Experimental study on the effect of olfactory training on olfactory function in mice with olfactory dysfunction / 中华耳鼻咽喉头颈外科杂志

Objective@#To observe the effect of olfactory training on mice with olfactory dysfunction induced by 3-methylindole (3-MI).@*Methods@#Thirty-one male BALB/c mice were randomly divided into 3 groups by random digits table: control group (group A, n=10), olfactory dysfunction group (group B, n=10) and olfactory dysfunction+olfactory training group (group C, n=11). Mice in group B and group C were intraperitoneally injected with 150 mg/kg 3-MI to induce olfactory dysfunction model, while mice in group A were intraperitoneally injected with corn oil of the same volume. From the first day after injection, mice in group C were treated with 4 kinds of odors by inhalation, while mice in group B were treated with distilled water by inhalation, with 2 times/d, 30 min/time/kind of odor, and continuous training for 28 d. Group A was not treated. Buried food pellet tests were conducted before injection and at 7, 14, 21 and 28 days after injection, respectively. The olfactory epithelium was harvested for observation of the number of olfactory marker protein (OMP) and the thickness of olfactory epithelium on the 28th day after injection. SPSS 23.0 software was used for statistical analysis.@*Results@#Before injection, all mice in each group had no olfactory dysfunction. At the 7th, 14th, 21st and 28th days after injection, the food finding time of mice in group C was shorter than that in group B, and the difference was statistically significant ((175.88±100.50) s vs (266.73±46.83) s, (132.00±84.62) s vs (264.10±48.50) s, (103.57±77.43) s vs (197.43±69.78) s, (67.79±32.54) s vs (176.63±61.06) s, all P<0.05), but food finding time of mice in group B and C was longer than that in group A (the food finding time of group A at the 7th, 14th, 21st and 28th days after injection was (27.13±5.36) s, (25.83±7.28) s, (23.13±2.72) s, (26.63±7.60) s, respectively, all P<0.05). At the 28th day after olfactory training, the number of OMP positive cells in group B and C were fewer than that in group A, and the difference was statistically significant ((108.00±28.19)/HP vs (288.22±84.06)/HP, (199.33±58.55)/HP vs (288.22±84.06)/HP, all P<0.05). The number of OMP positive cells in group C were higher than that in group B (P<0.05). The number of OMP positive cells had negative correlation with food finding time (r=-0.886, P<0.01). As for the thickness of the olfactory epithelium, the thickness of group B was thinner than that in group A and C, and the difference was statistically significant ((59.57±31.27) μm vs (114.55±40.70)μm vs (90.54±37.72) μm, all P<0.05).@*Conclusion@#Olfactory training can accelerate the recovery of olfactory function in 3-MI-induced olfactory impaired mice.

Experimental study on the effect of olfactory training on olfactory function in mice with olfactory dysfunction / 中华耳鼻咽喉头颈外科杂志

To observe the effect of olfactory training on mice with olfactory dysfunction induced by 3-methylindole (3-MI). Thirty-one male BALB/c mice were randomly divided into 3 groups by random digits table: control group (group A, 10), olfactory dysfunction group (group B, 10) and olfactory dysfunction+olfactory training group (group C, 11). Mice in group B and group C were intraperitoneally injected with 150 mg/kg 3-MI to induce olfactory dysfunction model, while mice in group A were intraperitoneally injected with corn oil of the same volume. From the first day after injection, mice in group C were treated with 4 kinds of odors by inhalation, while mice in group B were treated with distilled water by inhalation, with 2 times/d, 30 min/time/kind of odor, and continuous training for 28 d. Group A was not treated. Buried food pellet tests were conducted before injection and at 7, 14, 21 and 28 days after injection, respectively. The olfactory epithelium was harvested for observation of the number of olfactory marker protein (OMP) and the thickness of olfactory epithelium on the 28th day after injection. SPSS 23.0 software was used for statistical analysis. Before injection, all mice in each group had no olfactory dysfunction. At the 7th, 14th, 21st and 28th days after injection, the food finding time of mice in group C was shorter than that in group B, and the difference was statistically significant ((175.88±100.50) s (266.73±46.83) s, (132.00±84.62) s (264.10±48.50) s, (103.57±77.43) s (197.43±69.78) s, (67.79±32.54) s (176.63±61.06) s, all 0.05), but food finding time of mice in group B and C was longer than that in group A (the food finding time of group A at the 7th, 14th, 21st and 28th days after injection was (27.13±5.36) s, (25.83±7.28) s, (23.13±2.72) s, (26.63±7.60) s, respectively, all 0.05). At the 28th day after olfactory training, the number of OMP positive cells in group B and C were fewer than that in group A, and the difference was statistically significant ((108.00±28.19)/HP (288.22±84.06)/HP, (199.33±58.55)/HP (288.22±84.06)/HP, all 0.05). The number of OMP positive cells in group C were higher than that in group B (0.05). The number of OMP positive cells had negative correlation with food finding time (=-0.886, 0.01). As for the thickness of the olfactory epithelium, the thickness of group B was thinner than that in group A and C, and the difference was statistically significant ((59.57±31.27) μm (114.55±40.70)μm (90.54±37.72) μm, all 0.05). Olfactory training can accelerate the recovery of olfactory function in 3-MI-induced olfactory impaired mice.

Acute and chronic bovine pulmonary edema and emphysema in Uruguay / Edema e enfisema pulmonar agudo e crônico em bovinos do Uruguai

An outbreak of pulmonary edema and emphysema with acute and chronic cases is reported in a farm in Uruguay. In a herd of 40 Hereford steers, 20 died. The deaths began four days after a change of paddock, from an old pasture of Avena sativa to a lush growing pasture of the same grass. Acutely affected animals showed severe dyspnea, sialorrhea, cough, and subcutaneous edema, and died within 72 hours. Chronically affected steers showed dyspnea, respiratory noises, weight loss, and intolerance to exercise. The deaths began four days after the change of paddock. Ten days after the first death, the steers were withdrawn from the pasture, but continued dying throughout the following 40 days. Twenty animals died and six were necropsied. Grossly, the lungs were diffusely armed and glistening, with reddish and crepitant cut surface, and presented alveolar septae sharply distended by edema and emphysema. There was subpleural emphysema with air blebs distributed across the pleural surface. Presence of Dictyocaulus viviparus was observed in three steers. In some animals, the trachea was diffusely reddish with presence of pink foam; in some others, there was bloody liquid in the tracheal lumen. Histologic examination showed severe diffuse alveolar and interstitial emphysema, hyaline membranes adhered to the alveolar wall, thickening of the interlobular septae with proliferation of type II pneumocytes, and moderate-to-severe multifocal histiocytic, neutrophilic and eosinophilic infiltrate. In the trachea, there was submucosal hemorrhage and moderate multifocal eosinophilic and lymphocytic infiltrate. The steers with chronic signs presented similar lung lesions, but multifocal pulmonary fibrosis and cardiac dilatation were also observed. The diagnosis of acute bovine pulmonary emphysema and edema (ABPE) was based on the occurrence of the disease after introduction of the herd in a lush green pasture, on the characteristic gross and histologic lesions, and on the absence of other toxic or infectious agents causing similar lesions. Cattle raisers should be alert to the risks of occurrence of this disease after the introduction of the herds into paddocks with green and lush pastures.(AU)

Descreve-se um surto de edema e enfisema pulmonar com casos agudos e crônicos em bovinos em uma criação semi-intensiva no Uruguai. De um lote de 40 novilhos da raça Hereford morreram 20. As mortes começaram quatro dias após uma mudança de alimentação, de uma pastagem mais velha de Avena sativa, para uma pastagem recentemente plantada de aveia que estava em brotação. Os animais afetados apresentaram sinais clínicos agudos de dispneia, sialorreia, tosse e alguns desenvolveram edema subcutâneo, morrendo em até 72 horas. Outros novilhos mais cronicamente afetados apresentaram dispneia, ruídos respiratórios, perda de peso e intolerância ao exercício. As mortes começaram quatro dias após a mudança de pastagens. Dez dias após a primeira morte, os novilhos foram retirados do pasto, mas morreram ainda durante 40 dias mais. Ao total, morreram vinte animais e seis foram necropsiados. Nas necropsias dos animais mortos na fase aguda os pulmões estavam difusamente armados e brilhosos e ao corte de coloração avermelhada e crepitante, com os septos alveolares acentuadamente distendidos por edema e enfisema. Havia enfisema subpleural caracterizado por bolhas de ar distribuídas pela superfície pleural. Em três bovinos havia ainda presença de Dictyocaulus viviparus. Alguns animais apresentaram a traqueia difusamente avermelhada com espuma de coloração rósea ou liquido sanguinolento livre na luz traqueal. Histologicamente havia edema e enfisema alveolar e intersticial difuso severo, membranas hialinas espessas aderidas à parede alveolar, espessamento dos septos interlobulares com proliferação de pneumócitos tipo II e infiltrado inflamatório histiocítico, neutrofílico e eosinofílico multifocal moderado a severo. Na traqueia havia hemorragias na submucosa e infiltrado eosinofílico e linfocítico multifocal. Os novilhos com sinais crônicos apresentaram lesões pulmonares semelhantes, entretanto, foram observadas também, fibrose pulmonar multifocal e dilatação cardíaca. O diagnóstico de EEPAB baseou-se na ocorrência da doença após a introdução do rebanho em uma pastagem viçosa em brotação, nas características macroscópicas e histológicas e na ausência de outros agentes tóxicos ou infecciosos que causam lesões semelhantes. Se alerta para os riscos da ocorrência desta enfermidade, quando houver mudanças de pastagens.(AU)

Mouse Model for the Research of Sinusitis Induced Olfactory Dysfunction / 대한이비인후과학회지

Olfactory dysfunction is one of the most debilitating problem in chronic rhinosinusitis (CRS) patients, and exact mechanism underlying sinusitis induced olfactory dysfunction was not fully understood. In vivo manipulation for olfactory epithelium and fresh specimen for histopathological analysis are essential for research, but it is nearly impossible to do in human due to inaccessibility of olfactory epithelium and risk for complication. For this reason, several animal models using toxic materials, such as 3-methylindole or bromomethane, have been suggested for mimicking olfactory epithelial damage in CRS, but none of them could truly imitate the event which happens in real patient. Inducible olfactory inflammation (IOI) mouse is a transgenic mouse model selectively producing tumor necrosis factor-alpha (TNF-alpha) in sustentacular cell of olfactory epithelium. The production of TNF-alpha can be actively initiated by giving food containing doxycycline to IOI mouse, and inflammation is stopped in the absence of doxycycline. Both toxicity model and transgenic model have their own advantages and disadvantages, therefore appropriate model should be selected for optimal results.

Effect of Systemic Steroid on the Olfactory Epithelium Injured by 3-Methylindole in Mice

BACKGROUND AND OBJECTIVES: Various chemicals can affect the function of olfaction and steroids have been used for the treatment of olfactory dysfunction. In this study, we investigated the effect of chronic dexamethasone treatment on olfactory epithelium injured by 3-methylindole (3-MI). SUBJECTS AND METHODS: 0.75 mg/kg of dexamethasone and 0.15 mL of normal saline were administered to each of the 12 mice belonging to the experimental and control group respectively every other day from 1 week, before a single intraperitoneal administration of 175 mg/kg 3-MI, to 4 weeks after 3-MI injection. Three mice from each group were sacrificed every week, and olfactory epithelium was examined after H & E and immunohistochemical staining. RESULTS: On H & E staining, the height of the olfactory epithelium and the polarity of the cells showed no difference between the two groups. On olfactory marker protein (OMP) staining, the number of OMP-immunoreactive (IR) olfactory receptor cells was significantly increased in the experimental groups from 2 and 4 weeks after 3-MI injection compared with the control group. On proliferating cell nuclear antigen (PCNA) staining, PCNA-IR basal cells were significantly reduced in groups that received dexamethasone from 2 weeks to 3 weeks after injection compared with the control group. CONCLUSION: Dexamethasone shows no protective effect in early necrosis of olfactory epithelium by 3-MI, but showed positive effect on the regeneration of the olfactory receptor cells of olfactory epithelium.

Effect of Systemic Steroid on the Olfactory Epithelium Injured by 3-Methylindole in Rats / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Various chemicals can affect the function of olfaction and steroids have been used for the treatment of the olfactory dysfunction. In this study, we investigated the effect of chronic dexamethasone treatment on olfactory epithelium injured by 3-methylindole (3-MI). MATERIALS AND METHOD: 0.75 mg/kg of dexamethasone were administered to 12 experimental rats every other day for 1-4 weeks, following a single intraperitoneal administration of 150 mg/kg 3-MI at the first week. Three rats from each group were sacrificed every week, and olfactory epithelium were examined after H & E and immunohistochemical staining. RESULTS: On H & E staining, the height of the olfactory epithelium and the polarity of the cells showed no difference. On protein gene product 9.5 staining, the number of immunoreactive olfactory receptor cells significantly increased in the experimental groups from 2 and 4 weeks after 3-MI injection compared with the control group. On proliferating cell nuclear antigen staining, immunoreactive basal cells were significantly reduced in groups that received dexamethasone from 2 weeks to 3 weeks after injection compared with the control group. CONCLUSION: Dexamethasone shows no protective effect in early necrosis of olfactory epithelium by 3-MI and showed positive effect on the regeneration of the olfactory receptor cells of olfactory epithelium.

A Study on Recovery from Smell Dysfunction Induced by 3-Methylindole in Rats

BACKGROUND AND OBJECTIVES: Evaluating the olfactory function is as important in animal research as morphological study. However, it is difficult to gauge the smell function in rats because of the underdevelopment of current electrophysiologic measuring devices. The aim of this study is to assess changes in smell dysfunction induced by 3-methylindole (3-MI) in rats using an 8-odor olfactometer. MATERIALS AND METHOD: Eight female Sprague-Dawley rats were used. Ethyl acetate at 10(-4.0) (v/v) concentration was used as an S+ odorant, and six different concentrations (10 (-4.0), 10(-4.5), 10(-5.0), 10(-5.5), 10(-6.0), 10(-6.5)) of butanol mixed with ethyl acetate were used as an S- odorant. S+ and S- stimuli were delivered randomly using the 8-odor olfactometer. After injection of 3-MI at a dosage of 300 mg/kg, mixed odor discrimination test was performed for five weeks. RESULTS: Normal rats were able to discriminate ethyl acetate from ethyl acetate mixed with butanol to a concentration down to 10(-6.2) (v/v). Immediately after the 3-MI injection, the rats lost all capacity for smell. From 16 days later, the smell function began improving spontaneously. At the end of the fifth week, the discrimination threshold was 10(-5.7) (v/v), which was almost equal to the original level. CONCLUSIONS: Systematically administered 3-MI caused smell loss in rats. Though not completely, the smell function was recovered spontaneously. An olfactometer is a reliable and accurate device in evaluating the olfactory function in rats.