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1.
3-Methylindole-induced nasal mucosal damage in mice   总被引：1，自引：0，他引：1  
3-Methylindole (3MI) damages nasal olfactory epithelium in mice. Lesions were studied histologically from 30 minutes to 28 days after intraperitoneal injection of 400 mg 3MI/kg. Cellular swelling was apparent in olfactory epithelium by 6 hours after injection of 3MI, while respiratory epithelium was normal. Necrosis of olfactory epithelium and subepithelial glands was diffuse by 48 hours. Subsequent ulceration resulted in epithelial hyperplasia, squamous metaplasia, fibroplasia, and ossification. Partially occlusive intranasal fibrous and osseous tissue persisted through 28 days after 3MI injection.  相似文献   

2.
Horses may be exposed to aflatoxin B(1) (AFB(1)) via inhalation of mouldy dust, leading to high exposure of olfactory and respiratory tissues. In the present study the metabolic activation of AFB(1) was examined in olfactory and respiratory tissues in horse. The results showed covalent binding of AFB(1)-metabolites in sustentacular cells and cells of Bowman's glands in the olfactory mucosa, in some cells of the surface epithelium of nasal respiratory, tracheal, bronchial and bronchiolar mucosa and in some glands in these areas. Immunohistochemistry revealed that cells expressing proteins reacting with CYP 3A4- and CYP 2A6/2B6-antibodies had a similar distribution as those having capacity to activate AFB(1). Our data indicate that the cell-specific activation of AFB(1) correlates with presence of some CYP-enzymes in olfactory and respiratory tissues in horse.  相似文献   

3.
REASONS FOR PERFORMING STUDY: Eosinophilic granulocytes have been associated with parasite or immune-mediated diseases, but their functions in other disease processes remain unclear. Cause and timing of eosinophil migration into the equine gastrointestinal mucosa are also unknown. OBJECTIVE: To determine the effects of intestinal parasitism on eosinophils in equine large intestinal mucosa. METHODS: Large intestinal mucosal samples were collected from horses and ponies (n = 16) from the general veterinary hospital population, ponies (n = 3) raised in a parasite-free environment, ponies experimentally infected with 500 infective Strongylus vulgaris larvae and treated with a proprietary anthelmintic drug (n = 14), and a similar group of ponies (n = 7) that received no anthelmintic treatment. Total eosinophil counts and eosinophil distribution in the mucosa were determined by histological examination. A mixed model analysis was performed and appropriate Bonferroni adjusted P values used for each family of comparisons. P<0.05 was considered significant. RESULTS: There was no difference in large intestinal mucosal eosinophil counts and eosinophil distribution between ponies infected with S. vulgaris and those raised in a parasite-free environment. Experimental infection with S. vulgaris, with or without subsequent anthelmintic treatment, did not change eosinophil counts, and counts were similar to those for horses from the general population. CONCLUSIONS: Migration of eosinophils to the equine large intestinal mucosa appears to be independent of exposure to parasites. Large intestinal mucosal eosinophils may have more functions in addition to their role in defence against parasites.  相似文献   

4.
To study the role of cytochrome P-450-dependent mixed function oxidase reactions in equine 3-methylindole (3MI) toxicosis, ponies were given 20 mg of phenobarbital/kg of body weight at 72, 60, 48, 36, and 24 hours before 100 mg of oral 3MI/kg to induce cytochrome P-450 or no treatment (controls). Maximal 3MI plasma concentration was decreased and clearance was faster in phenobarbital-treated ponies. Plasma 3MI was still detectable 12 and 36 hours after dosing in phenobarbital-treated and control ponies, respectively. Phenobarbital treatment induced a distribution phase with transition from a 1-compartment to a 2-compartment extravascular model. Bronchiolitis occurred in all ponies 72 hours after 3MI, but was more severe in those treated with phenobarbital. Appearance of a distribution phase, increased total body clearance, and more severe bronchiolitis in phenobarbital-treated ponies indicated that mixed function oxidases are involved in metabolism and conversion of 3MI to a toxic metabolite.  相似文献   

5.
Male F344 rats received diet containing 3,000 ppm 2,6-dimethylaniline (DMA) after initiation with a single subcutaneous injection of 2,400 mg/kg of N-bis(2-hydroxypropyl)nitrosamine (DHPN), and histological and electron microscopic examinations of the nasal cavity were performed at 4, 13, 26 and 52 weeks to examine sequential changes induced by DMA. Severe atrophy of Bowman's glands and epithelial disarrangement were apparent from week 4, followed by dilatation and/or proliferation of Bowman's glands, degeneration of epithelial cells, and proliferation of undifferentiated epithelial cells from week 13. Focal glandular hyperplasias, dysplastic foci, and adenomas were observed from week 26, and carcinomas at 52 week. These nasal lesions were mostly evident in the olfactory mucosa in the nasal cavity, and their severity and/or incidences, other than atrophy of Bowman's glands, increased with the treatment period. Electron microscopically, carcinoma cells demonstrated desmosomes, dense secretory granules identical to those in normal Bowman's glands, a basement membrane, and microvilli. These results suggest that Bowman's glands are the target of DMA, giving rise to nasal carcinomas after DHPN-initiation.  相似文献   

6.
Nine young calves given respiratory syncytial virus by a combined intranasal and intratracheal route developed a severe respiratory tract disease in which coughing, tachypnea, and hyperpnea were prominent clinical features. Calves were euthanatized on postinoculation (initial) days (PID) 1 to 13. At necropsy, large areas of consolidation were present in the cranial, middle, accessory, and cranial parts of the caudal lung lobes of calves killed between PID 4 and 13. Histopathologic examination revealed widespread and severe lesions in small bronchi, bronchioli, and alveoli. Multinucleate epithelial syncytia on bronchiolar and alveolar walls, many containing eosinophilic intracytoplasmic inclusion bodies, were present in the lungs of calves killed on PID 4, 5, and 6. Necrosis and epithelial loss, hyperplasia, and metaplasia were also observed in the epithelium of small bronchi and bronchioli. The lumina of these airways were occluded to varying degrees with exudate. Exudate was present within alveoli, and interalveolar septa were markedly thickened. Collapse of the thickened septa produced large areas where alveolar air spaces were totally obliterated. Repair was evident in the lungs of calves killed at PID 10 and 13 with reepithelialization of damaged bronchiolar mucosa, organization of bronchiolar exudate leading to bronchiolitis obliterans, and peribronchial and peribronchiolar fibrosis. Inoculation of 3 calves by an intranasal route alone produced a less severe clinical disease with only minimal lesions present at necropsy.  相似文献   

7.
The objective of the study reported here was to characterise the microscopic appearance of peptic-injured equine gastric squamous epithelium in relation to the duration of peptic injury. Erosions and ulcers were induced in equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Specimens of normal gastric mucosa and mucosa with lesions created after 48 and 96 h of feed deprivation were compared for characteristics associated with angiogenesis and mucosal proliferation. Fifteen mature horses, 9 geldings and 6 mares, age 3-20 years, were divided into 3 groups. Group 1 (n = 5) had normal-appearing gastric squamous mucosal epithelium and had been killed due to problems unrelated to the gastrointestinal tract. Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for totals of 48 and 96 h feed deprivation, respectively. Following lethal injection of barbiturate, stomachs were removed and fixed by filling with 4-6 l 10% buffered formalin. Sections were made from lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. Measurements of total epithelial thickness, keratinised epithelium, nonkeratinised epithelium, epithelial projections, capillary extension into the epithelium and lamina propria thickness were made. The cross-sectional areas of arterial and venous vascular structures in the lamina propria at the lesions and their margins were measured using image analysis software. All horses, except one, in Group 2 developed erosions or ulcers in the gastric squamous epithelium after feed deprivation. There were several changes in the epithelium adjacent to erosions and ulcers, compared to normal epithelium, from horses in Groups 2 and 3: total epithelial thickness was significantly (P<0.05) greater, including both keratinised and nonkeratinised layers in most specimens; the length of epithelial projections and extent to which capillaries from the lamina propria extended toward the luminal surface, and the cross-sectional area of vascular structures (arterioles, capillaries, venules) in the lamina propria were significantly greater. Epithelial thickness of erosion beds was not significantly less than normal epithelium, although a greater proportion of the epithelium in erosions consisted of epithelial projections (Group 1, 23%; Group 2, 76%; Group 3, 72%). The cross-sectional area of vascular structures in the lamina propria beneath erosions was significantly greater than in normal mucosa only in Group 2 tissues, whereas in the lamina propria of ulcers it was significantly greater than in normal mucosa only in Group 3 tissues. The epithelial proliferation and increased vascular cross-sectional area in the lamina propria associated with peptic-induced gastric lesions are consistent with processes associated with the initiation of ulcer healing, and these changes temporally coincided with the initiation of peptic insult to the gastric squamous epithelium. These findings demonstrate that processes that promote ulcer healing begin soon after peptic injury and that they progress even with repeated peptic injury. Furthermore, our findings support observations that gastric ulcers often heal without medical intervention, and the theory that medications that reduce gastric acidity do not initiate healing, but rather facilitate ulcer healing by providing a microenvironment that is optimal for healing to proceed.  相似文献   

8.
Respiratory syncytial virus was the cause of a severe epizootic of bovine respiratory tract disease. The virus, isolated from a sick cow during the epizootic, produced cytopathic effect in a bovine turbinate cell line 14 days after it was inoculated. Additional support for the diagnosis came from the results of pathologic and serologic examinations. Lesions consistently present were severe necrotizing bronchiolitis and epithelial syncytia projecting from bronchiolar and alveolar walls. Also, in the cow from which the virus was isolated, there was tracheitis with a syncytial-like change involving the mucosal epithelium.  相似文献   

9.
Tracheal lesions in young turkeys infected with Bordetella avium   总被引：5，自引：0，他引：5  
Forty-six turkeys were inoculated intranasally with Bordetella avium at 3 days of age. Inoculated and non-inoculated turkeys (n = 72) were necropsied sequentially from post-exposure days (PED) 3 to 53. Tracheal lesions were studied histologically. Mild fibrinopurulent tracheitis, associated with bacterial colonization of ciliated epithelium, was seen at PED 7 to 10. At PED 14 and 21, there were numerous bacterial colonies, loss of ciliated cells, epithelial hyperplasia, depletion of mucus, and diffuse infiltration of lymphocytes and macrophages. At PED 28, the mucosa and tracheal rings were severely distorted. The mucosal epithelium, composed of immature epithelial cells and nononuclear leukocytes, had formed prominent longitudinal folds. Mucous glands were cystic and lined by low cuboidal epithelium. At PED 42 and 53, tracheas appeared normal, except for residual distortion of tracheal rings and shortened luminal epithelium.  相似文献   

10.
This study compared the severity of ischemic injury to the equine jejunal mucosa caused by arteriovenous obstruction (AVO) or venous obstruction (VO) with that caused by reperfusion after ischemia. The degree of mucosal damage and regeneration was scored according to a modified version of an established light microscopic classification for ischemic injury. Biopsy specimens taken after 3 and 4 hours of obstruction, and after 3 hours of obstruction and 1 hour of reperfusion, were compared. There were no changes in the severity of mucosal injury (characterized by epithelial sloughing, loss of villus architecture, and necrosis of crypt cells) at 4 hours of ischemia when compared with 3 hours of ischemia. The mucosal injury score increased by one grade in three of six and five of eight segments during reperfusion for the VO and AVO models, respectively; however, only the scores for the AVO model were significantly different from the injury caused by ischemia alone. Modification of reperfusion injury was attempted by the administration of intravenous (IV) allopurinol, dimethyl sulfoxide (DMSO), or intraluminal oxygen insufflation at the time of release of the AVO and VO. Treatments did not significantly alter either the severity of injury noted after 1 hour of reperfusion or the degree of mucosal regeneration after 48 hours of reperfusion. In this group of ponies, the severity of mucosal damage was greater after 1 hour of reperfusion for both AVO and VO.  相似文献   

11.
This study examined whether a product containing a pectinlecithin complex (Pronutrin) (1) could prevent gastric lesions induced in the equine gastric squamous epithelial mucosa using a protocol of intermittent feed deprivation that resulted in prolonged increased gastric acidity (Murray and Eichorn 1996). Eight ponies were used and served as their own controls in 2 trials in which there were 72 h cumulative deprivation (alternating 24 h with no feed, then 24 h free choice hay), with a 4-week interval between trials. Ponies were assigned randomly to receive either 250 g Pronutrin plus 200 g pelleted feed, or 450 g pelleted feed only. Ponies were conditioned to each treatment for 7 days and received Pronutrin and pellets or only pellets once daily during the feed deprivation protocol. Gastroscopy was performed at the beginning and conclusion of the feed deprivation protocol. The endoscopist (MJ.M.) was blinded as to treatments, and lesion severity was scored on a scale of 0-5. Gastroscopy revealed normal-appearing gastric mucosa at the beginning of feed deprivation, with the exception of 2 ponies which had focal squamous mucosal erosion and 1 pony with focal glandular mucosal erosion. After 72 h cumulative feed deprivation, each pony, except 1 pony in one of the trials, developed erosions or ulcers in the gastric squamous mucosa. There was no difference (P = 0.6) in the presence or severity of gastric lesions between treatments. Lesions did not develop in the gastric glandular mucosa as a result of the intermittent feed deprivation with either treatment. In this study, the pectin-lecithin complex in Pronutrin failed to prevent lesions in the gastric squamous mucosa induced by intermittent feed deprivation.  相似文献   

12.
The purpose of this experiment was to study the duration and distribution of equine influenza virus in actively infected ponies over a 3 wk period. Pony foals (6-8 mo old) were infected experimentally by nebulizing equine influenza subtype-2 virus ultrasonically through a face mask. Successful infection was clinically apparent as each of the foals (n = 6) had a febrile response, a deep hacking cough and mucopurulent nasal discharge for 7 to 10 d. The virus was isolated from nasopharyngeal swabs of all the ponies 3 and 5 d after infection and all the ponies seroconverted to the virus. Samples were taken from the nasopharynx, mid-trachea and the mainstem bronchus with cytology brushes through an endoscope as well as from bronchoalveolar lavage fluid. On days 3 to 7 post-infection, ciliacytophtorea (the presence of cilia and ciliated plates separated from columnar epithelial cells) was recognized on routine cytological stain. Indirect immunoperoxidase staining utilizing polyclonal antibodies demonstrated viral antigen in intact and fragmented ciliated epithelial cells and in fragments of ciliated plates. The infected cells and cell fragments were particularly evident on days 3 and 5 post-infection in the nasopharynx, mid-trachea and mainstem bronchus and on days 3 to 7 post-infection in the bronchoalveolar lavage samples. On days 7 and 21 post-infection, viral antigen was identified in vacuoles of alveolar macrophage-like cells collected by bronchoalveolar lavage. It can be concluded from this study that equine influenza virus can infect not only the upper airways but also the bronchial epithelium and that viral antigen can persist up to 21 d post-infection.  相似文献   

13.
Growth factors are important in healing and restoration of injured gastrointestinal tissues and, therefore, we characterised temporally the distribution and density of epidermal growth factor receptor (EGFr) in normal and peptic-injured gastric squamous epithelium of horses. Lesions were induced in the equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Fifteen mature horses, 9 geldings and 6 mares, age 3 to 20 years, were used and divided into 3 groups: Group 1 (n = 5) were subjected to euthanasia for problems unrelated to the gastrointestinal tract and had normal-appearing gastric squamous mucosal epithelium; Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for a total of 48 h and 96 h, respectively. Following lethal injection of a barbiturate, stomachs were removed and fixed by filling with 4- 6 l 10% buffered formalin. Sections were made from normal stomachs and lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. A modified avidin-biotin immunoperoxidase technique was used to stain the formalin-fixed tissue specimens for EGFr. A computerised image analysis system was used to measure area occupied by EGFr (EGFr area) and mean EGFr density in 4 zones within the epithelium extending from the basal cell layers toward the lumen. Measurements were made of epithelium in an erosion bed, at the margin of an ulcer or erosion, and 10-15 mm distant from the lesion margin. Additionally, EGFr area and density were measured in epithelial cells adjacent to capillaries in the epithelium. Intermittent feed deprivation resulted in erosion and ulceration of the gastric squamous epithelium of each horse. Mean EGFr area and density were greatest (P<0.05) in the basal layer of epithelia from all horses, and EGFr staining diminished progressively toward the lumen. Tissues from Group 3 had significantly greater EGFr area in the lesion margin than epithelia from Group 2. EGFr density was less in the epithelia of erosion beds from Groups 2 and 3 compared to normal epithelium, and EGFr area in Group 2 erosion bed epithelia was significantly less than in normal epithelium and epithelia of Group 3. EGFr area in cells adjacent to epithelial capillaries of Group 3 was significantly greater than that of Group 1. Mitotic cell activity was significantly greater in epithelia associated with ulcers and erosions in Groups 2 and 3 compared to normal tissues from Group 1 horses. Staining for EGFr in the glandular mucosa adjacent to squamous epithelium at the margo plicatus was inconsistent and typically faint when present. EGFr distribution in equine gastric squamous epithelium was greatest in regions of greatest cell proliferation, and these areas were in the basal layers of epithelium and immediately adjacent to capillaries. There was evidence that EGFr is induced in peptic-injured equine gastric squamous epithelium. A receptor ligand, EGF or transforming growth factoralpha, may be a factor in healing of gastric squamous mucosal ulcers in horses. Further research should be directed at identifying this ligand and determining its origin in equine gastric mucosa.  相似文献   

14.
Histological changes in the small intestine of 85 ovine fetuses were studied, with particular reference to the mucosa. In 24-day-old fetuses the endoderm of the intestine consisted of a single layer of epithelium. By the 26th day the epithelium was flattened and stratified. The first evidence of rudimentary villus formation was noted in 39-day-old fetuses. Intestinal glands were first observed at 56 days. Other mucosal structures were present by 101 days. At birth the intestinal mucosa was fully mature.  相似文献   

15.
C57BL/6N mice were treated to induce tolerance, to modulate the mixed function oxidase system or to deplete glutathione (GSH) before injection with 400 mg 3-methylindole (3MI)/kg. Effect of pretreatment was determined by histologic comparison of pulmonary and nasal lesions 24 hours after 3MI. beta-Naphthoflavone and 3MI pretreatment significantly decreased 3MI-induced bronchiolar epithelial damage in male and female mice, while phenobarbital protection was significant only in female mice. Only beta-naphthoflavone decreased nasal olfactory epithelial damage. Pretreatment with piperonyl butoxide, SKF 525-A, or alpha-naphthoflavone had no significant effect on development of lesions. Diethylmaleate pretreatment significantly increased mortality and bronchiolar damage in both sexes. Significant differences between male and female mice were not detected in any group. The results suggest that pretreatment with low doses of 3MI or induction of cytochrome P-448 or P-450 protects against 3MI toxicosis while GSH depletion increases mortality and pulmonary lesions.  相似文献   

16.
Perilla ketone was assessed for its usefulness as a model of equine restrictive pulmonary disease. Three ponies were given 18 mg/kg bodyweight synthetic perilla ketone in dimethyl sulphoxide. Within 24 h of administration, respiratory rate, peak inspiratory and expiratory flow rates and minute volume were increased. By 48 h there was a significant decrease in tidal volume, and blood pH and base excess were also decreased but not outside normal limits. At necropsy there was congestion and oedema of the lungs. Histologically there was diffuse alveolar injury but no evidence of significant obstruction in bronchial or bronchiolar lumina. It is assumed that perilla ketone toxicity in ponies produces a restrictive disease without a significant obstructive component.  相似文献   

17.
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18.
OBJECTIVE: To determine effects of reactive oxygen metabolites (ROMs), with and without flunixin meglumine, on equine right ventral colon (RVC) in vitro. ANIMALS: 18 healthy horses and ponies. PROCEDURES: In 3 groups of 6 animals each, short-circuit current and conductance were measured in RVC mucosa in Ussing chambers. The 3 groups received physiologic saline (0.9% NaCl) solution, IV, 10 minutes before euthanasia and tissue incubation in Krebs-Ringer-bicarbonate (KRB) solution; flunixin meglumine (1.1 mg/kg, IV) 10 minutes before euthanasia and tissue incubation in KRB solution; or physiologic saline solution, IV, 10 minutes before euthanasia and incubation in KRB solution with 2.7 x 10(5)M flunixin meglumine. Incubation conditions included control (no addition) and ROM systems, including addition of 1 mM xanthine and 80 mU of xanthine oxidase (to produce the superoxide radical), 1 mM H(2)O(2), and 1 mM H(2)O(2) and 0.5 mM ferrous sulfate (to produce the hydroxyl radical). RESULTS: All ROMs that were added or generated significantly increased the short-circuit current except in tissues coincubated with flunixin meglumine, and they induced mild epithelial vacuolation and apoptosis, but did not disrupt the epithelium nor change conductance, lactate dehydrogenase release, or [(3)H]mannitol flux. CONCLUSIONS AND CLINICAL RELEVANCE: Responses to ROMs could be attributed to increased chloride secretion and inhibited neutral NaCl absorption in equine RVC, possibly by stimulating prostaglandin production. The ROMs examined under conditions of this study could play a role in prostaglandin-mediated colonic secretion in horses with enterocolitis without causing direct mucosal injury.  相似文献   

19.
This investigation examines the histological and ultrastructural lesions of the colonic mucosa during terminal experimental infarction and subsequent reperfusion. Four ponies were anaesthetised and subjected to surgical torsion of the colon. Biopsies were collected at hourly intervals for 3 h, at which point the torsions were corrected. Circulation was re-established for 2 h and the bowel was re-biopsied at hourly intervals. The ponies were killed while under anaesthesia. During the 3 h experimental infarction, the bowel became macroscopically thickened and dark purple. Histologically, the mucosa degenerated from Grade 0 to Grade 3. Ultrastructurally, there was progressive micro-vascular distension with erythrodiapedesis and damage to the interstitial cells. Spaces developed between the bases and sides of the columnar epithelial cells and sloughing followed subsequently. During the 2 h reperfusion interval, the mucosa continued to degenerate rapidly to a Grade 5, and was characterised by extensive interstitial damage, oedema, cellular swelling, necrosis and mitochondrial damage. The results showed that the experimentally infarcted colonic mucosa degenerated sequentially. Following circulatory reestablishment, continued rapid mucosal degeneration characteristic of reperfusion injury occurred. Reperfusion injury is probably responsible, at least in part, for the often poor outcome of infarcted bowel in horses following surgical correction.  相似文献   

20.
3-methylindole was administered orally and intravenously to horses and ponies in order to determine the ability of this chemical to provide a model of equine pulmonary disease. Both routes produced a severe and sometimes fatal pulmonary disease, characterised by bronchiolitis. Clinical signs developed 48 to 72 h after dosing and were most severe between Days 4 and 10 post dosing. Intravenous administration of 3-methylindole produced lung injury more rapidly and at a lower dose rate than the oral route. It is suggested that the respiratory condition induced by this chemical could become a method for standardisation of lung function techniques and interpretation in equine obstructive pulmonary disease.  相似文献   

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