23 research outputs found

    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]

    Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

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    Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [<1.0 mmol/L] for at least 2 h) were identified among 26 patients. During GD, we found a significant increase of CMD lactate (from 4±2.3 to 5.4±2.9 mmol/L), pyruvate (126.9±65.1 to 172.3±74.1 μmol/L), and lactate/pyruvate ratio (LPR; 27±6 to 35±9; all, p<0.005), while brain oxygen and blood lactate remained normal. Dynamics of lactate and glucose supply during GD were further studied by analyzing the relationships between blood and CMD samples. There was a strong correlation between blood and brain lactate when LPR was normal (r=0.56; p<0.0001), while an inverse correlation (r=-0.11; p=0.04) was observed at elevated LPR >25. The correlation between blood and brain glucose also decreased from r=0.62 to r=0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel

    Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury.

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    Lactate promotes cerebral blood flow and is an efficient substrate for the brain, particularly at times of glucose shortage. Hypertonic lactate is neuroprotective after experimental brain injury; however, human data are limited. Prospective study (clinicaltrials.gov NCT01573507). Academic ICU. Twenty-three brain-injured subjects (13 traumatic brain injury/10 subarachnoid hemorrhage; median age, 59 yr [41-65 yr]; median Glasgow Coma Scale, 6 [3-7]). Three-hour IV infusion of hypertonic lactate (sodium lactate, 1,000 mmol/L; concentration, 30 µmol/kg/min) administered 39 hours (26-49 hr) from injury. We examined the effect of hypertonic lactate on cerebral perfusion (using transcranial Doppler) and brain energy metabolism (using cerebral microdialysis). The majority of subjects (13/23 = 57%) had reduced brain glucose availability (baseline pretreatment cerebral microdialysis glucose, < 1 mmol/L) despite normal baseline intracranial pressure (10 [7-15] mm Hg). Hypertonic lactate was associated with increased cerebral microdialysis lactate (+55% [31-80%]) that was paralleled by an increase in middle cerebral artery mean cerebral blood flow velocities (+36% [21-66%]) and a decrease in pulsatility index (-21% [13-26%]; all p < 0.001). Cerebral microdialysis glucose increased above normal range during hypertonic lactate (+42% [30-78%]; p < 0.05); reduced brain glucose availability correlated with a greater improvement of cerebral microdialysis glucose (Spearman r = -0.53; p = 0.009). No significant changes in cerebral perfusion pressure, mean arterial pressure, systemic carbon dioxide, and blood glucose were observed during hypertonic lactate (all p > 0.1). This is the first clinical demonstration that hypertonic lactate resuscitation improves both cerebral perfusion and brain glucose availability after brain injury. These cerebral vascular and metabolic effects appeared related to brain lactate supplementation rather than to systemic effects

    Kinetic Regime Change in the Tandem Dehydrative Aromatization of Furan Diels–Alder Products

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    Renewable production of <i>p</i>-xylene from [4 + 2] Diels–Alder cycloaddition of 2,5-dimethylfuran (DMF) and ethylene with H–Y zeolite catalyst in <i>n</i>-heptane solvent is investigated. Experimental studies varying the solid acid catalyst concentration reveal two kinetic regimes for the <i>p</i>-xylene production rate: (i) a linear regime at low acid site concentrations with activation energy <i>E</i><sub>a</sub> = 10.8 kcal/mol and (ii) a catalyst-independent kinetic regime at high acid site concentrations with activation energy <i>E</i><sub>a</sub> = 20.1 kcal/mol. We carry out hybrid QM/MM calculations with a three-layer embedded cluster ONIOM model to compute the energetics along the main reaction pathway, and a microkinetic model is constructed for the interpretation of the experimental kinetic data. At high solid acid concentrations, <i>p</i>-xylene production is limited by the homogeneous Diels–Alder reaction, whereas at low acid concentrations, the overall rate is limited by the heterogeneously catalyzed dehydration of the Diels–Alder cycloadduct of DMF and ethylene because of an insufficient number of acid sites, despite the dehydration reaction requiring significantly less activation energy. A reduced kinetic model reveals that the production of <i>p</i>-xylene follows the general kinetics of tandem reactions in which the first step is uncatalyzed and the second step is heterogeneously catalyzed. Reaction orders and apparent activation energies of quantum mechanical and microkinetic simulations are in agreement with experimental values

    Inhibition of Xylene Isomerization in the Production of Renewable Aromatic Chemicals from Biomass-Derived Furans

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    Inhibition of <i>p-</i>xylene isomerization in the presence of H-Y (Si/Al 2.6) and H-BEA (Si/Al 12.5) zeolites was studied under conditions relevant to <i>p-</i>xylene production from 2,5-dimethylfuran (DMF) and ethylene. Through examination of the reaction components, it was shown that both DMF and 2,5-hexanedione inhibit transalkylation and methyl shift reactions of <i>p-</i>xylene, while other reaction components, water and ethylene, do not. Retention of Brønsted acid sites after the reaction was shown through the use of <sup>27</sup>Al NMR for both H-Y and H-BEA zeolites, but with a reduction in the ratio of tetrahedrally coordinated aluminum (strong acid sites) to octahedrally coordinated aluminum (Lewis acid sites) coinciding with the disappearance of the framework aluminum. Diffuse reflectance spectroscopy has shown preferential adsorption of DMF and 2,5-hexanedione (DMF + H<sub>2</sub>O) relative to <i>p-</i>xylene to the Brønsted acid sites located in the super and sodalite cages of the H-Y. Desorption characteristics for DMF and <i>p-</i>xylene in H-Y and H-BEA were determined by thermogravimetric analysis, consistent with adsorption energetics of individual chemical species and dimeric complexes evaluated by an ONIOM method. Evaluation of three mechanisms, allowing for production of <i>p-</i>xylene from DMF and ethylene while also inhibiting <i>p-</i>xylene isomerization, supports high surface coverage of the active site with 2,5-hexanedione, supported by electronic structure calculations
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