Higher incidence of sperm granuloma in the epididymis of C57BL/6N mice / 한국실험동물학회지

C57BL/6N mice are inbred strains widely used in biomedical research. Hence, a large amount of basic data has been accumulated. However, in the field of histopathology, spontaneous data for relatively younger mice that are used more frequently are not yet abundant, in contrast to data for older mice and their neoplastic lesions. To acquire the essential background data required by various research and toxicological assessments, 120 mice of the C57BL/6N strain (10 and 13 weeks of age) were collected from two institutions (From Korea and Japan) and subjected to histopathological analyses of the major organs (liver, spleen, kidney, thymus, heart, testis, epididymis). The results showed significantly higher incidence of sperm granulomas in the epididymides (10-56%) of these mice, compared with that in other strains or species of lab animals. Upon closer inspection, oligospermia/clear cell hyperplasia, cellular debris, and tubular vacuolation were also observed in the epididymides with sperm granulomas. Moreover, diseased organs were significantly heavier than healthy ones. Immunohistochemical staining showed a significant increase in the chromatic figures of cysteine-dependent aspartate-directed proteases-3 (caspase-3) and cleaved-poly(ADP-ribose) polymerase (c-PARP), and damages to the tubule due to spontaneous apoptosis, which may have led to the sperms leaking out of the tubule, causing the granuloma. To conclude, spontaneous sperm granuloma can occur in 10- and 13-week-old C57BL/6N mice and may thus affect the results of various studies using these mice. Therefore, sperm granuloma in epididymis needs to be carefully considered as an important factor when design the study using C57BL/6N.

Effect of repeated Paecilomyces japonica treatment on rats / 대한수의학회지

Cordyceps is a fungus used as a traditional medicine in China, Japan, and Korea. Paecilomyces (P.) japonica is a new cordyceps that was recently cultivated on silkworm pupae in Korea. The present study evaluated the toxicological effects of P. japonica in rats. Forty rats were treated with oral doses of P. japonica (0, 20, 100, or 500 mg/kg/day) for 4 weeks. Twenty additional rats were treated with 0 or 500 mg/kg/day of P. japonica for 4 weeks and then maintained for 2 weeks without treatment. Clinical signs, body weight, food and water consumption, and organ weight as well as hematology, serum biochemistry, and histopathology data were examined. Body weight gain of the group treated with 500 mg/kg/day was significantly reduced. Microscopically, karyomegaly, single cell necrosis, and mitosis were observed in the renal tubular epithelium of all treated groups. In conclusion, P. japonica caused a reduction of body weight and renal injury in rats. The no observed adverse effect level (NOAEL) of P. japonica was less than 20 mg/kg/day.

Myxoid liposarcoma in a dog / 대한수의학회지

The pathological features of a mass in the back skin region of an 8-year-old castrated male dog are described herein. The cut section of the tumor was white to tan with a soft multilobulated mass containing hemorrhagic and necrotic foci and a mucinous-like composition. Microscopically, the tumor was composed of a mixture of lipocytes, lipoblasts, spindle cells and stellate cells and had a myxoid background. Oil red O staining revealed that the cytoplasm of neoplastic cells contained large numbers of lipid droplets. Immunohistochemically, tumor cells were positive for vimentin and S-100 protein. The skin mass was diagnosed as myxoid liposarcoma.

Expression of CD133, CD44, CK7, and OCT4 in Animal Cancers / 대한수의학회지

Cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumor-initiating cells. These cells possess the ability to self-renew and proliferate, and are thus able to form the tumor. In the present study cells that correspond to cancer stem cells in mammary and liver cancers in animals were identified by the expression of CD133, CD44, CK7, and OCT4 using immunochemistry. As a result, we found with CD133+ and CD44+ cancer stem cell-like phenotypes in mouse and canine hepatocellular carcinoma and canine mammary gland tumors. However, CK7+ and OCT4+ cells were not identified in animal mammary and liver cancer. CD133+ and CD44+ cells are wellknown stem cell lines and play key roles in development and metastasis in human cancer. These findings suggest that cancer stem cells are involved in animal tumorigenesis and may provide insight into mechanisms in cancer development as well as cancer diagnostics.

Chordoma in the Tail of a Ferret / 한국실험동물학회지

A chordoma is an uncommon tumor that originates from the remnants of the notochord and most commonly involves the cranial and caudal regions of the axial skeleton. Chordoma has been described in laboratory animals such as dogs, rats, minks, and ferrets. This report describes a case of a chordoma in the tail of a ferret. Grossly, a grayish-white, expansile, subcutaneous soft-tissue mass was observed in the tail. Histopathologically, the mass was a loosely placed, nodular, unencapsulated neoplasm within the dermis. In the mass, tumor lobules were intermingled with fibrous tissues. Fibrous tissues contained abundant extracellular basophilic material that was consistent with mucin. The tumor was composed of a close pack of adipocyte-like vacuolated cells (physaliferous cells). The cells were centrally or eccentrically located round nuclei and eosinophilic cytoplasm with large vacuoles. Immunohistologically, neoplastic cells were positive for vimentin and S-100 protein. Based on histopathologic findings and special staining characteristics, this case was diagnosed as chordoma.

Rectal Prolapse Associated with Recurrent Diarrhea in a Laboratory Cynomolgus Monkey (Macaca fascicularis) / 한국실험동물학회지

Rectal prolapse is a protrusion of one or more layers of the rectum through the anus. A 5-year-old laboratory cynomolgus monkey who had suffered from recurrent diarrhea died after surgical resection of a prolapsed rectum. On examination, the prolapsed rectum was a cylinder-shaped tissue whose surface was moist and dark red with a small amount of hemorrhage. Histologically, the rectum was characterized by a segmental to diffuse cellular infiltration in the submucosa and muscle layers. Inflammation in the rectum resulted in irritation of the myenteric plexus, which could cause hypermotility of the intestines, leading to chronic diarrhea. Rectal prolapse would result in economical loss or death of laboratory animals. However, rectal prolapse in the laboratory monkey could be easily overlooked because diarrhea or other symptoms resulting from rectal prolapse could be sometimes misunderstood as a primary problem. Therefore, researchers should suspect rectal prolapse if intestinal symptoms in the laboratory monkey are untreatable.

Involvement of the Fas and Fas ligand in testicular germ cell apoptosis by zearalenone in rat

Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin, is known to cause testicular toxicity in animals. In the present study, the effects of ZEA on spermatogenesis and possible mechanisms involved in germ cell injury were examined in rats. Ten-week-old Sprague-Dawley rats were treated with 5 mg/kg i.p. of ZEA and euthanized 3, 6, 12, 24 or 48 h after treatment. Histopathologically, spermatogonia and spermatocytes were found to be affected selectively. They were TUNEL-positive and found to be primarily in spermatogenic stages I-VI tubules from 6 h after dosing, increasing gradually until 12 h and then gradually decreasing. Western blot analysis revealed an increase in Fas and Fas ligand (Fas-L) protein levels in the ZEA-treated rats. However, the estrogen receptor (ER)alpha expression was not changed during the study. Collectively, our data suggest that acute exposure of ZEA induces apoptosis in germ cells of male rats and that this toxicity of ZEA is partially mediated through modulation of Fas and Fas-L systems, though ERalpha may not play a significant role.

Pathological features of bone marrow transplantation-related toxicity in a mouse

In this case report, we present a mock-transduced bone marrow (BM) transplantation in a mouse, which was found moribund and autopsied to evaluate pathogenesis. Macroscopically, red discoloration of systemic organs was observed. Hematological values revealed a decrease in white blood cells, red blood cells, hematocrit, hemoglobin, and platelets, but an increase in reticulocytes. In BM cytology, hematopoietic cell lines were severely depleted. Histopathologically, hemorrhage in the cerebellar parenchyma, hemosiderin deposition and hemorrhage in the heart, necrosis and telangiectasia in liver, pulmonary parenchymal cysts, spermatogenic germ cells necrosis, atrophy and hemorrhage in testis, oligospermia and hemorrhage in the epididymis, and atrophy of BM, thymus and spleen were observed. In conclusion, autoimmune-like complications such as hematological value change, BM dysplasia and systemic hemorrhage appear to be the lethal cause of the mouse transplanted with mock-transduced BM.

Attenuation of ischemia-reperfusion injury by ascorbic acid in the canine renal transplantation

This study examined the effects of ascorbic acid on the attenuation of an ischemia-reperfusion (I/R) injury after a canine renal transplantation. Eight beagle dogs were subjected to a renal auto-transplantation followed by the administration of ascorbic acid (treatment group) and the same amount of vehicle (physiological saline, control group). Blood samples were collected from these dogs to perform the kidney function tests and the invasive blood pressure was measured in the renal artery at pre- and post-anastomosis. The antioxidant enzymes of level 72 h after the transplant were measured. The kidneys were taken for a histopathology evaluation at day 21. The kidney function tests showed a significant difference between the control and treatment group. The invasive blood pressure in the renal artery was similar in the groups. The activity of the antioxidant enzymes in the blood plasma was significant lower in the control group than in the treatment group. The histopathology findings revealed the treatment group to have less damage than the control group. The results of this study suggest that ascorbic acid alone might play a role in attenuating I/R injury and assist in the recovery of the renal function in a renal transplantation model.

Histopathological changes of testes and eyes by neutron irradiation with boron compounds in mice

This study was performed to investigate the biological effects of boron neutron capture therapy (BNCT) on the testes and eyes in mice using HANARO Nuclear Reactor, Korea Atomic Energy Research Institute. BNCT relies on the high capacity of (10)B in capturing thermal neutrons. Sodium borocaptate (BSH, 75 ppm, iv) and boronophenylalanine (BPA, 750 ppm, ip) have been used as the boron delivery agents. Mice were irradiated with neutron (flux: 1.036739E +09, Fluence 9.600200E+12) by lying flat pose for 30 (10 Gy) or 100 min (33 Gy) with or without boron carrier treatment. In 45 days of irradiation, histopathological changes of the testes and eyes were examined. Thirty-three Gy neutron irradiation for 100 min induced testicular atrophy in which some of seminiferous tubules showed complete depletion of spermatogenic germ cells. Lens epithelial cells and lens fiber were swollen and showed granular changes in an exposure time dependent manner. However, boron carrier treatment had no significant effect on the lesions. These results suggest that the examination of histopathological changes of lens and testis can be used as "biological dosimeters" for gauging radiation responses and the HANARO Nuclear Reactor has sufficient capacities for the BNCT.

Effects of Benzoapyrene, 2-Bromopropane, Phenol and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on Proinflammatory Cytokines Gene Expression by Mice Spleen Cells

The detrimental effects of environmental pollutants on the health of the individual are generally accepted, although the mechanisms of these effects remain to be incompletely understood. In the present study, we examined the effects of B[a]P, 2-BP, phenol and TCDD on proinflammatory cytokine gene expression in mice spleen cells which were stimulated with anti-CD3. 10-9M TCDD increased IFN gammar and TNF alpha gene expression, but suppressed IL-1 gene expression. 10-6M phenol inhibited IL-1, IL-6 and TNF alpha gene expression, and 10-6M of 2-BP downregulated TNF alpha gene expression. However, 10-6M of B[a]P did not influence on IL-1, IL-6, IFN gammar and TNF alpha gene expression. These findings suggest that TCDD may impair the immune functions of mice by enhancing proinflammatory cytokines production, whereas phenol and 2-BP may impair the functions by inhibiting the production of these cytokines.

Immunohistochemical Study on the Vasopressinergic and Oxytocinergic Neurons in the Hypothalamus of water-deprived mongolian gerbil (Meriones unguiculatus) / 대한해부학회지

Mongolian gerbil has been as an model animal for studing the neurological diseases such as stroke and epilepsy because of the congenital incompleteries in Willis circle, as well as the investigation of water metabolism because of the long time-survival in the condition of water-deprived desert condition, compared with other animal species. In order to accomplish this research, first of all another divided the laboratory animals 5 groups of which each group include the 5 animals. In this study of the long term water deprived condition author investigatied the vasopressinergic and oxytocinergic magnocellular neurons of the hypothalamus by using a quantitative immunohistochemistry, measured the plasma osmolalities at the time of sacrifice of indivisual animals, and the body weights every day during water-deprived. The results obtained in this study were summarized as followings: 1. The body weights and decreasing rates of the body weight in water-deprived animal groups were continuosly decreased. 2. The plasma osmolalities were increased from the 5th water-deprived day, after then the gradually increase reached nearly its equilibrium state at the 10th water-deprived day. 3. Vasopressin and oxytocin immunoreactive cells were mainly observed in PVN, SON and a few in the lateral magnocellular area of hypothalamus. 4. The number of VP immunoreactive cells in paraventricular and supraoptic nucleus were abruptly decreas-ed until the 5th day in the supraoptic nucleus in number and until the 10th day in the paraventricular nucleus of water-deprived. 5. The OT secreting cells were severely decreased on the 5th water deprived day in paraventricular and supraoptic nucleus, after than these cells were very slowly decreased until to the 38th water deprived day.