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

The changes of the anterior cerebral artery/olfactory artery junction, one of the favorite sites of aneurysm formation, in rats treated with unilateral ligation of the common carotid artery and renal hypertension were investigated by light microscopy. The initial changes of aneurysm occurred not at the apex itself, but on the distal side of the major branch adjacent to the apex, at the intimal pad and the neighboring distal portion. Here the internal elastic lamina showed various degenerative changes and disappearance. The neighboring distal portion adjacent to the intimal pad showed a shallow depression associated with a thinning of the media due to a decrease of medial smooth muscle cells in number even in some control animals. Such degenerative changes of the internal elastic lamina and medial smooth muscle cells caused by hemodynamic stress due to branching structure, including intimal pads, augmented by the experimental treatment, are supposed to be the basis for aneurysm formation.
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PMID:Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study. 376

The 4-h LC50 of acetaldehyde in rats was determined and found to be 13,300 ppm (24.0 g/m3 air). In a 4-week study groups of 10 male and 10 female rats were exposed to 0, 400, 1000, 2200 or 5000 ppm acetaldehyde for 6 h/day, 5 days/week. Treatment-related changes observed at the 5000 ppm level included dyspnoea and excitation during the first 30 min of each exposure, yellow-brown fur, severe growth retardation, more neutrophils and less lymphocytes in the blood, a reduced production of urine with a high density, increased lung weights, and severe degenerative, hyperplastic and metaplastic changes of the nasal, laryngeal and tracheal epithelium. Major lesions seen at 1000 and 2200 ppm comprised growth retardation and an increased production of urine in males, slight to moderate degeneration with or without hyper- and metaplasia of the nasal epithelium, and only at 2200 ppm, minimal epithelial changes in the larynx and trachea. The only change observed at the 400 ppm level that could be attributed to acetaldehyde was slight degeneration of the nasal olfactory epithelium seen as loss of microvilli and thinning and disarrangement of the layer of epithelial cells.
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PMID:Inhalation toxicity of acetaldehyde in rats. I. Acute and subacute studies. 712 64

In recent years microvillar cells (MVC) have been identified in the olfactory epithelium of numerous species, including rodents, canines, and primates. However, there is no consensus on the morphologic or histochemical features of this cell, nor is the function of these cells currently known. Previous studies have examined MVC during development and in the mature olfactory epithelium, but not after toxic insult. A microvillar cell, defined by specific morphologic criteria, was studied in adult male Long-Evans rats exposed via inhalation to either 200 ppm methyl bromide for 4 h/day, 4 days/week for 2 weeks, or to 635 micrograms/m3 nickel for 6 h/day for 16 consecutive days, and sacrificed serially over several months. The pattern of recovery for MVC differed according to the severity and specificity of the insult to the olfactory epithelium. With methyl bromide, all cell types were completely depleted from olfactory epithelium immediately after injury, including MVC. MVC were slow to repopulate the epithelium, and appeared only when olfactory epithelium was complete in other respects. With nickel exposure, where the major effect was a gradual decrease in sustentacular cells with a thinning of the apical cytoplasm thickness, MVC showed a decline during exposure, but reappeared during recovery. In both cases, there was no difference in olfactory function, even when MVC were absent from the olfactory epithelium. A mature olfactory epithelium appears to be necessary to support the presence of this MVC, suggesting that it is not crucial to the regeneration processes or recovery of olfactory function, but perhaps plays some role, as yet undefined, in the unperturbed olfactory epithelium.
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PMID:Microvillar cells of the olfactory epithelium: morphology and regeneration following exposure to toxic compounds. 771 50

Experimentally, inorganic, sulfated nickel compounds (Ni2+) have been shown to produce histological lesions in the nasal mucosa of rats, more specifically, atrophy of the olfactory epithelium. The present project was designed to assess the effects of inhalation of nickel sulfate hexahydrate on behavioral, histological, and neurochemical aspects of the olfactory system. Male Long-Evans rats were exposed to either background air (control) or 635 micrograms Ni/m3 for 16 consecutive days, 6 hr/day. Exposure resulted in selective lesions to the olfactory epithelium. The number of bipolar sensory receptor cells was slightly reduced and there was a significant decrease in the thickness of the olfactory epithelium. This was due primarily to a significant loss of the sustentacular cell population, with a thinning of the apical cytoplasm, concomitant with a reduction in the number of microvilli at the surface of these cells. Significant decreases in carnosine level, consistent with the nickel sulfate exposure, were observed. However, there were no changes in olfactory function as measured by either absolute threshold or two-oder discrimination tasks.
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PMID:Behavioral, histological, and neurochemical effects of nickel (II) on the rat olfactory system. 787 34

To investigate the effects of sulfur dioxide (SO2) on olfactory epithelium, an experiment was performed with 56 mice from the same colony. Experimental animals were divided into three groups consisting of a 30-min exposure group (group 1), a 60-min exposure group (group 2), and a 120-min exposure group (group 3). The olfactory mucosa in these mice were studied by light microscopy immediately, and after 24 h, 48 h, or 72 h exposure to 20 ppm of SO2. Edema, loss of cilia, epithelial thinning, and epithelial desquamation in the olfactory epithelium were observed in groups 2 and 3. The basal lamina and the connective tissue were well preserved throughout the entire mucosa. Injuries to olfactory epithelium became severer with exposure time. These changes were further pronounced 24 h after exposure. Regenerated epithelia were not observed in any group. Scanning electron microscopic findings were consistent with light microscopic findings. Olfactory epithelial surface were consistent with light microscopic findings. Olfactory epithelial surface was sloughed off and revealed, underlining intact basal lamina. The results of this study suggest that early lesions of olfactory epithelium after exposure to SO2 may be primarily degenerative.
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PMID:Histopathologic changes in the olfactory epithelium in mice after exposure to sulfur dioxide. 797 18

It has previously been shown that the hilus of the dentate gyrus responds to odors (e.g. toluene) with a burst of fast waves and to electrical stimulation of the olfactory bulb with an evoked potential consisting of an early component immediately after the stimulus artifact, a second component with a 16-18-ms latency and additional late components. Spectral analysis revealed that odor-induced fast-wave bursts in the olfactory bulb and dentate gyrus both had a peak frequency of 15-20 Hz and were highly coherent. Unilateral intrahippocampal injections of colchicine or kainic acid were used in an attempt to destroy granule and pyramidal cells, respectively, while saline was injected on the opposite side as a control. Recordings from chronically implanted electrodes in the olfactory bulb and dentate gyrus demonstrated that saline had no effect while either neurotoxin abolished the odor-induced fast waves. In addition, the late 16-18-ms component of the dentate-evoked potentials after single-pulse stimulation of the olfactory bulb was abolished by either kainic acid or colchicine; the early dentate response, probably a volume-conducted olfactory response, was not abolished. Histological analysis indicated that kainic acid produced widespread non-specific damage in the hippocampal formation. Kainic acid-treated tissue exhibits a thinning of granule cell and molecular layers of the dentate gyrus as well as cell loss in CA3 and part of CA1.
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PMID:The neurotoxins colchicine and kainic acid block odor-induced fast waves and olfactory-evoked potentials in the dentate gyrus of the behaving rat. 853 32

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

Chemical destruction of the olfactory mucosa leads to a neuronal regeneration. A new organotypic culture model is perfected to improve the regenerating processes study. Explants of neuroepithelium attached to olfactory bulbs were removed from adult mice and cultured, 12 h after ZnSO4 intranasal application. After 3 days in culture, explants showed a necrosis in the olfactory epithelium and a thinning of the olfactory bulb nervous layer. From the fifth day of culture, and mostly the tenth, new cells showed positive immunoreactivity with the olfactory marker protein (OMP), meaning they were regenerating olfactory neurons. Simultaneously, OMP immunoreactivity increased in the nervous and glomerular layers of the olfactory bulb, indicating epithelio-bulbar reconnection. This organotypic culture model could allow further investigations on the regenerating process kinetic.
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PMID:Organotypic culture of neuroepithelium attached to olfactory bulb from adult mouse as a tool to study neuronal regeneration after ZnSO4 neuroepithelial trauma. 1050 2


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