Reducing Hemorrhagic Complication by Dabigatran Via Neurovascular Protection After Recanalization With Tissue Plasminogen Activator in Ischemic Stroke of Rat

This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study

Polyamorphic Transformations in Fe‐Ni‐C Liquids: Implications for Chemical Evolution of Terrestrial Planets

During the formation of the Earth’s core, the segregation of metallic liquids from silicate mantle should have left behind evident geochemical imprints on both the mantle and the core. Some distinctive geochemical signatures of the mantle‐derived rocks likely own their origin to the metal‐silicate differentiation of the primitive Earth, setting our planet apart from undifferentiated meteorites as well as terrestrial planets or moons isotopically and compositionally. Understanding the chemical evolution of terrestrial planetary bodies requires knowledge on properties of both liquid iron alloys and silicates equilibrating under physicochemical conditions pertinent to the deep magma ocean. Here we report experimental and computational results on the pressure‐induced structural evolution of iron‐nickel liquids alloyed with carbon. Our X‐ray diffraction experiments up to 7.3 gigapascals (GPa) demonstrate that Fe‐Ni (Fe90Ni10) liquids alloyed with 3 and 5 wt % carbon undergo a polyamorphic liquid structure transition at approximately 5 GPa. Corroborating the experimental observations, our first‐principles molecular dynamic calculations reveal that the structural transitions result from the marked prevalence of three‐atom face‐sharing polyhedral connections in the liquids at >5 GPa. The structure and polyamorphic transitions of liquid iron‐nickel‐carbon alloys govern their physical and chemical properties and may thus cast fresh light on the chemical evolution of terrestrial planets and moons.Key PointsThe X‐ray diffraction measurements reveal a liquid structure transition in the Fe‐Ni‐C liquids at ~5 GPaCalculations show that the nature of the liquid transition is the favoring of three‐atom motifs connections in the high‐pressure liquids at >5 GPaThe structural change may affect the physicochemical properties of the liquids, influencing the chemical evolution of terrestrial bodiesPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141684/1/jgrb52447_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141684/2/jgrb52447-sup-0001-Data_S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141684/3/jgrb52447.pd

CO3+1 network formation in ultra-high pressure carbonate liquids

Carbonate liquids are an important class of molten salts, not just for industrial applications, but also in geological processes. Carbonates are generally expected to be simple liquids, in terms of ionic interactions between the molecular carbonate anions and metal cations, and therefore relatively structureless compared to more “polymerized” silicate melts. But there is increasing evidence from phase relations, metal solubility, glass spectroscopy and simulations to suggest the emergence of carbonate “networks” at length scales longer than the component molecular anions. The stability of these emergent structures are known to be sensitive to temperature, but are also predicted to be favoured by pressure. This is important as a recent study suggests that subducted surface carbonate may melt near the Earth’s transition zone (~44 km), representing a barrier to the deep carbon cycle depending on the buoyancy and viscosity of these liquids. In this study we demonstrate a major advance in our understanding of carbonate liquids by combining simulations and high pressure measurements on a carbonate glass, (K2CO3-MgCO3) to pressures in excess of 40 GPa, far higher than any previous in situ study. We show the clear formation of extended low-dimensional carbonate networks of close CO32− pairs and the emergence of a “three plus one” local coordination environment, producing an unexpected increase in viscosity with pressure. Although carbonate melts may still be buoyant in the lower mantle, an increased viscosity by at least three orders of magnitude will restrict the upward mobility, possibly resulting in entrainment by the down-going slab

Comparison of Clinical and Radiologic Results of Mini-Open Transforaminal Lumbar Interbody Fusion and Extreme Lateral Interbody Fusion Indirect Decompression for Degenerative Lumbar Spondylolisthesis

Study DesignRetrospective study.PurposeIn this study, we compared the postoperative outcomes of extreme lateral interbody fusion (XLIF) indirect decompression with that of mini-open transforaminal lumbar interbody fusion (TLIF) in patients with lumbar degenerative spondylolisthesis.Overview of LiteratureThere are very few reports examining postoperative results of XLIF and minimally invasive TLIF for degenerative lumbar spondylolisthesis, and no reports comparing XLIF and mini-open TLIF.MethodsForty patients who underwent 1-level spinal fusion, either by XLIF indirect decompression (X group, 20 patients) or by mini-open TLIF (T group, 20 patients), for treatment of lumbar degenerative spondylolisthesis were included in this study. Invasiveness of surgery was evaluated on the basis of surgery time, blood loss, hospitalization period, and perioperative complications. The Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ), disc angle (DA), disc height (DH), and slipping length (SL) were evaluated before surgery, immediately after surgery, and at 12 months after surgery. Cross-sectional spinal canal area (CSA) was also measured before surgery and at 1 month after surgery.ResultsThere was no significant difference between the groups in terms of surgery time or hospitalization period; however, X group showed a significant decrease in blood loss (p<0.001). Serious complications were not observed in either group. In clinical assessment, no significant differences were observed between the groups with regard to the JOABPEQ results. The change in DH at 12 months after surgery increased significantly in the X group (p<0.05), and the changes in DA and SL were not significantly different between the two groups. The change in CSA was significantly greater in the T group (p<0.001).ConclusionsPostoperative clinical results were equally favorable for both procedures; however, in comparison with mini-open TLIF, less blood loss and greater correction of DH were observed in XLIF

The Viscosity of Carbonate‐Silicate Transitional Melts at Earth's Upper Mantle Pressures and Temperatures, Determined by the In Situ Falling‐Sphere Technique

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Lutetium incorporation in magmas at depth:changes in melt local environment and the influence on partitioning behaviour

International audienceThe structure of two Lu doped (4000 ppm) model end member silicate liquids, a highly polymerised haplogranite (Si-Al-Na-K-O) and a less polymerised anorthite-diopside (Si-Al-Mg-Ca-O), have been studied up to 8 GPa using in situ x-ray diffraction techniques. The results are the first to identify trace rare Earth element incorporation in silicate melts at high pressure. At pressures below 5 GPa, the bonding environment of Lu-O was found to be dependent on composition with coordination number CN Lu−O = 8 and bond distance r Lu−O = 2.36Å36Å in the haplogranite melt, decreasing to CN Lu−O = 6 and r Lu−O = 2.29Å29Å in the anorthite-diopside melt. This compositional variance in coordination number at low pressure is consistent with observations made for Y-O in glasses at ambient conditions and is coincident with a dramatic increase in the partition coefficients previously observed for rare Earth elements with increasing melt polymerisation. With increasing pressure we find that CN Lu−O and r Lu−O remain constant in the haplo-granite melt. However, an abrupt change in both Lu-O coordination and bond distance is observed at 5 GPa in the anorthite-diopside melt, with CN Lu−O increasing from 6 to 8-fold and r Lu−O from 2.29 to 2.39Å39Å. This occurs over a similar pressure range where a change in the P-dependence in the reported rare Earth element partition coefficients is observed for garnet-, clinopyroxene-, and olivine-melt systems. This work shows that standard models for predicting trace elements at depth must incorporate the effect of pressure-induced structural transformations in the melt in order to realistically predict partitioning behaviour

Interrelated changes in gamma-glutamyltransferase activity and HDL-cholesterol level in the sera of patients with alcoholic liver injury.

&lt;p&gt;The levels of HDL-cholesterol and gamma-glutamyltransferase in the sera of 17 patients with alcoholic liver injury were followed after abstinence and compared with those of 11 patients with acute non-alcoholic hepatitis. The activity of gamma-glutamyltransferase decreased in all cases irrespective of the type of liver injuries. The level of HDL-cholesterol also decreased in 11 of 17 cases with alcoholic liver injury. The other alcoholics, in whom HDL-cholesterol level increased or showed no definite change after withdrawal of alcohol, had severe and advanced liver injuries. In non-alcoholic hepatitis, the HDL-cholesterol level increased as normal liver functions were restored except for one case with cholestatic features. It was concluded that alcohol intake can increase HDL-cholesterol level even in the presence of a concomitantly induced hepatic lesion.&lt;/p&gt;</p