Allergic rhinitis a chronic inflammatory disease of the upper airways that has a major impact on the quality of life of patients and is a socio-economic burden. Understanding the underlying immune mechanisms is central to developing better and more targeted therapies. The inflammatory response in the nasal mucosa includes an immediate IgE-mediated mast cell response as well as a latephase response characterized by recruitment of eosinophils, basophils, and T cells expressing Th2 cytokines including interleukin (IL)-4, a switch factor for IgE synthesis, and IL-5, an eosinophil growth factor and on-going allergic inflammation. Recent advances have suggested new pathways like local synthesis of IgE, the IgE-IgE receptor mast cell cascade in on-going allergic inflammation and the epithelial expression of cytokines that regulate Th2 cytokine responses (i.e., thymic stromal lymphopoietin, IL-25, and IL-33). In this review, we briefly review the conventional pathways in the pathophysiology of allergic rhinitis and then elaborate on the recent advances in the pathophysiology of allergic rhinitis. An improved understanding of the immune mechanisms of allergic rhinitis can provide a better insight on novel therapeutic targets.
Basophils ; Chemokines ; Cytokines ; Eosinophils ; Epithelial Cells ; Humans ; Immunoglobulin E ; Inflammation ; Interleukin-5 ; Interleukins ; Mast Cells ; Nasal Mucosa ; Quality of Life ; Rhinitis, Allergic ; T-Lymphocytes

PURPOSE: The pathogenesis of nasal polyposis (NP) is unclear. Eosinophils and mast cells are considered to play important roles in this process. In addition, the levels of Th2-type cells are increased, irrespective of the atopic status of the patient with NP. In this context, we and others have shown high levels of thymus and activation-related chemokine/CCL17, macrophage-derived chemokine, eotaxin, and RANTES in patients with NP. Forkhead box P3 (FOXP3) plays a key role in CD4+CD25+ regulatory T-cell function and represents a specific marker for regulatory T cells (Tregs). Decreased expression of FOXP3 has been reported in allergic diseases. The present study was designed to evaluate the presence and potential roles of Tregs, defined by the expression of FOXP3 protein, in NP. METHODS: Using immunohistochemistry, we estimated the numbers of FOXP3+ cells in the epithelium and lamina propria of the NPs of 17 patients with chronic rhinosinusitis with NP and the nasal mucosa of 15 patients with allergic rhinitis (AR). The number of FOXP3+ cells in NPs was compared with that in the nasal mucosa of patients with AR, and the numbers of FOXP3+ cells in atopic and non-atopic NP were also compared. RESULTS: The number of FOXP3+ cells in the lamina propria of patients with NP was significantly lower than that in the nasal mucosa of the AR patients (2.79 vs. 5.99, P=0.008). There was no statistically significant difference noted for the numbers of FOXP3+ cells between the epithelium of the NP and the nasal mucosa (3.60 vs. 2.39, P=0.180). Furthermore, the numbers of CD4+FOXP3+ cells were lower in NPs than in the allergic nasal mucosa. There was no difference in the number of FOXP3+ cells between the atopic and non-atopic NP patients. CONCLUSIONS: Fewer Tregs (i.e., decreased FOXP3 expression) are found in NPs than in the nasal mucosa of AR patients. As the severity of eosinophilic, Th2-type inflammation and the levels of inflammatory mediators are much higher in NPs than in the nasal mucosa of AR patients, an inverse co-relationship may exist between these parameters and the number of Tregs. The deficiency of Tregs in NP may account for the more pronounced Th2-type inflammation seen in these patients.
Chemokine CCL22 ; Chemokine CCL5 ; Eosinophils ; Epithelium ; Humans ; Immunoglobulin E ; Immunohistochemistry ; Inflammation ; Mast Cells ; Mucous Membrane ; Nasal Mucosa ; Rhinitis ; Rhinitis, Allergic, Perennial ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Thymus Gland

PURPOSE: Nasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. Previous studies have shown elevated levels of thymic stromal lymphopoietin (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and its potential role in nasal polyposis. METHODS: Messenger RNA expression for TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining and nasal polyp tissue IgE, by ELISA. RESULTS: Messenger RNA expression for TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells, endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and nasal polyps. The number of TSLP+ cells was significantly greater in the nasal mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from atopics was significantly greater than that of non-atopics and that in the allergic nasal mucosa. The number of TSLP+ cells correlated well with the number of eosinophils and the levels of IgE in nasal polyps. CONCLUSIONS: The high expression of TSLP in nasal polyps and its strong correlation to eosinophils and IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by regulating the Th2 type and eosinophilic inflammation.
Asthma ; Chemokine CCL17 ; Chemokine CCL22 ; Cytokines ; Dermatitis, Atopic ; Endothelial Cells ; Eosinophils ; Epithelial Cells ; Fibroblasts ; Goblet Cells ; Humans ; Immunoglobulin E ; Immunohistochemistry ; Inflammation ; Lymphocytes ; Mast Cells ; Models, Animal ; Nasal Mucosa ; Nasal Polyps ; Real-Time Polymerase Chain Reaction ; Rhinitis ; Rhinitis, Allergic, Perennial ; RNA, Messenger

To administer oral anticancer drugs safely, the simple suspension method has been introduced in many hospitals. Therefore, concerning drugs for which it is unclear whether or not this method is applicable, testing must be able to be conducted at any time. In this study, we investigated 20 oral anticancer drugs to expand information on the application of the simple suspension method. Disintegration/suspension and permeability tests were conducted, as described in the 3rd version of the Tube Administration Handbook for Oral Drugs. All products were disintegrated/suspended after 10 minutes. On permeability tests, there was no residue in any tube for tubal feeding. On the final evaluation, the products were regarded as suitable (grade 1). Bicalutamide tablets (80 mg, TCK and KN), which were analyzed in this study, were regarded as suitable (grade 1) on the final evaluation. On the other hand, the simple suspension method is not applicable for a brand-name drug, Casodex^® tablets (80 mg). This may be related to the different additives. Furthermore, the results suggest that, even when the simple suspension method is not applicable for a brand-name drug, it may become applicable for generic drugs. This may provide a new merit for promoting the use of generic drugs.

Placenta previa presents a highest risk to pregnancy, and placenta accreta is the most serious. Placenta accreta requires cesarean delivery and often results in massive obstetric hemorrhage and higher maternal morbidity. Challenges associated with cesarean delivery techniques may contribute to increased maternal blood loss and morbidity rates. Several recent obstetric studies reported the usefulness of transverse uterine fundal incision for managing placenta accreta. We present a case of placenta percreta that was treated by a transverse fundal incision. We successfully avoided cutting through the placenta and helped decrease maternal blood loss. After delivery, the patient underwent a cesarean hysterectomy. Postoperative day 48, she experienced watery discharge and was diagnosed with vaginal fistula. We present our case and review the literature.
Hemorrhage ; Humans ; Hysterectomy* ; Placenta ; Placenta Accreta* ; Placenta Previa ; Pregnancy ; Vaginal Fistula*