Phospholipidosis in rats treated with amiodarone: serum biochemistry and whole genome micro-array analysis supporting the lipid traffic jam hypothesis and the subsequent rise of the biomarker BMP.

To provide mechanistic insight in the induction of phospholipidosis and the appearance of the proposed biomarker di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP), rats were treated with 150 mg/kg amiodarone for 12 consecutive days and analyzed at three different time points (day 4, 9, and 12). Biochemical analysis of the serum revealed a significant increase in cholesterol and phospholipids at the three time points. Bio-analysis on the serum and urine detected a time-dependent increase in BMP, as high as 10-fold compared to vehicle-treated animals on day 12.

Gavage-related reflux in rats: identification, pathogenesis, and toxicological implications (review).

After oral gavage dosing of rats, reflux may occur, resulting in serious respiratory effects and mortality. Published information on gavage-related reflux is limited, as it has not yet been a focus of research. Nevertheless, it represents a recurrent challenge in daily toxicology practice of oral gavage dosing.

Unexpected nasal changes in rats related to reflux after gavage dosing.

In a three-week oral gavage toxicity study in rats, a high incidence of respiratory symptoms and high mortality was noted in compound-dosed rats only. Because of audible respiration, an effect in the upper respiratory tract was suspected and the nasal cavity was included for examination. Histology revealed extensive necrosis and purulent inflammation within the nasal passages, indicative of direct irritation.

Impact of gavage dosing procedure and gastric content on adverse respiratory effects and mortality in rat toxicity studies.

Unscheduled mortality preceded by adverse respiratory clinical signs in rats dosed by oral gavage may not only be caused by technical gavage error or systemic toxicity but may also be caused by gastro-esophageal reflux and subsequent aspiration of high concentrations of drug formulation. In a 3 week oral gavage rat toxicity study for an early drug development compound, preterminal deaths (approximately 20% of animals) at high doses (≥1000 mg kg(-1) ) and concentrations (≥60 mg ml(-1) ) were preceded by recurrent dyspnea, rales or excessive salivation, without evidence of accidental intrapulmonary gavage error. Histological evaluation revealed extensive necrosis and inflammatory changes in the upper respiratory tract, especially in the nasal turbinates and/or nasopharynx.

Substituted azoloquinolines and -quinazolines as new potent farnesyl protein transferase inhibitors.

A series of (4-chlorophenyl)-alpha-(1-methyl-1H-imidazol-5-yl)azoloquinolines and -quinazolines was prepared. These compounds displayed potent Farnesyl Protein Transferase inhibitory activity and tetrazolo[1,5-a]quinazolines are promising agents for oral in vivo inhibition.

[The effect of treatment with vitamin E or selenium on the course of salinomycin poisoning in swine].

Experimentally induced salinomycin toxicosis in weanling pigs showed typical clinical signs of an intoxication with a polyether antibiotic. Severe ataxia and recumbency were the most prominent symptoms, which could be attributed to acute skeletal muscle necrosis by estimation of muscle enzyme activities (creatine kinase, aspartate aminotransferase) and histopathological examination. Intoxication had neither influence on concentrations of vitamin E and selenium-dependent glutathione peroxidase in plasma and different organs nor on contents of fatty acids in skeletal muscles.

[Scanning electron microscopic findings of the navicular bone and deep flexor tendon in podotrochlosis of horses].

In 25 adult horses the podotrochlea of 49 forelimbs was examined by means of light and electron microscopy in order to correlate clinical and morphological findings. According to the clinical diagnosis the animals were divided into three groups: lameness due to syndrome of podotrochlosis (group 1) or due to tendopathy (group 2) and horses without lameness (group 3). The most striking pathological findings of the navicular bone and the opposite surface of the deep flexor tendon were found in horses with podotrochlosis, consisting of loss of cartilage and tendon matrix with denudation of collagen fibrils, superficial degeneration and necrosis, focal occurrence of fissures and far-reaching defects, sometimes accompanied by adhesions between tendon and navicular bone surface.

[Tibial aplasia and agenesis in a rabbit (case report)].

The occurrence of a tibial aplasia (left side) and agenesia (right side) in a rabbit (aged 4 weeks) is reported. Apart from extreme distorsions of the fibular bones, there were no other skeletal malformations.

Streptococcus canis arthritis in a cat breeding colony.

This is the first description of a pathologic condition--arthritis in cats affecting mainly one joint, i.e. monarthritis--caused by Streptococcus canis (S.

Ultrastructural findings in horses with chronic obstructive pulmonary disease (COPD). II: Pathomorphological changes of the terminal airways and the alveolar region.

Extensive light and electron microscope studies (transmission and scanning electron microscopy) of the bronchioles and alveolar region, in 28 horses suffering chronic obstructive pulmonary disease (COPD) and eight control horses, revealed good correlation between clinical severity and morphological changes. In the bronchiolar epithelium the non-ciliated bronchiolar epithelial (Clara) cells, in particular, showed ultrastructural alterations and, even in the mild stages of disease, these presented degenerative changes and lack of differentiation. Together with loss of granulation in the Clara cells and metaplasia of the goblet cells, cells were seen with unusual intracytoplasmic lamellar inclusion, the number of which increased sharply with clinical severity.

Detection of canine distemper viral antigen in formalin-fixed and paraffin-embedded tissue of a fitch (Mustela putorius), using an immunoperoxidase technique.

The present study describes how a naturally infected fitch (Mustela putorius) caused an outbreak of canine distemper in a colony of insufficiently vaccinated dogs. The detection of canine distemper virus (CDV) on paraffin sections of different organs of the fitch and one of the dead dogs was achieved using a monoclonal antibody against the nucleocapsid protein (NP) of CDV and the avidin-biotin-peroxidase complex (ABC) technique.