Longitudinal monitoring adipose-derived stem cell survival by PET imaging hexadecyl-4-¹²4I-iodobenzoate in rat myocardial infarction model.

This study aims to monitor how the change of cell survival of transplanted adipose-derived stem cells (ADSCs) responds to myocardial infarction (MI) via the hexadecyl-4-(124)I-iodobenzoate ((124)I-HIB) mediated direct labeling method in vivo. Stem cells have shown the potential to improve cardiac function after MI. However, monitoring of the fate of transplanted stem cells at target sites is still unclear. Rat ADSCs were labeled with (124)I-HIB, and radiolabeled ADSCs were transplanted into the myocardium of normal and MI model. In the group of (124)I-HIB-labeled ADSC transplantation, in vivo imaging was performed using small-animal positron emission tomography (PET)/computed tomography (CT) for 9 days. Twenty-one days post-transplantation, histopathological analysis and apoptosis assay were performed. ADSC viability and differentiation were not affected by (124)I-HIB labeling. In vivo tracking of the (124)I-HIB-labeled ADSCs was possible for 9 and 3 days in normal and MI model, respectively. Apoptosis of transplanted cells increased in the MI model compared than that in normal model. We developed a direct labeling agent, (124)I-HIB, and first tried to longitudinally monitor transplanted stem cell to MI. This approach may provide new insights on the roles of stem cell monitoring in living bodies for stem cell therapy from pre-clinical studies to clinical trials.

Canine nail bed keratoacanthoma diagnosed by immunohistochemical analysis.

A 10-year-old, Shih Tzu dog was presented with an enlarged, curled 2nd nail in the left forelimb. Digital amputation was performed and the mass was diagnosed as a nail bed keratoacanthoma (infundibular keratinizing acanthoma) histopathologically. There was no recurrence postoperatively. This is the first case report of a canine nail bed keratoacanthoma diagnosed by histologic and immunohistochemical examination including Ki-67 and p53 expression.

Kératocanthome d'un lit d'ongle canin diagnostiqué à l'aide d'une analyse immunohistochimique. Un chien Shih Tzu âgé de 10 ans a été présenté avec un deuxième ongle recourbé et hypertrophié sur la jambe avant gauche. Une amputation du doigt a été réalisée et la masse a été diagnostiquée en histopathologie comme un kératocanthome de lit d'ongle (acanthome kératinisant infundibulaire). Il n'y a pas eu de récurrence après l'opération. Il s'agit du premier rapport de kératocanthome de lit d'ongle canin diagnostiqué à l'aide d'un examen histologique et immunohistochimique incluant l'expression Ki-67 et p53.(Traduit par Isabelle Vallières).

Abnormal changes in both mandibular salivary glands in a dog: Non-mineral radiopaque sialoliths.

A 10-year-old Maltese dog was presented with a firm mass on the left side of his neck. Physical examination confirmed a firm mass in the left and a submandibular swelling in the right cervical region. Sialolithiasis and associated sialocele in both mandibular salivary glands were suspected and bilateral sialoadenectomy was performed. The stones were identified as non-mineral sialoliths.

Changements anormaux dans les deux glandes salivaires mandibulaires chez un chien : sialolithes radiopaques non minéraux. Un chien Maltais âgé de 10 ans a été présenté avec une masse ferme du côté droit du cou. L'examen physique a confirmé une masse ferme dans l'enflure gauche et sous-mandibulaire dans la région cervicale droite. La sialolithiase et une sialocèle connexe dans les deux glandes salivaires mandibulaires ont été suspectées et une sialoadénectomie bilatérale a été réalisée. Les pierres ont été identifiées comme des sialolithes non minéraux.(Traduit par Isabelle Vallières).

Positron emission tomography/computed tomography imaging features of renal cell carcinoma and pulmonary metastases in a dog.

A 9-year-old spayed female cocker spaniel dog was referred for hematuria. A large abdominal mass and multiple pulmonary nodules were identified radiographically. A whole-body 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography/computed tomography (PET/CT) scan revealed intensely increased uptake in a renal mass and the pulmonary nodules. Renal cell carcinoma was diagnosed on histological examination.

Caractéristiques de la tomographie à émission de positrons et de l'imagerie à tomographie par ordinateur des métastases du carcinome cellulaire rénal et pulmonaire chez un chien. Une chienne Cocker spaniel stérilisée âgée de 9 ans a été référée pour l'hématurie. Une grande masse abdominale et des nodules pulmonaires multiples ont été identifiés par radiographie. Un balayage par tomographie à émission de positrons et par tomographie par ordinateur de l'ensemble du corps en utilisant le fluoro-d-2-désoxie-2-glucose [18F] a révélé le captage accru intensif dans une masse rénale et des nodules pulmonaires. Le carcinome des cellules rénales a été diagnostiqué à l'examen histologique.(Traduit par Isabelle Vallières).

Comparison of shear-wave velocities obtained with shear-wave elastography of various peripheral lymph nodes in healthy Beagles.

OBJECTIVE: To compare shear-wave velocities (SWVs) with shear-wave elastography of various peripheral lymph nodes (LNs). ANIMALS: 11 healthy Beagles. PROCEDURES: For each dog, bilateral mandibular, medial retropharyngeal, superficial cervical, axillary, superficial inguinal, and popliteal LNs were evaluated with shear-wave elastography in sagittal and transverse scanning planes. Depth of each lymph node was recorded, and intra- and interobserver reliability was determined. RESULTS: SWVs for all LNs were significantly higher in the sagittal scanning plane, compared with those in the transverse scanning plane. The SWV of the most superficial LN, the mandibular LN, was significantly higher, compared with that for the other LNs, except for the medial retropharyngeal LN. The SWV of the deepest LN, the medial retropharyngeal LN, was as high as that for the mandibular LN. Intra- and interobserver reliability was excellent. CONCLUSIONS AND CLINICAL RELEVANCE: SWVs for normal peripheral LNs of Beagles may serve as a reference to compare with those for other breeds and diseased LNs. Scanning plane, LN depth, and interfering tissues between the LN and the transducer may affect SWV. Shear-wave elastography may not be operator dependent.

Canine hippocampal formation composited into three-dimensional structure using MPRAGE.

This study was performed to anatomically illustrate the living canine hippocampal formation in three-dimensions (3D), and to evaluate its relationship to surrounding brain structures. Three normal beagle dogs were scanned on a MR scanner with inversion recovery segmented 3D gradient echo sequence (known as MP-RAGE: Magnetization Prepared Rapid Gradient Echo). The MRI data was manually segmented and reconstructed into a 3D model using the 3D slicer software tool. From the 3D model, the spatial relationships between hippocampal formation and surrounding structures were evaluated. With the increased spatial resolution and contrast of the MPRAGE, the canine hippocampal formation was easily depicted. The reconstructed 3D image allows easy understanding of the hippocampal contour and demonstrates the structural relationship of the hippocampal formation to surrounding structures in vivo.

The safety and efficacy of a new self-expandable intratracheal nitinol stent for the tracheal collapse in dogs.

To evaluate the potential utility of a self-expandable intratracheal nitinol stent with flared ends for the treatment of tracheal collapse in dogs, endotracheal stenting therapy was performed under fluoroscopic guidance in four dogs with severe tracheal collapse. During the 4 to 7 month followup, after stent implantation, clinical signs, including dyspnea and respiratory distress, dramatically improved in all dogs. The radiographs showed that the implanted stents improved the tracheal collapse, and there were no side effects such as collapse, shortening or migration of the stents. In conclusion, the self-expandable intratracheal nitinol stents provided adequate stability to the trachea and were effective for attenuating the clinical signs associated with severe tracheal collapse.

Vasopressor therapy using vasopressin prior to crystalloid resuscitation in irreversible hemorrhagic shock under isoflurane anesthesia in dogs.

In the present study, we tested the hypothesis that vasopressin administration prior to crystalloid resuscitation can be used to improve hemodynamic and oxygen delivery functions. Hemorrhagic shock was experimentally induced by maintaining mean arterial pressure at 60 mmHg for 30 min in sixteen healthy dogs weighing from 8 to 10.6 kg. Vasopressin was administered and then volume resuscitation was performed for the 6 dogs of V-C group, while vasopressin was administered at the end of volume resuscitation in the 5 dogs of C-V group. The control group (n=5) was administered 0.4 IU/kg of vasopressin after induction of shock without fluid resuscitation. In all groups, hemodynamic parameters were measured pre- and post-hemorrhage and for 60 min after fluid resuscitation. The dogs in V-C group had substantially increased systolic arterial pressure (SAP) for 60 min and improved pulmonary capillary wedge pressure (PCWP), cardiac output (CO), oxygen delivery, and oxygen consumption indexes compared with C-V and control groups. Diastolic pressure and systemic vascular resistance was significantly lower in the V-C group than those in the C-V and control groups (P<0.05). In the V-C group, there was effective and rapid restoration of the SAP, CO, PCWP, and oxygen delivery parameters after treatment. This study indicates that vasopressin administration before crystalloid resuscitation is a more efficient way of improving hemodynamic and oxygen delivery functions in hemorrhagic shock in dogs.

A comparison of combination therapy (cyclosporine plus prednisolone) with sole prednisolone therapy in 7 dogs with necrotizing meningoencephalitis.

Administration of immunosuppressive doses of glucocorticosteroids is the traditional primary treatment in necrotizing meningoencephalitis (NME) in dogs. However, response is variable and clinical signs often recur quickly with tapering dosage. Prognosis is poor and long-term therapy causes many complications. In the present study, we compared the long-term effects of combination (cyclosporine plus prednisolone) therapy with sole prednisolone therapy in management in dogs with NME. All NME cases in this study were examined with magnetic resonance imaging and cerebrospinal fluid analysis, and confirmed by histopathologic examination. The mean survival time of combination therapy group was 305.7 +/- 94.7 days. The mean survival time of sole prednisolone therapy group was 58.3 +/- 30.5 days. This case report demonstrates that combination treatment of cyclosporine with prednisolone is more effective in survival time than administration of only prednisolone in NME cases.

Evaluation of safety and efficacy of adipose-derived stem cells in rat myocardial infarction model using hexadecyl-4-[¹²4I]iodobenzoate for cell tracking.

This study was aimed to evaluate the effect of (124)I-labeling with hexadecyl-4-iodobenzoate (HIB) on gene expression related to cell cycle, DNA repair, transcription, proliferation and differentiation of adipose-derived stem cells (ADSCs). [(124)I]HIB showed high labeling efficiency with ADSCs (51.3±1.3%, 0.3-2.0 Bq/cell) and there is no morphological change of ADSCs. In the microarray analysis of gene expression pattern, differences were not observed between non-labeled and [(124)I]HIB-labeled ADSCs. We demonstrated that (124)I-labeling with HIB did not affect the biological properties of ADSCs.

Ectopic liver and gallbladder in a cloned dog: Possible nonheritable anomaly.

Ectopic liver and gallbladder are rare anomalies usually not accompanied by any symptoms and are found during surgical exploration or autopsy. We aimed to find a cause of this anomaly using somatic cell nuclear transfer (SCNT) technology, which can produce genetically identical organisms. A cloned beagle having ectopic organs was produced and died on the day of birth. Major and ectopic organs were fixed and underwent histologic analysis. SCNT was performed using cells derived from the dead puppy to produce reclones. Normality of internal organs in the original donor dog and recloned dogs was evaluated by computed tomography. While a liver without the gallbladder was located in the abdominal cavity of the cloned dog, a well-defined, reddish brown mass with a small sac was also positioned outside of the thoracic cavity. Histologically, they presented as normal liver and gallbladder. Five reclones were produced, and computed tomography results revealed that the original donor dog and reclones had normal liver and gallbladder structure and location. This is the first report of both ectopic liver and gallbladder in an organism and investigation on the etiology of these abnormalities. Normal organ structure and position in the original donor dog and reclones suggests that the ectopic liver and gallbladder is a possible nonheritable anomaly.

Adenovirus-mediated expression of human sodium-iodide symporter gene permits in vivo tracking of adipose tissue-derived stem cells in a canine myocardial infarction model.

INTRODUCTION: In vivo tracking of the transplanted stem cells is important in pre-clinical research of stem cell therapy for myocardial infarction. We examined the feasibility of adenovirus-mediated sodium iodide symporter (NIS) gene to cell tracking imaging of transplanted stem cells in a canine infarcted myocardium by clinical single photon emission computed tomography (SPECT). METHODS: Beagle dogs were injected intramyocardially with NIS-expressing adenovirus-transfected canine stem cells (Ad-hNIS-canine ADSCs) a week after myocardial infarction (MI) development. (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) and (99m)Tc-pertechnetate ((99m)TcO4(-)) SPECT imaging were performed for assessment of infarcted myocardium and viable stem cell tracking. Transthoracic echocardiography was performed to monitor any functional cardiac changes. RESULTS: Left ventricular ejection fraction (LVEF) was decreased after LAD ligation. There was no significant difference in EF between the groups with the stem cell or saline injection. (125)I uptake was higher in Ad-hNIS-canine ADSCs than in non-transfected ADSCs. Cell proliferation and differentiation were not affected by hNIS-carrying adenovirus transfection. (99m)Tc-MIBI myocardial SPECT imaging showed decreased radiotracer uptake in the infarcted apex and mid-anterolateral regions. Ad-hNIS-canine ADSCs were identified as a region of focally increased (99m)TcO4(-) uptake at the lateral wall and around the apex of the left ventricle, peaked at 2 days and was observed until day 9. CONCLUSIONS: Combination of adenovirus-mediated NIS gene transfection and clinical nuclear imaging modalities enables to trace the fate of transplanted stem cells in infarcted myocardium for translational in vivo cell tracking study for prolonged duration.

Doppler ultrasonographic evaluation of renal arterial resistive and pulsatility indices in overhydrated Beagles.

OBJECTIVE: To determine renal arterial resistive index (RI) and pulsatility index (PI) and clinical signs of overhydration induced by IV administration of saline (0.9% NaCl) solution and to assess RI and PI as variables for monitoring of dogs to detect overhydration. ANIMALS: 10 clinically normal Beagles. PROCEDURES: Each dog received saline solution at a maintenance rate (2.5 mL/kg/h) and a rate 3 times that of the maintenance rate (overhydration rate; 7. 5 mL/kg/h). Values of RI and PI were determined with pulsed-wave Doppler ultrasonographic examination of renal interlobar or arcuate arteries before saline solution administration, every hour during 5 hours of administration, and 1 hour after administration was stopped. RESULTS: No significant changes in RI or PI were detected during administration of saline solution at the maintenance rate. However, RI (starting 1 hour after the beginning of fluid administration [mean ± SD value, 0.589 ± 0.012]) and PI (starting 2 hours after the beginning of fluid administration [value, 0.867 ± 0.052]) were significantly lower during administration at the overhydration rate than they were during administration at the maintenance rate. Clinical signs of overhydration were observed in all dogs starting 4 hours after the beginning of fluid administration at the overhydration rate. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated overhydration of dogs caused significant decreases in RI and PI prior to detection of clinical signs of overhydration. Ultrasonographic determination of renal arterial RI and PI seemed to be a noninvasive and sensitive method for evaluation of overhydration in dogs.

Use of canine small intestinal submucosa allograft for treating perineal hernias in two dogs.

Here, we describe two dogs in which canine small intestinal submucosa (SIS) was implanted as a biomaterial scaffold during perineal herniorrhaphy. Both dogs had developed severe muscle weakness, unilaterally herniated rectal protrusions, and heart problems with potential anesthetic risks. Areas affected by the perineal hernia (PH) located between the internal obturator and external anal sphincter muscles were reconstructed with naïve canine SIS sheets. In 12 months, post-operative complications such as wound infections, sciatic paralysis, rectal prolapse, or recurrence of the hernia were not observed. Symptoms of defecatory tenesmus also improved. Neither case showed any signs of rejection or specific immune responses as determined by complete and differential cell counts. Our findings demonstrate that canine SIS can be used as a biomaterial scaffold for PH repair in dogs.

Characterization of physiologic 18F-FDG uptake with PET-CT in dogs.

We evaluated the whole body distribution of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in seven beagle dogs using positron emission tomography/computed tomography. The mean and maximum standard uptake values (SUV) for various tissues were computed. The SUV of the aortic blood pool was 0.65 +/- 0.19. Moderate uptake was present in brain (3.40 +/- 1.01). Mild uptake was present in orbital muscles, soft palate, laryngeal and pharyngeal region, mandibular salivary gland, myocardium, liver, pancreas, kidney, and intestine. 18F-FDG uptake would be normally higher in these tissues because of normal physiologic activity. Mean and maximum SUV values of the eye, skeletal muscle, bone tissue, spleen, adrenal gland, stomach, tongue, gall bladder, and lung were similar to or lower than that of the aortic blood pool. These data provide a normal baseline for comparing pathologic 18F-FDG uptake.

Positron emission tomography features of canine necrotizing meningoencephalitis.

A Yorkshire terrier and a Chihuahua were referred for acute onset, generalized tonic-clonic seizures and were suspected to have meningoencephalitis based on magnetic resonance (MR) imaging findings. Brain lesions appeared hyperintense with T2-weighted imaging and hypointense with T1-weighted imaging, and were characteristic of necrotizing meningoencephalitis. Both dogs were diagnosed with necrotizing meningoencephalitis based on pathologic findings. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) was performed on both animals before euthanasia with the permission of the owner. In FDG-PET images, these lesions seen in MR images were characterized by multifocal or diffuse hypometabolism. Our FDG-PET results provided evidence of glucose hypometabolism in areas of necrosis and cavitation associated with necrotizing meningoencephalitis. FDG-PET has the potential to provide valuable diagnostic information in dogs with suspected necrotizing encephalitis.