Inhibitory Effects of Chlorella Extract on Airway Hyperresponsiveness and Airway Remodeling in a Murine Model of Asthma

Chlorella extract （CE） has been shown to induce production of T helper-1 cytokines, and regulate serum IgE levels in animal models of asthma. We aimed to evaluate whether CE could inhibit ovalbumin （OVA）-induced airway hyperresponsiveness （AHR） and airway remodeling in a murine model of asthma. Balb/c mice were allocated to four groups: a control group （no OVA exposure, not given CE）, a CE group （no OVA exposure, given CE）, an asthma group （sensitized/challenged with OVA, not given CE） and a CE＋asthma group （sensitized/challenged with OVA, given CE）. In the asthma and CE＋asthma groups, mice were sensitized with OVA on day 0 and day 12, and then challenged with OVA on three consecutive days. In the CE and CE＋asthma groups, the mice were given feed containing 2％ CE. We assessed AHR to methacholine, and analyzed bronchoalveolar lavage fluid （BALF）, serum, lung tissue and spleen cells. Administration of CE was associated with significantly lower AHR in OVA-sensitized and challenged mice. CE administration was also associated with marked reduction of total cells, eosinophils and T helper-2 cytokines （IL-4, IL-5 and IL-13） in BALF. In addition, administration of CE significantly decreased the numbers of periodic acid-Schiff （PAS）-positive cells in OVA-sensitized and challenged mice. Administration of CE also directly suppressed IL-4, IL-5 and IL-13 production in spleen cells of OVA-sensitized and challenged mice. These results indicate that CE can partly prevent AHR and airway remodeling in a murine model of asthma

A Comparison of Adverse Effect Profiles of Two Anti-IL-5 Therapies in Adults with Uncontrolled Asthma―A Network Meta-analysis of Phase 3 Trials―

The aim of this study was to compare the adverse effect profiles of mepolizumab（MPZ）and benralizumab（BRZ）in adults with uncontrolled asthma. A network meta-analysis of phase 3 trials was conducted to compare the adverse effects of MPZ and BRZ in patients with uncontrolled asthma. The MEDLINE-PubMed, Scopus and the Cochrane library databases were searched to identify any relevant articles. The outcome measures of fatal adverse events, headache, and injection site reaction are presented as odds ratios（ORs）with 95％ confidence intervals（CIs）. The surface under the cumulative curve（SUCRA）for each outcome was also compared among MPZ, BRZ, and placebo treatments. Four randomized controlled trials of MPZ（100mg s/c every four weeks）（100-MPZ）or BRZ（30mg s/c every eight weeks）（30-BRZ）met the criteria for inclusion in the study. The ORs and 95％ CIs of 100-MPZ compared with BRZ for fatal adverse events, headache, and injection site reaction were 0.26（0.01-4.90）, 0.79（0.40-1.54）, and 2.32（0.79-6.80）, respectively. SUCRAs for 100-MPZ, 30-BRZ, and placebo were 0.8, 0.3, and 0.4 for fatal adverse events, 0.5, 0.1, and 0.8 for headache, and 0.0, 0.6, and 0.8 for injection site reaction, respectively. There were no significant differences in the incidence of fatal adverse events, headache, and injection site reaction between MPZ and BRZ treatment. However, the SUCRA values indicate an association between administration of BRZ and the occurrence of fatal adverse event or headache, or between administration of MPZ and the occurrence of injection site reaction. Moreover, the incidence odds of injection site reaction were significantly higher in the MPZ group than in the placebo group. Further analysis will be needed to clarify the details of safety profiles of these anti-IL-5 therapies

Familial pancreatic cancer: Concept, management and issues

Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion ( Caucasian) and a younger onset are common also in FPC. In European countries, “anticipation” is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (PanIN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990s and several surveillance projects for high-risk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society