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.     

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.     

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.     

Expression of secretory phospholipase A2s in human atherosclerosis development

Secretory phospholipase A2s (sPLA2s) contribute to the hydrolysis of phospholipid. Among them, sPLA2-IIA, -V, and -X have been regarded as enhancers of lipid accumulation in arterial intima. However, the distribution and production of the other types of sPLA2 in human aortic wall remain unclear. Therefore, in this study, the distribution and production of seven types of sPLA2 including IIA, IID, IIE, IIF, III, V, and X in atherosclerosis development in the human aorta were comprehensively examined by immunohistochemistry and in situ hybridization (ISH). The extent of sPLA2s expression increased with atherosclerosis development, but only sPLA2-IIF was never observed in the normal aorta. Double-immunostaining demonstrated that sPLA2-V expression was limited to smooth muscle cells (SMCs), although the other sPLA2s were expressed in both macrophages and SMCs. ISH using sPLA2 cDNAs revealed that the expression pattern of each mRNA was consistent with the results of immunohistochemistry for each corresponding sPLA2. These results indicate that the seven types of sPLA2 are expressed with various patterns in all stages of atherosclerosis development and may play an atherogenic role through degradation of phospholipid.     

Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.     

Non-high-density lipoprotein cholesterol and the development of coronary heart disease and stroke subtypes in a general Japanese population: The Hisayama Study

Background and purpose

It has not been fully determined whether non-high-density lipoprotein cholesterol (non-HDLC) levels are involved in vascular events, especially stroke, in general Asian populations. We evaluated the association between non-HDLC levels and the risk of type-specific cardiovascular disease in a prospective cohort study in Japan.

Methods

A total of 2452 community-dwelling Japanese subjects aged ≥40 years were followed prospectively for 24 years.

Results

The age- and sex-adjusted incidence of coronary heart diseases (CHD) significantly increased with elevating non-HDLC levels (P for trend < 0.001), but no such association was observed for ischemic and hemorrhagic strokes. With regard to ischemic stroke subtypes, the age- and sex-adjusted incidence of lacunar infarction significantly increased with elevating non-HDLC levels (P for trend < 0.01), and such tendency was seen for atherothrombotic infarction (P for trend = 0.098), while a significant inverse association was observed for cardioembolic infarction (P for trend = 0.007). After adjustment for confounders, namely, age, sex, diabetes, body mass index, systolic blood pressure, electrocardiogram abnormalities, current drinking, current smoking, and regular exercise, the associations remained significant for CHD [adjusted hazard ratio (HR) for a 1 standard deviation of non-HDLC concentrations = 1.17, 95% confidence interval (CI) = 1.02 to 1.35], atherothrombotic infarction (adjusted HR = 1.39, 95% CI = 1.09 to 1.79), and cardioembolic infarction (adjusted HR = 0.64, 95% CI = 0.47 to 0.85).

Conclusions

Our findings suggest that elevated non-HDLC levels are a significant risk factor for the development of atherothrombotic infarction as well as CHD but reduce the risk of cardioembolic infarction in the general Japanese population.     

The safety and effectiveness profile of daily teriparatide in a prospective observational study in Japanese patients with osteoporosis at high risk for fracture: interim report

This postmarketing surveillance study assessed the safety and effectiveness of daily teriparatide treatment in patients with osteoporosis in a Japanese clinical setting. In this prospective, multicenter, observational study, patients with osteoporosis at high risk for fracture received subcutaneous injections of teriparatide (20 μg/day) for a maximum of 24 months. For this interim report, data from 1,671 patients were eligible for analysis at the cutoff date. The mean age was 75.3 years; 93 % of patients (1,552/1,671 patients) were women. There were 117 adverse drug reactions (ADRs) reported in 101 of 1,671 patients (6.04 %); the most common reported ADRs were nausea, dizziness, headache, and palpitations. No clinically significant safety issues were identified, although 5 serious ADRs were reported in 4/1,671 (0.24 %) patients. At 12 months, 71.9 % of patients remained on teriparatide treatment. From 1 month, there were rapid increases in the biomarkers of bone formation P1NP and, to a lesser extent, BAP. In contrast, increases in the biomarkers of bone resorption, serum NTX, urinary NTX, and TRACP5b, were smaller. After 12 months of treatment, there was an increase in bone mineral density at the lumbar spine, femoral neck, and total hip, and a decrease in the Visual Analog Scale score for back pain. The incidence of new vertebral and nonvertebral fractures was 1.21 % and 3.18 %, respectively. In conclusion, the favorable safety profile and effectiveness of teriparatide observed in this population of Japanese patients with osteoporosis were accompanied by relatively high persistence with treatment, which is a key factor in the success of osteoporosis treatment.