Background: Human obstructive airway diseases are histopathologically characterized by inflammatory cell infiltration, goblet cell hyperplasia, and mucus hypersecretion in airways. We prepared a rat model of airway injury by exposure of sulfur dioxide (SO₂) and then evaluated the effects of S-carboxymethylcysteine (S-CMC), a mucoregulant. Methods: Rats were exposed to SO₂ gas for 44 days and orally given S-CMC at 250 mg/kg, twice daily, from 21 to 44 days of exposure for histopathological and immunohistochemical evaluation. Results: SO₂ exposure induced inflammatory cell infiltration and mucus cell increase in rat airways. S-CMC treatment significantly decreased this inflammatory cell infiltration in proximal and peripheral airways. Morphometrically, SO₂ exposure significantly increased the number of Alcian blue (pH 2.5)- and periodic acid-Schiff (AB/PAS)-positive cells in rat airways (11.8 × 10^–2 cell/nuclear profiles per micrometer basement membrane) compared to normal rat airways (1.6 × 10^–2 cell/nuclear profiles per micrometer basement membrane). S-CMC treatment significantly decreased the number of AB/PAS-positive cells (4.4 × 10^–2 cell/nuclear profiles per micrometer basement membrane, p < 0.01 vs. SO₂-exposed rats). Immunohistochemically, SO₂ exposure increased the expression of mucin 5AC (MUC5AC) protein in the airway epithelium of rats, but S-CMC treatment inhibited the increase. Conclusions: The increased mucus cells and MUC5AC protein expression seem associated with SO₂-induced airway inflammation in rats. The fact that S-CMC suppresses airway inflammation and the increase in mucus cells and MUC5AC protein expression suggests that this mucoregulant may be advantageous in the treatment of inflammatory airway diseases with goblet cell hyperplasia.

-Busulfan, an antineoplastic agent that targets small follicles (primordial and primary follicles), was given orally to female Sprague-Dawley rats (0, 0.1, 0.5, or 1.5 mg/kg/day; n = 10 in each ovarian morphology. Isolated ovaries were used for histopathological analysis and follicle counts. In addition, a female fertility study was conducted by giving the same dose levels of busulfan from 2 weeks female reproduction. In the 2-week study, all rats treated with busulfan showed normal estrous cyclicity number of small follicles at 1.5 mg/kg. In the female fertility study, increases in dead embryos and post--ductive performance and 0.5 mg/kg for early embryonic development. In conclusion, the present study -logical analysis of stage-based follicles are needed to detect small follicle depletion in a general toxicity

Abstract:We encountered with a case of spontaneously occurring malignant cystic schwannoma on the intracranial trigeminal nerve in a rat (32-week-old male Crj:Wistar). The tumor was intermixtures of the solid and cystic areas. The solid area was densely cellular, and pleomorphic spindle-shaped cells with elongated bizarre nuclei, and mitoses were present. The cystic area was less cellular, and cells with less cytoplasm were sporadically present in the area. Morphologically and immunohistochemically (staining with S-100), the solid and cystic areas were considered typical Antoni type A and B, respectively. Taken together, the results indicate that the tumor is a spontaneous malignant cystic schwannoma. In this connection, most cells lining the cysts were positive for S-100 and negative for Factor VIII, while HE staining showed that degenerative vessels were absent in the tumor. Therefore, in this case, we assumed that the origin of the cysts was not from the vessel but from the tumor per se. ( Spontaneously occurring peripheral nerve tumors of rats are infrequent and especially malignant schwannoma in the intracranial trigeminal nerve is rare [1][2][3][4] . Experimentallyinduced tumors of cranial, spinal, and peripheral nerves have been reported in rats treated with direct-acting alkylating agents (for example, N-nitrosoethylurea, methylmethane sulfonate) 5 , and such tumors sporadically with cysts are found in the central and peripheral nerve in rats. However, spontaneous occurrence of intracranial schwannoma with cysts is extremely rare and uncertain. Recently, we encountered with a case of spontaneously occurring malignant cystic schwannoma on the intracranial trigeminal nerve in rats, and will report here on its gross, histological and immunocytochemical characteristics.A 32-week-old male Crj:Wistar rat (SPF, Charles River, Japan) found in the extreme state of rapid body weight loss, emaciation, unkempt fur, and dyspnea, was euthanized under deep ether anesthesia to death in line with the standard operational procedures for the institutional animal care management. At necropsy, edema-like infiltrative mass was found at the bottom of the cranial cavity (Fig. 1). The pituitary gland and the trigeminal nerve were involved in this mass. The mass compressed the ventral brain. Other findings included small-in-size spleen and liver, involution of thymus, discoloration of prostate, and dilatation of brain ventricle.The cranium including the tumor was fixed in 10% buffered formalin. A protrusion (probably pituitary gland) from the brain base was removed and used for tissue specimen without decalcification. The entire rest (the cranium, tumor, and brain base) was decalcified with 5% formic acid in formalin, and then the center and portion near to the nasal cavity of the tumor was sectioned in a coronary form and paraffin-embedded. For light-microscopic observation, the protrusion, the cranium, and the nasal cavity were stained with hematoxylin-eosin (HE), Klüver-Barreta's stain. For immuno-histochemical observation, ea...

N-Ethyl-N-nitrosourea (ENU) is known to induce a wide spectrum of tumors in various organs in adult experimental animals. The renal and neuroectdermal tumors are known as representative lesions by transplacental exposure to ENU in the offspring animals. However, little information is available about tumorigenicity in other organs and tissues in offspring when their mother animals are treated with ENU during gestation. Thus, the purpose of this study was to evaluate the effects of transplacentally treated-ENU on the various organ tumorigenicity in offspring rats. ENU was injected intraperitoneally to female Sprague-Dawley (SD) rats with a single dose at 50 mg/kg on the 18th day of gestation. After spontaneous delivery, 44 male and 64 female offspring, including moribund and dead after birth, were subjected to the evaluation of carcinogenicity. At the 54th to 55th week of birth, all surviving offspring were euthanized under ether anesthesia for histopathology. ENU showed a wide spectrum of transplacental tumorgenesis in the kidney, central nervous system, peripheral nervous system, thyroid gland, and teeth. The tumors of the thyroid and teeth were characteristic in particular in this study. The thyroid tumors included various histopathological types (follicular cell adenoma and adenocarcinoma, C-cell adenoma and carcinoma, squamous cell carcinoma, and fibroma). As a characteristic tumor of the teeth, ameloblastic odontoma was detected in 3 (one male and 2 females) of 108 offspring. In conclusion, the results indicate that the transplacental exposure of a single ENU dose induces various types of thyroid gland tumors and odontogenic tumors as well as the renal or neuroectodermal tumors in rat offspring. (J Toxicol Pathol 2004; 17: 7-16)

A mixed epithelial and stromal tumor (MEST) of the kidney was found in a 22-month-old female Marshall beagle. Histopathologically, this lesion was well demarcated and was composed of a mixture of epithelial and stromal elements. The epithelial elements, which contained columnar or ciliated columnar epithelia, had cystic and tubular growth patterns. The tubular lumina contained eosinophilic materials, which were positive for periodic acid Schiff and alcian blue (pH 2.5). Immunohistochemically, the epithelia were positively stained with proliferative cell nuclear antigen (PCNA) and showed co-expression of cytokeratin and vimentin. Morphologically, these proliferative ductal structures were suggestive of a primitive duct arising from the mesonephric or paramesonephric tubule. The stromal elements were characterized by proliferation of spindle cells embedded in a collagen-rich eosinophilic matrix. Additionally, stromal cells were positive for PCNA, vimentin and muscle markers (α-smooth muscle actin and desmin). Therefore, this lesion was ultimately diagnosed as a MEST of the kidney.