Byakkokaninjinto (BN) is a Kampo preparation used for the treatment of xerostomia induced by drug, ageing, Sjogren syndrome, etc. The mechanism for BN to induce salivary secretion has not been made ...clear. In this study, various rat thirst models were prepared using muscarinic receptor blockers, such as 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) and atropine, or adrenoceptor blockers, such as phentolamine and propranolol, in order to investigate the efficiency of BN. When BN was orally administered to the rats in the dose range of 100 to 300 mg/kg, the salivary secretion increased in a dose-dependent manner. The suppression of salivary secretion induced by phentolamine, atropine, and 4-DAMP was recovered by the additional treatment of BN. Interestingly, BN treatment increased the expression of aquaporin 5 in rats, which is known to regulate salivary secretion from the submandibular gland. These results suggested that BN increased the expression of aquaporin 5 through activation of muscarinic M3 receptor and enhanced salivary secretion.
Abstract Recognition systems employed by airway epithelial cells to respond to microbial exposure include the action of Toll-like receptors (TLRs). We investigated the presence and function of TLR2, ...3, and 4 in primary cultures of human nasal polyp epithelial cells. dsRNA stimulation significantly enhanced the expression and secretion of RANTES, IP-10, IL-8, and GM-CSF. LPS also exhibited stimulatory action, but it was much weaker than dsRNA. Peptidoglycan had no significant stimulatory action on the genes. Flow cytometry showed that the nasal polyp epithelial cell mainly expressed TLR3 in an intracellular compartment, but expression of TLR2 and TLR4 was very low on both the cell surface and in the cell. The immune response of primary nasal polyp epithelial cells induced by TLR3 could not be blocked by anti-TLR3 antibody. Among the TLR ligands evaluated, dsRNA, the ligand for TLR3, mediated the strongest pro-inflammatory effects in primary nasal polyp epithelial cells.
Glucocorticoids (GCs) bind to the cellular glucocorticoid receptors (GRs) to exert anti-inflammatory and immunosuppressive actions. We investigated the changes in the expressions of the two GR ...isoforms, GR-alpha and GR-beta, in nasal polyps treated with GC. Immunofluorescent staining revealed prominent expression of GR-alpha in the inflammatory cell infiltrate in the polyps obtained from patients with chronic sinusitis and bronchial asthma. Furthermore, while the expression of GR-alpha was significantly reduced following GC treatment, that of GR-beta remained unchanged. The results of real-time PCR also revealed that the prominent expression of GR-alpha mRNA in the polyps decreased following GC treatment, while the expression of GR-beta mRNA remained unchanged. The observations indicate that GR-alpha may play the major role in the inflammation associated with nasal polyps and the ratio of the expression level of GR-beta to that of GR-alpha may serve as a useful index of the clinical efficacy of GC treatment.
Conclusion: The significant up-regulation of matrix metalloproteinase (MMP)-9 mRNA, which is not modulated by tissue inhibitor of metalloproteinase (TIMP)-1, is an additional source of increased ...proteolytic activity in virus-infected upper airways that might contribute to the exacerbation of chronic rhinosinusitis with nasal polyps. Objectives: Chronic rhinosinusitis is often exacerbated by viral infection. We hypothesized that a disruption of the mechanisms that regulate the activity of MMPs during viral infection is one possible mechanism responsible for the exacerbation. In the present study we attempted to achieve a better understanding of MMP expression in nasal epithelial cells after viral infection. Materials and methods: Human nasal epithelial cells were isolated from nasal polyp specimens obtained during endoscopic endonasal surgery in chronic rhinosinusitis patients. We investigated the expression of MMP-2, MMP-9, and TIMP-1 mRNA in primary human nasal polyp epithelial cells after dsRNA stimulation. Results: Among the genes whose expression was evaluated, only expression of MMP-9 mRNA increased significantly after dsRNA stimulation.
Abstract Objective In Japan, fourteen-membered ring macrolides, antibacterial agents, and S-carboxymethylcysteine (SCMC; carbocisteine), a mucolytic, are commonly used to treat chronic rhinosinusitis ...(CRS), and they are also used in combination. However, no large-scale randomized study has examined the effects of these pharmacotherapies. The aim of this study is to evaluate the effect of combined administration of clarithromycin (CAM), a fourteen-membered ring macrolide, and SCMC, compared with CAM single therapy. Methods Patients with CRS were centrally registered and randomly assigned to treatment with CAM (200 mg/day) alone (monotherapy group) or CAM (200 mg/day) in combination with SCMC (1500 mg/day; combination group) for 12 weeks. We assessed the clinical efficacy of the treatments using measures of subjective symptoms and objective findings, health-related quality of life (HRQOL) determined by the 20-Item Sino-Nasal Outcome Test (SNOT-20) score and computed tomography (CT) score. Results Four hundred twenty-five subjects were enrolled (combination group, 213; monotherapy group, 212). At week 12 of treatment, the rate of effectiveness was significantly higher in the combination group (64.2%) compared with the monotherapy group (45.6%; P = 0.001). In addition, objective findings, including characteristics of nasal discharge ( P = 0.008) and post-nasal discharge ( P = 0.002) were significantly improved in the combination group. In both groups, SNOT-20 and CT scores were significantly improved from week 0 ( P < 0.001), and were not significantly different between groups. Conclusion The results indicated that long-term combination therapy with SCMC at a dose of 1500 mg/day and CAM at a dose of 200 mg/day is effective for improving subjective symptoms and objective findings in adult patients with CRS.
Abstract Objective The objective of this study was to assess the reliability and validity of a Japanese version of the 20-Item Sino-Nasal Outcome Test SNOT-20, which is one of the quality-of-life ...(QOL) evaluation sheets for chronic rhinosinusitis (CRS), and assess its reliability and validity. Methods The SNOT-20 was conducted in patients with CRS and in healthy volunteers. The response rate was evaluated as the feasibility of this test, and reliability and internal consistency were assessed as reliability. In addition, concurrent validity and discriminant validity were assessed as validity. Results Regarding the feasibility of this test, the response rate for each question item in the SNOT-20 was nearly 100% for all 20 items. For reliability, test–retest reliability was r = 0.890 and the internal consistency was α = 0.903. For validity, the concurrent validity was r = 0.162 when compared with objective findings in the nasal cavity, and was r = 0.431 when compared with the score for general physical condition, which evaluate the patient's general condition. Discriminant validity was significantly higher in patients with CRS than in healthy volunteers ( p < 0.001). Moreover, when the discriminant validity was assessed using an ROC (receiver operating characteristic) curve, it was found that ROC-AUC (the area under the curve) = 0.775. Conclusion The reliability and validity of a Japanese version of the SNOT-20 were assessed in this study. It is thought that the SNOT-20 serves as a useful QOL evaluation sheet for CRS.
Tranilast is an anti‐allergic agent that blocks the release of chemical mediators, such as histamine and leukotrienes from mast cells, and has been reported to suppress keloid and hypertrophic scar ...formation. Since matrix metalloproteinases (MMPs) play an essential role in tissue remodelling, this study was undertaken to determine whether tranilast suppresses MMP production from neutrophils after lipopolysaccharide (LPS) stimulation in‐vitro. Neutrophils from five healthy donors (1times105 cells/mL) were stimulated with 1.0 μg mL−1 LPS in the presence or absence of various concentrations of tranilast for 24 h. MMP‐7, MMP‐8, MMP‐9 and tissue inhibitor of metalloproteinase (TIMP)‐1 levels in the culture supernatants were assayed by ELISA. In addition, the influence of tranilast on MMP mRNA expression and transcriptional factor activation in cells cultured for 12 h and 4 h was also evaluated by reverse transcriptase—polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA), respectively. Tranilast inhibited MMP and TIMP‐1 production from neutrophils when cells were treated with the agent at more than 5.0times10−5 m. It also suppressed MMP mRNA expression and transcriptional factor activation induced in neutrophils by LPS stimulation. The results suggest that tranilast inhibits the formation of keloid scarring through the suppression of factors such as MMPs and TIMP, which are essential for tissue remodelling, from inflammatory cells.
Abstract Carcinoid tumors arise from neuroendocrine cells, many of which are present in the digestive tract and lungs. There have been few reports of carcinoid tumors occurring in the nose and ...paranasal sinus area, and they are very rare. We encountered a patient with a carcinoid tumor that arose in the nose and paranasal sinuses, and we report the case with a review of the literature. The patient was a 75-year-old woman who began to experience right-sided nasal obstruction, and when her nose began to bleed on the right-side she was examined in our department. A tumor lesion that easily bled and had filled the right nasal cavity was observed. CT revealed a mass lesion with a marked contrast enhancement in the right nasal cavity, ethmoid sinus, and sphenoid sinus, and MRI showed numerous flow voids in the interior that seemed to be tumor blood vessels. The tumor was excised through a lateral rhinotomy. The histopathological diagnosis was a carcinoid tumor. Tumor recurrence was subsequently detected in the vicinity of the opening of the sphenoid sinus, and because the tumor was tending to grow larger, the tumor was resected. The patient has been followed up in the outpatient clinic, recurrence-free.
Low-dose and long-term administration of 14-membered macrolide antibiotics, so called macrolide therapy, has been reported to favorably modify the clinical conditions of chronic airway diseases. ...Since there is growing evidence that macrolide antibiotic-resistant bacteria's spreaders in the populations received macrolide therapy, it is strongly desired to develop macrolide antibiotics, which showed only anti-inflammatory action. The present study was designed to examine the influence of clarithromycin (CAM) and its metabolized materials, M-1, M-4 and M-5, on free radical generation from nasal polyp fibroblasts (NPFs) through the choice of nitric oxide (NO), which is one of important effector molecule in the development of airway inflammatory disease in vitro.
NPFs (5 × 105 cells/ml) were stimulated with 1.0 μg/ml lipopolysaccharide (LPS) in the presence of agents for 24 hours. NO levels in culture supernatants were examined by the Griess method. We also examined the influence of agents on the phosphorylation of MAPKs, NF-κB activation, iNOS mRNA expression and iNOS production in NPFs cultured for 2, 4, 8, and 12 hours, respectively.
The addition of CAM (> 0.4 μg/ml) and M-4 (> 0.04 μg/ml) could suppress NO production from NPFs after LPS stimulation through the suppression of iNOS mRNA expression and NF-κB activation. CAM and M-4 also suppressed phosphorylation of MAPKs, ERK and p38 MAPK, but not JNK, which are increased LPS stimulation. On the other hand, M-1 and M-5 could not inhibit the NO generation, even when 0.1 μg/ml of the agent was added to cell cultures.
The present results may suggest that M-4 will be a good candidate for the agent in the treatment of chronic airway inflammatory diseases, since M-4 did not have antimicribiological effects on gram positive and negative bacteria.
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