Resveratrol Downregulates Cyp2e1 and Attenuates Chemically Induced Hepatocarcinogenesis in SD Rats

Cyp2e1 plays an important role in chemically induced hepatocarcinogenesis. Resveratrol (REV) is known to prevent diethylnitrosamine (DEN)-induced hepatocarcinogenesis, but its effects on this process induced by DEN and 2-acetylaminofluorene (2-AAF) and the role of Cyp2e1 remain unclear. In this study, glutathione S-transferase placental form (GST-P)-positive foci were used as a marker of hepatocarcinogenesis. REV or diallyl disulfide (DADS, an inhibitor of Cyp2e1) significantly reduced both the area and number of GST-P-positive foci induced by DEN and 2-AAF. Treatment with REV or DADS also markedly decreased the expression of Cyp2e1 in the rat liver. By immunohistochemical staining of serial liver sections, we found that the expression of Cyp2e1 in GST-P-positive foci showed three distinct patterns: decreased in GST-P foci, increased in GST-P foci when compared with surrounding liver tissue and mixed type. The number of GST-P foci with increased Cyp2e1 expression was greater than the number of GST-P foci with decreased Cyp2e1. Protein levels of GST-P and Cyp2e1 were also higher in foci compared with surrounding liver tissue. REV or DADS significantly reduced the expression of GST-P and Cyp2e1 in both foci and surrounding liver tissue. Taken together, these results suggested that REV has a significant inhibitory effect on chemically induced hepatocarcinogenesis, which may be attributed to downregulation of Cyp2e1.     

Compound maxillary odontoma in a young German shepherd dog

A three-month-old, male German shepherd dog was admitted with a facial mass of two months' duration. Clinical examination showed a round mass, 3 cm in diameter, in the left infraorbital area. The upper last premolar deciduous tooth was not erupted. No other abnormalities were detected. Radiological examination revealed a posterior maxillary mass of mixed opacity. The mass was surgically excised. Histopathological examination demonstrated a connective tissue stroma containing foci of irregular enamel and dentine, resembling rudimentary teeth (denticles), surrounded by new bone formation. Morphology and structure of the denticles were also confirmed by scanning electron microscopy. A compound odontoma was diagnosed. One year after surgery, the dog was free of clinical signs.     

GNATHOSTOMIASIS IN THREE CATS

SUMMARY A fatal infection with Gnathostoma spinigerum causing a perforated stomach is described in a 3-year-old cat. In a second debilitated case a small serosal perforation was found on a gastric lesion, while a third cat in good condition is described with a well developed stomach lesion but without perforation. Histopathological changes in the stomach were found in the submucosa and consisted of marked proliferation of fibrous tissue containing foci of inflammatory cells, necrotic tracts and a cavity in which the adult nematodes were found.     

Immunohistopathological findings in the lungs of calves naturally infected with Mycoplasma bovis

Histology and immunohistochemistry were used to analyse the lesions and distribution of Mycoplasma bovis antigen in the lungs of 18 naturally infected calves. Microscopic examination of pneumonic lungs revealed two distinct patterns of necrosis and inflammation. The first pattern was observed in six of 18 (33.3%) calves in which microscopic lesions were characterized by large irregular areas of coagulative necrosis surrounded by a dense zone of degenerated neutrophils. Moderate amounts of mycoplasmal antigen were in the centre and periphery of these necrotic foci and, to a lesser extent, in mononuclear cells of the peribronchial lymphoid tissue. The second pattern was observed in 18 of 18 (100%) calves and consisted of rounded foci of caseous necrosis composed by granular eosinophilic material surrounded by a rim of granulation tissue. Large amounts of M. bovis antigen were detected in the centre and periphery of these necrotic foci and, to a lesser extent, in the peribronchial lymphoid tissue, and alveolar and interstitial macrophages. It was concluded that both caseous and coagulative necrosis of the lung parenchyma was primarily caused by M. bovis. Infection with M. bovis should be suspected in bovine necrotic bronchopneumonia, particularly in cases in which the pulmonary necrosis is part of a pyogranulomatous inflammation centred around airways. The pattern of caseous necrosis with pyogranulomatous inflammation is characteristic of M. bovis infection while the pattern of coagulative necrosis is similar to and must be differentiated from Mannheimia haemolytica and Haemophilus somnus infection.     

Cutaneous habronemiasis in horses and domestic donkeys (Equus asinus asinus)

Cutaneous habronemiasis in 15 horses and 5 donkeys is described. The lesions were distributed in many parts of the body involving the medial canthus, shoulder and pectoral regions, knee and fetlock joints, abdominal wall and prepuce. Some animals had more than one lesion. The lesions were ulcerative and filled with soft light red granulation tissue. When curretted, the deeper layers revealed a dense fibrous tissue with calcified foci. Close examination of the lesions showed that the superficial layer of this dense fibrous tissue contained small caseated and necrotic foci. The same features prevailed in lesions involving the muscular areas, but the deeper layers consisted of a dense granuloma with no evidence of cicatrization. Curretted material digested in potassium hydroxide revealed fragments of larvae of the nematode suggestive of Draschia or Habronema. The histopathological changes were severe and comprised: necrotic foci in a dense fibrous stroma infiltrated with eosinophils, macrophages and few giant cells. Sections of the larvae surrounded by eosinophils were encountered in lesions of the muscular areas. Curretting and excision of the lesion were effective and produced complete healing of the wound by scar tissue formation.     

Diffuse mesenteric lipodystrophy (massive fat necrosis) in a cat

Clinical, radiographic, and pathological findings of diffuse mesenteric lipodystrophy in a 3-year-old, female domestic short-haired cat are described. The animal had fallen from a height of approximately 20 metres 6 weeks previously, after which it developed respiratory distress and anorexia. The cat was thin, exhausted and had rapid, shallow, open-mouthed breathing. Serial upper gastrointestinal contrast radiographs showed a prolonged transit time of the contrast medium due to restricted gastric emptying, and filling defects of the duodenojejunal portions of the small intestines. The cranial abdominal cavity contained large, firm, white masses that adhered to most of the anterior abdominal organs. The intestinal walls were completely surrounded by large, hard, lobulated masses of lipomatous tissue. The masses were characterised histologically by extensive areas of coagulative necrosis of adipocytes containing foci of saponification. The lesions resembled those of massive fat necrosis or lipomatosis in cattle, pigs and deer.     

The Pathology of Vinyl Chloride Exposed Mice

Outbred albino laboratory mice were exposed to 50 p.p.m. and 500 p.p.m. vinyl chloride by inhalation 6 hrs./day, 5 days/week during 52 and 26 weeks, respectively. Pathologic examination showed the presence of histologically benign alveologenic lung adenomas, haem-angiosarcomas in fat tissue as well as a few benign and malignant tumours at various sites. Only one liver haemangiosarcoma was noted. All animals exposed to 500 p.p.m. developed tumours; 71 % of the animals given 50 p.p.m. were tumour bearing. The frequency of all tumours, number of tumour foci and size of foci in both groups suggest a dose-dependent carcinogenic effect of vinyl chloride. Haemocoelia due to blood vessel rupture was a common cause of death. Telangiectasis of the liver was also observed in a few animals. The role of fat tissue as well as blood vessel involvement in the pathology of vinyl chloride is discussed.     

Hemothorax associated with telangiectatic osteosarcoma in a dog

Hemothorax in a dog was attributed to bleeding from an intrathoracic mass attached to the sixth through the tenth ribs. The mass contained numerous cavernous, blood-filled spaces as well as bands of osteoid and occasional foci of osseous tissue. The diagnosis was telangiectatic osteosarcoma. Telangiectatic osteosarcoma is an uncommon variant of osteosarcoma. Cavernous, blood-filled spaces and paucity of bone are important histologic features. Metastasis was described in one of the seven telangiectatic osteosarcomas reported in dogs, and none was found in this case.     

Experimental infections with wild and mutant Yersinia pseudotuberculosis strains in rabbits

Experimental oral infections of rabbits with a wild-type Yersinia pseudotuberculosis strain (pIB102), and two null-mutants (yopK and ypkA) were carried out with the aim to explore the possibility to use mutant strains of Y. pseudotuberculosis as live carrier vaccine strains. The infectious process of the three strains proceed with passing hyperthermia, leucocytosis with granulocytosis, moderate monocytosis and a transient lymphopenia, better demonstrated at mutant strain infections. Short-term bacterial dissemination into the brain and viscera was observed at yopK infection. An augmented resistance to bactericidal activity of leucocytes at the initial phase of infection was followed by an increased sensitivity discovered earlier in case of yopK strain accompanied by at least 70- and 20-fold, respectively, for ypkA lower virulence for mice. The level of attenuation of yopK was accompanied by significant Yersinia specific IgG and IgM antibody response. Inflammatory foci were found by morphological examination in brain, lung and small intestines after infection with the wild-type strain, while such foci were only observed in brain and mesenterial lymph nodes after infection with the yopK mutant. After infection with the ypkA mutant foci were found in brain and spleen of the infected animals. Morphological changes in the lymphatic tissue of rabbits infected with mutant strains were consistent with induction of immunogenesis. The data suggest that genetically constructed yopK null-mutant exhibits characteristics that makes the strain suitable to be used as a live carrier vaccine to deliver heterologous antigens.     

Feather folliculoma in a captive-bred barn owl (Tyto alba).

Proliferative cutaneous lesions are frequently encountered in examination of avian species. Tumors of the skin have been reported in many bird species, although comparatively less is known about the incidence of integumentary neoplasia in nondomesticated species than in production or companion species. An adult male, 9-yr-old, captive-bred barn owl (Tyto alba) was presented for examination of a proliferative skin mass of several months' duration on the left wing. An excisional biopsy was performed, and the owl recovered uneventfully. Light microscopic examination of tissue sections of the mass revealed a focal, unencapsulated, well-demarcated, multiloculated mass that consisted of variably sized cystic spaces lined by stratified squamous epithelium and containing concentric laminations of keratin and foci of feather differentiation. A histopathologic diagnosis of feather folliculoma was made. This neoplasm has not previously been described in owls. Its incidence and documentation are significant in that this neoplasm should be considered as a differential diagnosis of proliferative skin lesions in this raptorial species.     

Ascarid-associated hepatic foci in turkeys

Hepatic foci are a serious economic problem for most turkey-producing areas in the United States. Current estimates indicate that as much as 43% of the flocks sent to slaughter may experience condemnations because of hepatic foci. The present experiments were designed to duplicate naturally occurring lesions with Ascaridia dissimilis. Newly hatched poults were placed on fresh litter and given feed containing either 500 embryonated A. dissimilis ova/bird/day (from day of hatch) or no ova, in three experiments. Hepatic foci were reproduced in exposed poults in all three experiments, indicating that A. dissimilis is directly involved in the etiology of hepatic foci.     

Distribution of penicillin G in serum and tissue cage fluid in cattle

The penetration of penicillin into tissue cage fluid (TCF) in calves was studied after intravenous and intramuscular injection. The penicillin concentrations in TCF were lower than in serum and maximum was reached much later. Intravenous injection of benzyl-penicillin gave significantly higher levels in TCF than intramuscular injection. The penetration after procaine penicillin was very slow. The results showed that the serum peak rather than the area under curve determines the penetration of penicillin. Repeated intramuscular injections of benzylpenicillin and procaine penicillin caused an accumulation of penicillin in TCF. Similar levels were however reached by one single intravenous injection. The clinical counterparts to the used tissue cage model are abscesses. It was concluded that if high penicillin concentration are desireable in such foci, the drug must be given in a way that gives as high serum peaks as possible.     

Bronchus associated lymphoid tissue in the lungs of cattle: relationship to age

The occurrence and morphological features of bronchus associated lymphoid tissue (BALT) were examined by light and electron microscopy in the non-pneumonic left lungs of five age groups of cattle from neonate to aged adult. The amount of BALT was correlated with age. It was absent in neonatal lungs and increased progressively with age until it declined in aged adult cattle. Within age groups the occurrence and morphology of BALT was variable. Widely scattered lymphoid aggregates were the predominant morphological type of BALT in the bovine lung. Follicular development in BALT foci was less frequent and quite variable within individual lungs. Morphologically distinct lymphoepithelium overlying BALT foci could not be demonstrated in non-pneumonic bovine lungs.     

Pathologic features of chronic pneumonia in pigs with experimentally induced African swine fever.

Chronic pneumonia developed in 14 pigs inoculated with an attenuated strain of African swine fever (ASF) virus. The pathogenesis of the pneumonia was as follows: (1) Interalveolar septums became thickened by accumulation of lymphocytes and monocytes; (2) lung developed focal areas of lymphocytes and macrophages; (3) necrosis began abruptly in these foci, beginning with the cells in the alveolar lumens, developing in centrifugal direction, and eventually affecting all structures in its path; (4) necrotic tissue became calcified; and (5) a mantle of mononuclear cells (including plasma cells) and fibrous tissue formed around the necrotic area. Viremia occurred in the 14 pigs at postinoculation day (PID) 14, and precipitating antibody was increased significantly at PID 58.     

Pathological, clinical and mycological findings in experimental aspergillosis infections of starlings

A group of 24 wild starlings (Sturnus vulgaris), in undefined age categories but at least post-pubertal, constituted the material of this study. Six starlings were kept as a control group and 18 starlings served as the infection group. The starlings in the infection group were infected with inoculums of 1.35 x 10(6)/0.2 ml Aspergillus fumigatus via intratracheal route whereas the control group was administered only placebo in the same way. Six, four, two, four and two birds died on 2, 3, 4, 5 and 6 days post inoculation respectively. At the necropsy of the dead birds, caseous foci were determined in the lungs, on the air sacks, myocardium, thoracic wall and abdominal serosa. In the histopathological examination of the white-yellowish caseous foci ranging from pinhead to chick pean in size, necrotic granulomatous foci consisting of macrophages, heterophil leukocytes and gigant cells encapsulated with a fibrous tissue were observed. Hyphae and spores of A. fumigatus were determined in these foci using the Gridley staining method.     

Osteocartilaginous metaplasia in the right atrial myocardium of healthy adult sheep.

Among 172 hearts from clinically normal adult sheep aged 1.5 to 7 years evaluated for the presence of cartilage and/or bone in the right atrial myocardium, 3.49% (6/172) had palpable evidence of osteocartilaginous foci. An additional 8% prevalence was estimated based on radiographs of hearts that contained < or =1 mm foci of nonpalpable, radiographically dense bone. Microscopically, the nodules in the atria were characterized by mature lamellar bone enclosing adipose tissue, with occasional new bone formation by endochondral ossification. No degenerative changes were evident in the affected atrial myocardium, suggesting that these lesions were clinically insignificant background changes.     

Yersinia pseudotuberculosis Infection in a Cat

A diagnosis of Yersinia pseudotuberculosis in a cat was established by microbiological and histological means. Clinical signs were general malaise, anorexia and vomition. Significant laboratory findings included a serum glutamicpyruvic transaminase elevation and the presence of urine bilirubin and urobilinogen. Histological examination of liver biopsies revealed numerous varying-sized foci of caseation necrosis containing large numbers of Gram-negative coccobacilli. Bacteriological techniques, treatment and control measures are discussed.     

Cutaneous Hemangiosarcoma in a Dog

A male golden retriever of unknown age presented with multiple cutaneous and subcutaneous masses from the left elbow to the digits. Histopathologically, multiple tumor foci had formed from the dermis to the subcutaneous tissue. Tumor foci consisted of a vascular structure, alveolar structure and solid proliferative area. The borders among these areas were not clear. Some neoplastic cells resembled a mature endothelium, while others were large pleomorphic cells. Immunohistochemically, the tumor cells were usually strongly positive for CD31 and often positive for PROX-1, the lymphatic endothelial cell marker. Based on these findings, the tumor was diagnosed as a hemangiosarcoma with lymphatic differentiation.     

Susceptibility of liver proliferative lesions in heterozygous p53 deficient CBA mice to various carcinogens

To investigate the liver tumorigenic sensitivity to various carcinogens in heterozygous p53 deficient [p53 (+/-)] CBA mice and their wild-type littermates [p53 (+/+) mice], 71 p53 (+/-) and 74 p53 (+/+) CBA mice (male, 6-12 weeks of age) were given diet containing 4,000 or 0 ppm flumequine (FL) for 26 weeks or a single intraperitoneal injection of 5 mg/kg body weights dimethylnitrosamine (DMN) at start of the study in Exp. 1, diet containing 6,000 or 0 ppm di(2-ethylhexyl)-phthalate (DEHP) for 26 weeks in Exp. 2, or diet containing 12,000, 6,000 or 0 ppm phenolphthalein (PhP) for 26 weeks in Exp. 3. All surviving animals of these groups were killed after completion of treatment of the test substances for 26 weeks. In the FL groups, the incidences of hepatocellular altered foci in p53 (+/-) mice, the multiplicities of those in p53 (+/-) and p53 (+/+) mice were significantly increased as compared to the corresponding control groups. The incidences and multiplicities of altered foci in the DMN groups were higher than those in the corresponding control groups in p53 (+/-) and p53 (+/+) mice, but no significant differences were indicated between the groups. There were no significant differences in the incidences, multiplicities and proliferating cell nuclear antigen labeling indices of altered foci in the FL or DMN groups between p53 (+/-) and p53 (+/+) mice. There were no significant differences in the incidences and multiplicities of altered foci between the DEHP or PhP and control groups. The present results suggest that p53 gene knocked out heterozygously does not enhance the chemical hepatocarcinogenesis in CBA mice.