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Biomedical subjects

Nobuyuki Tomizawa

Publications and source records attributed to Nobuyuki Tomizawa.

6 recordsLinked to original sources

Safety of reduced-dosage ketoprofen for long-term oral administration in healthy dogs.

OBJECTIVE: To evaluate the safety of reduced-dosage ketoprofen (RDKET) for long-term oral administration in healthy dogs. ANIMALS: 14 healthy Beagles. PROCEDURES: Racemic ketoprofen (0.25 mg/kg, PO) and gelatin capsules, as a drug-free placebo, were each administered to 7 dogs for 30 days. Dogs were periodically monitored via physical examination, blood analyses, endoscopic examinations, fecal occult blood tests (tetramethylbenzidine and guaiac methods), renal function tests (effective renal plasma flow and glomerular filtration rate), urinalyses, urinary enzyme indices (N-acetyl-beta-D-glucosaminidase and gamma-glutamyl-transferase), and hemostatic function tests (buccal mucosa bleeding time, cuticle bleeding time, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration). RESULTS: Pyloric antrum lesion grade was significantly higher in the RDKET group on day 28, compared with the pretreatment and control group grades. Fecal occult blood grade measured by use of the tetramethylbenzidine method was significantly higher in the RDKET group on day 30, compared with the pretreatment grade. No other significant differences were detected between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: RDKET induced mild to moderate gastric mucosal injuries especially in the pyloric antrum in healthy Beagles, whereas no adverse effects were observed in renal function or hemostasis. Fecal occult blood tests may be useful as screening tests for adverse gastrointestinal effects induced by RDKET in dogs.

Administration, Oral↗

Analysis of genetic variations in the exon 27 region of the canine BRCA2 locus.

Mammary tumors are the most common tumor type in women as well as in female dogs. The BRCA2 gene encodes a large nuclear protein that is involved in DNA repair, and mutations in the human BRCA2 confer an increased risk of female mammary tumors. The BRCA2 protein acts as a tumor suppressor, and inactivation of BRCA2 by loss of heterozygosity is implicated in mammary carcinogenesis. In this study, to establish an appropriate polymorphic marker for loss of heterozygosity analysis of the canine BRCA2, we analyzed the genomic sequences of the exon 27 regions of 30 mammary-tumor-bearing and 21 tumor-free dogs. In addition to 10204ins/delAAA, which is the only polymorphism previously identified for the canine BRCA2 locus, we discovered four novel single nucleotide polymorphisms. The analysis of these five polymorphisms revealed the presence of four allele types. Since 10204ins/delAAA was the most common of the five polymorphisms identified, we developed a PCR-based assay method to assay for this polymorphism. We believe that this method is valuable for loss of heterozygosity analysis of the canine BRCA2 gene in tumor pathogenesis.

Animals↗

Effects of long-term oral administration of ketoprofen in clinically healthy beagle dogs.

To investigate the adverse effects of long-term administration of ketoprofen in dogs, ketoprofen (1 mg/kg) was administered to five clinically healthy beagle dogs (ketoprofen group) and gelatin capsules (control group) were administered to four clinically healthy beagle dogs for 30 days. We monitored the dogs through periodic physical examination, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests, urinalysis, urinary enzyme indices and cuticle bleeding time analysis. The lesions in the stomach, especially in the pyloric antrum, and fecal occult blood progressively worsened in the ketoprofen group. However, the differences between the ketoprofen group and the control group were not statistically significant. One dog in the ketoprofen group temporarily exhibited a decrease in renal plasma flow and two dogs exhibited enzymuria. However, these changes did not persist and the other examinations showed no significant difference between premedication and postmedication in the ketoprofen group. Therefore, the adverse effects of long-term administration of ketoprofen observed in this study were not clinically important in healthy dogs. Nevertheless, further investigation of adverse renal effects from long-term administration of ketoprofen is necessary in the dogs with subclinical renal disease.

Animals↗

Insertion/deletion polymorphism in the BRCA2 nuclear localization signal.

Mutations in human BRCA2 confer an increased risk of female breast cancer. In this study, we found a novel insertion/deletion polymorphism (10204insAAA causing amino acid change M3332IK) in canine BRCA2, which is located in the putative second nuclear localization signal (NLS2) and C-terminal Rad51-binding region. The nuclear localization of the insAAA C-terminus was more efficient than localization of the delAAA sequence when NLS1 was mutated. Strong, comparable Rad51 binding was observed for both the insAAA and delAAA C-termini. Dogs with the insertion/deletion polymorphism will provide a new model for studying the function of BRCA2.

Alleles↗

MRI identification of dorsal hippocampus homologue in human brain.

We investigated hippocampal substructure in the rat, cat, dog, and human by means of magnetic resonance imaging to elucidate phylogenetic differences in longitudinal organization. Multidirectional high-resolution images obtained with a 3 T scanner revealed that the dorsal part of the hippocampus was well developed in the rat, cat, and dog brain, and was homologous to the hippocampal tail, a poorly-developed posterior part, in the human. We conclude that the dorsal hippocampus of laboratory animals corresponds to the hippocampal tail in the human brain, which is considered to be hypoplastic and of less importance clinically than more anterior regions. These data may help in understanding phylogenetic, and in correlating results from animal experiments with clinical findings on the functions and pathologies of the human hippocampus.

Animals↗

Morphological variations in brachial plexus of beagle dogs: evaluation of utility as sources of allogeneic nerve grafts.

Basic studies were carried out to apply frozen allogeneic nerve grafts in dogs after wide-ranging defects of the brachial plexus due to surgical resection of tumor. In this study, morphological variations in branching patterns of the brachial plexus were examined in ten beagle dogs, to evaluate whether the brachial plexus might represent a useful source of allogeneic nerve grafts. Spatial relationships between the axillary lymph node, which had the possibility of carcinomatous metastasis, and the musculocutaneous (MC) nerve, which was important for the function of the forelimbs, were also investigated. In all ten cases examined, the brachial plexus received ventral roots from the fifth cervical nerve to the first thoracic nerve. No significant variation in the branching pattern was found in any nerve except the phrenic, MC and dorsal thoracic nerves. Four communicating branches were observed and had some morphological variations which might be negligible for nerve grafting. Considering previous physiological and anatomical reports, the most important nerve to be reunited in graft operations for functional recovery is the radial nerve. The MC nerve and median or ulnar nerve should also be considered as possibilities for reuniting. Distances between the axillary lymph nodes and the MC nerve ranged from 11.2 mm to 21 mm (mean +/- SD: 16.1 +/- 2.3 mm). In conclusion, it was suggested that morphological variations in the brachial plexus were technically acceptable to apply allogeneic nerve grafts at least in beagle dogs.

Animals↗