• 대한약리학회지
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• 제12권2호
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• pp.1-6
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• 1976

The effects of phenoxybenzamine and other related drugs were studied for their interaction with caerulein on gallbladder contraction in anesthetized animals and isolated gallbladder strips. Cholecystostomy and cystic duct ligation were made on anesthetized dog, cat and pig. Pressure changes of gallbladder were measured by a physiological pressure transducer connected to polygraph recorder. Isolated rabbit gallbladder strips were placed in a muscle chamber containing Locke-Ringer solution maintained at $38^{\circ}C$. The contractile responses were measured by a force-displacement transducer connected to polygraph recorder. Caerulein ($30{\sim}200$ ng/kg i.v.) produced marked contraction of gallbladder in situ and the cholecystokinetic potencies appear in decreasing order; dog, cat and pig. The response of caerulein was abolished by the large doses of phenoxybenzamine (15 mg/kg i.v.) but not affected with dibenamine, phentolamine or tolazoline. Cholecystokinetic effect of methacholine or barium chloride was also partially inhibited by phenoxybenzamine and the effect of caerulein was weakly inhibited intravenous injection of cyclophosphamide or papaverine. In isolated rabbit gallbladder strips, the response of contraction to caerulein were progressively inhibited by pretreatment of phenoxybenzamine along with time exposed. These results lead to the conclusion that phenoxytenzamine may inherently inhibit the contractile response of gallbladder to caerulein, and this effect was not related with ${\alpha}-adrenergic$ receptor blocking action.

• Journal of Microbiology
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• 제43권1호
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• pp.11-16
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• 2005

Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of bronchial asthma. Neovastat, having significant antitumor and antimetastatic properties, is classified as a naturally occurring multifunctional antiangiogenic agent. We evaluated the therapeutic effect of Neovastat on airway inflammation in a mouse model of asthma. BALB/c mice were immunized subcutaneously with ovalbumin (OVA) on days 0, 7, 14, and 21 and challenged with inhaled OVA on days 26, 29, and 31. Neovastat was administrated by gavage (5 mg/kg body weight) three times with 12 h intervals, beginning 30 min before OVA inhalation. On day 32, mice were challenged with inhaled methacholine, and enhanced pause (Penh) was measured as an index of airway hyperresponsiveness. The severity of airway inflammation was determined by differential cell count of bronchoalveolar lavage (BAL) fluid. The MMP-9 concentration in BAL fluid samples was measured by ELISA, and MMP-9 activity was measured by zymography. The untreated asthma group showed an increased inflammatory cell count in BAL fluid and Penh value compared with the normal control group. Mice treated with Neovastat had significantly reduced Penh values and inflammatory cell counts in BAL fluid compared with untreated asthmatic mice. Furthermore, mice treated with Neovastat showed significantly reduced MMP-9 concentrations and activity in BAL fluid. These results demonstrate that Neovastat might have new therapeutic potential for airway asthmatic inflammation.

• 대한본초학회지
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• 제29권6호
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• pp.27-33
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• 2014

Objectives : The aims of this study were to exploring the therapeutic effect of Imperatae Rhizoma Extract(IRE) on Asthma. Methods : To investigate biological modulation activities of IRE, we conducted the cell-based assay whether IRE could regulate T helper 2 cells activity with EL4 T cells and mouse splenocytes, and followed animal study to conform the efficacy of their therapeutic potential on OVA-induced asthmatic mouse. Results : In cell study, IRE suppress the nuclear translocation of GATA binding protein-3 protein in phorbol 12-myristate 13-acetate/Ionomycin-stimulated EL4 T cells and Interleukine(IL)-4, IL-5 and IL-13 production in splenocytes at concentration dependent manner. In animal study, IRE-treated groups both 100mg/ml and 200mg/ml improve airway hypersensitibility reaction(AHR) response to methacholine about 30% and 40% with positive control group. Peritoneal blood analysis reveal that eosinophil number and ovalbumin-specific IgE is reduced by IRE treatment. Cell number of eosinophil is also reduced in bronchoalveolar lavage of IRE group like to peritoneal cell and real time-polymerase chain reaction data show that expression levels of IL-4, IL-5 and IL-13 were down regulated in lung tissue. Finally, histological analysis indicate that IRE protect the bronchial tissue damages through the accumulation of inflammatory cells and collagen, and these effect may be cause by interfering Th2 cells activity. Conclusions : Our data represent that IRE potentiates therapeutic activities to the allergic diseases such as asthma by regulating Th2 cells differentiation.

• Journal of Preventive Medicine and Public Health
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• 제23권3호
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• pp.338-344
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• 1990

This study investigated the symptoms, medical and occupational history of 424 workers of 5 reactive dye Industries in the Inchon area in Korea. The study was performed on March 6 and July 19, 1989. The tests applied to the subjects were : serum total IgE, specific IgE, skin prick test with 7 inhalatory antigens, pulmonary function test, chest X-ray, methacholine test, and bronchoprovocation test. The workers were classified according to these tests into 4 groups (healthy, realtively healthy, need careful medical observation, and occupational asthma), and were compared in terms of the group characteristics and the symptom prevalence. The prevalece of occupational asthma of workers in reactive dye was 5.9% Significant differences were observed among the 4 groups. The groups were significantly different in the variables of sex and duration of smoking among their general characteristics ; and dyspnea, wheezing, chest pain, cough, nasal symptoms and sore throat among symptoms ; asthma, bronchitis, and other respiratory diseases with respect to their past medical history. This study suggests that we should pay special attention to the workers exposed to the risk of occupational asthma.

• Clinical and Experimental Pediatrics
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• 제53권8호
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• pp.795-800
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• 2010

Purpose: B cell-activating factor (BAFF) is a tumor-necrosis factor (TNF) superfamily member best known for its role in the survival and maturation of B cells. BAFF activity is observed in naive cells as well as in effector/memory T cells. We aimed to explore whether BAFF in sputum is expressed at elevated levels in asthmatic airways and associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children. Methods: One hundred and fifty-four asthmatic children and 98 healthy children were enrolled in the study. Sputum supernatants were collected and sputum BAFF and eosinophil cationic protein (ECP) levels were measured. We performed pulmonary function tests and methacholine challenge tests, while measuring total eosinophil count, total serum IgE, and serum ECP in all subjects. Results: Asthmatic children had significantly higher levels of BAFF in induced sputum [26.50 (10.50-100.27) pg/mL] compared to healthy children [18.32 (7.68-44.63) pg/mL; $P$=0.011]. Sputum BAFF positively correlated with sputum eosinophils (${\gamma}$=0.406, $P$<0.001) and sputum ECP (${\gamma}$=0.789, $P$<0.001). Significant negative correlations were found between sputum BAFF and FEV1 (${\gamma}$=-0.291, $P$<0.001) or post-bronchodilator FEV1 (${\gamma}$=-0.334, $P$<0.001), whereas nonsignificant correlations were found between sputum BAFF and bronchial hyperresponsiveness, serum eosinophil count, and serum ECP. Conclusion: These findings suggest that BAFF may play a role in childhood asthma, and BAFF levels in sputum could be a supportive marker that represents airway inflammation, especially eosinophilic inflammation.

• 한국환경보건학회지
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• 제34권2호
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• pp.117-123
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• 2008

Allergic diseases have been dramarically increased over recent years, especially in industrialized countries. Oxidative stress has been believed to playa significant role in the occurrence of the allergic inflammatory responses. Although previous studies concerning oxidative stress and systemic inflammation have been reported, few data is available, and other allergic diseases, except for asthma, are hardly studied about the association with oxidative stress. This study evaluated the relationship between allergic disease and Malondialdehyde (MDA) as an indicator of oxidative stress. The study population was 197 male adults living in an industrial area. The ISAAC questionnaire was used to confirm wheezing and rhinitis, and atopy was evaluated by skin prick test. MDA was analyzed by spectrophotometer. To examine bronchial hyperresponsiveness (BHR), methacholine test was performed, and the index of bronchial responsiveness (BR index) was calculated. We used multivariate logistic regression model and general linear model with SAS program. We found significant associations of MDA with brindex (p=0.023), rhinitis (p=0.016), atopy (p=0.03), adjusted by age, smoking, and body mass index (BMI). On the contrary, there was no significant difference of MDA with the status of asthma. Our result suggests that oxidative stress may playa major role in the occurrence of allergic response in male adults.

• Tuberculosis and Respiratory Diseases
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• 제70권3호
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• pp.235-241
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• 2011

Background: The rising prevalence of asthma may be associated with the rising prevalence of obesity in developed nations. There are several studies showing that obesity increases the risk of asthma in adults. We investigated the association of each body composition scale and bronchial hyper-responsiveness. Methods: This study involved a retrospective review of the existing records for 279 subjects with respiratory symptoms, who underwent a pulmonary function test, a methacholine challenge test and a body composition test between May 2007 and June 2009. Results: Of the 279 subjects, 179 (64%) were female. There was a statistically significant difference in fat free mass and in fat free mass index between the normal bronchial responsiveness group and bronchial hyper-responsiveness group (p=0.036; p=0.000). There was no significant differences in body mass index, in fat mass and fat free mass index in the normal bronchial responsiveness group and bronchial hyper-responsiveness group in males. However in females, body mass index and fat free mass index were increased in the bronchial hyper-responsiveness group (p=0.044; p=0.000). Total body water (kg), fat free mass (kg) and soft lean mass (kg) were significantly different between the normal bronchial responsiveness group and bronchial hyper-responsiveness group (p=0.002; p=0.000; p=0.000). Conclusion: This study showed significant differences in fat free mass and in fat free mass index between the normal bronchial responsiveness group and the bronchial hyper-responsiveness group. In females, BMI, soft lean mass, and total body water showed significant differences between the normal bronchial responsiveness group and the bronchial hyper-responsiveness group. We concluded that bronchial hyper-responsiveness was associated with not only body mass index but also fat free mass index in female bronchial asthma.

• BMB Reports
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• 제45권5호
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• pp.311-316
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• 2012

Sulforaphane (1-isothiocyanato-4-(methylsulfinyl)-butane), belonging to a family of natural compounds that are abundant in broccoli, has received significant therapeutic interest in recent years. However, the molecular basis of its effects remains to be elucidated. In this study, we attempt to determine whether sulforaphane regulates the inflammatory response in an ovalbumin (OVA)-induced murine asthma model. Mice were sensitized with OVA, treated with sulforaphane, and then challenged with OVA. Sulforaphane administration significantly alleviated the OVA-induced airway hyperresponsiveness to inhaled methacholine. Additionally, sulforaphane suppressed the increase in the levels of SOCS-3 and GATA-3 and IL-4 expression in the OVA-challenged mice. Collectively, our results demonstrate that sulforaphane regulates Th2 immune responses. This sutdy provides novel insights into the regulatory role of sulforaphane in allergen-induced Th2 inflammation and airway responses, which indicates its therapeutic potential for asthma and other allergic diseases.

• Journal of Preventive Medicine and Public Health
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• 제40권1호
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• pp.59-63
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• 2007

Objectives : Nitrogen dioxide $(NO_2)$ has been inconsistently associated with gradual decreases in lung function. Here, we studied the effects of $NO_2$ exposure in asthmatics by examining the association between changes in lung function and concentrations of $NO_2$ which were personally measured. Methods : Peak expiratory flow (PEF) and daily personal exposures to $NO_2$ were recorded on 28 patients with asthma (confirmed by methacholine provocation test) over 4 weeks. We used generalized estimating equations to assess the relationship between personal $NO_2$ exposure and PEF, adjusting for potential confounders such as age, gender, outdoor particulate matter, temperature, humidity, and exposure to environmental tobacco smoke. Results : The personal $NO_2$ exposures were higher than the corresponding ambient levels. The mean personal: ambient ratio for $NO_2$ was 1.48. The personal $NO_2$ exposures were not associated with the morning PEF, evening PEF, or the diurnal PEF variability. However, environmental tobacco smoke was negatively associated with both the morning and evening PEF. Conclusions : Among the asthmatic adults who participated in this study, we found no apparent impact of personal $NO_2$ exposures on the peak expiratory flow.

• 약학회지
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• 제36권3호
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• pp.220-229
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• 1992

The muscarinic acetylcholine receptors of the dog unpregant uterus were characterized using $[^3H]quinuclidinyl$ benzilate(QNB) as a radioligand and the binding of muscarinic receptor agonists and antagonists in the uterus was compared to that in the urinary bladder which contains almost exclusively the M2 receptors in order to determine the receptor subtypes in the uterus. $[^3H]QNB$ binding to uterus and bladder was rapid, saturable and reversible. Scatchard analysis of the saturation data gave linear plots and the Hill coefficients were close to unit, which indicated that each preparation contained a single population of specific binding sites for $[^3H]QNB$. The KD values(120 pM) for QNB were almost identical in both organs, whereas the $B_{max}$ value of 256 fmol/mg protein in the uterus was significantly different from that of 563 fmol/mg protein in the bladder. Muscarinic agonists and antagonists inhibited in a competitive manner the $[^3H]QNB$ binding to the same extent in both organs. The competition binding studies using antagonists(atropine and pirenzepine) exhibited a single binding site and this site had a low affinity for pirenzepine with the Ki value of about 330 nM. However, high and low affinity binding sites were observed with carbachol, methacholine and oxotremorine. These binding studies with agonists and antagonists did not show any differences in drug affinities between uterus and bladder. These results indicate that the muscarinic receptors in the uterus are M2 receptors which have a low affinity for pirenzepine.