Background: The center for international relations was established in 2007 and it has organized a program for accepting international students for short periods since 2009 to enhance internationalization at the medical school.

Methods: The number of inbound and outbound students, and the number of overseas medical schools with an Academic Agreement and a Memorandum of Understanding with our institution from 2008 to 2013 were counted, and the relevant achievements were evaluated.

Results: The number of inbound students increased from 0 in 2008 to 14 in 2013, and the number of outbound students also increased from 1 in 2008 to 12 in 2013. The number of overseas medical schools with an Academic Agreement and a Memorandum of Understanding also increased from 1 to 3. The number of scholarship applications to go overseas also increased from 2 to 12.

Discussion: Organizing a well-established program for inbound students probably contributed to developing the international environment within the school for both inbound and outbound students, and to enhancing discussion of student exchange with potential partner universities. The center for international relations has functioned as a hub for the students and relevant departments by centralizing information, which has markedly communication improved.

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

Introduction: There has been no case report in which hyperpigmentation developed on the skin area where a transdermal fentanyl patch was applied in a patient. Case report: A 43-year-old man with recurrence of postoperative rectal cancer was treated by cetuximab plus irinotecan and panitumumab plus FOLFIRI. For cancer pain, transdermal fentanyl patch (Fentos®) was administered, and radiation from behind was performed. Hyperpigmentation then appeared on the chest and the abdominal skin sites where the patches were applied. The hyperpigmentation nearly disappeared four months after the fentanyl patch was discontinued. Discussion: The cause of the pigmentation was possibly due to post inflammatory hyperpigmentation secondary to contact dermatitis. It was desirable to conduct patch test and skin biopsy for making an accurate diagnosis. Conclusion: We should pay a careful attention to hyperpigmentation of the skin where a transdermal fentanyl patch is applied.

PURPOSE: Allergic rhinitis (AR) and asthma share many characteristics, but structural changes are observed far less often in AR. Matrix metalloproteinases (MMPs) constitute a family of Zn-dependent endopeptidases that can decompose the extracellular matrix and basement membrane, and regulate cell infiltration. We analyzed the expression of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in allergic nasal mucosa after nasal allergen challenge (NAC) and determined their relationship to inflammatory cells. METHODS: Nasal mucosa specimens were obtained at surgery performed for hypertrophied turbinates. We performed NAC with house dust mite (HDM) allergen disks and control disks, and took biopsies at 30 minutes, 6 hours, and 12 hours after NAC. Cells expressing MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, as well as eosinophils and mast cells, were analyzed immunohistochemically. The MMPs and TIMPs in allergic nasal mucosa were quantified using enzyme-linked immunosorbent assays. RESULTS: At 30 minutes post-NAC, HDM-exposed nasal mucosa exhibited significantly more MMP-2+, MMP-9+, MMP-13+, TIMP-1+, and TIMP-2+ cells compared with control mucosa, and the numbers of MMP-9+ and TIMP-1+ cells correlated strongly with the number of mast cells. At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa. At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils. Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa. CONCLUSIONS: We demonstrated increased expression of MMP-2, MMP-9, and MMP-13 in allergic nasal mucosa, high MMPs-to-TIMP-1 ratios, and a strong correlation between MMP-9 and mast cells and between MMP-13 and eosinophils. The imbalance between MMPs and TIMPs may contribute to the migration of inflammatory cells such as eosinophils and mast cells to the nasal mucosa of AR patients, suggesting a possible active role of MMPs in AR.
Asthma ; Basement Membrane ; Biopsy ; Endopeptidases ; Eosinophils ; Extracellular Matrix ; Humans ; Mast Cells ; Matrix Metalloproteinases ; Metalloproteases ; Mucous Membrane ; Nasal Mucosa ; Pyroglyphidae ; Rhinitis ; Rhinitis, Allergic, Perennial ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2 ; Turbinates

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

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

OBJECTIVEThe purpose of this study is to delineate the association between residents' perception of the neighborhood's environments and walking time in objectively different regions in Japan.

METHODSTwo regions were selected as high and low walkable regions on the basis of differences in their residential density, mixed land use and street connectivity. The subjects in this study were participants in a health promotion program focused on walking sponsored by local governments. A questionnaire was sent to the participants asking about how their perception of the neighborhood's environment related to walking, and the time spent walking per week. There were 237 residents from the high walkable region and 195 from the low walkable region who completed the study survey.

RESULTSThe high walkable region had a larger residential density, a high mixed land use and a higher street connectivity than the low walkable region. Walking time, and the scores of the perception of the neighborhood's environment for the high walkable region residents were significantly higher than those for the low walkable region residents. Thus, residents' perception of the neighborhood's environment generally reflected the actual physical environmental characteristics. Residents in the high walkable region whose scores for accessibility and aesthetics were high, spent significantly more walking time. Residents in the low walkable region whose scores for accessibility, safety, convenience and aesthetics were high, spent significantly more walking time.

CONCLUSIONThe study results suggested that the neighborhood's environment may influence daily walking time. The perceptions of the neighborhood's environmental factors that correlate with walking times differ between the different regional physical environments. Therefore, to promote physical activity, the consideration of environmental factors unique to residents' neighborhood's environments is needed.

Purpose: The objective of this study was to investigate whether body fat rate (BFR) and triceps skinfold thickness (TSF) are associated with estimated fentanyl absorption in patients treated with the fentanyl transdermal matrix patch for moderate to severe cancer pain, by measuring the residual content of fentanyl in used matrix patches. Methods: Adult Japanese inpatients experiencing chronic cancer-related pain and receiving treatment for the first time with a transdermal fentanyl matrix patch (Durotep®MT patch) were included in the present study. During the initial application period, BFR was measured using a body fat scale, and TSF was measured by an experienced nurse with an adipometer. One patch was collected from each patient. The residual fentanyl content in used matrix patch was determined by high-performance liquid chromatography. The transdermal fentanyl delivery efficiency was estimated based on the fentanyl content of the used matrix patches. Results: Fifteen adult patients (5 males and 10 females) were included in this study. Nine patches with a release rate of 12.5μg/h and 6 patches with a release rate of 25μg/h were collected. The application site was the chest or upper arm. BFR and TSF both showed a significant positive correlation with delivery efficiency. Conclusion: In malnourished or low-body fat patients receiving DMP, pain intensity should be more carefully monitored, and fentanyl dose adjustment may be required. Additional parameters, such as nutritional status including body fat change, the degree of dry skin, and plasma fentanyl concentration, also require detailed evaluation. Palliat Care Res 2010; 5(2): 206-212

This study used topographic near-infrared spectroscopy (NIRS) to characterize frontal lobe activation while individuals actively or passively listened to exciting or calm music. Participants were 22 healthy female volunteers (mean age, 21± 4.1 years). Initial analysis showed that oxy-Hb significantly decreased in many channels when subjects listened to calm music. In contrast, oxy-Hb significantly increased when subjects listened to lively music. In addition, after listening to calm music, cortisol, α-amylase, and immunoglobulin A significantly decreased. A subsequent analysis showed that oxy-Hb signif-icantly increased when subjects listened to music while clapping to its rhythm compared with when subjects listened to music only. Our study suggests that calm music reduces levels of human stress and enables effective relaxation. In addition, our data suggests that clapping to the rhythm of music increases brain activation. Therefore, active music therapy may be more effective than passive music therapy with respect to brain activation. Such active therapy (i.e., playing rather than listening to music) may improve functional and psychological status, and cooperative abilities.

Objective: In this study, we conducted a questionnaire survey of hospital pharmacists throughout Japan with the aim of identifying the most-requested in-hospital preparations and off-label use drugs, and exploring the possibility of commercializing them.Methods: The Commercialization Study Group of the Japanese Society of Hospital Pharmacists conducted a questionnaire survey on the Japanese Society of Hospital Pharmacists website targeting hospital pharmacists who are members of the Japanese Society of Hospital Pharmacists. The period of the survey was from February 1, 2019 until January 21, 2020. In the questionnaire, the respondents wrote specific product names (generic names), specifications, and dosage forms that they would like to see improved and made commercially available in a free-text format. In addition, respondents chose their reasons for wanting the product to be improved or made commercially available from a list.Results: A total of 1,627 drugs were requested to be made commercially available. After duplicates and insufficient descriptions were excluded, the total was 553. The drugs that were most frequently requested were Levothyroxine suppositories, followed by Mohs’ ointment and Ulinastatin vaginal suppositories.Discussion: This survey identified certain drugs that pharmacists want to be commercialized and the specific reasons why. In-hospital preparations not only benefit patients whose diseases are becoming more complex and difficult to treat with existing prescription drugs, but also enable pharmacists to demonstrate their abilities. We believe that the commercialization of these important in-hospital preparations and off-label drugs will help avoid various risks associated with dispensing them and enhance the pharmacy profession. For this reason, pharmaceutical drug companies should conduct further surveys on the actual use of and literature research on the efficacy and safety of the drugs that were ranked high on the questionnaire and start considering their commercialization.