Masaaki Katayama

Interaction of clarithromycin with cyclosporine in cats: pharmacokinetic study and case report

Clarithromycin (CLM) has been known to increase the cyclosporine (CsA) trough levels in human transplant patients. However, the interaction of CLM with CsA has not been reported in cats. In this study, the effects of oral dosing of CLM on the pharmacokinetics and dosing of CsA in cats were investigated. Co-administration of CLM with CsA resulted in significant increases of oral bioavailability of CsA. In addition, CLM reduced the CsA dosage required to maintain the therapeutic CsA trough levels to almost 35% of the initial CsA therapy and the dose frequency was successfully replaced from a twice a day schedule to once a day in a feline kidney transplant patient. The addition of CLM to the regular CsA-based immunosuppression could be used as an effective alternative to classical ketoconazole treatment in feline kidney transplant patients and may result in substantial cost saving and convenience for the cat owners.

Effects of multiple oral dosing of itraconazole on the pharmacokinetics of cyclosporine in cats

Itraconazole (Icz) has been known to increase the cyclosporine (CsA) trough level in human transplant patients. However, the interaction of Icz with CsA has not been reported in cats. In this study, the effect of multiple dosing of Icz on the pharmacokinetics of CsA in three healthy cats was investigated. The treatments included CsA 5 mg/kg alone and CsA 5 mg/kg+multiple-dose of Icz 10 mg/kg. Co-administration of Icz with CsA resulted in significant increases of oral bioavailability of CsA. The results of our study suggest that administration of multiple therapeutic doses of Icz may decrease the required CsA dosage in CsA-based immunosuppressive therapy used for renal transplantation in cats.

Simplified procedure for the estimation of glomerular filtration rate following intravenous administration of iodixanol in cats

OBJECTIVE To compare the use of a single-sample method involving IV administration of iodixanol with a multisample method involving inulin for the estimation of glomerular filtration rate (GFR) in cats. ANIMALS 24 cats, including 15 healthy cats and 9 cats with naturally occurring renal diseases. PROCEDURES Each cat was coadministered iodixanol (a nonionic contrast medium; dose providing 40 mg of I/kg) and inulin (50 mg/kg), IV, and blood samples were collected 60, 90, and 120 minutes later. Serum iodixanol and inulin concentrations were determined by means of high-performance liquid chromatography and colorimetry, respectively. Serum urea nitrogen and creatinine concentrations were also measured. RESULTS Analysis of the data from healthy cats and cats with naturally occurring renal diseases revealed an excellent correlation between GFR values estimated by the multisample and single-sample methods with iodixanol. Likewise, GFR values estimated from the single-sample method with iodixanol were closely correlated with those calculated from the multisample method with inulin. CONCLUSIONS AND CLINICAL RELEVANCE For estimation of GFR in cats, use of a single-sample method with iodixanol, instead of a multisample procedure, may be an expedient tool in both clinical and research settings because of its benefits to patient well-being as a result of reduced stress associated with blood sample collection.

A Single-Blood-Sample Method Using Inulin for Estimating Feline Glomerular Filtration Rate

BACKGROUND Application of a multisample method using inulin to estimate glomerular filtration rate (GFR) in cats is cumbersome. OBJECTIVES To establish a simplified procedure to estimate GFR in cats, a single-blood-sample method using inulin was compared with a conventional 3-sample method. ANIMALS Nine cats including 6 clinically healthy cats and 3 cats with spontaneous chronic kidney disease. METHODS Retrospective study. Inulin was administered as an intravenous bolus at 50 mg/kg to cats, and blood was collected at 60, 90, and 120 minutes later for the 3-sample method. Serum inulin concentrations were colorimetrically determined by an autoanalyzer method. The GFR in the single-blood-sample method was calculated from the dose injected, serum concentration, sampling time, and estimated volume of distribution on the basis of the data of the 3-sample method. RESULTS An excellent correlation was observed (r = 0.99, P = .0001) between GFR values estimated by the single-blood-sample and 3-sample methods. CONCLUSIONS AND CLINICAL IMPORTANCE The single-blood-sample method using inulin provides a practicable and ethical alternative for estimating glomerular filtration rate in cats.

Fluconazole decreases cyclosporine dosage in renal transplanted dogs.

The effect of fluconazole (Fcz) on the cyclosporine (CsA) dosage was investigated in renal transplanted dogs receiving CsA-based immunosuppressive therapy. Initially, CsA was administered orally twice daily to raise the blood trough level between 400 and 600 ng/ml. After the addition of Fcz, the CsA dosage was adjusted to maintain its therapeutic blood concentration. Fcz significantly decreased CsA dosage in both normal and renal transplanted dogs, but a higher dosage of CsA was needed in renal transplanted dogs. In conclusion, Fcz decreases required CsA dosage and thereby reduces the cost of immunosuppressive therapy in canine renal transplantation.

Evaluation of anticancer effects and enhanced doxorubicin cytotoxicity of xanthine derivatives using canine hemangiosarcoma cell lines.

Methylxanthine derivatives increase cAMP and are known to have diuretic, cardiac, and central nervous system stimulatory effects. Moreover, caffeine inhibits the development of tumors induced by various carcinogens. The aim of this work was to elucidate the anticancer effects on apoptosis of xanthine derivatives alone and with doxorubicin in canine hemangiosarcoma cells. Xanthine derivatives with or without doxorubicin were administered to cells, and the effects were investigated by measuring tumor cell proliferation, cell death (cytotoxicity) induction, and apoptosis by the expression of annexin V or caspase 3/7. Both caffeine and theophylline induced apoptosis, and the treated cells expressed annexin V and caspase 3/7. Both drugs enhanced doxorubicin-induced cytotoxicity; however, hypoxanthine showed no effect. These results indicate that theophylline is similar to caffeine; both drugs may enhance doxorubicin-induced cytotoxicity by inhibiting ATM/ATR kinases. Our data suggest that caffeine and theophylline have anticancer effects and can improve the treatment effect in canine hemangiosarcoma patients.

Gliomatosis Cerebelli in a Saint Bernard Dog

A 6-year-old, neutered male Saint Bernard dog was presented with a 1-month history of ataxia, hypermetria and head tilt. High-field magnetic resonance imaging revealed a mass in the cerebellar vermis. During necropsy examination, a cream-coloured irregular area was observed in the cerebellar white matter. Microscopically, the mass comprised a diffuse neoplastic proliferation of spindle cells with oval pleomorphic nuclei in the white and grey matter of the cerebellum and pons and in the subpial area. Neoplastic infiltration was not found in the cerebrum. Immunohistochemistry revealed that the neoplastic cells were positive for vimentin and partially positive for glial fibrillary acidic protein. Based on these findings, the neoplastic lesion was diagnosed as gliomatosis cerebelli, without involvement of the cerebrum.

Canine Bone Marrow Stromal Cells Promote Functional Recovery in Mice with Spinal Cord Injury

ABSTRACT Regenerative therapy has begun to be clinically applied in humans and dogs to treat neurological disorders, such as spinal cord injury (SCI). Here, we show the therapeutic potential of transplantation of cultured canine bone marrow stromal cells (BMSCs) into mice with SCI. Canine BMSC transplantation therapy was performed, immediately after the spinal cord was injured. Canine BMSC therapy enhanced functional recovery of the hind limbs in mice with SCI. Nestin-positive cells were observed only in the lesion of mice with SCI that received BMSCs. These results suggest that canine BMSCs promote functional recovery in mice with SCI and that migration of nestin-positive cells may contribute to the efficacy of the BMSC treatment.

Tailor-Made Plate Design and Manufacturing System for Treating Bone Fractures in Small Animals

We propose the use of a computer-aided design (CAD) system for treating bone fractures in small animals. During surgical planning, the veterinarian sketches a simple plate by referring to computed tomography images. A CAD operator then uses polygonal approximation (triangulation) of the surface of the bone region to model the plate. After the approximated shape is imported into the CAD system as a triangular mesh, a detailed design of the plate is prepared by referring to the abovementioned sketch. The plate can be designed to match the bone surface since the plate surface follows the curvature of the surface of the exported triangular mesh. The bone shape and the plate are eventually converted into polygons, and a structural model identical to the fractured part of the bone can be reproduced using a 3D printer, which allows for alignment to be performed at full scale. In this study, we examine the applicability of the proposed system by designing the most appropriately shaped plates for bone fracture therapy for small dogs brought to a veterinary clinic for treatment.

Kite Shield-Shaped Wedge Recession for Treatment of Medial Patellar Luxation in Seven Small-Breed Dogs.

OBJECTIVE To document the trochlear depth (TD) and clinical outcome after kite shield-shaped wedge (K-wedge) recession trochleoplasty in toy-breed dogs with medial patellar luxation (MPL). STUDY DESIGN Case series. ANIMALS Seven toy-breed dogs (<5 kg) with uni- or bilateral grades II-IV MPL (10 stifles). METHODS A K-wedge recession trochleoplasty was performed in all dogs in combination with other surgical procedures as treatment for MPL. The TD, the ratio of the proximal TD to patella thickness, and the presence of osteophytes were determined from computed tomography images taken pre-, and 1 and 12 months postoperative. Lameness scores and MPL grade were also recorded. RESULTS The TD and the ratio of proximal TD to patella thickness increased significantly immediately postoperative and remained increased at 1 and 12 months postoperative. The osteophyte score was significantly higher at 12 months postoperative than preoperative. All dogs had a reduction in MPL grade and improvement in lameness postoperative. CONCLUSION K-wedge recession trochleoplasty was successful in treating MPL in a series of toy-breed dogs and offers an alternate to other trochlear recession techniques.