Nonproliferative and Proliferative Lesions of the Rat and Mouse Skeletal Tissues (Bones, Joints, and Teeth).

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is an initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the skeletal tissues and teeth of laboratory rats and mice, with color photomicrographs illustrating examples of many common lesions. The standardized nomenclature presented in this document is also available on the internet (http://www.goreni.org/). Sources of material were databases from government, academic and industrial laboratories throughout the world.

Ectopic thyroid tissue in the periaortic area, cardiac cavity and aortic valve in a Beagle dog - a case report.

Microscopic examination of the heart of a clinically normal 14-month-old female Beagle dog revealed the presence of ectopic thyroid tissue at the base of the heart, around the aorta, and intracardially at the level of the left ventricle and the aortic valve. The tissue was composed of well-differentiated follicles lined by a cuboidal epithelium and containing colloid. Follicular cells and colloid exhibited strong thyroglobulin immunoreactivity, while no parafollicular cells were noted and the immunoreactions for calcitonin remained consistently negative. Although in the dog ectopic thyroid tumors represent 1-10% of all heart base neoplasms (Capen, 1978; Bracha et al., 2009), to the best of our knowledge, nonneoplastic ectopic thyroid tissue has not been reported in the heart of the dog itself or within the dog aortic valve.

Sublingual and submandibular blood collection in mice: a comparison of effects on body weight, food consumption and tissue damage.

In a large number of animal experiments, blood collection is crucial for achieving the study aim. Requirements on sampling techniques used include their practicability, their effectiveness in terms of obtaining the desired blood volume, sample quality and low impact on animal's wellbeing. Numerous methods for blood collection from mice have been published. For large blood volumes, submandibular and sublingual bleeding was developed as alternatives to the retrobulbar bleeding method, which is considered controversial as it results in severe tissue damage. Only a few studies report the use of submandibular and sublingual techniques in mice. In particular, the degree of tissue damage or influence on animal's wellbeing due to submandibular bleeding in conscious mice has not yet been clearly assessed. This gap in the knowledge base has been filled by our exploratory study that revealed clear differences between both techniques. Defence movements during submandibular blood collection in conscious mice resulted in more complications and revealed insufficient blood sample quality due to the prolonged duration of blood collection. In addition, it is likely that these movements may have caused lesions to be more pronounced. Changes in red blood cell parameters (red blood cell count, haemoglobin and haematocrit), in glucose and in total protein concentrations observed in anaesthetized animals were most likely related to anaesthesia. Sublingually punctured mice gained significantly more body weight than submandibularly punctured mice, likely due to less severe tissue lesions and improved healing processes. Based on these results, we recommend the sublingual blood collection technique to be used in mice. However, if the submandibular bleeding technique is used, it should be performed in anaesthetized mice only.

Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies.

Cytotoxic concentrations of imatinib mesylate (10-50 microM) were required to trigger markers of apoptosis and endoplasmic reticulum stress response in neonatal rat ventricular myocytes and fibroblasts, with no significant differences observed between c-Abl silenced and nonsilenced cells. In mice, oral or intraperitoneal imatinib treatment did not induce cardiovascular pathology or heart failure. In rats, high doses of oral imatinib did result in some cardiac hypertrophy. Multi-organ toxicities may have increased the cardiac workload and contributed to the cardiac hypertrophy observed in rats only. These data suggest that imatinib is not cardiotoxic at clinically relevant concentrations (5 microM).

Blood collection from the sublingual vein in mice and hamsters: a suitable alternative to retrobulbar technique that provides large volumes and minimizes tissue damage.

Blood examination is a key element in studies of laboratory animals. In rodents, retrobulbar venous plexus puncture is a commonly used method for obtaining a blood sample. Although this technique yields large volumes of blood, the disadvantage is that it can lead to severe tissue damage. The aim of the present study was to develop the puncture of V. sublingualis as a suitable alternative technique for drawing blood in mice and other rodents. In rats, this method has been established for collecting large blood volumes. During the first part of the study, the sublingual bleeding technique was developed for use in mice and hamsters. Guinea pigs, however, do not have a sublingual vein; therefore, in this species the method is not possible. In the second part of the study, retrobulbar and sublingual methods were compared using male CD-1 mice. When compared with the retrobulbar method, sublingual venepuncture showed less tissue destruction in mice, with a decreased mean severity in the histological examination. In conclusion, sublingual venepuncture can be recommended as a suitable, alternative blood collection technique, because of the reduced risk of tissue damage in mice and hamsters.

Cerebral meningioangiomatosis in a CD-1 mouse: a case report and comparison with humans and dogs.

Meningioangiomatosis is a rare proliferative disorder of the central nervous system. Several cases have been described in humans, a few in dogs, one case in a cow and one in a horse; meningioangiomatosis has never been recorded in rodents. The pathogenesis of this condition remains obscure and it is uncertain whether it represents a neoplastic or malformative process. Meningioangiomatosis is usually characterized by a plaque-like leptomeningeal proliferation of mainly spindle-shaped cells and small blood vessels, extending along the Virchow-Robin spaces into the adjacent neural parenchyma. In this report, we presented a brain lesion displaying the histopathological key features of the meningioangiomatosis and involving the base of the cerebrum (fronto-basal area) and the brainstem, found in a male CD-1 mouse. The histopathological and immunohistochemical results are discussed, and compared with those previously reported in other cases of meningioangiomatosis.

Malignant spinal meningioma in a CD-1 mouse.

Spontaneous meningiomas are extremely rare tumors in small laboratory animals, except in some strains of rats and in the B6C3F1 mouse. We report the case of a male CD-1 mouse in poor health condition, with severe apathy and partial paresis of hindlegs. No macroscopic lesion was noticed at necropsy. Microscopic examination revealed the presence of a malignant meningioma (approximately 3mm in diameter) at the distal lumbar level of the spinal cord, invading the vertebral canal, and bilaterally the ventral and dorsal nerve roots and the dorsal root ganglia. The tumor displayed highly cellular sheets of polygonal cells with a well-delineated, abundant, eosinophilic cytoplasm and scarce fibrovascular stroma; epithelioid and sarcomatous areas were also present. The mitotic activity was moderate. Tumor cells expressed vimentin immunoreactivity and were negative for periodic acid-Schiff (PAS), silver impregnation for reticulin, chromogranin A, glial fibrillary acidic protein (GFAP), cytokeratin (CK) and S-100 protein. The diagnosis of malignant spinal meningioma was based on the morphologic features of the neoplasm, the evidence of local invasion and the immunohistochemical results.