Lack of Herpes Virus Entry Mediator Signals in Thymocytes Impairs Conventional CD8 T Cell Selection and Promotes Memory-like CD8 T Cell Development.

Thymocytes having diverse Ag specificities are selected in response to self-MHC-peptide expressed in thymic epithelial cells, which contributes to the formation of a T cell repertoire. However, it is not well understood whether additional signals from epithelial cells are required to drive positive selection. In this study, we found that one of the TNFR superfamily members, herpes virus entry mediator (HVEM), when expressed on thymocytes provides signals for positive selection. HVEM deficiency in double-positive (DP) thymocytes impaired positive selection of CD8 thymocytes. HVEM-deficient thymocytes in OT-1 TCR transgenic mice exhibited significant defects in positive selection and impaired CD69 upregulation of selected thymocytes. HVEM ligands (lymphotoxin-like, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes, and B and T lymphocyte attenuator) were expressed in cortical thymic epithelial cells. Weak TCR ligation combined with HVEM signals enhanced ERK activation in DP thymocytes developed in vitro. Insufficient signals for positive selection in HVEM-deficient DP thymocytes led to the development of innate memory-like CD8 T cells expressing high levels of CD122, along with the increased development of PLZF+ NKT cells. These results suggest that thymocytes receive activation signals through HVEM during positive selection. Thus, our findings provide evidence that the threshold of thymocyte positive selection is set by signals from TCR in association with HVEM.

Biomechanical effects of cranial closing wedge osteotomy on joint stability in normal canine stifles: an ex vivo study.

BACKGROUND: Cranial closing wedge osteotomy (CCWO) is a functional stabilisation technique for cranial cruciate ligament (CrCL) ruptures. This biomechanical study aimed to evaluate the influence of CCWO on the stability of the stifle joint. Eighteen Beagle stifle joints were divided into two groups: control and CCWO. The stifle joints were analyzed using a six-degree-of-freedom robotic joint biomechanical testing system. The joints were subjected to 30 N in the craniocaudal (CrCd) drawer and proximal compression tests and 1 Nm in the internal-external (IE) rotation test. Each test was performed with an extension position, 135°, and 120° of joint angle. RESULTS: The stifle joints were tested while the CrCLs were intact and then transected. In the drawer test, the CCWO procedure, CrCL transection, and stifle joint flexion increased CrCd displacement. The CCWO procedure and CrCL transection showed an interaction effect. In the compression test, the CCWO procedure decreased and CrCL transection and stifle joint flexion increased displacement. In the IE rotation test, CCWO, CrCL transection, and stifle joint flexion increased the range of motion. CONCLUSIONS: CCWO was expected to provide stability against compressive force but does not contribute to stability in the drawer or rotational tests. In the CCWO-treated stifle joint, instability during the drawer test worsened with CrCL transection. In other words, performing the CCWO procedure when the CrCL function is present is desirable for stabilizing the stifle joint.

Evaluation of the quadriceps muscle length to femoral length ratio in small breed dogs with medial patellar luxation.

OBJECTIVE: To determine the quadriceps muscle length (QML) to femoral length (FL) ratio (QML/FL) and its associated factors in small breed dogs with medial patellar luxation (MPL) and to compare the differences in the QML/FL between MPL grades. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Small breed dogs (<10 kg) with MPL: 78 dogs (134 limbs). METHODS: Medical records and computed tomography (CT) images from 2008-2020 were reviewed. Furthermore, age, bodyweight, sex, laterality, MPL grade, femoral inclination angle (FIA), femoral torsion angle (FTA), anatomical lateral distal femoral angle (aLDFA), and patellar ligament length to patellar length ratio were included in the regression analysis to determine the factors associated with QML/FL. Each measurement parameter was compared among the four MPL grade groups. RESULTS: The final model demonstrated that the QML/FL increased with increasing age (p = .004) and decreased with increasing FTA and aLDFA (p = .015 and p < .001, respectively). The MPL grade IV group had a lower QML/FL than the grade I, II, and III groups (p = .002, p < .001, and p < .001, respectively). CONCLUSION: Among small breed dogs, those with MPL grade IV had a shortened QML associated with femoral deformities. CLINICAL SIGNIFICANCE: Noninvasive evaluation of the QML/FL improves our understanding of the length mismatch between the quadriceps muscle and the femur.

Partial tarsal arthrodesis with closing wedge ostectomy for treatment of bilateral twisted leg deformity in a cat.

A 5-month-old male domestic shorthair cat was presented with severe bilateral hind-limb deformities that caused the cat to walk on the dorsal aspect of the metatarsals. Computed tomography (CT) images revealed that the calcaneus was externally rotated, and the distal end of the calcaneus was turned medially to the talus in both hind limbs. The cat was diagnosed with twisted leg deformity, a congenital tarsal hyperextension deformity (clubfoot). Based on CT images, closing wedge ostectomy was done at the level of the tarsometatarsal joint with the wider part facing laterally. Partial transection of the common calcaneal tendon was not performed. Nine weeks after surgery, the cat was able to walk and jump, with its paws correctly placed on the ground, despite the limited range of motion in the tarsal joints. Based on radiographs with maximum tarsal flexion, the angle of the partial tarsal arthrodesis limited the range of motion. This is apparently the first case report describing CT images and closing wedge ostectomy in a cat with twisted leg deformity. Key clinical message: This article reports the findings obtained from CT imaging of a cat with twisted leg deformity. The current case was successfully managed by closing wedge ostectomy without partial transection of the common calcaneal tendon.

Arthrodèse partielle du tarse avec ostectomie de fermeture pour le traitement d'une déformation bilatérale des pattes tordues chez un chat. Un chat domestique à poil court mâle âgé de 5 mois a été présenté avec de graves déformations bilatérales des membres postérieurs qui ont amené le chat à marcher sur la face dorsale des métatarsiens. Les images de tomodensitométrie (CT) ont révélé que le calcanéus était en rotation externe et que l'extrémité distale du calcanéum était tournée médialement vers le talus dans les deux membres postérieurs. Le chat a été diagnostiqué avec une déformation de la jambe tordue, une déformation congénitale du tarse en hyperextension (pied bot). Sur la base d'images par CT, une ostectomie de fermeture a été réalisée au niveau de l'articulation tarsométatarsienne avec la partie la plus large tournée latéralement. Aucune section partielle du tendon calcanéen commun n'a été réalisée. Neuf semaines après l'opération, le chat était capable de marcher et de sauter, les pattes correctement posées au sol, malgré l'amplitude de mouvement limitée des articulations du tarse. Sur la base de radiographies avec une flexion tarsienne maximale, l'angle de l'arthrodèse partielle du tarse limitait l'amplitude de mouvement. Il s'agit apparemment du premier rapport de cas décrivant des images CT et une ostectomie de fermeture chez un chat présentant une déformation de la jambe tordue.Message clinique clé:Cet article rapporte les résultats obtenus à partir de l'imagerie CT d'un chat avec une déformation des pattes tordues. Le cas actuel a été géré avec succès par une ostectomie de fermeture sans section partielle du tendon calcanéen commun.(Traduit par Dr Serge Messier).

Adrenocorticotropic hormone-producing pituitary adenoma with pituitary apoplexy treated by surgical decompression: a case report.

BACKGROUND: Pituitary-dependent hypercortisolism (PDH) is one of the most common endocrine disorders in veterinary medicine. However, there are few reports on pituitary tumor apoplexy (PTA) in dogs and no reports on its surgical intervention in veterinary medicine. Accordingly, the appropriate treatment is unknown. Herein, a case of PDH and PTA in a dog treated surgically is described. CASE PRESENTATION: A mongrel female dog (spayed; age, 8 years and 8 months; weight, 6.1 kg) with persistently elevated alkaline phosphatase underwent adrenocorticotropic hormone (ACTH) stimulation testing (post-stimulation cortisol: 20.5 µg/dL), abdominal ultrasonography (adrenal gland thickness: left, 5.7 mm; right, 8.1 mm), and brain magnetic resonance imaging (MRI) (pituitary-to-brain ratio [PBR], 0.61) at the referral hospital, resulting in a diagnosis of PDH (day 0). On day 9, the dog visited XXXX for the preparation of pituitary surgery to treat PDH. However, on days 10-15, the dog developed a loss of energy and appetite, bloody diarrhea, vomiting, and a decreased level of consciousness. However, on day 16, the dog's condition recovered. A preoperative MRI scan performed on day 52 (the day of surgery) showed apoplexy in the dorsal pituitary region (PBR, 0.68). Based on the PTA findings, the risks of surgery were described to the owner, and approval was obtained. At the time of trans-sphenoidal surgery, a partial pituitary resection was performed with preservation of the PTA area due to adhesions between the PTA area of the right side of the pituitary and surrounding tissues. The resected pituitary tissue was diagnosed as an ACTH-producing adenoma, with necrotic and hemorrhagic findings. As of day 290, endogenous ACTH and cortisol levels did not exceed the reference range. CONCLUSIONS: The acute signs that occurred on days 10-15 were most likely caused by PTA. Therefore, when signs similar to those detected in acute hypoadrenocorticism are observed in dogs with PDH, it is necessary to include PTA as a differential diagnosis. Trans-sphenoidal surgery may be effective in PDH-affected dogs that develop PTA, but careful attention should be paid to tissue adhesions secondary to hemorrhage that may occur after PTA.

Surgical treatment of middle ear cholesteatoma using an oral approach in 2 dogs.

Middle ear cholesteatoma is caused by the formation of epidermoid cysts that result in distention and enlargement of the tympanic bulla with subsequent destruction of surrounding tissues. We report treatment of middle ear cholesteatoma in 2 dogs, via an oral surgical approach. Abnormal tympanic bulla contents and the wall compressing the pharynx were successfully removed in both cases. Computed tomography imaging, surgical findings, and histopathology results were consistent with middle ear cholesteatoma in both cases. The outcomes in both cases suggest that an oral surgical approach may be an alternative treatment for middle ear cholesteatoma in dogs. Key clinical message: Despite the limited number of cases described herein, our report indicates that the direct oral approach for canine cholesteatoma may be and alternative approach.

Traitement chirurgical du cholestéatome de l'oreille moyenne par approche orale chez deux chiens. Le cholestéatome de l'oreille moyenne est causé par la formation de kystes épidermoïdes qui entraînent une distension et l'élargissement de la bulle tympanique avec destruction subséquente des tissus environnants. Nous rapportons le traitement d'un cholestéatome de l'oreille moyenne chez deux chiens, via une chirurgie par approche buccale. Le contenu anormal de la bulle tympanique et la paroi comprimant le pharynx ont été enlevés avec succès dans les deux cas. L'imagerie par tomodensitométrie, les résultats chirurgicaux et les résultats histopathologiques étaient compatibles avec un cholestéatome de l'oreille moyenne dans les deux cas. Les résultats dans les deux cas suggèrent qu'une approche chirurgicale orale peut être un traitement alternatif pour le cholestéatome de l'oreille moyenne chez le chien.Message clinique clé :Malgré le nombre limité de cas décrits ici, notre rapport indique que l'approche orale directe pour le cholestéatome canin peut être une approche alternative.(Traduit par Dr Serge Messier).

Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-ß1: Induction of Cystathionine γ-Lyase and Cystathionine ß-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways.

Transforming growth factor-ß1 (TGF-ß1) occurs at high levels at damage sites of vascular endothelial cell layers and regulates the functions of vascular endothelial cells. Reactive sulfur species (RSS), such as cysteine persulfide, glutathione persulfide, and hydrogen persulfide, are cytoprotective factors against electrophiles such as reactive oxygen species and heavy metals. Previously, we reported that sodium trisulfide, a sulfane sulfur donor, promotes vascular endothelial cell proliferation. The objective of the present study was to clarify the regulation and significance of RSS synthesis in vascular endothelial cells after exposure to TGF-ß1. Bovine aortic endothelial cells in a culture system were treated with TGF-ß1 to assess the expression of intracellular RSS, the effect of RSS on cell proliferation in the presence of TGF-ß1, induction of RSS-producing enzymes by TGF-ß1, and intracellular signal pathways that mediate this induction. The results suggest that TGF-ß1 increased intracellular RSS levels to modulate its inhibitory effect on proliferation. The increased production of RSS, probably high-molecular-mass RSS, was due to the induction of cystathionine γ-lyase and cystathionine ß-synthase, which are RSS-producing enzymes, and the induction was mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 pathways in vascular endothelial cells. TGF-ß1 regulates vascular endothelial cell functions such as proliferation and fibrinolytic activity; intracellular high-molecular-mass RSS, which are increased by TGF-ß1, may modulate the regulation activity in vascular endothelial cells.

Effect of durotomy in dogs with thoracolumbar disc herniation and without deep pain perception in the hind limbs.

OBJECTIVE: To determine the effectiveness of durotomy as an adjunct to surgical decompression in dogs with thoracolumbar intervertebral disc herniation (TL-IVDH) and loss of deep pain perception (DPP) in the hind limbs. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n = 116) with TL-IVDH and loss of DPP treated with hemilaminectomy. METHODS: Signalment, surgical site, recovery rate, incidence of progressive myelomalacia (PMM), time elapsed from onset of paraplegia of the hind limbs to surgery (TPS), and the length of area of hyperintensity of the spinal cord on magnetic resonance T2-weighted images compared with L2 vertebral body length (LHT2) were compared between dogs treated with hemilaminectomy alone and those treated with adjunct durotomy. Multivariate logistic regression analyses were used to test the association between outcomes and the external view of the spinal cord parenchyma after durotomy. RESULTS: The percentage of dogs regaining ambulation was greater when durotomy was performed (56.9%) than when dogs were treated with hemilaminectomy alone (38.5%; P = .04). In the hemilaminectomy group, 14 dogs died of suspected PMM, while no PMM was detected in the durotomy group. Durotomy, breed, surgical site, and LHT2 influenced recovery. No association was detected between age, sex, body weight, and TPS and recovery. CONCLUSION: Performing a durotomy in combination with decompression improved the return to function and prevented PMM in our clinical setting. CLINICAL SIGNIFICANCE: Surgeons should consider durotomy in dogs with TL-IVDH and loss of DPP in hind limbs to improve surgical outcome.

Histone H1 quantity determines the efficiency of chromatin condensation in both apoptotic and live cells.

Although chromatin condensation is a well-known hallmark of apoptosis, the generation mechanism has not been clarified. Histone H1, a positively-charged abundant nuclear protein, is located in the linker region of chromatin. There are several Histone H1 subtypes that are encoded by variant genes. Using serial histone H1-deletion mutant cells established from the chicken B-cell leukemia line DT40, we found that apoptotic chromatin condensation was decreased in relation to histone H1 protein level and that the chromatin in nuclei prepared from the live null mutant cells had a high accessibility of DNases and transposase. This indicated that linker histone H1 was the general chromatin condensation factor and that the loss of histone H1 generated open chromatin in both apoptotic and live cells.

N822K- or V560G-mutated KIT activation preferentially occurs in lipid rafts of the Golgi apparatus in leukemia cells.

BACKGROUND: KIT tyrosine kinase is expressed in mast cells, interstitial cells of Cajal, and hematopoietic cells. Permanently active KIT mutations lead these host cells to tumorigenesis, and to such diseases as mast cell leukemia (MCL), gastrointestinal stromal tumor (GIST), and acute myeloid leukemia (AML). Recently, we reported that in MCL, KIT with mutations (D816V, human; D814Y, mouse) traffics to endolysosomes (EL), where it can then initiate oncogenic signaling. On the other hand, KIT mutants including KITD814Y in GIST accumulate on the Golgi, and from there, activate downstream. KIT mutations, such as N822K, have been found in 30% of core binding factor-AML (CBF-AML) patients. However, how the mutants are tyrosine-phosphorylated and where they activate downstream molecules remain unknown. Moreover, it is unclear whether a KIT mutant other than KITD816V in MCL is able to signal on EL. METHODS: We used leukemia cell lines, such as Kasumi-1 (KITN822K, AML), SKNO-1 (KITN822K, AML), and HMC-1.1 (KITV560G, MCL), to explore how KIT transduces signals in these cells and to examine the signal platform for the mutants using immunofluorescence microscopy and inhibition of intracellular trafficking. RESULTS: In AML cell lines, KITN822K aberrantly localizes to EL. After biosynthesis, KIT traffics to the cell surface via the Golgi and immediately migrates to EL through endocytosis in a manner dependent on its kinase activity. However, results of phosphorylation imaging show that KIT is preferentially activated on the Golgi. Indeed, blockade of KITN822K migration to the Golgi with BFA/M-COPA inhibits the activation of KIT downstream molecules, such as AKT, ERK, and STAT5, indicating that KIT signaling occurs on the Golgi. Moreover, lipid rafts in the Golgi play a role in KIT signaling. Interestingly, KITV560G in HMC-1.1 migrates and activates downstream in a similar manner to KITN822K in Kasumi-1. CONCLUSIONS: In AML, KITN822K mislocalizes to EL. Our findings, however, suggest that the mutant transduces phosphorylation signals on lipid rafts of the Golgi in leukemia cells. Unexpectedly, the KITV560G signal platform in MCL is similar to that of KITN822K in AML. These observations provide new insights into the pathogenic role of KIT mutants as well as that of other mutant molecules.

Hyperadrenocorticism Caused by a Pituitary Ganglioglioma in a Dog.

An 11-year-old castrated male Chihuahua dog was presented with complaints of polyuria, polydipsia, abdominal enlargement, and alopecia. Hyperadrenocorticism was diagnosed on the basis of clinical signs, blood tests, adrenocorticotropin-stimulation test results, and an elevated serum adrenocorticotropin concentration. Contrast-enhanced magnetic resonance imaging showed that the pituitary gland was enlarged, compatible with a pituitary macroadenoma. Pituitary-dependent hyperadrenocorticism was suspected, and transsphenoidal hypophysectomy was thus performed for complete resection of the tumor. After surgery, the serum adrenocorticotropin concentration normalized and the hyperadrenocorticism resolved. Histological and immunocytochemical analyses revealed a benign tumor composed of mature neuronal cells and glial cells, suggestive of a ganglioglioma with immunolabeling for adrenocorticotropin. Careful analysis of the resected tumor revealed no pituitary adenoma tissue. The clinical and histopathologic findings indicated that the ganglioglioma was directly responsible for the hyperadrenocorticism. This is the first case of hyperadrenocorticism caused by a ganglioglioma in a dog.

Persistence of vertebral growth plate cartilage in aged cynomolgus monkeys.

Growth plates at each end of vertebral bodies play a pivotal role in longitudinal spinal growth. Epiphyseal closures are formed in adult humans. Although monkeys are frequently employed in bone and disc research, the age of epiphyseal closure has not been well documented. In this study, histological analyses of lumbar vertebral end plates and the surrounding tissue were performed in 11 normal cynomolgus monkeys aged approximately 9 to 15 years, and unclosed growth plate cartilage was detected in all the end plates. The data from this study constitute the first documentation of persistent vertebral growth plate cartilage in cynomolgus monkeys. The persistence of growth plate cartilage in cynomolgus monkeys approximately 15 years of age or younger, which differs from the complete epiphyseal closure exhibited in adult humans, may affect the biomechanical behavior of the spine. This is an important factor to consider in extrapolating the results of spine and intervertebral disc research using cynomolgus monkeys to adult humans.

Xanthine oxidoreductase activation is implicated in the onset of metabolic arthritis.

A metabolic syndrome (MetS) is accompanied by hyperuricemia, during which xanthine oxidoreductase (XOR) catalyzes the production of uric acid. In the cohort study, a correlation between uric acid concentration in the synovial fluid and osteoarthritis (OA) incidence is observed. The purpose of our study was to elucidate XOR function in terms of correlation between MetS and OA. Seven week-old male C57BL6J mice were fed normal diet (ND) or high fat diet (HFD) with or without febuxostat (FEB), a XOR inhibitor. HFD stimulated xanthine oxidase activity in the IPFP and the visceral fat. OA changes at the site of the knee joints had progressed due to HFD, but these changes were reduced upon FEB administration. IL-1ß expression in the HFD group was increased in accordance with the enhancement of NLRP3 or iNOS expression in the IPFP, whereas it was inhibited by FEB administration. In the organ culture system, when the IPFP was stimulated with insulin, IL-1ß expression was increased in accordance with the increase of NLRP3 expression; however, they were reduced by FEB administration. Based on the above results, we showed that inflammasome activation accompanied by an increase in XOR activity contributed to IPFP inflammation followed by OA progression.

Escherichia coli-derived recombinant human bone morphogenetic protein-2 combined with bone marrow-derived mesenchymal stromal cells improves bone regeneration in canine segmental ulnar defects.

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 µg) 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 µg/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 µg 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 µg with 10(7) and 10(5) cells groups, while non-uniformity of the bone mineral density was improved in the 560 µg with 10(7) and 10(5) cells groups and 140 µg/10(7) cells group. Mechanically, the maximum loads at failure were significantly higher in the 560 µg 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 µg with 10(7) and 10(5) cells and 140 µg 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.

Enhancement of Runx2 expression is potentially linked to ß-catenin accumulation in canine intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) greatly affects the 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. Because IVDD develops as early as within the first year of life, we used canines as a model to investigate the in vitro mechanisms underlying IVDD. The mechanism underlying age-related IVDD, however, is poorly understood. Several research groups have suggested that Wnt/ß-catenin signaling plays an important role in IVDD. However, the role of Wnt/ß-catenin signals in IVD cells is not yet well understood. Here, we demonstrate that Wnt/ß-catenin signaling could enhance Runx2 expression in IVDD and lead to IVD calcification. Nucleus pulposus (NP) tissue was obtained from Beagle dogs after evaluation of the degeneration based on magnetic resonance imaging (MRI). Histological analysis showed that lack of Safranin-O staining, calcified area, and matrix metalloproteinase (MMP) 13-positive cells increased with progression of the degeneration. Furthermore, the levels of ß-catenin- and Runx2-positive cells also increased. Real-time reverse-transcription polymerase chain reaction analysis showed that the MRI signal intensity and mRNA expression levels of ß-catenin and Runx2 are correlated in NP tissues. Moreover, supplementation of LiCl induced ß-catenin accumulation and Runx2 expression. In contrast, FH535 inhibited LiCl-induced upregulation. These results suggest that Runx2 transcript and protein expression, potentially in combination with ß-catenin accumulation, are enhanced in degenerated and calcified intervertebral discs of CDBs.

Pivotal role of Sirt6 in the crosstalk among ageing, metabolic syndrome and osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disorder commonly associated with metabolic syndrome. As ageing and obesity has a great impact on the initiation/severity of OA, herein we sought to investigate the involvement of Sirt6 in the crosstalk between ageing and metabolic syndrome/OA. Sirt6 haploinsufficiency in mice promoted the expression of inflammatory cytokines in the IPFP. Enhanced inflammation of the IPFP in the aged Sirt6 ± HFD group was paralleled with accelerated OA change, including osteophyte growth and chondrocyte hypertrophy. Conversely, mesenchyme-specific Sirt6-deficient mice revealed both attenuated chondrocyte hypertrophy and proteoglycan synthesis, although chondrocyte senescence was enhanced as shown in the aged WT mice. Thus Sirt6 has key roles in the relationship among ageing, metabolic syndrome, and OA.

A comparison of thoracolumbar intervertebral disc extrusion in French Bulldogs and Dachshunds and association with congenital vertebral anomalies.

OBJECTIVES: To compare data for French Bulldogs and Dachshunds that had hemilaminectomy for thoracolumbar intervertebral disc extrusion (T-L IVDE) by 1 surgeon and to evaluate the association between IVDE and congenital vertebral anomalies. DESIGN: Retrospective case series. ANIMALS: French Bulldogs (n = 47) and 671 Dachshunds. METHODS: Age, gender, vertebral anomaly, kyphosis/kyphoscoliosis, IVDE site, non-recovery and progressive hemorrhagic myelomalacia development from grade 5 (paraplegia without deep nociception) were compared between the 2 breeds. RESULTS: French Bulldogs were significantly younger (P = .00001), more likely to be male (P = .023), and more likely to have a congenital vertebral anomaly and kyphosis/kyphoscoliosis (P < .00001) than Dachshunds. The frequencies of French Bulldogs with IVDE within typical sites (T11-L3) were significantly lower (P = .0005) and within caudal sites (L3-L7) significantly higher (P = .0001) compared with Dachshunds. None of the French Bulldogs had IVDE within the kyphotic/kyphoscoliotic segment. The frequency of lumbar IVDE (L1-L5) in French Bulldogs with kyphosis/kyphoscoliosis was significantly higher (P = .003) compared with French Bulldogs without kyphosis/kyphoscoliosis. In grade 5 dogs, the risk of developing progressive hemorrhagic myelomalacia in French Bulldogs was significantly higher (P = .03) than in Dachshunds. CONCLUSION: The distribution of IVDE site in French Bulldogs within the thoracolumbar and lumbar spine was different from Dachshunds. IVDE sites were not located at the sites of vertebral anomaly. French Bulldogs appeared to have T-L IVDE at younger ages, with higher male predisposition and higher risk of developing progressive hemorrhagic myelomalacia from grade 5 compared with Dachshunds.

Stress Changes in the Canine Radius after Locking Plate Fixation Using Finite Element Analysis.

OBJECTIVE: The aim of this study was to evaluate the stress changes in the radii beneath the locking plates (LP) of dogs implanted with LP using finite element analysis (FEA). STUDY DESIGN: The study included radii harvested from eight dogs. After computed tomography (CT) scans of the forelimb, the articular surface of the radius was fixed using resin. Material tests were conducted to identify the yield and fracture points and for verification with FEA. The CT data of the radius were imported into FEA software. The radii were classified into three groups based on the placement of the LP (nonplate placement, intact group; 1 mm above the radial surface, LP + 1 mm group; 3 mm above the radial surface, LP + 3 mm group). Equivalent, maximum, and minimum principal stresses and minimum principal strain were measured after FEA at the radial diaphysis beneath the plate. RESULTS: In shell elements, the LP + 1 mm and LP + 3 mm groups showed a significantly lower maximum principal stress compared with the intact group. In solid elements, the LP + 1 mm and LP + 3 mm groups showed a significantly higher equivalent stress and a significantly lower maximum principal stress compared with the intact group. CONCLUSION: When an axial load is applied to the radius, LP placement reduces the tension stress on the cortical bone of the radius beneath the plate, possibly related to implant-induced osteoporosis and bone formation in the cortical bone beneath the plate.

Three cases of dogs with osteosarcoma of the forelimb treated with liquid nitrogen for limb-sparing surgery using autologous bone.

Osteosarcoma treatment with limb-sparing surgery using liquid nitrogen can be applied to canine patients experiencing diminished quality of life after leg amputation. In particular, forelimb amputation may affect gait more than hindlimb amputation. In this study, limb-sparing surgery using liquid nitrogen was applied to primary osteosarcomas arising in the proximal scapula of a Welsh Corgi, the proximal humerus of a Golden Retriever, and the distal radius of a Great Pyrenees, according to the protocol of Tsuchiya et al. In all cases, postoperative radiographic examination revealed bone union between the treated and matrix bones. All patients recovered their gait postoperatively. These results suggest that limb-sparing surgery using liquid nitrogen-treated autologous bone is an effective option for patients with osteosarcoma.