Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hexamethylphosphoramide (HMPA) was given orally (100 mg/kg/day) to: a) conventional rats of Sprague-Dawley and Long-Evans substrains known to have indigenous Mycoplasma pulmonis infection, b) uninfected pathogen-free (PF) Fischer rats, and c) PF and axenic Fischer rats inoculated intranasally with M. pulmonis strains having a wide range of virulence. Treated rats infected with virulent M. pulmonis, either naturally or experimentally, developed severe clinical signs of murine respiratory mycoplasmosis (MRM) with mortalities of 25 to 60% compared to relatively mild MRM and no deaths in untreated, infected controls. Deaths were attributed to unusually severe lung lesions of MRM (extreme neutrophilic exudation into major bronchi and bronchiectasis) with ulceration of respiratory mucosa and hemorrhage. Rhinitis also was increased in severity by HMPA in conventional rats, but not in experimentally infected PF or axenic rats. Severity of otitis media and tracheitis was not affected by HMPA. Incidence of lesions of MRM was unchanged except for increased frequency of gross lung lesions. In the absence of M. pulmonis infection, HMPA treatment of rats caused thinning and microulceration of respiratory epithelium in major bronchi without inflammatory lung disease. Other effects induced by HMPA, with or without the infection, were destruction and fibrous replacement of olfactory epithelium, atrophy of testes, and reduced weight gains. It was concluded that HMPA markedly enhances both rate of progression and severity of the pneumonia while inconsistently potentiating the rhinitis of MRM in rats. Previous studies of HMPA are emphasized as an additional example in which the synergistic effects of an experimental chemical and an indigenous pathogen of laboratory rats have given misleading experimental results.
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PMID:Enhancement of natural and experimental respiratory mycoplasmosis in rats by hexamethylphosphoramide. 124 84

As part of a long-term inhalation toxicity study with acetaldehyde in rats, progression and regression of nasal lesions were studied in animals exposed to 0, 750, 1500 and 3000/1500 ppm of the test compound for 52 weeks and killed after recovery periods of 26 or 52 weeks. Major compound-related nasal lesions found at the end of the exposure period comprised: (a) thinning of the olfactory epithelium with loss of sensory and sustentacular cells at all concentrations; this condition was accompanied by focal basal cell hyperplasia in low- and mid-concentration animals; (b) hyper- and metaplasia of the respiratory epithelium frequently accompanied by keratinisation and occasionally by proliferations of atypical basal cells in the top-concentration group; and (c) rhinitis in several top-concentration rats. There was strong evidence on the one hand that the hyper- and metaplastic changes found in the respiratory epithelium and the basal cell hyperplasia seen in the olfactory epithelium after 52 weeks of exposure may progress to neoplasms despite discontinuation of the treatment. On the other hand these hyper- and metaplastic changes may regress during the recovery period. Regeneration of the olfactory epithelium was evident in several low- and mid-concentration animals, but not in top-concentration rats. The regenerated epithelium was seen as a layer of stratified undifferentiated epithelium containing small nerve bundles, tiny groups of sensory cells, and groups of epithelial cells resembling acinar cells of the glands of Bowman. Furthermore, replacement of olfactory epithelium by respiratory epithelium was a frequent finding. It was concluded that rat olfactory epithelium severely damaged by acetaldehyde may regenerate, most probably from basal cells, provided the olfactory epithelium has not been fully destroyed.
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PMID:Inhalation toxicity of acetaldehyde in rats. IV. Progression and regression of nasal lesions after discontinuation of exposure. 342 85

Pasteurella multocida type D toxin is a peptide shown to induce severe atrophic rhinitis in the pig as the result of an increased osteoclastic resorption of the ventral nasal turbinates. In the present study, the effects of the toxin on the histological, cytochemical and ultrastructural features of the osteoclast population of the rat were examined. Pasteurella multocida toxin induced atrophy of the ventral and dorsal nasal turbinates and thinning of the nasal bones. The number and size of the long bone metaphyseal osteoclasts were significantly increased, but not the number of nuclei per cell. Osteoclasts of toxin-treated rats had more developed clear zones and ruffled borders than those of the controls and their cytoplasmic vacuoles were more abundant and larger. We concluded that P. multocida toxin stimulates bone resorption by osteoclasts in the rat by increasing resorption activity and by increasing their number. Its action is not limited to the nasal turbinates but occurs also in the other bones, such as the long bones.
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PMID:Effects of Pasteurella multocida toxin on the osteoclast population of the rat. 847 61

CI-959, 5-methoxy-3-(1-methylethoxy)-N-1H-tetrazol-5-yl-benzo[b]thio phene-2-carboxamide, an anti-inflammatory agent, was considered for development as a treatment for rhinitis. Two-week topical nasal studies in Wistar rats and Beagle dogs were performed to assess nasal toxicity of CI-959. Rats were given daily doses in the right nostril of 0.05 ml of solutions of varying concentrations (0.5, 2, 10, 20, 30, 60, and 90 mg/ml; doses of 0.08, 0.3, 1.6, 3.2, 4.8, 9.6, and 14.6 mg/kg) of CI-959. Beagle dogs were given daily doses in the right nostril of 0.5 ml of 10, 20, 30, 60, and 90 mg/ml solutions (doses of 0.5, 0.8, 1.2, 2.8, and 3.7 mg/kg) of CI-959. Rats given > or = 60 mg/ml either lost weight or had decreased weight gain. Salivation at dosing was seen in both species. Four sections of nasal cavity were examined from each animal. In rats, 0.5 mg/ml was the "no effect" dose; minimal changes were seen at 2 mg/ ml, and significant changes were dose related in severity at > or = 10 mg/ml in all 4 nasal levels. Degeneration and necrosis of respiratory and olfactory epithelia were minimal to moderate in severity. Adhesions and fibro-osseous proliferation of ethmoturbinates, epithelial hyperplasia, squamous metaplasia, and exudate were also seen. In dogs, 10 mg/ml was the no effect dose; respiratory epithelium was affected at > or =20 mg/ml. Respiratory epithelial degeneration was minimal to mild, with loss of ciliated and goblet cells and thinning of mucosa. Distribution of degeneration increased with increased concentrations. In both species, in accordance with the suggested action of CI-959, infiltration with neutrophils was not significant. CI-959 was locally toxic to nasal cavity respiratory and olfactory epithelia in rats and respiratory epithelium in dogs.
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PMID:Nasal toxicity of CI-959, a novel anti-inflammatory drug, in Wistar rats and Beagle dogs. 986 87

Pasteurella multocida is responsible for a variety of diseases of veterinary importance, including the pig disease progressive atrophic rhinitis (PAR). The feasibility of using the mouse as an experimental model of PAR was evaluated. We experimentally infected the upper respiratory tract of immature mice with a pig isolate of P. multocida that produces the toxin responsible for causing the nasal lesions characteristic of PAR. We tracked the health status and weight gain of these mice for one month following infection, after which the mice were killed and the integrity of the nasal turbinates was examined. Mice infected with P. multocida appeared healthy throughout the study, although the growth rate of these mice was reduced significantly compared with non-infected control animals. Infected animals also demonstrated marked nasal atrophy analogous to that seen in naturally occurring PAR of swine, with shortening and thinning of the turbinate scrolls and inflammatory cell involvement. The mouse therefore provides a convenient model for the further investigation of PAR of swine.
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PMID:An experimental mouse model of progressive atrophic rhinitis of swine. 1550 91