Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion

Background: Acute coronary syndrome leads to systemic responses, including activation of the sympathetic nervous system, inflammation of atherosclerotic lesions, changes in metabolism and gene expressions of remote organs such as the spleen, bone marrow, and liver. Clinical trials and experimental studies have demonstrated that therapy with adipose-derived regenerative cells (ADRCs) attenuates myocardial ischemia/reperfusion (I/R) injury. The aim of this study is to investigate the role of ADRCs in regulating systemic reactions following I/R.Methods: Isolated ADRCs were obtained from green fluorescent protein transgenic male mice. Flow cytometry revealed that freshly isolated ADRCs expressed stem cell markers CD90 and Sca-1, and mesenchymal lineage marker. These cells exhibited multilineage differentiation into adipogenic, osteogenic, and chondrogenic lineages. Wild-type mice were subjected to 30 min of left ascending coronary ischemia and 24 h reperfusion. Freshly isolated ADRCs (105 cells) or vehicle (VEH), were administered intravenously through the tail at the time of reperfusion.Results: Compared to VEH, administration of ADRCs significantly reduced circulating troponin levels 24 h after I/R. Using quantitative real-time polymerase chain reaction analysis, the present study confirms that I/R-induced increase of factor X mRNA expression in the liver and was significantly inhibited by ADRCs compared to VEH. Administration of ADRCs significantly reduced the I/R-induced increase in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-18 seen in mice receiving VEH.Conclusions: These results suggest that administration of ADRCs could have an important role in reducing myocardial injury and regulating the hepatic gene expression profile following I/R

Augmented single-unit muscle sympathetic nerve activity in heart failure with chronic atrial fibrillation

Atrial fibrillation (AF) is a common complication in heart failure (HF) patients. However, it remains unclear whether irregular ventricular response patterns induced by AF increase sympathetic nerve activity. We measured resting multi- and single-unit muscle sympathetic nerve activity (MSNA) in 21 age-matched HF patients with chronic AF (n= 11) rhythm or sinus rhythm (SR, n= 10). The multi-unit MSNA, which was expressed as total activity, was similar between HF + AF patients and HF + SR patients. However, the single-unit MSNA in HF + AF patients was significantly greater than that in HF + SR patients (62 ± 9 spikes min -1vs. 42 ± 4 spikes min -1, P < 0.05). Moreover, the incidence of multiple firing of single-unit MSNA within a given burst was augmented in HF + AF patients as compared with HF + SR patients (48 ± 8%vs. 26 ± 3%, P < 0.01). A significant negative relationship was observed between the reduced diastolic pressure induced by a prolonged cardiac interval in AF subjects and single-unit MSNA frequency within one cardiac interval in each HF + AF subject. The firing characteristics of single-unit MSNA were different between HF patients with AF and HF patients with SR; particularly, those with a prolonged long RR interval showed multiple firings of single-unit MSNA. These findings suggest that AF per se leads to the instantaneous augmentation of single-unit MSNA induced by decreased diastolic pressure, which might partially contribute to disease progression in HF patients. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society

Absence of in vivo selection for K13 mutations after artemether–lumefantrine treatment in Uganda

Additional file 1. Eligibility criteria for recruitment into the therapeutic efficacy study and the molecular study

Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events

Objective: Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. Methods: 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. Results: During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). Conclusions: Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. © Published by the BMJ Publishing Group Limited

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

Current status of space gravitational wave antenna DECIGO and B-DECIGO

Deci-hertz Interferometer Gravitational Wave Observatory (DECIGO) is the future Japanese space mission with a frequency band of 0.1 Hz to 10 Hz. DECIGO aims at the detection of primordial gravitational waves, which could be produced during the inflationary period right after the birth of the universe. There are many other scientific objectives of DECIGO, including the direct measurement of the acceleration of the expansion of the universe, and reliable and accurate predictions of the timing and locations of neutron star/black hole binary coalescences. DECIGO consists of four clusters of observatories placed in the heliocentric orbit. Each cluster consists of three spacecraft, which form three Fabry-Perot Michelson interferometers with an arm length of 1,000 km. Three clusters of DECIGO will be placed far from each other, and the fourth cluster will be placed in the same position as one of the three clusters to obtain the correlation signals for the detection of the primordial gravitational waves. We plan to launch B-DECIGO, which is a scientific pathfinder of DECIGO, before DECIGO in the 2030s to demonstrate the technologies required for DECIGO, as well as to obtain fruitful scientific results to further expand the multi-messenger astronomy.Comment: 10 pages, 3 figure

Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

Aldosterone is implicated in the pathogenesis of several cardiovascular diseases, including ischemia reperfusion (I/R) and myocardial infarction, and also causes oxidative stress and inflammation in cardiovascular systems. Benidipine, a long-acting T-and L-type calcium channel blocker, reduces infarct size following myocardial I/R in rabbits. Benidipine also inhibits the production of aldosterone in vitro. However, the precise mechanism of this phenomenon in vivo remains unknown. We therefore evaluated whether benedipine has a beneficial role through the regulation of oxidative stress in myocardial I/R. C57BL/6J mice were subjected to 30 min of left ascending coronary I/R. Benidipine was administered orally at 3 mg kg -1daily for 3 weeks without any changes in hemodynamic variables. Benidipine significantly reduced infarction size (13.4±2.5%) compared with controls (25.5±3.6%). Urinary 8-hydroxy-2′ deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, increased significantly after I/R. I/R induced increases in 8-OHdG were significantly lower with benidipine. Local myocardial 8-OHdG was also elevated in I/R, but this augmentation was significantly suppressed with benidipine. The plasma aldosterone concentration (PAC) significantly increased 2 days after I/R and remained elevated at least 7 days after I/R. Treatment with benidipine significantly decreased I/R-induced elevation of the PAC. I/R-induced markers of fibrosis in hearts also reduced in benidipine. These results suggest that the administration of benidipine reduces myocardial infarct size as well as systemic oxidative stress after I/R. These phenomena are partially linked to reduced plasma aldosterone levels. © 2012 The Japanese Society of Hypertension All rights reserved

The status of DECIGO

DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) is the planned Japanese space gravitational wave antenna, aiming to detect gravitational waves from astrophysically and cosmologically significant sources mainly between 0.1 Hz and 10 Hz and thus to open a new window for gravitational wave astronomy and for the universe. DECIGO will consists of three drag-free spacecraft arranged in an equilateral triangle with 1000 km arm lengths whose relative displacements are measured by a differential Fabry-Perot interferometer, and four units of triangular Fabry-Perot interferometers are arranged on heliocentric orbit around the sun. DECIGO is vary ambitious mission, we plan to launch DECIGO in era of 2030s after precursor satellite mission, B-DECIGO. B-DECIGO is essentially smaller version of DECIGO: B-DECIGO consists of three spacecraft arranged in an triangle with 100 km arm lengths orbiting 2000 km above the surface of the earth. It is hoped that the launch date will be late 2020s for the present

Current status of space gravitational wave antenna DECIGO and B-DECIGO

The Deci-hertz Interferometer Gravitational Wave Observatory (DECIGO) is a future Japanese space mission with a frequency band of 0.1 Hz to 10 Hz. DECIGO aims at the detection of primordial gravitational waves, which could have been produced during the inflationary period right after the birth of the Universe. There are many other scientific objectives of DECIGO, including the direct measurement of the acceleration of the expansion of the Universe, and reliable and accurate predictions of the timing and locations of neutron star/black hole binary coalescences. DECIGO consists of four clusters of observatories placed in heliocentric orbit. Each cluster consists of three spacecraft, which form three Fabry–Pérot Michelson interferometers with an arm length of 1000 km. Three DECIGO clusters will be placed far from each other, and the fourth will be placed in the same position as one of the other three to obtain correlation signals for the detection of primordial gravitational waves. We plan to launch B-DECIGO, which is a scientific pathfinder for DECIGO, before DECIGO in the 2030s to demonstrate the technologies required for DECIGO, as well as to obtain fruitful scientific results to further expand multi-messenger astronomy