of the pituitary. Prior to TSS, all 25 clogs showed hypercortisolemia. After TSS, the ACTH stimulation test showed continued low serum cortisol concentrations in 21 dogs (84%). In addition, the serum thyroid stimulating hormone concentrations decreased sequentially, while the serum T4 concentrations tended to increase due to the postoperative hormone substitution therapy utilized to avoid secondary hypothyroidism. In recital to serum chemistry. alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total cholesterol are commonly increased in can Cushing's disease. In this study. ALP. ALT and total cholesterol were increased in 23 eases (92%), 19 cases (76%) and 20 cases (80%). respectively. However. postoperatively, these concentrations gradually decreased. The postoperative serum concentrations of ALP at I year, that of ALT at six months to 2 years and that of total cholesterol over the course of the 4 years decreased significantly compared with the concentrations before TSS. These results show that TSS is an effective treatment for canine Cushing's disease and for long-term improvement of hypercortisolemia. Moreover. TSS is effective in improvement or hypercortisolism, such as increased concentrations of serum ALP. ALT and total cholesterol.

An 11-year-old male mixed breed dog diagnosed with Gushing's disease and diabetes mellitus was treated by hypophysectomy After surgery. the hypercortisolemia disappeared and the diabetes status improved The insulin requirement to control hyperglycemia gradually decreased At 12 weeks after surgery, there was no requirement for insulin and we suspected the diabetes was completely resolved In the present case diabetes mellitus seems to be secondary to Cushing's disease In conclusion, this mixed breed dog with coexisting Cushing's disease and diabetes mellitus is the first case showing the effectiveness of hypophysectomy to treat diabetes mellitus secondary to Cushing's disease in dogs

盲導犬とは視覚障害を持つヒトを誘導するための使役犬であり、そのため、盲導犬自身が視覚障害を生じることは使役を果たすために重大な問題となる。本研究では視覚障害の原因となる白内障の発生を繁殖計画により制御することを目指して、最初の段階として、盲導犬として訓練期間中のラブラドールレトリバーにおける若年白内障の発生状況を調査したのでその概要を報告する。盲導犬として訓練中のラブラドールレトリバー213頭について威嚇瞬目反応、対光反射、眼圧測定、細隙灯生体顕微鏡検査を実施し、白内障が検出された個体ごとに白内障の形成部位、年齢、性別、血縁について調査を行った。若年白内障は12頭17眼に認められ、白内障発生個体の平均年齢は1.24±0.24歳、発生率は5.63%であった。白内障発生個体12頭うち、水晶体後部に白内障が観察されたのは11頭であった。血縁についての調査では、白内障発生個体で同じ両親から生まれた個体は2頭1組（Group A）、父犬が同じである場合が2組（Group B, C）、母犬が同じである場合は3組（Group A, D, E）で認められた。本研究におけるラブラドールレトリバーの白内障の発生率は北米での調査においてコントロール群とされた雑種または交雑種の白内障発生率よりも高く、このことから本犬種における白内障の好発傾向が再確認された。本研究における白内障発生率は英国やオランダにおける本犬種の白内障発生率よりもやや低い成績となった。この原因としてはこれらの研究が全年齢を対象とした報告であったのに対して、本研究が盲導犬として訓練中の若齢犬を対象とした研究であり、より高齢での白内障の発生を検出できなかったことが考慮された。よって、本研究の対象犬については引き続き、追跡調査の必要があると考えられた。白内障の形成部位についての検討では検出された白内障のほとんどが水晶体後部に存在し、この傾向は既報でのラブラドールレトリバーの白内障所見と同様な傾向であった。白内障発生個体の血縁関係の調査では明らかな血縁関係が認められ、遺伝性素因が強く関連していると考えられた。よって、盲導犬の選定においては白内障個体を避けるべきであり、また、今後は更に白内障発生の危険を回避できるような繁殖計画の策定とその改善に努める必要があると考えられた。

The effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility and cyclic nucleotide contents in porcine iris sphincter were investigated. Forskolin and sodium nitroprusside inhibited carbachol (CCh)-induced contraction in a concentration-dependent manner. Various selective PDE inhibitors, vinpocetine (type 1), erythro -9-(2-hydroxy-3-nonyl)adenine (EHNA, type 2), milrinone (type 3), Ro20-1724 (type 4) and zaprinast (type 5), also inhibited CCh-induced contraction in a concentration-dependent manner. The rank order of potency of IC(50) was zaprinast > Ro20-1724 > EHNA >= milrinone > vinpocetine. In the presence of CCh (0.3 mu M), vinpocetine, milrinone and Ro20-1724 increased cAMP, but not cGMP, contents. In contrast, zaprinast and EHNA both increased cGMP, but not cAMP, contents. This indicates that vinpocetine-, milrinone- and Ro20-1724-induced relaxation is correlated With cAMP, While EHNA- and zaprinast-induced relaxation is correlated with cGMP in porcine iris sphincter.

Cushing's disease caused by pituitary corticotroph adenoma in dogs is usually treated by medical treatment, and the efficacy of this treatment has been reported. However, controversy remains as to whether reduced negative feedback through the inhibition of cortisol secretion, similar to Nelson's syndrome, may appear as an adverse effect. The purpose of this study was to investigate the effect of reduced negative feedback through the inhibition of cortisol secretion by daily trilostane administration on the pituitary-adrenal axis in clinically normal dogs. Dogs were administered 5 mg/kg trilostane twice a day every day for 8 weeks (n=8) or 16 weeks (n=3). After the initiation of trilostane administration, plasma adrenocorticotropic hormone (ACTH) concentrations were increased remarkably. As assessed by magnetic resonance imaging (MRI) during administration, the pituitary became enlarged. After trilostane administration, the cytoplasmic areas of the pituitary corticotrophs were increased and the ratio of pituitary corticotrophs to all cells in the anterior lobe was greater in the trilostane-treated dogs than that in untreated animals. In addition, histological examinations revealed bilateral adrenal cortical hyperplasia. Using real-time PCR quantification, the expression of proopiomelanocortin (POMC) mRNA in the pituitary and ACTH receptor (ACTH-R) mRNA in the adrenal gland was greater in the dogs treated with trilostane than in untreated dogs. These results indicate that reduced negative feedback induced hyperfunction of the pituitary corticotrophs and pituitary enlargement in healthy dogs. These changes suggest that the inhibition of cortisol secretion by trilostane may increase the risk for accelerating the growth of corticotroph adenomas in dogs with Cushing's disease. (C) 2008 Elsevier Inc. All rights reserved.

Pituitary thyrotroph hyperplasia results from prolonged primary hypothyroidism in humans, mice and rats. In dogs with Cushing's disease, many cases have low serum thyroid hormones concentrations due to euthyroid sick syndrome. A 6-year-old castrated male Beagle diagnosed with Cushing's disease had a high serum thyroid Stimulating hormone (TSH) concentration that was treated by hypophysectomy. On histological examination, the resected pituitary gland contained both a corticotroph adenoma and thyrotroph hyperplasia. The TSH-positive cell ratio in this case was greater than that of healthy Beagles. In the present case, the pituitary thyrotroph hyperplasia was probably caused by primary hypothyroidism. In conclusion, this Beagle is the first histological confirmation of the coexistence of a corticotroph adenoma and thyrotroph hyperplasia.

The posterior lobe of the pituitary gland (PL) normally shows characteristic high signal intensity (SI) on T1-weighted MR images (T1WI) in humans. The high S1 is thought to represent storage of arginine vasopressin (AVP) in the PL. Normal dogs also show a high SI on T1WIs, but the origin is unclear. In the present study, we investigated whether the high Sl in the PL on T1WIs in normal dogs is caused by AVP. We examined the Sl in the PL on T1WIs. plasma AVP concentrations and plasma osmolality in normal dogs after excessive AVP secretion was induced by hypertonic saline overload. In addition, functional changes in the supraoptic nucleus and paraventricular nucleus of the hypothalamus under AVP secretion-stimulated conditions were examined immunohistologically. Under hypertonic saline overload, plasma osmolality and plasma AVP concentrations gradually increased, while the Sl of the PL gradually decreased. This suggests that AVP secretion was stimulated by elevated osmolality. Moreover, there was a significant negative correlation between plasma AVP concentrations and the SI ratio of the PL. An immunohistochemical study of the hypothalamus nucleus revealed that AVP-immunopositive cells significantly increased in the hypertonic saline loaded dogs. We concluded that the high SI in the PL in TIWIs in normal dogs was caused by AVP stored at the site, and examination of the Sl in the PL using MRI is useful for diagnosis of abnormal pituitary glands.

We investigated the epidemiological characteristics of intervertebral disc herniation (IVDH) in Japan in a large population using a retrospective study. The sample population was dogs (n=297) with IVDH in Japan. Medical records were reviewed for breed, sex, age, affected interspace and neurological severity. The dogs were comprised of 132 cases of cervical IVDH (C-IVDH) and 165 cases of thoracolumbar IVDH (TL-IVDH). In Japan, the Dachshund, Beagle and Shih Tzu tended to suffer from both C-IVDH and TL-IVDH. The Shiba Inu, a characteristic Japanese dog breed, suffered from both C-IVDH and TL-IVDH, although there was little data relating to the whole breed. Male dogs tended to suffer from C-IVDH and TL-IVDH at a rate almost twice that of females in Japan. Among the three predominant dog breeds, the Dachshund, Beagle and Shih Tzu, the Dachshund tended to suffer from both C-IVDH and TL-IVDH at an earlier age than the Beagle, and the Beagle tended to Suffer from both C-IVDH and TL-IVDH earlier than the Shih Tzu. Among the three predominant breeds, the Shih Tzu, in particular, tended to suffer from both C-IVDH and TL-IVDH at multiple sites. Our data from Japan were in partial agreement with previous data from the U.S.A., and epidemiological characteristics of IVDH peculiar to Japan were also identified.

Thrombosis is a potential complication of hyperadrenocorticism (HAC) in dogs. An 8-year-old male Beagle diagnosed with pituitary-dependent HAC had complicated with thrombosis in the caudal vena cava and abdominal aorta, which was treated by hypophysectomy and antithrombotic therapy. After hypophysectomy, hypercortisolemia disappeared and the general condition was also significantly improved. Ultrasonography after hypophysectomy revealed that the thrombus remained in the abdominal aorta, but the thrombus in the caudal vena cava had disappeared. However 692 days after the hypophysectomy, the dog had an acute onset of dyspnea and died. Postmortem examination revealed the presence of thrombi in the abdominal aorta and the pulmonary artery. Observations from this case show that HAC dogs must be attention to thrombosis.

Objective-To determine the effects of intestinal ischemia and reperfusion on the expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNAs in the jejunum, liver, and lungs of dogs. Animals-8 healthy adult Beagles. Procedures-In each dog, the cranial mesenteric artery was occluded for 0 (control group; n = 4) or 60 (I-R group; 4) minutes, followed by reperfusion for 480 minutes; serum TNF-alpha and IL-6 activities and expression levels of TNF-alpha and IL-6 mRNAs in jejunal, hepatic, and lung tissues were measured before and at the end of the ischemic period and at intervals during reperfusion. For each variable, values were compared between the control and I-R groups at each time point. Results-Compared with the control group, serum IL-6 activity increased significantly after 180 minutes of reperfusion in the I-R group; also, jejunal TNF-alpha mRNA expression increased significantly after 60 (peak) and 180 minutes of reperfusion. In the I-R group, expressions of IL-6 mRNA in the liver and TNF-alpha and IL-6 mRNAs in the lungs increased significantly at 480 minutes of reperfusion, compared with the control group. Serum TNF-alpha activity, expression of IL-6 mRNA in the jejunum, and expression of TNF-alpha mRNA in the liver in the control and I-R groups did not differ. Conclusions and Clinical Relevance-Results indicated that the liver, lungs, and jejunum contributed to the production of TNF-alpha and IL-6 after intestinal ischemia and reperfusion in dogs, suggesting that intestinal ischemia and reperfusion induce a systemic proinflammatory cytokine response in dogs.

Fluconazole (Fcz) is successfully used in human organ transplant patients as an antifungal therapy. However, Fcz can increase the cyclosporine (CsA) trough level and lead to CsA nephrotoxicity. In canine renal transplantation, CsA has been used as a major immunosuppressant, and it is important to control its trough level. However, the interaction of Fcz with CsA has not yet been reported in dogs. In this study, the effect of Fcz treatment on the pharmacokinetics of CsA in four healthy beagles was investigated using a four-period crossover design. The treatments included CsA alone (A), CsA + multiple-dose Fcz 50 mg (B), CsA + multiple-dose Fcz 25 mg (C) and CsA + single-dose Fcz 50 mg (D). Blood CsA concentrations were measured at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hr after CsA administration. The AUC(0-12) and C-max values for treatment B were significantly higher than those for the other treatments. In particular, the AUC(0-12) of treatment B was about two times higher than that of treatment A. Fcz administration did not significantly prolong the half-life or mean residence time of CsA. The results of our study show that administration of multiple therapeutic doses of Fcz can significantly increase the CsA blood concentration, which might partially depend upon the Fcz blood concentration. When Fcz is used in CsA-based canine renal transplantation, it may be necessary to adjust the CsA trough level by decreasing the dose.

The purpose of this study was to determine factors correlated with the severity of radiographic osteoarthritis (OA) scoring in dogs with cranial cruciate ligament rupture (CrCLR). Three radiographs of stifle joints (craniocaudal, mediolateral, and mediolateral radiograph with 90 degree flexion of the stifle and tarsal joints) were obtained from 36 dogs with CrCLR (Clinical group) and from 22 dogs without stifle joint disease (Control group). Information about these dogs was collected from the owners and from medical records. Radiographic OA scores in each dog in the clinical group were determined from radiographs using a numeric grading system previously reported. The tibial plateau angle (TPA) in each dog in both groups was measured on mediolateral radiographs with 90 degree flexion of the stifle and tarsal joints. The Mann-Whitney's U test was used for comparing variables between the clinical group and the control group, and Spearman's rank correlation test was used for evaluating correlations between radiographic OA scores and variables in the clinical group. No significant differences were detected between the clinical group and the control group for any of the variables. There were two positive correlations; one between the radiographic OA score and TPA (r=0.395, p=0.014); and the other between body weight and OA score (r=0.399, p=0.013) in the clinical group. Our results indicate that body weight and TPA could affect the severity of the radiographic OA score in dogs with CrCLR.

緑内障、非感染性全眼球炎、外傷に罹患した犬42症例46眼に対し、眼球内容を摘出した後にシリコン義眼の強膜内挿入術を施した。46眼中45眼(97.8%)で比較的安定した経過を得た。しかし、1眼(2.2%)では術後に角膜穿孔が発生したため、シリコン義眼を除去した。犬種別での強膜内シリコン義眼挿入は多い順にシー・ズー（13眼）、柴（7眼）、アメリカン・コッカー・スパニエル（6眼）の順であった。使用したシリコン義眼の最頻値はシー・ズー18mm、アメリカン・コッカー・スパニエル16mm、柴16mmであった。術後の問診で眼球摘出よりも強膜内シリコン義眼挿入術の結果に美容上満足していると答えたのは、手術が成功した41例の飼い主全員であった。以上のことから、強膜内シリコン義眼挿入術はその適応症を的確に判断して応用することにより、投薬の煩わしさから解放され、美容上の観点からも価値が高いと考察された。