Bioprotective role of platelet-derived microvesicles in hypothermia:insight into the differential characteristics of peripheral and splenic platelets

Abstract Background: Most platelets are present in peripheral blood, but some are stored in the spleen. Because the tissue environments of peripheral blood vessels and the spleen are quite distinct, the properties of platelets present in each may also differ. However, no studies have addressed this difference. We previously reported that hypothermia activates splenic platelets, but not peripheral blood platelets, whose biological significance remains unknown. In this study, we focused on platelet-derived microvesicles (PDMVs) and analyzed their biological significance connected to intrasplenic platelet activation during hypothermia. Methods: C57Bl/6 mice were placed in an environment of −20 °C, and their rectal temperature was decreased to 15 °C to model hypothermia. Platelets and skeletal muscle tissue were collected and analyzed for their interactions. Results: Transcriptomic changes between splenic and peripheral platelets were greater in hypothermic mice than in normal mice. Electron microscopy and real-time RT-PCR analysis revealed that platelets activated in the spleen by hypothermia internalized transcripts, encoding tissue repairing proteins, into PDMVs and released them into the plasma. Plasma microvesicles from hypothermic mice promoted wound healing in the mouse myoblast cell line C2C12. Skeletal muscles in hypothermic mice were damaged but recovered within 24 h after rewarming. However, splenectomy delayed recovery from skeletal muscle injury after the mice were rewarmed. Conclusions: These results indicate that PDMVs released from activated platelets in the spleen play an important role in the repair of skeletal muscle damaged by hypothermia

Nationwide registry of sepsis patients in Japan focused on disseminated intravascular coagulation 2011-2013

Using an energy-resolved mass spectrometer and a time-resolved Langmuir probe, the distribution of bombarding ion energies, their fluxes and energy fluxes at a substrate in an asymmetric bi-polar pulsed DC magnetron have been determined. The discharge was operated in Ar at a pressure of 0.53 Pa with a Ti target and pulsed DC frequencies of 100 and 350 kHz with a range of duty cycles (from 50 to 96%). At 100 kHz, the Ar+and Ti+ time-averaged ion energy distribution functions (IEDFs) reveal three peaks, which are at low energy (<10 eV), in a mid-range (20-50 eV) and at high energy (60-100 eV). We correlate these peaks with distinct phases of the discharge voltage. At 350 kHz the IEDFs show four peaks reflecting a more complex voltage waveform. The low-energy ions are generated in the `on' phase when the plasma potential is typically a few volts above ground. The Ti+ energy spectra show a remnant of the original sputter-neutral energy distribution function. The mid-range ions are produced in the quiescent region of the voltage reverse phase, when the plasma potential is raised globally a few volts above the cathode potential, typically 10-30 V. The high-energy ions are generated in a period of ~0.3 µs, during the discharge voltage overshoot, when the target potential rises to typically over +140 V. However, given the time resolution of the Langmuir probe (0.5 µs), it is not possible to determine if plasma potential is lifted globally to this high potential or only close to the cathode. At 350 kHz, these `fast' ions make up to about a quarter of the total ion flux at the substrate and an upper bound transient power flux of about 2.5 times the maximum delivered in the `on' phase. The total power flux to a substrate in the sustained phase of the discharge is found to increase with frequency and reverse time

Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production

<div><p>Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production.</p></div