Osamu Katsuta

Cadmium-Induced Dental Lesions in Ovariectomized Rats

The effects of cadmium chloride on both incisor and molar teeth of ovariectomized female rats were studied histopathologically. The rats were injected intravenously with the compound at doses of 1.0 and 2.0 mg/kg, 5 days/wk. Six rats per group were sacrificed at 4, 8, and 13 wk. Discoloration of the incisors was observed in the rats of the 2.0-mg/kg group from 8 wk. Histopathologic examination of the incisor demonstrated decreased iron-containing pigment in ameloblasts and destruction of the enamel organ. These changes were accompanied with accumulation of cadmium and loss of iron in the teeth. Necrosis of the dental pulp occurred from the coronal end of both the incisor and molar teeth extended to the apical, deep portion of the teeth. The dental pulp of the molar teeth, which is shorter than that of the incisor, was mildly affected by cadmium intoxication. These findings suggested that intradental ischemia due to cadmium toxicity may have contributed to the development of the pulpal necrosis.

Intravenous 1α, 25[OH]2 vitamin D3 (calcitriol) pulse therapy for bone lesions in a murine model of chronic cadmium toxicosis

The aim of the present study was to clarify the therapeutic effects of 1α, 25[OH]2 vitamin D3 (calcitriol) pulse injection on bone lesions induced in a rat model of chronic cadmium toxicosis. Ovariectomized (OVX) and control‐operated (sham‐OVX) rats were given repeated intravenous injections of 0.5 mg/kg/day CdCl2 for 70 weeks. The rats were then treated intravenously with 0.02 μg/kg/day calcitriol 3 days per week for 8 weeks. CdCl2 treatment induced increases in osteoid volumes of the femur cortex and trabecula. This change was accompanied by an increase in the volume of iron deposition at the mineralization front of the trabeculae and a reduction in mineral density. Abnormalities of bone metabolic parameters, which were increases in the blood calcium, inorganic phosphorous, bone‐specific alkaline phosphatase, parathyroid hormone (PTH) and osteocalcin levels, and in the urine deoxypyridinoline (D‐PYR) level, were also induced. Calcitriol treatment increased the blood calcium and inorganic phosphorous levels, and reduced the blood PTH level. Decreases in blood tartrate‐resistant acid phosphatase and urine d‐PYR levels were also induced indicating that bone resorption was suppressed. The findings indicated that the increased osteoid volume of the cortex and Fe‐deposition volume of the trabecula were improved. These effects or improvements were observed in the sham‐OVX rats but not in the OVX rats.

Glomerular lesions in spontaneously occurring diabetic WBN/Kob Rats

Glomerular lesions in WBN/Kob male rats with spontaneous diabetes were examined histopathologically. The glomerulopathy caused by diabetes was compared with lesions in chronic progressive nephropathy of non-diabetic SD and F344 male aged rats. Diffuse and global thickening of the mesangial area was observed only in WBN/Kob rats and showed a statistically significant correlation with serum glucose concentrations. Therefore, it suggested that the mesangial thickening was a result of hyperglycaemia. Fibrin cap-like lesions were seen in both WBN/Kob and non-diabetic SD or F344 male rats. The severity of these lesions was closely related to that of chronic progressive nephropathy and, therefore, the fibrin cap-like lesions were considered to be due to the chronic progressive nephropathy.

Case report: spontaneous hemangiosarcoma in the pancreas of a Fischer rat.

Spontaneous hemangioma or hemangiosarcoma is sometimes found in the viscera and soft tissue of rats and mice. However, there is no report of the tumor occurring in the pancreas of rats. We report a pancreatic hemangiosarcoma in a 109-wk-old, male Fischer 344 rat, which was used in the control group of a carcinogenicity study. The tumor destroyed and compressed the normal pancreatic tissue and displayed a high density in terms of the numerous capillaries and strands of endothelial tumor cells. A reticulin stain revealed a dense network formation. The frequency of proliferating cell nuclear antigen-positive staining showed active proliferation of the tumor cells. Immunohistochemically, some of the tumor cells stained positive with factor VIII-related antigen, and ultrastructurally, Weibel-Palade bodies were rarely observed in the cytoplasm of the tumor cell. From these findings, the tumor was diagnosed as a hemangiosarcoma that occurred naturally in the pancreas.

Vascular leiomyoma of the mesentery in a dog

A 4-year-old male, miniature Schnauzer dog showed two large masses in the mesentery at necropsy. Histological examination of both masses revealed plain smooth muscle tumour cells intermingled with thick-walled blood vessels. The bundles of tumour cells often extended from the periphery of the vessels. Mitotic figures were rare. From these findings, the tumour was diagnosed as a vascular leiomyoma (angiomyoma), previously unreported in animals. The term, vascular leiomyoma, was proposed to describe this tumour in order to avoid confusion with hamartomatous angiomyoma.

Chronic Cadmium Treatment Induces Tubular Nephropathy and Osteomalacic Osteopenia in Ovariectomized Cynomolgus Monkeys

In an attempt to establish a primate model of chronic cadmium toxicosis, we ovariectomized cynomolgus monkeys and treated them with CdCl2 by repeated intravenous injections for 13 to 15 months. The animals showed normocytic-normochromic anemia. The cadmium treatment resulted in increases of urinary enzyme activity indicative of renal tubular degeneration. Histopathology of the kidney revealed renal proximal tubular atrophy accompanied by interstitial fibrosis. Decreased bone mineral density was evident in the trabecular and cortical zones of the lumbar vertebra and femur, with osteoid accumulation around the trabeculae and Haversian canals. Iron deposition at the mineralization front and osteoclasts hyperplasia were indicative of impairment of bone mineralization and an increase of resorption. Blood inorganic phosphorus and 1α,25(OH)2 vitamin D3 levels decreased and urinary deoxypyridinoline level increased in cadmium-treated animals. The renal and bone lesions closely resemble those of itai-itai disease patients, the most severe case of cadmium toxicosis in terms of clinical chemistry and histopathology. Thus, ovariectomized monkeys chronically exposed to cadmium can serve as a primate itai-itai disease model, which is beneficial for developing novel therapeutic methods, investigating the mechanisms of the renal and bone lesions, and establishing more clearly defined criteria for diagnosing the disease.

Granule cell type cerebellar hypoplasia in a beagle dog

Cerebellar hypoplasia characterized by severe depletion of granule cells and almost intact Purkinje cells was found in a male 19-month-old beagle dog used in a toxicity study. Microscopically, there was a narrow space lacking granule cells between the row of Purkinje cells and the medulla. Gliosis was not seen in any portion of the cerebellum including this space. No significant changes were seen in the Purkinje cells except for occasional cytoplasmic vacuolation. In the molecular layer and medulla, no histopathological abnormalities were observed.

A Spontaneous Mutation: Amelogenesis Imperfecta with Cysts in Rats

Amelogenesis imperfecta (AI) is an inherited dental disease of enamel formation in humans, and there are various phenotypes due to the combination of enamel quality and quantity. We encountered four female IGS rats with spontaneous AI including odontogenic cysts in the incisor teeth. Histopathologically, in the incisors of the rats, the enamel organ was disorganized with the remaining enamel matrix residing within the enamel space. The expanding cysts derived from the enamel organ were formed in the periosteal connective tissue on the labial side. At the bottom of the tooth germs, the precursor cells of the epithelial root sheath were arranged regularly and the enamel organs were preserved to the same degree as those of normal rats. In the molar teeth of the affected rats an enamel matrix remained on the neck and crown of the erupted teeth; however, no abnormality was observed at the tooth root. Although an animal model of AI has been developed from mutants of the SHR-SP rat strain, the present cases represent another potential model of the disease because of the differences in the way the enamel matured and the odontogenic cyst formation in the incisors.