Sympathetic withdrawal is associated with hypotension after hepatic reperfusion

Objective: Post-reperfusion syndrome (PRS), severe hypotension after graft reperfusion during liver transplantation, is an adverse clinical event associated with poorer patient outcomes. The purpose of this study was to determine whether alterations in autonomic control in liver transplant recipients prior to graft reperfusion are associated with the subsequent development of PRS. Methods: Heart rate variability (HRV), systolic arterial blood pressure (SBP) variability, and baroreflex sensitivity of 218 liver transplant recipients were evaluated using 5 min of ECG and arterial blood pressure signals 10 min before graft reperfusion along with other clinical parameters. Logistic regression analyses were performed to assess predictors of PRS occurrence. Results: Seventy-seven patients (35 %) developed PRS while 141 did not. There were significant differences in SBP (110 ± 16 vs. 119 ± 16 mmHg, P < 0.001) and the ratio of low frequency power to high frequency power (LF/HF) of HRV (1.0 ± 1.4 vs. 2.1 ± 3.7, P = 0.003) between the PRS group and No-PRS group. In multivariate logistic regression analysis, predictors were LF/HF (odds ratio 0.817, P = 0.028) and SBP (odds ratio 0.966, P < 0.001). Interpretation: Low LF/HF and SBP measured before hepatic graft reperfusion were significantly correlated with subsequent PRS occurrence, suggesting that sympathovagal imbalance and depressed SBP may be key factors predisposing to reperfusion-related severe hypotension in liver transplant recipients

Thiol-linked peroxidase activity of human ceruloplasmin

AbstractHuman ceruloplasmin exhibited different antioxidant effects according to the electron donors in a metal-catalyzed oxidation system. Purified ceruloplasmin did not play a significant role in the protection of DNA strand breaks in the ascorbate/Fe3+/O2 system. However, when ascorbates were replaced with a thiol-reducing equivalent such as dithiothreitol, DNA strand breaks were significantly prevented by the same amount of ceruloplasmin. Ceruloplasmin did not catalyze the decomposition of H2O2 in the absence of reduced glutathione. On the contrary, ceruloplasmin showed a potent peroxidase ability to destroy H2O2 in the presence of reduced glutathione. In conclusion, the removal of H2O2 by human ceruloplasmin is not simply stoichiometric but thiol-dependent

El Niño Southern Oscillation sensitivity to cumulus entrainment in a coupled general circulation model

A series of 200 year long integrations is performed using the Geophysical Fluid Dynamics Laboratory CM2.1 by varying the Tokioka parameter, a minimum entrainment rate threshold in the cumulus parameterization. Changing the threshold alters both the tropical Pacific mean state and the El Niño Southern Oscillation (ENSO) variability. Increasing the Tokioka parameter causes a basin-wide cooling in the tropical Pacific with the reduction of high clouds. The degree of cooling in the western part of the basin is bigger than that in the east. As a result, the east-west asymmetry in the tropical Pacific sea surface temperature (SST) decreases with increasing the Tokioka parameter. Accompanied with the reduced east-west SST asymmetry are the increase of mean precipitation over the eastern Pacific and the eastward shift of the atmospheric responses to the ENSO-related SST forcing. The eastward shifted wind stress anomaly associated with ENSO leads to the stronger ENSO variability. In this way the magnitude of ENSO simulated in this model increases with the Tokioka parameter. Implication of our results on the relationship between the tropical Pacific mean state and ENSO is discussed

Oxygen-deficient triple perovskites as highly active and durable bifunctional electrocatalysts for oxygen electrode reactions

Highly active and durable bifunctional oxygen electrocatalysts have been of pivotal importance for renewable energy conversion and storage devices, such as unitized regenerative fuel cells and metal-air batteries. Perovskite-based oxygen electrocatalysts have emerged as promising nonprecious metal bifunctional electrocatalysts, yet their catalytic activity and stability still remain to be improved. We report a high-performance oxygen electrocatalyst based on a triple perovskite, Nd1.5Ba1.5CoFeMnO9-delta (NBCFM), which shows superior activity and durability for oxygen electrode reactions to single and double perovskites. When hybridized with nitrogen-doped reduced graphene oxide (N-rGO), the resulting NBCFM/N-rGO catalyst shows further boosted bifunctional oxygen electrode activity (0.698 V), which surpasses that of Pt/C (0.801 V) and Ir/C (0.769 V) catalysts and which, among the perovskite-based electrocatalysts, is the best activity reported to date. The superior catalytic performances of NBCFM could be correlated to its oxygen defect rich structure, lower charge transfer resistance, and smaller hybridization strength between O 2p and Co 3d orbitals

Regulation of ADAM10 and ADAM17 by Sorafenib Inhibits Epithelial-to-Mesenchymal Transition in Epstein-Barr Virus-Infected Retinal Pigment Epithelial Cells

PURPOSE. The a-disintegrin-and-metalloprotease (ADAM) family proteins are widely expressed in the different layers of the retina throughout development. The effect of ADAM proteins on the epithelial-to-mesenchymal transition (EMT) in proliferative vitreoretinopathy (PVR) or AMD is yet to be elucidated. In this study we used Epstein-Barr virus (EBV)-transformed adult retinal pigment epithelial (ARPE) cells to investigate how sorafenib, a multikinase inhibitor, modulates ADAM proteins to control EMT. METHODS. Epithelial to mesenchymal transition and related mechanisms in EBV-infected ARPE cells were determined by RT-PCR, Western blot, invasion assay, ELISA assay, and gene silencing with siRNA. RESULTS. Mesenchymal-like ARPE/EBV cells exhibited considerably increased cellular migration and invasion compared with ARPE cells and produced EMT-related cytokines. Sorafenib significantly inhibited production of TGF-b1, VEGF, IL-6, IL-8, MCP-1, and TNF-a and blocked the activation of migration-related signaling molecules, such as HIF-1a, p-STAT3, MMP2, and Ang-1. The expression of mature ADAM10, ADAM17, and cleaved Notch 1 proteins in ARPE/EBV cells was downregulated after treatment with sorafenib through the regulatory activity of nardilysin (NRD-1). Gene silencing of NRD-1 in ARPE/EBV cells attenuated secretion of EMT-related cytokines and expression of ADAM10 and 17 and upregulated epithelial markers. CONCLUSIONS. Sorafenib controls the mesenchymal characteristics of EBV-infected ARPE cells. Nardilysin and ADAM family proteins might be new targets for the prevention or control of EMT in retinal diseases

Nonlinear impact of the Arctic Oscillation on extratropical surface air temperature

The Arctic Oscillation (AO) is the leading climate mode of sea level pressure (SLP) anomalies during cold season in the Northern Hemisphere. To a large extent, the atmospheric climate anomalies associated with positive and negative phases of the AO are opposite to each other, indicating linear impact. However, there is also significant nonlinear relationship between the AO and other winter climate variability. We investigate nonlinear impacts of the AO on surface air temperature (SAT) using reanalysis data and a multi-millennial long climate simulation. It is found that SAT response to the AO, in terms of both spatial pattern and magnitude, is almost linear when the amplitude of the AO is moderate. However, the response becomes quite nonlinear as the amplitude of the AO becomes stronger. First, the pattern shift in SAT depends on AO phase and magnitude, and second, the SAT magnitude depends on AO phase. In particular, these nonlinearities are distinct over the North America and Eurasian Continent. Based on the analyses of model output, we suggest that the nonlinear zonal advection term is one of the critical components in generating nonlinear SAT response, particularly over the North America. Key Points: - We investigate nonlinear impacts of the AO on surface air temperature - The response becomes nonlinear for the strong AO events - The nonlinear advection is a critical component for the nonlinear SAT respons

Pathogenicity of severe fever with thrombocytopenia syndrome virus in mice regulated in type I interferon signaling

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease, which causes high fever, thrombocytopenia, and death in humans and animals in East Asian countries. The pathogenicity of SFTS virus (SFTSV) remains unclear. We intraperitoneally infected three groups of mice: wild-type (WT), mice treated with blocking anti-type I interferon (IFN)-α receptor antibody (IFNAR Ab), and IFNAR knockout (IFNAR−/−) mice, with four doses of SFTSV (KH1, 5 × 105 to 5 × 102 FAID50). The WT mice survived all SFTSV infective doses. The IFNAR Ab mice died within 7 days post-infection (dpi) with all doses of SFTSV except that the mice were infected with 5 × 102 FAID50 SFTSV. The IFNAR−/− mice died after infection with all doses of SFTSV within four dpi. No SFTSV infection caused hyperthermia in any mice, whereas all the dead mice showed hypothermia and weight loss. In the WT mice, SFTSV RNA was detected in the eyes, oral swabs, urine, and feces at 5 dpi. Similar patterns were observed in the IFNAR Ab and IFNAR−/− mice after 3 dpi, but not in feces. The IFNAR Ab mice showed viral shedding until 7 dpi. The SFTSV RNA loads were higher in organs of the IFNAR−/− mice compared to the other groups. Histopathologically, coagulation necrosis and mononuclear inflammatory cell infiltration in the liver and white pulp atrophy in the spleen were seen as the main lesions in the IFN signaling lacking mice. Immunohistochemically, SFTSV antigens were mainly detected in the marginal zone of the white pulp of the spleen in all groups of mice, but more viral antigens were observed in the spleen of the IFNAR−/− mice. Collectively, the IFN signaling-deficient mice were highly susceptible to SFTSV and more viral burden could be demonstrated in various excreta and organs of the mice when IFN signaling was inhibited.The research was supported by the Republic of Korea (Government-wide R&D Fund project for infectious disease research (GFID), HG18C0084)

Effects of endocrine disrupting chemicals on expression of phospholipid hydroperoxide glutathione peroxidase mRNA in rat testes

Phospholipid hydroperoxide glutathione peroxidase (PHGPx), an antioxidative selenoprotein, is modulated by estrogen in the testis and oviduct. To examine whether potential endocrine disrupting chemicals (EDCs) affect the microenvironment of the testes, the expression patterns of PHGPx mRNA and histological changes were analyzed in 5-week-old Sprague-Dawley male rats exposed to several EDCs such as an androgenic compound [testosterone (50, 200, and 1,000 µg/kg)], anti-androgenic compounds [flutamide (1, 5, and 25 mg/kg), ketoconazole (0.2 and 1 mg/kg), and diethylhexyl phthalate (10, 50, and 250 mg/kg)], and estrogenic compounds [nonylphenol (10, 50, 100, and 250 mg/kg), octylphenol (10, 50, and 250 mg/kg), and diethylstilbestrol (10, 20, and 40 µg/kg)] daily for 3 weeks via oral administration. Mild proliferation of germ cells and hyperplasia of interstitial cells were observed in the testes of the flutamide-treated group and deletion of the germinal epithelium and sloughing of germ cells were observed in testes of the diethylstilbestrol-treated group. Treatment with testosterone was shown to slightly decrease PHGPx mRNA levels in testes by the reverse transcriptionpolymerase chain reaction. However, anti-androgenic compounds (flutamide, ketoconazole, and diethylhexyl phthalate) and estrogenic compounds (nonylphenol, octylphenol, and diethylstilbestrol) significantly upregulated PHGPx mRNA in the testes (p < 0.05). These findings indicate that the EDCs might have a detrimental effect on spermatogenesis via abnormal enhancement of PHGPx expression in testes and that PHGPx is useful as a biomarker for toxicity screening of estrogenic or antiandrogenic EDCs in testes