• Biomolecules & Therapeutics
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• v.10 no.3
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• pp.156-164
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• 2002

In the present study, we tried to investigate whether polymerized basic amino acid e.g. poly-L-lysine (PLL) which has the degree of polymerization under 50mer significantly affects the physiological and stimulated mucin release from cultured hamster tracheal surface epithelial cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^3{H}$-glucosamine for 24 hr and chased for 30 min in the presence of either PLLs or adenosine triphosphate (ATP) and PLL to assess the effects on basic or ATP-stimulated $^3{H}$-mucin release. Possible cytotoxicities of PLLs were assessed by measuring lactate dehydrogenase (LDH) release from HTSE cel1s during treatment. The results were as follows: PLLs significantly inhibited basic mucin release from cultured HTSE cells in a dose-dependent manner from the range of 46mer to 14mer; PLL 46mer significantly inhibited the stimulated mucin release by ATP from cultured HTSE cells; there was no significant release of LDH from cultured HTSE cells during treatment. We conclude that PLLs inhibit both physiological and stimulated mucin release from airway epithelial cells without significant cytotoxicity and PLL lost its activity under the range of 14mer. This finding suggests that polymer of basic amino acid like PLL might function as a regulator for hypersecretion of mucus manifested in various respiratory diseases.

• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.263-269
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• 2001

In this study, we tried to investigate whether poly-L-arginine (PLA) (MW 10,800) significantly affect mucin release from cultured hamster airway goblet cells and the mucosubstances of hypersecretory air-way goblet cells of rats. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^3$H-glucosamine for 24 hr and chased for 30 min in the presence of varying concentrations of PLA to assess the effects on $^3$H-mucin release. Possible cytotoxicities of PLA were assessed by measuring both Lactate Dehydrogenate (LDH) release and by checking the possible changes on the morphology of HTSE cells during treatment. For in vivo experiment, hyperplasia of rat airway goblet cells and increase in intraepithelial mucosubstances were induced by exposing rats to SO$_2$ for 3 weeks and varying concentrations of PLA were administered inhalationally to assess the effects on the mucosubstances of airway goblet cells of rats. The results were as follows : (1) PLA significantly inhibited mucin release from cultured HTSE cells in a dose-dependent manner; (2) there was no significant release of LDH and no significant change on the morphology of cultured HTSE cells during treatment; (3) PLA also affected the intraepithelial mucosubstances of hypersecretory rats and restored them to the levels of control animals. We conclude that PLA inhibit mucin release from airway goblet cells without significant cytotoxicity and possibly normalize the hypersecretion of airway mucosubstances in vivo. This finding suggests that PLA might function as an airway mucoregulative agent.

• Journal of Yeungnam Medical Science
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• v.40 no.4
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• pp.435-441
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• 2023

Pheochromocytomas and paragangliomas (PPGLs) may secrete hormones or bioactive neuropeptides such as interleukin-6 (IL-6), which can mask the clinical manifestations of catecholamine hypersecretion. We report the case of a patient with delayed diagnosis of paraganglioma due to the development of IL-6-mediated systemic inflammatory response syndrome (SIRS). A 58-year-old woman presented with dyspnea and flank pain accompanied by SIRS and acute cardiac, kidney, and liver injuries. A left paravertebral mass was incidentally observed on abdominal computed tomography (CT). Biochemical tests revealed increased 24-hour urinary metanephrine (2.12 mg/day), plasma norepinephrine (1,588 pg/mL), plasma normetanephrine (2.27 nmol/L), and IL-6 (16.5 pg/mL) levels. ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/CT showed increased uptake of FDG in the left paravertebral mass without metastases. The patient was finally diagnosed with functional paraganglioma crisis. The precipitating factor was unclear, but phendimetrazine tartrate, a norepinephrine-dopamine release drug that the patient regularly took, might have stimulated the paraganglioma. The patient's body temperature and blood pressure were well controlled after alpha-blocker administration, and the retroperitoneal mass was surgically resected successfully. After surgery, the patient's inflammatory, cardiac, renal, and hepatic biomarkers and catecholamine levels improved. In conclusion, our report emphasizes the importance of IL-6-producing PPGLs in the differential diagnosis of SIRS.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.1
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• pp.198-218
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• 2002

On the basis of Imjeungjinamuian(臨證指南醫案), authors investigated the pathogenesis and treatment of ophthalmotolaryngobgic diseases from the viewpoint of Onbyeong(溫病). 1. The symptoms and diseases investigated according to department were as follows;. 1) Ophthalmology : blepharitis, blepharedema, lacrimal hypersecretion, hyperemia, ophthalmalgla, photopsia, visual disturbance, mydriasis 2) Otology : full-feeling, otorrhea, otalgla, mastoiditis, tinnitus, hearing disturbance, vertigo 3) Rhinology : rhinorrhea, nasal obstruction, sinusitis, epistaxis 4) Laryngology : sore throat, hoarseness 5) The Others : headache, cough, asthma 2. The pathogenesis and treatment of ophthalmotolaryngologic diseases were as follows. 1) When the pathogenesis of hyperemia, otorrhea, otalgia, mastoiditis, hearing disturhance. epistaxis, sore throat, headache and cough are wind-stagnanc(風鬱), wind-warm(風溫), wind-fire(風火), wind-dryness(風燥), dryness-heat(燥熱), the treatment of pungent-cool-evaporating(辛凉解表) with Dajosan(茶調散), Mori Folium(桑葉), Lonicerae Flos(金銀花), Forsythiae Fructus(連翹), Viticis Fructus(蔓荊子), Prunellae Spica(夏枯草), Arctii Fructus(牛蒡子), etc can be applied. 2) When the pathogenesis of hoarseness, cough and asthma are cold(寒), cold with endogenous heat(寒包熱, 外冷內熱), water retention(水邪), fluid retention(伏飮), impairment of YangKi by overexertion(勞傷陽氣), the treatment of pungent-warm-evaporating(辛溫解表) with Mahaenggamseoktang(麻杏甘石湯), Socheongryongtang(小靑龍湯), Jeongryeokdaejosapyetang(정력대조사폐탕), Gyejitang(桂枝湯), Armeniacae Amarum Semen(杏仁), etc can be applied. 3) When the pathogenesis of photopsia, otorrhea, otalgia, rhinorrhea, sinusitis, epistaxis, sore throat, hoarseness, headache and cough are stagnancy-induced heat(鬱熱), wind-dryness(風燥), wind-heat(風熱), summer heat(暑熱), summer wind(暑風), insidious summer heat(伏暑), autumn heat(秋暑), autumn wind(秋風), autumn dryness(秋燥), dryness-heat(燥熱), heat in Ki system(氣分熱), insidious warm(溫伏), brain discharge by fire in Ki system(氣火 腦熱), heat in stomach(胃熱), endogenous fire by deficiency of Yin(陰虛內火), deficiency of Yin in stomach(胃陰虛), the treatment of Ki-cooling(淸氣) with Bangpungtongseongsan(防風通聖散), Ikweonsan(益元散), Gyejibaekhotang(桂枝白虎湯), Geumgwemaekmundongtang(금궤맥문동탕), Gyeongokgo(瓊玉膏), Sojae Semen Praeparatum(두시), Scutellariae Radix(黃芩), Phyllostachys Folium(竹葉), Adenophorae Radix(沙參), Mori Cortex(桑白皮), Fritillariae Cirrhosae Bulbus(貝母), etc can be applied. 4) When the pathogenesis of blepharitis, hyperemia, ophthalmalgia, full-feeling, otorrhea, otalgia, tinnitus, hearing disturbance, sinusitis, hoarseness, headache and cough are fire in liver(肝火), fire in gallbladder(膽火), ministerial fire in Soyang system(少陽相火), wind-stagnancy(風鬱), stagnancy-induced fire(鬱火), brain discharge by phlegm-fire(痰火 腦熱), the treatment of mediation(和解) with Gardeniae Fructus(梔子), Moutan Cortex(牧丹皮), Saigae Tataricae Cornu(羚羊角), Artemisiae Annuae Herba(靑蒿), Cyperi Rhizoma(香附子), Poria(적복령), etc can be applied. 5) When the pathogenesis of blepharedema and cough are dampness in both spleen and lung(脾肺濕) damp-heat(濕熱), damp-phlegm(濕痰), the treatment of dampness-resolving(化濕) with Poria(백복령), Coicis Semen(薏苡仁), Tetrapanacis Medulla(通草), Armeniacae Amarum Semen(杏仁), Talcum(滑石), etc can be applied. 6) When the pathogenesis of vertigo and cough are deficiency of Yong(營虛), heat in Yong, system(營熱), the treatment of Yong-cooling(淸營) with Rehmanniae Radix(生地黃), Liriopis Tuber(麥門冬), Biotae Semen(柏子仁), Lilii Bulbus(百合), Phyllostachys Folium(竹葉), etc can be applied. 7) When the pathogenesis of epistaxis are heat in blood system of heart(心血熱), reversed flow of fire(火上逆), overexertion(努力), the treatment of blood-cooling(凉血) with Rhinoceri Cornu(犀角), Rehmanniae Radix(生地黃), Moutan Cortex(牧丹皮), Salviae Miltiorrhizae Radix(丹參), Scrophulariae Radix(玄蔘), etc can be applied. 8) When the pathogenesis of nasal obstruction is pathogen-stagnancy(邪鬱), the treatment of resuscitation(開竅) with Sosang(少商, LU11) acupuncture can be applied. When the pathogenesis of hoarseness is evil Ki(穢濁), the treatment of resuscitation(開竅) with Arctii Fructus(牛蒡子), Lasiosphaera Seu Calvatia(馬勃), Curcumae Radix(鬱金), etc can be applied. When the pathogenesis of headache is stasis of both Ki and blood(氣血瘀痺), the treatment of resuscitation(開竅) with Cnidii Rhizoma(川芎), Asari Herba Cum Radice(細辛), Scorpio(全蝎), moxibustion(灸), etc can be applied. 9) When the pathogenesis of lacrimal hypersecretion, visual disturbance, mydriasis, tinnitus, hearing disturbance, sinusitis, epistaxis, hoarseness and cough are deficiency of Yin(陰虛), deficiency of kidney(腎虛), deficiency of both liver and kidney(肝腎虛), deficiency of both heart and kidney(心腎虛), brain discharge by deficiency of Yin(陰虛 腦熱), exuberance of Yang in liver(肝陽上亢), overexertion(勞損), the treatment of Yin-replenishing(滋陰) with Yukmijihwanghwan(六味地黃丸), Hojamhwan(虎潛丸), Jeobutang(猪膚湯), Lycii Fructus(枸杞子), Polygoni Multiflori Radix(何首烏), Rehmanniae Radix(生地黃), Schizandrae Fructus(五味子), Liriopis Tuber(麥門冬), Asini Gelatinum(阿膠), etc can be applied. 10) When the pathogenesis of ophthalmalgia, mydriasis, vertigo and headache are deficiency of Yin in liver(肝陰虛), exuberance of Yang in liver(肝陽上亢), endogenous wind(內風), excess in upper and deficiency in lower part(上實下虛), the treatment of Yin-replenishing(滋陰) and endogenous wind-calming(熄風) with Rehmanniae Radix Preparat(熟地黃), Lycii Fructus(枸杞子), Polygoni Multiflori Radix(何首烏), Paeoniae Radix Alba(白芍藥), Ostreae Concha(牡蠣), Saigae Tataricae Cornu(羚羊角), Chrysanthemi Flos(菊花), etc be applied. 11) When the pathogenesis of mydriasis, sinusitis, hoarseness, headache, cough and asthma are exhaustion of vital essence(精氣無收藏), brain discharge(腦髓不固), floating Yang(陽虛浮), exsanguination(失血), deficiency of both Yin and Yang(陰陽不足), overexertion(勞損), deficiency of Yang in kidney(腎陽虛), the treatment of Yang-restoring and exhaustion-arresting(回陽固脫) with Yangyeongtang(養營湯), Cheonjinhwan(天眞丸), Bokmaektang(복맥탕), Geonjungtang(建中湯), Dogihwan(都氣丸), Singihwan(腎氣丸), Jinmutang(眞武湯), Ostreae Concha(牡蠣), Nelumbinis Semen(蓮子肉), etc can be applied. 12) When the pathogenesis of lacrimal hypersecretion, vertigo and headache are deficiency of stomach and endogenous wind(胃虛內風), endogenous wind with phlegm(內風挾痰), liver check of stomach(肝木橫擾), the treatment of concomitant-treating of both liver and stomach(肝胃同治) with Paeoniae Radix Alba(白芍藥), Uncariae Ramulus Et Uncus(釣鉤藤), Gastrodiae Rhizoma(天麻), Astragali Radix(황기), Pinelliae Rhizoma(半夏), etc can be applied. When the pathogenesis of asthma is failure of kidney to promote inspiration(腎不納氣), the treatment of kidney-tonifing and inspiration-promoting(補腎納氣) with Singihwan(腎氣丸), Psoraleae Fructus(補骨脂), Juglandis Semen(胡桃), Aquilariae Resinatum Lignum(沈香), etc can be applied. When the pathogenesis of asthma is deficiency of Ki(氣虛), the treatment of Ki-reinforcing(補氣) with Sagunjatang(四君子湯), Insamgeonjungtang(人參建中湯), etc can be applied.

• Journal of the Korea Institute of Military Science and Technology
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• v.16 no.2
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• pp.218-224
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• 2013

Organophosphorus compounds are irreversible inhibitors of cholinesterase enzyme. Exposure causes a progression of toxic signs, including hypersecretion, tremor, convulsion, respiratory distress, epileptiform seizure, brain injuries and death. To protect brain injuries, administration of diazepam as a neuroprotectant is now considered essential for severely exposed nerve agent casualties. However, studies have shown diazepam to provide less than total protection against the neuropathological consequences of nerve agent exposure. In this context, extensive studies have been carried out to find out effective alternative drugs to protect brain from epileptiform seizures induced by organophosphate compounds intoxication. It has been reported that a combination of carbamate and anticholinergic or antiglutamatergic can be a very effective medical countermeasure in dealing with the threat of organophosphorous poisoning. In this study, experimental animals including rats and guinea pigs were implanted with microelectrodes on their brain sculls, and treated with various centrally acting drugs such as physostigmine and procyclidine prior to soman challenge, and then its electroencephalography(ECoG) was monitored to see anticonvulsant effects of the drugs. It was found that seizure activities in ECoG were not always in proportion to clinical signs induced by soman intoxication, and that combinative pretreatment with physostigmine plus procyclidine effectively stopped the seizures induced by organophosphorous poisoning.

• Tuberculosis and Respiratory Diseases
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• v.80 no.1
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• pp.60-68
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• 2017

Background: Mucus hypersecretion from airway epithelium is a characteristic feature of airway inflammatory diseases. Tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) regulates mucin synthesis. Glucocorticoids including mometasone fuorate (MF) have been used to attenuate airway inflammation. However, effects of MF on mucin production have not been reported. Methods: Effects of MF and budesonide (BUD) on the phorbol-12-myristate-13-acetate (PMA)-induction of mucin and TNF-${\alpha}$ in human airway epithelial cells (NCI-H292) were investigated in the present study. Confluent NCI-H292 cells were pretreated with PMA (200 nM) for 2 hours. Subsequently, the cells were stimulated with MF (1-500 ng/mL) or BUD (21.5 ng/mL) for 8 hours. Dexamethasone ($1{\mu}g/mL$) was used as the positive control. Real-time polymerase chain reaction was used to determine MUC2 and MUC5AC mRNA levels. The level of total mucin, MUC2, MUC5AC, and TNF-${\alpha}$ in culture supernatants were measured using enzyme-linked immunosorbent assay. Results: MF and BUD significantly suppressed MUC2 and MUC5AC gene expression in PMA-stimulated NCI-H292 cells. The inhibitory effects of the two steroid drugs were also observed in the production of total mucin, MUC2 and MUC5AC proteins, and TNF-${\alpha}$. Conclusion: Our findings demonstrated that MF and BUD attenuated mucin and TNF-${\alpha}$ production in PMA-induced human airway epithelial cells.

• Applied Microscopy
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• v.20 no.1
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• pp.51-64
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• 1990

This experiment was performed to study the morphological changes of the goblet cells in the rabbit duodenal mucosa after common bile duct ligation. Healthy adult rabbits weighting about 2kg body weight were divided to normal and bile duct ligated groups. Common bile duct ligation was performed under ether anesthesia. Experimental animals were sacrificed on the 1st, 3rd, 5th, 7th and 14th day after the operation. Mucosal specimens from the upper part of duodenum were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde, followed by 1% osmium tetroxide, embedded in araldite mixture, cut with LKB-V ultratome, stained with uranyl acetate - lead citrate, and observed with JEM 100 CX II electron microscope. Observed results were as follow : 1. In the early stages(1st-5th day) of the experiments, the goblet cells showed apocrine and merocrine secretion. But those of the late stage(7th and 14th day) groups showed exocytotic merocrine secretion. 2. In the late stage of the experiments, there found than increase of newly formed goblet cells that contain electron lucent cytoplasms. 3. In the goblet cells of normal rabbit, mucous granules with higher or lower electron densities are found together in the cytoplasm, and electron lucent mucous granules occasionally fused together. But in the early stage of the common bile duct ligation, goblet cells contained granules of higher electron densities. 4. Considering the above findings, common bile duct ligation probably initiates the hypersecretion of mucous granules of goblet cells in the early stage, and may facilitate the differentiation of goblet cells in the later stage.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.685-695
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• 2009

Objectives : In this study, the author tried to investigate whether Geonpye-tang(GPT) significantly affects PMA-, EGF- or TNF-alpha-induced MUC5AC mucin production and gene expression from human airway epithelial cells. Materials and Methods : Effects of the agent on PMA-, EGF- or TNF-alpha-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of GPT and treated with PMA (10ng/ml) or EGF (25ng/ml) or TNF-alpha (0.2nM), to assess both effect of the agent on PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production by enzyme-linked immunosorbent assay (ELISA) and gene expression by reverse transcription-polymerase chain reaction (RT-PCR). Possible cytotoxicity of the agent was assessed by examining the rate of survival and proliferation of NCI-H292 cells after treatment with the agent over 72 hrs (SRB assay). Results : (1) GPT significantly inhibited PMA-induced and EGF-induced MUC5AC mucin production from NCI-H292 cells. However, GPT did not affect TNF-alpha-induced MUC5AC mucin production. (2) GPT significantly inhibited the expression levels of PMA-, EGF- or TNF-alpha-induced MUC5AC genes in NCI-H292 cells (3) GPT did not show significant cytotoxicity to NCI-H292 cells. Conclusion : This result suggests that GPT can affect the production and gene expression of respiratory mucin observed in diverse respiratory diseases accompanied by mucus hypersecretion. This can explain the traditional use of GPT in oriental medicine. Effects of GPT with their components should be further investigated using animal experimental models that reflect pathophysiology of airway diseases through future studies.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.18 no.2
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• pp.108-112
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• 2007

Otolaryngological manifestations of acid reflux include a wide range of pharyngeal and laryngeal symptoms ; and the constellation of symptoms has been called laryngopharyngeal reflux (LPR). In the absence of definite diagnostic criteria, LPR disease remains a subjective entity. A diagnosis of LPR is usually based on response of symptoms to empirical treatment. Investigative modalities such as pH monitoring and, more recently, impedance studies are generally reserved for treatment failures. LPR usually requires more aggressive and prolonged treatment to achieve regression of both symptoms and laryngeal findings. The suppression of gastric acid and secretion with anti-secretary agents has been the mainstay of medical treatment for patients with acid-related disorders. The suppression of gastric acid secretion achieved with Hz-receptor antagonist $(H_2RA)$ has proved suboptimal for relief of reflux symptoms. The rapid development of tolerance and rebound acid hypersecretion after the with-drawal of $H_2RA$ limit their clinical use. Proton pump inhibitors (PPI) have been proved to be very effective for suppressing intragastric acidity, but the optimal dose and duration is unknown. Current evidence indicates that pharmacologic intervention should include, at a minimum, a 3 month trial of twice daily PPI. Symptoms of LPR improve over 2 months of therapy. The physical findings of LPR resolve more slowly than the symptoms and this continues through out at least 6 months of treatment. For most patients with LPR, twice daily dosing with a PPI is usually recommended for an initial treatment for a period of no less than 6 months treatment, and lifetime treatment may be required.

• Toxicological Research
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• v.24 no.4
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• pp.253-261
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• 2008

Allergic asthma is a worldwide public health problem and a major socioeconomic burden disease. It is a chronic inflammatory disease marked by airway eosinophilia and goblet cell hyperplasia with mucus hypersecretion. Mouse models have proven as a valuable tool for studying human asthma. In the present report we describe a comparison of mouse asthma models. The experiments were designed as follows: Group I was injected with ovalbumin (OVA, i.p.) on day 1 and challenged with 1% OVA (aerosol exposure) on days $14{\sim}21$. Group II was injected on day 1, 14 and aerosol-immunized on days $14{\sim}21$. Group III was injected on day 1, 14 and immunized by 1% OVA aerosol on days $18{\sim}21$. We assessed asthma induction by determining the total number of white blood cells (WBC) and eosinophils as well as by measuring cytokine levels in bronchoalveolar lavage fluid (BALF). In addition, we evaluated the histopathological changes of the lungs and determined the concentration of immunoglobulin E (IgE) in serum. Total WBC, eosinophils, Th2 cytokines (IL-4, IL-13) and IgE were significantly increased in group I relative to the other groups. Moreover, histopathological studies show that group I mice show an increase in the infiltration of inflammatory cell-in peribronchial and perivascular areas as well as an overall increase in the number of mucus-containing goblet cells relative to other groups. These data suggest that group I can be a useful model for the study of human asthma pathobiology and the evaluation of existing and novel therapeutic agents.