Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury.

Monitoring and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is a standard of care after traumatic brain injury (TBI). However, the pathophysiology of so-called secondary brain injury, i.e., the cascade of potentially deleterious events that occur in the early phase following initial cerebral insult-after TBI, is complex, involving a subtle interplay between cerebral blood flow (CBF), oxygen delivery and utilization, and supply of main cerebral energy substrates (glucose) to the injured brain. Regulation of this interplay depends on the type of injury and may vary individually and over time. In this setting, patient management can be a challenging task, where standard ICP/CPP monitoring may become insufficient to prevent secondary brain injury. Growing clinical evidence demonstrates that so-called multimodal brain monitoring, including brain tissue oxygen (PbtO2), cerebral microdialysis and transcranial Doppler among others, might help to optimize CBF and the delivery of oxygen/energy substrate at the bedside, thereby improving the management of secondary brain injury. Looking beyond ICP and CPP, and applying a multimodal therapeutic approach for the optimization of CBF, oxygen delivery, and brain energy supply may eventually improve overall care of patients with head injury. This review summarizes some of the important pathophysiological determinants of secondary cerebral damage after TBI and discusses novel approaches to optimize CBF and provide adequate oxygen and energy supply to the injured brain using multimodal brain monitoring.

Effect of an I.V. bolus of phenylephrine or ephedrine on skin blood flow during spinal anesthesia

Effet d'un bolus intraveineux de ph��nylephrine ou d'��phedr��ne sur le flux sanguin cutan�� lors d'une anesth��sie rachidienne Introduction : La ph��nylephrine et l'��phedrine sont des substances vaso-actives utilis��es de routine pour corriger des ��pisodes d'hypotension art��rielle induits par l'anesth��sie intrarachidienne. L'influence de ces deux vasopresseurs sur le flux sanguin cutan�� (FSC) dans ce contexte n'a jusqu'�� maintenant pas ��t�� d��crite. Cette ��tude ��value l'effet d'une injection intraveineuse de 75 ��g de ph��nylephrine ou de 7.5 mg d'��phedrine sur le FSC mesur�� par Laser Doppler, dans les zones concern��es parle bloc sympathiqu�� induit par l'anesth��sie intrarachidienne (membres inf��rieurs) et dans les zones non concern��es (membres sup��rieurs). M��thode :Apr��s acceptation par le Comit�� d'��thique, et obtention de leur accord ��crit, 20 patients devant subir une intervention chirurgicale ��lective en d��cubitus dorsal sous anesth��sie. intrarachidienne ont ��t�� inclus dans cette ��tude randomis��e en double insu. Le FSC a ��t�� mesur�� en continu par deux sondes fix��es l'une �� la cuisse (zone avec bloc sympathique) et l'autre sur l'avantbras (zone sans bloc sympathique). Les valeurs de FSC ont ��t�� enregistr��es apr��s l'anesth��sie rachidienne (valeur contr��le), puis apr��s l'injection i.v. d�� ph��nylephrine (10 patients) ou d'��phedrine (10 patients) pour corriger une hypotension d��finie comme une chute de 20 mmHg de la pression art��rielle systolique. Les variations de FSC exprim��es en pourcentage de la valeur contr��le moyenne (+/- ��cart type) ont ��t�� analys��es par le test t de Student. R��sultats :Les donn��es d��mographiques des patients et le niveau sensitif induit par l'anesth��sie rachidienne sont similaires dans les deux groupes. Aux doses utilis��es, seule l'��phedrine restaure la pression art��rielle aux valeurs pr��c��dant l'anesth��sie rachidienne. La ph��nylephrine augmente le FSC de l'avant-bras de 44% (+/- 79%) et de la cuisse de 34% (+/-24%), alors que l'��phedrine diminue le d��bit sanguin cutan�� de l'avant-bras de 16% (+/- 15%) et de la cuisse de 22% (+/-11%). Conclusion : L'injection intraveineuse de ph��nylephrine et d'��phedrine ont des effets oppos��s sur le flux sanguin cutan��, et cette r��ponse n'est pas modifi��e par le bloc sympathique.. Cette diff��rence peut s'expliquer par la distribution des sous-types de r��cepteurs adr��nergiques alpha et leur pr��dominance relative dans les veines et les art��res de diff��rents diam��tres perfusant le tissu sous-cutan�� et la peau. L'��phedrine, ��n raison de sa meilleure efficacit�� pour traiter les ��pisodes d'hypotension art��rielle apr��s anesth��sie intrarachidienne devrait ��tre pr��f��r�� �� la ph��nylephrine, leurs effets oppos��s sur le flux sanguin cutan�� n'��tant pas pertinents en pratique clinique. SUMMARY Background: Phenylephrine or ephedrine is routinely used to correct hypotensive episodes fallowing spinal anaesthesia (SA). The influence of these two vasopressors on skin blood flow (SBF) has not yet been described. We have therefore evaluated the effects of an i.v. bolus of 75 ��g phenylephrine or 7.5 mg of ephedrine on SBF measured by laser Doppler flowmetry during sympathetic blockade induced by SA. Methods: With Ethical Committee approval and written consent, 20 patients scheduled for elective procedures in supine position under SA were enrolled in this double-blind randomized study. SBF was measured continuously by two probes fixed at the thigh (area with sympathic blockade) and forearm level (area without sympathic blockade) respectively. SBF values were recorded after SA (control values) and then after a bolus administration of phenylephrin�� (n=10) or ephedrine (n=10) when systolic blood pressure decreased by 20 mmHg. Changes were expressed as percentage of control SBF values and analysed by Student's paired t-test. Results: Patient characteristics and dermatomal sensory levels were similar in both groups. Phenylephrine increases mean SBF at the forearm level by 44% (79%) [mean (SD)j and at the thigh by 34% (24%). Ephedrine decreases SBF at the forearm level by 16% (15%) and at the thigh by 22% (il%). Ephedrine bolus restores arterial blood pressure to pre-anaesthesia values, whereas phenylephrine does not. Conclusion: Administrati��n of phenylephrine and ephedrine has opposite effects on skin blood flow and sympathetic blockade does not modify this response. These findings could be explained by the distribution of the alpha-adrenor��ceptor subtypes and their relative predominance among veins and arteries of different size perfusing the subcutaneous tissue and the skin. Ephedrine, due to its better efficacy to correct hypotensive episodes following SA, should be preferred, to phenylephrine, their opposite effects on SBF being not relevant for clinical practice.

An experimental study of discharge partitioning and flow structure at symmetrical bifurcations

Recent research has examined the factors controlling the geometrical configuration of bifurcations, determined the range of stability conditions for a number of bifurcation types and assessed the impact of perturbations on bifurcation evolution. However, the flow division process and the parameters that influence flow and sediment partitioning are still poorly characterized. To identify and isolate these parameters, three-dimensional velocities were measured at 11 cross-sections in a fixed-walled experimental bifurcation. Water surface gradients were controlled, and systematically varied, using a weir in each distributary. As may be expected, the steepest distributary conveyed the most discharge ( was dominant) while the mildest distributary conveyed the least discharge ( was subordinate). A zone of water surface super-elevation was co-located with the bifurcation in symmetric cases or displaced into the subordinate branch in asymmetric cases. Downstream of a relatively acute-angled bifurcation, primary velocity cores were near to the water surface and against the inner banks, with near-bed zones of lower primary velocity at the outer banks. Downstream of an obtuse-angled bifurcation, velocity cores were initially at the outer banks, with near-bed zones of lower velocities at the inner banks, but patterns soon reverted to match the acute-angled case. A single secondary flow cell was generated in each distributary, with water flowing inwards at the water surface and outwards at the bed. Circulation was relatively enhanced within the subordinate branch, which may help explain why subordinate distributaries remain open, may play a role in determining the size of commonly-observed topographic features, and may thus exert some control on the stability of asymmetric bifurcations. Further, because larger values of circulation result from larger gradient disadvantages, the length of confluence-diffluence units in braided rivers or between diffluences within delta distributary networks may vary depending upon flow structures inherited from upstream and whether, and how, they are fed by dominant or subordinate distributaries. Copyright (C) 2011 John Wiley & Sons, Ltd.

Effects of adrenergic and cholinergic blockade on insulin-induced stimulation of calf blood flow in humans.

Euglycemic hyperinsulinemia stimulates both sympathetic nerve activity and blood flow to skeletal muscle, but the mechanism is unknown. Possible mechanisms that may stimulate muscle blood flow include neural, humoral, or metabolic effects of insulin. To determine whether such insulin-induced vasodilation is modulated by stimulation of adrenergic or cholinergic mechanisms, we obtained, in eight healthy lean subjects, plethysmographic measurements of calf blood flow during 3 h of hyperinsulinemic (1 mU.kg-1.min-1) euglycemic clamp performed alone or during concomitant beta-adrenergic (propranolol infusion), cholinergic (atropine infusion), or alpha-adrenergic (prazosin administration) blockade. Euglycemic hyperinsulinemia alone increased calf blood flow by 38 +/- 10% (means +/- SE) and decreased vascular resistance by 27 +/- 4% (P < 0.01). The principal new observation is that these insulin-induced vasodilatory responses were not attenuated by concomitant propranolol or atropine infusion, nor were they potentiated by prazosin administration. In conclusion, these findings provide evidence that during euglycemic hyperinsulinemia in lean healthy humans stimulation of muscle blood flow is not mediated primarily by beta-adrenergic or cholinergic mechanisms. Furthermore, alpha-adrenergic mechanisms do not markedly limit insulin-induced stimulation of muscle blood flow.

El Advergaming en el digital signage: actores que determinan la obtenci��n del "flow experience" de acuerdo a la ubicaci��n de un dispositivo de emisi��n de contenido digital, din��mico e interactivo con videojuegos de marca

En la recerca d���eines que suposen la interactivitat com a punt clau en el model de comunicaci��, la present investi- gaci�� aborda l�����s de videojocs amb contingut publicitari o ���advergaming��� com a punt central d���estudi i pret��n es- tablir els factors que determinen una experi��ncia de joc ��ptima a trav��s de l�����s de pantalles digitals com a mitj�� difusor d���aquest tipus de contingut. Parlarem de ���flow experience��� o teoria de la psicologia po- sitiva segons el seu creador i precursor Mih��ly Cs��kszent- mih��lyi, i ser�� la perspectiva des de la qual pretenem desenvolupar aquest estudi, entenent el ���flow experience��� com l���estat ��ptim o nivell m��s alt d���experi��ncia d���usuari que es pot assolir durant una activitat

Continuous arterial spin labeling of mouse cerebral blood flow using an actively-detuned two-coil system at 9.4T.

Among numerous magnetic resonance imaging (MRI) techniques, perfusion MRI provides insight into the passage of blood through the brain's vascular network non-invasively. Studying disease models and transgenic mice would intrinsically help understanding the underlying brain functions, cerebrovascular disease and brain disorders. This study evaluates the feasibility of performing continuous arterial spin labeling (CASL) on all cranial arteries for mapping murine cerebral blood flow at 9.4 T. We showed that with an active-detuned two-coil system, a labeling efficiency of 0.82 �� 0.03 was achieved with minimal magnetization transfer residuals in brain. The resulting cerebral blood flow of healthy mouse was 99 �� 26 mL/100g/min, in excellent agreement with other techniques. In conclusion, high magnetic fields deliver high sensitivity and allowing not only CASL but also other MR techniques, i.e. (1)H MRS and diffusion MRI etc, in studying murine brains.

Combination of fluorescent reporters for simultaneous monitoring of root colonization and antifungal gene expression by a biocontrol pseudomonad on cereals with flow cytometry.

Some root-associated pseudomonads sustain plant growth by suppressing root diseases caused by pathogenic fungi. We investigated to which extent select cereal cultivars influence expression of relevant biocontrol traits (i.e., root colonization efficacy and antifungal activity) in Pseudomonas fluorescens CHA0. In this representative plant-beneficial bacterium, the antifungal metabolites 2,4-diacetylphloroglucinol (DAPG), pyrrolnitrin (PRN), pyoluteorin (PLT), and hydrogen cyanide (HCN) are required for biocontrol. To monitor host plant effects on the expression of biosynthetic genes for these compounds on roots, we developed fluorescent dual-color reporters suited for flow cytometric analysis using fluorescence-activated cell sorting (FACS). In the dual-label strains, the constitutively expressed red fluorescent protein mCherry served as a cell tag and marker for root colonization, whereas reporter fusions based on the green fluorescent protein allowed simultaneous recording of antifungal gene expression within the same cell. FACS analysis revealed that expression of DAPG and PRN biosynthetic genes was promoted in a cereal rhizosphere, whereas expression of PLT and HCN biosynthetic genes was markedly less sustained. When analyzing the response of the bacterial reporters on roots of a selection of wheat, spelt, and triticale cultivars, we were able to detect subtle species- and cultivar-dependent differences in colonization and DAPG and HCN gene expression levels. The expression of these biocontrol traits was particularly favored on roots of one spelt cultivar, suggesting that a careful choice of pseudomonad-cereal combinations might be beneficial to biocontrol. Our approach may be useful for selective single-cell level analysis of plant effects in other bacteria-root interactions.

Mutant HbpR transcription activator isolation for 2-chlorobiphenyl via green fluorescent protein-based flow cytometry and cell sorting.

Mutants were produced in the A-domain of HbpR, a protein belonging to the XylR family of σ(54)-dependent transcription activators, with the purpose of changing its effector recognition specificity from 2-hydroxybiphenyl (2-HBP, the cognate effector) to 2-chlorobiphenyl (2-CBP). Mutations were introduced in the hbpR gene part for the A-domain via error-prone polymerase chain reaction, and assembled on a gene circuitry plasmid in Escherichia coli, permitting HbpR-dependent induction of the enhanced green fluorescent protein (egfp). Cells with mutant HbpR proteins responsive to 2-CBP were enriched and separated in a flow cytometry-assisted cell-sorting procedure. Some 70 mutants were isolated and the A-domain mutations mapped. One of these had acquired true 2-CBP recognition but reacted hypersensitively to 2-HBP (20-fold more than the wild type), whereas others had reduced sensitivity to 2-HBP but a gain of 2-CBP recognition. Sequencing showed that most mutants carried double or triple mutations in the A-domain gene part, and were not located in previously recognized conserved residues within the XylR family members. Further selection from a new mutant pool prepared of the hypersensitive mutant did not result in increased 2-CBP or reduced 2-HBP recognition. Our data thus demonstrate that a one-step in vitro 'evolutionary' adaptation of the HbpR protein can result in both enhancement and reduction of the native effector recognition.

Characterization of Human Late Outgrowth Endothelial Progenitor-Derived Cells under Various Flow Conditions.

Background: Endothelial progenitor-derived cells (EPC) are a cell therapy tool in peripheral arterial disease and for re-endothelialization of bypasses and stents. Objective: To assess EPC behavior under flow conditions normally found in vivo. Results: EPC were isolated from human cord blood, cultured on compliant tubes and exposed in an in vitro flow system mimicking hemodynamic environments normally found in medium and large arteries. EPC exposed for 24 h to unidirectional (0.3 �� 0.1 or 6 �� 3 dynes/cm(2)) shear stress oriented along flow direction, while those exposed to bidirectional shear stress (0.3 �� 3 dynes/cm(2)) or static conditions had random orientation. Under bidirectional flow, tissue factor (TF) activity and mRNA expression were significantly increased (2.5- and 7.0-fold) compared to static conditions. Under low shear unidirectional flow TF mRNA increased 4.9 �� 0.5-fold. Similar flow-induced increases were observed for TF in mature umbilical vein-derived endothelial cells. Expression of tissue-type plasminogen activator (t-PA), urokinase (u-PA) and monocyte chemotactic protein 1 (MCP1) were reduced by 40-60% in late outgrowth endothelial progenitor-derived cells (LO-EPC) exposed to any flow environment, while MCP1, but not t-PA or u-PA, was decreased in HUVEC. Conclusions: Flow, in particular bidirectional, modifies the hemostatic balance in LO-EPC with increased TF and decreased plasminogen activator expression.

Determination of sea surface salinity and wind speed by L-band microwave radiometry from a fixed platform

The European Space Agency Soil Moisture andOcean Salinity (SMOS) mission aims at obtaining global maps ofsoil moisture and sea surface salinity from space for large-scale andclimatic studies. It uses an L-band (1400���1427 MHz) MicrowaveInterferometric Radiometer by Aperture Synthesis to measurebrightness temperature of the earth���s surface at horizontal andvertical polarizations ( h and v). These two parameters will beused together to retrieve the geophysical parameters. The retrievalof salinity is a complex process that requires the knowledge ofother environmental information and an accurate processing ofthe radiometer measurements. Here, we present recent resultsobtained from several studies and field experiments that were partof the SMOS mission, and highlight the issues still to be solved.

Note on the blocking flow shop problem

We present some results attained with different algorithms for the Fm|block|Cmax problem using as experimental data the well-known Taillard instances.