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.

A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function.

The Predictive Safety Testing Consortium's first regulatory submission to qualify kidney safety biomarkers revealed two deficiencies. To address the need for biomarkers that monitor recovery from agent-induced renal damage, we scored changes in the levels of urinary biomarkers in rats during recovery from renal injury induced by exposure to carbapenem A or gentamicin. All biomarkers responded to histologic tubular toxicities to varied degrees and with different kinetics.

Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies.

Kidney toxicity accounts both for the failure of many drug candidates as well as considerable patient morbidity. Whereas histopathology remains the gold standard for nephrotoxicity in animal systems, serum creatinine (SCr) and blood urea nitrogen (BUN) are the primary options for monitoring kidney dysfunction in humans. The transmembrane tubular protein kidney injury molecule-1 (Kim-1) was previously reported to be markedly induced in response to renal injury.

Urinary clusterin, cystatin C, beta2-microglobulin and total protein as markers to detect drug-induced kidney injury.

Earlier and more reliable detection of drug-induced kidney injury would improve clinical care and help to streamline drug-development. As the current standards to monitor renal function, such as blood urea nitrogen (BUN) or serum creatinine (SCr), are late indicators of kidney injury, we conducted ten nonclinical studies to rigorously assess the potential of four previously described nephrotoxicity markers to detect drug-induced kidney and liver injury. Whereas urinary clusterin outperformed BUN and SCr for detecting proximal tubular injury, urinary total protein, cystatin C and beta2-microglobulin showed a better diagnostic performance than BUN and SCr for detecting glomerular injury.

Repair of sparfloxacin-induced photochemical DNA damage in vivo.

The induction and subsequent repair of photochemically induced DNA damage by sparfloxacin was assessed in different tissues of juvenile Wistar rats. The animals were treated once orally with 500 mg kg(-1) of sparfloxacin and irradiated 3 hours later with 7 J cm(-2) UVA. Induction and repair of DNA damage was studied in the skin, retina and cornea using the alkaline comet assay.

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.

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.

Class III beta-tubulin isotype: a key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology.

The expression of the cytoskeletal protein class III beta-tubulin isotype is reviewed in the context of human central nervous system development and neoplasia. Compared to systemic organs and tissues, class III beta-tubulin is abundant in the brain, where it is prominently expressed during fetal and postnatal development. As exemplified in cerebellar neurogenesis, the distribution of class III beta-tubulin is neuron associated, exhibiting different temporospatial gradients in the neuronal progeny of the external granule layer versus the neuroepithelial germinal matrix of the velum medullare.

TCH346 prevents motor symptoms and loss of striatal FDOPA uptake in bilaterally MPTP-treated primates.

The neuroprotective efficacy of the propargylamine TCH346 was studied in the primate model of Parkinson's disease, the bilaterally MPTP-treated monkey. Male rhesus monkeys received 2.5 mg MPTP into the left carotid artery and, 8 weeks later, 1.

Protein kinase B alpha/Akt1 regulates placental development and fetal growth.

Protein kinase B alpha (PKB alpha/Akt1) is implicated in the regulation of metabolism, transcription, cell survival, angiogenesis, cell migration, growth, and tumorigenesis. Previously, it was reported that PKB alpha-deficient mice are small with increased neonatal mortality (Cho, H., Thorvaldsen, J.

On the neuronal/neuroblastic nature of medulloblastomas: a tribute to Pio del Rio Hortega and Moises Polak.

The concept that medulloblastomas represent cerebellar neuroblastic tumours was championed by del Rio Hortega in the 1930s and was critically reappraised in the 1960s by Moises Polak. Whereas the aetiology and molecular pathogenesis of medulloblastomas remain unresolved, there is now compelling evidence in support of a fundamentally neuronal tumour phenotype. Tumour cells express in a differentiation-dependent manner a repertoire of neuronal cytoskeletal, synaptic, and other lineage-associated proteins.

Pheochromocytomas and ganglioneuromas in the aging rats: morphological and immunohistochemical characterization.

We investigated, morphologically and immunohistochemically, 74 medullary adrenal tumors, including 64 pheochromocytomas (14 malignant and 50 benign), 9 ganglioneuromas, and 1 malignant schwannoma. The tumors were detected in 2-year-old Wistar and Sprague-Dawley rats from carcinogenicity studies. Morphologically, benign pheochromocytomas were characterized by monomorphic, small, basophilic cells with almost absence of mitoses.

Localization of the neuronal class III beta-tubulin in oligodendrogliomas: comparison with Ki-67 proliferative index and 1p/19q status.

The class III beta-tubulin isotype (betaIII) is widely regarded as a neuronal marker in development and neoplasia. Whereas the expression of betaIII in neuronal/neuroblastic tumors is differentiation-dependent, the aberrant expression of this cytoskeletal protein in astrocytomas is associated with an ascending gradient of malignancy. To test the generality of this observation we have compared the immunoreactivity (IR) profiles of the betaIII isotype with the Ki-67 nuclear antigen proliferative index in 41 archival, surgically excised oligodendrogliomas (32 classical [WHO grade II] and 9 anaplastic [WHO grade III]).