Effect of Suplatast Tosilate on Antileukotriene Non-Responders with Mild-to-Moderate Persistent Asthma

ABSTRACTBackgroundImmunomodulatory therapy has been recently introduced for the management of asthma. Suplatast tosilate (ST), a new immune-modifying drug, is known to improve the airway function by inhibiting the release of Th-2 cytokines. However, its efficacy as a controller listed in the guideline, Global Initiative for Asthma 2005 has not been established. In this study we investigated the role of ST in leukotriene receptor antagonist (LTRA) non-responders with mild-to-moderate persistent asthma before initiating corticosteroids inhalation therapy.MethodsThis was a prospective open-level clinical trial. LTRAs was given to 41 patients with asthma for 4 weeks and clinical efficacy was assessed using daily symptom scores. The 10 patients, aged 2.5-8.5 years, who failed to show clinical improvement, were defined as LTRA non-responders. After a 1-week washout period, the efficacy of ST was investigated and compared with LTRA non-responders for the following 4 weeks.ResultsLTRA non-responders showed a significant improvement in the average symptom score, peak expiratory flow, use of rescue medication and the proportion of symptom-free days with ST therapy.ConclusionsST is a good choice for patients who have failed to respond to LTRAs. ST should therefore be added to the list of treatment options for such patients

Spatial Distribution of Drifted-wood Hazard following the July 2017 Sediment-hazards in the Akatani river, Fukuoka Prefecture, Japan

In recent years, heavy rainfall leading to floods, landslides and debris-flow hazards have had increasing impacts on communities in Japan, because of climate change and structural immobilism in a changing and ageing society. Decreasing rural population lowers the human vulnerability in mountains, but hazards can still leave the mountain to the plains and sea, potentially carrying drifted-wood. The aim of the paper is to measure the distribution of wood-debris deposits created by the 2017 Asakura disaster and to rethink the distribution and spatial extension of associated disaster-risk zoning. For this purpose, the authors: (1) digitized and measured the distribution of drifted-wood, (2) statistically analyzed its distribution and (3) calculated the potential impact force of individual drifted timber as a minimal value. The results have shown that there is a shortening of the wood debris as they travel downstream and that the geomorphology has an important control over deposition zones. The result of momentum calculation for different stems’ length show spatially differentiated hazard-zones, which limit different disaster-risk potentials. From the present finding, we can state that we (1) need to develop separate strategies for sediments and wood debris (2) and for wood hazards, zonations can be generated depending on the location and the size of the deposited trees that differs spatially in a watershed

Psychological Reactance to Mobility Restrictions Due to the COVID-19 Pandemic: A Japanese Population Study

In Japan, mobility restrictions were enforced by the government to abate the spread of COVID-19. The current study examined whether experiences of such mobility restrictions affected motivation for future going-out activities. To this end, we conducted a one-time online survey of 1,000 adults in Tokyo to measure going-out activities in four different time periods at once: before the spread of infection, during and after the emergency declaration, and after the end of the pandemic (future desire). In addition, to examine the impact of preferences for online services that make it easier to stay home, we measured the usage history of online services to obtain food during the mobility restriction period. Results indicated that desire for going-out activities after the end of the pandemic increased compared with those before the pandemic, particularly for leisure-related purposes. In addition, the use of online services to obtain food tended to suppress the increased desire for future going-out activities, although this effect was not significant. In conclusion, mobility restrictions resulted in motivational arousal for going-out activities after the end of the pandemic. Our findings indicate that psychological reactance plays a role in determining going-out activities in the future

Integrated Evaluation of Soil Carbon Budget by Manure Application on Forage Production

Grasslands and forage crop fields produce forages and also have many services and functions such as repositories of biodiversity, climate regulation and soil conservation (Sala and Paruelo, 1997). Carbon budget is one of these important ecosystem services by high levels of carbon sequestration below ground (Hungate et al., 1997). Manure application increases carbon budget and also affects forage production, NO3- leaching to underground water and N2O emission to atmosphere. Integrated evaluation of these various environmental impacts is important to find optimum condition for forage production and environmental impacts. LIME2 (Life-cycle Impact assessment Method based on Endpoint modeling 2, Itsubo and Inaba, 2010) is one of the methods to evaluate environmental impacts and to integrate them into a single index of environmental damages with the unit of Japanese yen. By comparing this index to economic benefit of forage production, integrated evaluation of environmental damages and profit of farmers is achieved. In this study, the effects of manure application to forage production, carbon budget, NO3- leaching and N2O emission were evaluated and optimum level of manure application level was estimated with LIME2 integration factors

Comparative proteomic analysis of Salmonella enterica serovar Typhimurium ppGpp-deficient mutant to identify a novel virulence protein required for intracellular survival in macrophages

<p>Abstract</p> <p>Background</p> <p>The global ppGpp-mediated stringent response in pathogenic bacteria plays an important role in the pathogenesis of bacterial infections. In <it>Salmonella enterica </it>serovar Typhimurium (<it>S</it>. Typhimurium), several genes, including virulence genes, are regulated by ppGpp when bacteria are under the stringent response. To understand the control of virulence genes by ppGpp in <it>S</it>. Typhimurium, agarose 2-dimensional electrophoresis (2-DE) combined with mass spectrometry was used and a comprehensive 2-DE reference map of amino acid-starved <it>S</it>. Typhimurium strain SH100, a derivative of ATCC 14028, was established.</p> <p>Results</p> <p>Of the 366 examined spots, 269 proteins were successfully identified. The comparative analysis of the wild-type and ppGpp⁰mutant strains revealed 55 proteins, the expression patterns of which were affected by ppGpp. Using a mouse infection model, we further identified a novel virulence-associated factor, STM3169, from the ppGpp-regulated and <it>Salmonella</it>-specific proteins. In addition, <it>Salmonella </it>strains carrying mutations in the gene encoding STM3169 showed growth defects and impaired growth within macrophage-like RAW264.7 cells. Furthermore, we found that expression of <it>stm3169 </it>was controlled by ppGpp and SsrB, a response regulator of the two-component system located on <it>Salmonella </it>pathogenicity island 2.</p> <p>Conclusions</p> <p>A proteomic approach using a 2-DE reference map can prove a powerful tool for analyzing virulence factors and the regulatory network involved in <it>Salmonella </it>pathogenesis. Our results also provide evidence of a global response mediated by ppGpp in <it>S. enterica</it>.</p

Thiamine tetrahydrofurfuryl disulfide promotes voluntary activity through dopaminergic activation in the medial prefrontal cortex

A physically active lifestyle is associated with better health in body and mind, and it is urgent that supporting agents for such lifestyles be developed. In rodents, voluntary locomotor activity as an active physical behavior may be mediated by dopaminergic neurons (DNs). Thiamine phosphate esters can stimulate DNs, and we thus hypothesized that thiamine tetrahydrofurfuryl disulfide (TTFD), a thiamine derivative, promotes locomotor activity via DNs in rats. Acute i.p. administration of TTFD enhanced rat locomotor activity in a normal cage. In vivo microdialysis revealed that TTFD-enhanced locomotor activity was synchronized with dopamine release in the medial prefrontal cortex (mPFC). Antagonism of the dopamine D1 receptor, but not D2 receptor, in the mPFC fully suppressed TTFD-enhanced locomotor activity. Finally, we found a TTFD dose-dependent increase in voluntary wheel running. Our findings demonstrate that DNs in the mPFC mediates TTFD-enhanced locomotor activity, suggesting the potential of TTFD to induce active physical behavior

Umbilical Cord Blood as an Alternative Source of Reduced-Intensity Hematopoietic Stem Cell Transplantation for Chronic Epstein-Barr Virus–Associated T or Natural Killer Cell Lymphoproliferative Diseases

AbstractChronic Epstein-Barr virus–associated T/natural killer cell lymphoproliferative diseases represented by chronic active Epstein-Barr virus infection are lethal but are curable with several courses of chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Recently, we reported that reduced-intensity conditioning (RIC) provided better outcomes than myeloablative conditioning because RIC was less toxic. However, it was unclear whether cord blood transplantation (CBT) works in the context of RIC. We retrospectively analyzed 17 patients who underwent RIC followed by bone marrow transplantation (RIC-BMT) and 15 patients who underwent RIC followed by CBT (RIC-CBT). The representative regimen was fludarabine and melphalan based. The overall survival rates with RIC-BMT and RIC-CBT were 92.9% ± 6.9% and 93.3% ± 6.4%, respectively (P = .87). One patient died of lung graft-versus-host disease after RIC-BMT, and 1 patient died of multiple viral infections after RIC-CBT. Although cytotoxic chemotherapy was also immunosuppressive and might contribute to better donor cell engraftment after RIC-HSCT, the rate of engraftment failure after RIC-CBT was still higher than that after RIC-BMT (not significant); however, patients who had experienced graft failure were successfully rescued with a second HSCT. Unrelated cord blood can be an alternative source for RIC-HSCT if a patient has no family donor

The inhibitory effects of a RANKL-binding peptide on articular and periarticular bone loss in a murine model of collagen-induced arthritis: a bone histomorphometric study

Showing the effects of OP3-4 on the proliferation and differentiation of cartilage cell line ATDC5. A Results of proliferation assay on day 1 with the noninduction medium. B Alcian blue-positive area ratio in the cartilage induction medium on day 10. **p <0.01 vs. vehicle control, #p <0.05 vs. 100 ÎźM OP3-4. (JPEG 384 kb