ABSTRACT
Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC4, D4 and E4) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.
Subject(s)
Mice , Animals , Respiratory Mucosa/pathology , Receptors, Leukotriene/metabolism , Quinolines/therapeutic use , Pulmonary Fibrosis/pathology , Muscle, Smooth/pathology , Mucus/metabolism , Mice, Inbred BALB C , Lung/pathology , Leukotrienes/biosynthesis , Leukotriene Antagonists/therapeutic use , Hypertrophy , Hyperplasia , Goblet Cells/pathology , Drug Evaluation, Preclinical , Dose-Response Relationship, Drug , Disease Models, Animal , Cysteine/biosynthesis , Collagen/metabolism , Asthma/drug therapy , Anti-Asthmatic Agents/therapeutic use , Airway Obstruction/drug therapy , Acetates/therapeutic useABSTRACT
To investigate etiological role of Epstein-Barr virus [EBV] DNA in breast cancer. Materials and The presence of EBV DNA in 57 breast cancertissues was investigated with a sensitive PCR assay. The breast cancer tissues were from invasive ductular [n = 28], lobular [n = 20] and other miscellaneous carcinomas [n = 9]. Tissues from normal breasts and patients with various benign breast diseases [n = 55]: fibrocystic disease [n = 34], fibroadenoma [n= 16], hyperplasia, and granulomatous mastitis [n = 5], were used as control samples, flesults: EBV DNA was detected in 13 [23%] cancerous tissues [7 ductular, 4 lobular, 2 other carcinoma] and 19 [35%] in the control tissues. The difference between EBV presence in malignant and benign tissues was not statistically significant [p>0.05]. The presence of EBV DNA was detected almost equally in both breast cancer and normal tissues, which indicates no etiological role for EBV in breast cancer. We suggest further etiological studies