Effects of Azelnidipine plus OlmesaRTAn versus amlodipine plus olmesartan on central blood pressure and left ventricular mass index: the AORTA study

Takeshi Takami1, Yoshihiko Saito21Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2First Department of Internal Medicine, Nara Medical University, Kashihara, JapanPurpose: The aim of this study was to compare the effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP) and left ventricular mass index (LVMI) in hypertensive patients.Patient and methods: Patients with brachial systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg daily) for 12 weeks. The patients were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg daily) or amlodipine (5 mg daily) (25 patients/group) for a further 24 weeks. CBP and LVMI were measured at baseline and at the end of the study.Results: Baseline characteristics were similar in both groups. The decrease in brachial BP was similar in both groups. CBP and LVMI decreased significantly in both groups (both, P < 0.001). However, the decreases in CBP and LVMI were significantly greater with olmesartan/azelnidipine than with olmesartan/amlodipine (CBP, P < 0.001; LVMI, P = 0.002).Conclusions: These findings indicate that olmesartan/azelnidipine had greater effects on CBP and LVMI than did olmesartan/amlodipine, even though the reduction in brachial BP was similar in both groups. These differential effects on CBP and LVMI may have important implications for cardiovascular risk reduction.Keywords: central blood pressure, left ventricular mass index, augmentation index, brachial-ankle pulse wave velocity, olmesartan/azelnidipin

Dual Targeting of CDK4/6 and cMET in Metastatic Uveal Melanoma.

Uveal melanoma (UM) is the most common cancer of the eye in adults. Up to 50% of UM patients subsequently develop metastases, especially in the liver. It has been reported that the retinoblastoma (RB) pathway is deregulated in more than 90% of UM despite the rarity of mutations in the RB1 gene itself. CDK4/6 inhibition (CDK4/6i) is a rational strategy for treatment of UM. In this report, we investigated the antiproliferative activity of a selective CDK4/6 inhibitor on metastatic UM. A CDK4/6 inhibitor suppressed UM cell lines growth in in vitro and in vivo experiments. Hepatocyte growth factor (HGF) decreased the effect of CDK4/6 inhibitor on metastatic UM cell lines. When CDK4/6i was combined with cMET inhibitor, enhanced growth suppression was observed in metastatic UM tumors grown in human-HGF knock-in xenograft mouse models. HGF is enriched in the liver and the majority of liver metastases from UM express activated forms of cMET; therefore, signaling through cMET could contribute to the resistance mechanisms against CDK4/6i, especially in UM patients with hepatic metastasis. Together, these results provide a rationale for the use of cMET inhibitor in combination with a CDK4/6 inhibitor for the treatment of metastatic UM

Follow-up survey of Japanese medical students’ interactions with the pharmaceutical industry

Interaction of medical students with the pharmaceutical industry is common. However, students are thought to be vulnerable to the influence of this interaction, and regulations to limit such interactions are required. The Japan Pharmaceutical Manufacturers Association revised its promotion code in 2013 and specified upper limits for promotional aids. We aimed to investigate whether Japanese medical students’ interactions with the pharmaceutical industry changed from 2012 to 2016. This study solicited the participation of all medical schools in Japan. An anonymous cross-sectional survey was administered to medical students from May 2016 to March 2017 to investigate their interactions with the pharmaceutical industry. The results were compared with those of a previous study conducted in 2012. Forty of the 80 medical schools in Japan participated. The student response rate was 74.1%, with 6771 (3395 preclinical, 3376 clinical) evaluable responses. More than 98% of clinical students had previously accepted stationery, a brochure, or a lunch, and significantly higher percentages of clinical students had accepted these items in 2016 than in 2012 (p < .001). The interactions between clinical students and pharmaceutical companies increased slightly between 2012 and 2016. This study will hopefully promote discussion regarding the regulation of student–industry interactions

Five-minute resolved spatial distribution of radiocesium in sea sediment derived from the Fukushima Dai-ichi Nuclear Power Plant

AbstractThe spatial distributions of radiocesium concentration in sea sediment to a core depth of 14 cm were investigated in the offshore region from the Fukushima Prefecture to the northern part of the Ibaraki Prefecture in February and July 2012, at a spatial resolution of 5 min of latitude and longitude. The concentrations in the area south of the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) were generally higher than those in the area north of it. In the southern area, a band of especially high concentration with a width about 20 km was present in the region shallower than 100 m, and a narrow minimal concentration band was found along the 200-m isobaths. In more than half of all cases, the vertical core profiles of radiocesium concentration generally showed an exponential decreasing trend with depth. However, in the area north of the FDNPP, where the radiocesium concentrations tended to be very low, radiocesium concentrations that had similar or larger magnitude compared with those of the most-surface layer were often found in deeper layers. Relatively good correlations were found between radiocesium concentrations and grain sizes of the most-surface sediment. The vertical profile of radiocesium concentration also had a relationship with grain size. In other case, the radiocesium concentration in the sediment seems to have had a dependence on the radiocesium concentration in bottom seawater, suggesting that the quantity of radiocesium supplied and the grain size were major factors determining the spatial distribution pattern of the radiocesium concentration after the FDNPP accident

Atomistic origin of high-concentration Ce³⁺ in {100}-faceted Cr- substituted CeO₂ nanocrystals

Improving the potential of promising CeO2-based nanocatalysts in practical applications requires an atomic-scale analysis of the effects of active dopants on the distribution of Ce valence states and the formation of oxygen vacancies (VOs). In this study, a Cr dopant is introduced into the cubic {100}-faceted CeO2 nanocrystals (NCs) with an average size of 7.8 nm via supercritical water. The Cr dopants substitute Ce sites in the amount of approximately 3 mol%. Based on the aberration-corrected STEM-EELS, the effects of Cr dopant on the distribution of cation valence states in the Cr-doped CeO2 NCs are investigated layer by layer across the ultrafine Cr-substituted CeO2 NC perpendicular to the {100} exposed facet. It is found that an increased amount of Ce3+ cations is present in Cr-substituted CeO2 NCs, particularly in the internal atomic layers, compared to the pristine CeO2 NCs. The atomic-scale analysis of the local structure combined with theoretical calculations demonstrates that Cr dopant reduces the formation energy of VOs and increases mobility of oxygen atoms for the nano-sized CeO2. These effects, in principle, result in an improved oxygen storage capacity and provide a fundamental understanding of role of the dopant in the formation and distribution of VOs in the doped CeO2 NCs

Expression of nephronectin is inhibited by oncostatin M via both JAK/STAT and MAPK pathways

AbstractNephronectin (Npnt), also called POEM, is an extracellular matrix protein considered to play critical roles as an adhesion molecule in the development and functions of various tissues, such as the kidneys, liver, and bones. In the present study, we examined the molecular mechanism of Npnt gene expression and found that oncostatin M (OSM) strongly inhibited Npnt mRNA expression in MC3T3-E1 cells from a mouse osteoblastic cell line. OSM also induced a decrease in Npnt expression in both time- and dose-dependent manners via both the JAK/STAT and MAPK pathways. In addition, OSM-induced inhibition of osteoblast differentiation was recovered by over-expression of Npnt. These results suggest that OSM inhibits Npnt expression via the JAK/STAT and MAPK pathways, while down-regulation of Npnt by OSM influences inhibition of osteoblast differentiation

Effects of Thinning on Flow Peaks in a Forested Headwater Catchment in Western Japan

This study examined the changes in rainfall-runoff characteristics in the year prior to and after intensive thinning of 50% in number in a steep headwater catchment, covered with 46-year-old Japanese cedar and cypress in western Japan. The magnitude of event peak flow, event quick flow, event water yield, and event response time did not change after thinning. Because 70% of rainfall events had multiple flow peaks, relationships between each flow peak and the rainfall just prior to that peak were also analyzed. The increases in accumulated quick flow, flow rise and flow drop were significant after thinning. The flow drop following each flow peak increased, and led to a lower initial flow in subsequent peaks, resulting in no increase in peak size. The flow peaks in events with over 30 mm rainfall amount and over 2 mm/h average rainfall intensity showed significant increases in flow peak, flow rise, flow drop, and accumulated quick flow, which suggests that the catchment exhibited more shallow flow paths during large rainfall amounts after thinning. No changes were identified using event-based analysis, but changes in flow peaks were detected, which indicates the importance of examining all flow peaks when investigating rainfall-runoff characteristics of headwater catchments