Analysis of antioxidant prenylflavonoids in different parts of Macaranga tanarius,the plant origin of Okinawan propolis

Objective:To analyze the antioxidant prenylilavonoids in different parts of Macaranga tanarius(M.tanarius)(Euphorbiaceae)including the leaf,petiole,stem,leaflet,flower and fruit(only in female plant),and to evaluate their antioxidant properties.Methods:Methanol extracts of each part of M.tanarius were prepared and five prenylilavonoids in them were quantitatively analyzed using HPLC.The fruits from female plant were further separated into seed,pericarp,and glandular trichome.After the quantitative analyses of prenylflavonoids in each part of M.tanarius,antioxidant activity of the extracts was evaluated by 2,2-diphenyl-l-picryI-hydrazyl(DPPH)radical scavenging assay.Results:The leaf of M.tanarius contained two prenylflavonoids as main components in both male and female plants.Both flowers(male and female)contained five kinds of prenylflavonoids.In the petiole,stem and leaflet of both male and female plants,the prenylflavonoids were not delected or their amounts were very low.Five kinds of prenylflavonoids were detected in the seed,pericarp and glandular trichome of female M.tanarius.In particular,the glandular trichome had the highest level of total prenylflavonoids(235 mg/g of fresh plant).DPPH radical scavenging activity of all parts was more than 30%.Conclusions:We found that different parts of M.tanarius contained antioxidant prenylflavonoids.In particular,not only the glandular trichome but also the leaf contained prenylflavonoids,which indicated that M.tanarius may be developed as a functional plant,because the leaves of this plant can be easily collected.     

Short‐ and long‐term effect of sitagliptin after near normalization of glycemic control with insulin in poorly controlled Japanese type 2 diabetic patients

Aims/Introduction

The aim of the present study was to examine the short‐ and long‐term effect of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin in poorly controlled type 2 diabetic patients.

Materials and Methods

We consecutively enrolled a total of 30 type 2 diabetic patients whose glycated hemoglobin levels (National Glycohemoglobin Standardization Program) were ≥7.4%, stopped all oral antidiabetic drugs and started insulin therapy. When fasting plasma glucose levels became <140 mg/dL, we carried out the first oral glucose tolerance test (OGTT). After 1‐week sitagliptin treatment (50 mg/day), the second OGTT was carried out. Furthermore, we evaluated the long‐term efficacy of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin.

Results

After 1‐week sitagliptin treatment, the area under the curve of insulin was markedly increased, and the area under the curve of glucagon and glucose was markedly decreased. Duration of diabetes and insulin secretory capacity were correlated with the effect of sitagliptin. Furthermore, interestingly, near normalization of glycemic control with insulin therapy for 1–2 weeks brought out the long‐term effectiveness of sitagliptin on glucose tolerance for 24 weeks, which was not observed with other antidiabetic drugs.

Conclusions

These findings suggest that near normalization of glycemic control with insulin improves the clinical response to sitagliptin in poorly controlled type 2 diabetic patients.     

Comparison of tofogliflozin versus glimepiride as the third oral agent added to metformin plus a dipeptidyl peptidase-4 inhibitor in Japanese patients with type 2 diabetes: A randomized, 24-week,open-label,controlled trial (STOP-OB)

Metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i) is the most common therapy for Japanese patients with type 2 diabetes. This 24-week, multicentre, open-label, parallel-group trial randomized patients on dual therapy to add-on tofogliflozin (20 mg/day, n = 33) or glimepiride (0.5 mg/day, n = 31). The primary outcome was change in body fat percentage. The secondary outcomes included changes in HbA1c, fat mass, fat-free mass, liver function variables and uric acid. Tofogliflozin and glimepiride reduced HbA1c to a similar extent. Body fat percentage did not change from baseline in either group. Fat mass was reduced by tofogliflozin but was increased by glimepiride (by −2.0 ± 1.7 kg and +1.6 ± 1.6 kg, P = .002). Fat-free mass was also reduced by tofogliflozin and increased by glimepiride (by −1.3 ± 1.3 kg and +0.9 ± 2.0 kg, P < .001). Alanine aminotransferase and uric acid levels were reduced by tofogliflozin (P = .006 and P < .001, respectively). These data provide novel information useful for selecting the third oral agent for patients whose diabetes is inadequately controlled with metformin plus DPP-4i dual therapy.     

Study protocol of a multicenter registry of patients with rheumatoid arthritis starting biologic therapy in Japan: Tsurumai Biologics Communication Registry (TBCR) Study

Biologic agents have proven to be effective against rheumatoid arthritis (RA) in clinical trials and post-marketing surveillance (PMS) studies. However, limited follow-up periods and strict criteria for recruitment might lead to an underestimation of adverse events. To document the long-term course of patients with RA treated with biologics in clinical settings, we established the Tsurumai Biologics Communication Registry (TBCR). First, we retrospectively collected data of patients registered for any biologic PMS study or clinical trial at participating institutes. Thus far, thirteen institutes have joined the registry and 860 patients have been identified. Comparing baseline characteristics by age and initiation year of biologics, young patients had significantly less joint damage and dysfunction and a higher dose of concomitant methotrexate (MTX) compared to older patients. Older age and functional class were significantly related to the incidence of adverse events that resulted in discontinuation of the 1st biologic treatment. The TBCR is in its initial stages, and information on all patients newly starting biologic therapy at participating institutes is being collected prospectively. Differences in baseline characteristics by age and initiation year of biologics need to be carefully evaluated in order to report on drug-related survival and long-term prognosis, using follow-up data in the near future.     

Factors promoting resident deaths at aged care facilities in Japan: a review

Due to an increasingly ageing population, the Japanese government has promoted elderly deaths in aged care facilities. However, existing facilities were not designed to provide resident end‐of‐life care and the proportion of aged care facility deaths is currently less than 10%. Consequently, the present review evaluated the factors that promote aged care facility resident deaths in Japan from individual‐ and facility‐level perspectives to exploring factors associated with increased resident deaths. To achieve this, MEDLINE, CINAHL, Web of Science and Ichushi databases were searched on 23 January 2016. Influential factors were reviewed for two healthcare services (insourcing and outsourcing facilities) as well as external healthcare agencies operating outside facilities. Of the original 2324 studies retrieved, 42 were included in analysis. Of these studies, five focused on insourcing, two on outsourcing, seven on external agencies and observed facility/agency‐level factors. The other 28 studies identified individual‐level factors related to death in aged care facilities. The present review found that at both facility and individual levels, in‐facility resident deaths were associated with healthcare service provision, confirmation of resident/family end‐of‐life care preference and staff education. Additionally, while outsourcing facilities did not require employment of physicians/nursing staff to accommodate resident death, these facilities required visits by physicians and nursing staff from external healthcare agencies as well as residents' healthcare input. This review also found few studies examining outsourcing facilities. The number of healthcare outsourcing facilities is rapidly increasing as a result of the Japanese government's new tax incentives. Consequently, there may be an increase in elderly deaths in outsourcing healthcare facilities. Accordingly, it is necessary to identify the factors associated with residents' deaths at outsourcing facilities.     

Clinical role of serum programmed death ligand 1 in patients with hepatocellular carcinoma: Where does it come from?

Programmed death ligand 1 (PD-L1) is a key target for the treatment of several malignancies. The present study was conducted to clarify the role of serum PD-L1 in hepatocellular carcinoma (HCC). Serum PD-L1 (sPD-L1) was examined by an enzyme-linked immunosorbent assay in 153 patients with HCC who underwent curative hepatectomy at Kumamoto University in 2011–2016. The expression of PD-L1 in tissue (tPD-L1) was investigated by immunohistochemistry. The clinical roles of the PD-L1 expression in both serum and tissue were examined. The sPD-L1 was significantly elevated in HCC patients compared to patients without any malignant or inflammatory disease (234 vs. 93 pg/mL, p < 0.0001). The percentage of the tPD-L1-positive area (%tPD-L1) in the background liver was significantly higher than in the tumor (1.52% vs. 0.48%, p < 0.0001). The %tPD-L1 in the background liver but not in the tumor was significantly correlated with the sPD-L1 level (p = 0.0079). The sPD-L1, %tPD-L1 in the tumor, and %tPD-L1 in the background liver were not correlated with the overall survival after surgery. PD-L1-expressing cells in the background liver, but not in the tumor tissue, appeared to contribute to the sPD-L1 level. The sPD-L1 level may thus not indicate the tumor burden in patients with HCC.     

Detection of N-(1-deoxy-d-fructos-1-yl) Fumonisins B2 and B3 in Corn by High-Resolution LC-Orbitrap MS

The existence of glucose conjugates of fumonisin B₂ (FB₂) and fumonisin B₃ (FB₃) in corn powder was confirmed for the first time. These “bound-fumonisins” (FB₂ and FB₃ bound to glucose) were identified as N-(1-deoxy-d-fructos-1-yl) fumonisin B₂ (NDfrc-FB₂) and N-(1-deoxy-d-fructos-1-yl) fumonisin B₃ (NDfrc-FB₃) respectively, based on the accurate mass measurements of characteristic ions and fragmentation patterns using high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS) analysis. Treatment on NDfrc-FB₂ and NDfrc-FB₃ with the o-phthalaldehyde (OPA) reagent also supported that d-glucose binding to FB₂ and FB₃ molecules occurred to their primary amine residues.