237 research outputs found
Assessment of the interplay between blood and skin vascular abnormalities in adult purpura fulminans
RATIONALE: Purpura fulminans in adults is a rare but devastating disease. Its pathophysiology is not well known. OBJECTIVES: To understand the pathophysiology of skin lesions in purpura fulminans, the interplay between circulating blood and vascular alterations was assessed. METHODS: Prospective multicenter study in four intensive care units. Patients with severe sepsis without skin lesions were recruited as control subjects. MEASUREMENTS AND MAIN RESULTS: Twenty patients with severe sepsis and purpura fulminans were recruited for blood sampling, and skin biopsy was performed in deceased patients. High severity of disease and mortality rates (80%) was observed. Skin biopsies in purpura fulminans lesions revealed thrombosis and extensive vascular damage: vascular congestion and dilation, endothelial necrosis, alteration of markers of endothelial integrity (CD31) and of the protein C pathway receptors (endothelial protein C receptor, thrombomodulin). Elevated plasminogen activating inhibitor-1 mRNA was also observed. Comparison with control patients showed that these lesions were specific to purpura fulminans. By contrast, no difference was observed for blood hemostasis parameters, including soluble thrombomodulin, activated protein C, and disseminated intravascular coagulation markers. Bacterial presence at the vascular wall was observed specifically in areas of vascular damage in eight of nine patients tested (including patients with Streptococcus pneumoniae, Neisseria meningitidis, Escherichia coli, and Pseudomonas aeruginosa infection). CONCLUSIONS: Thrombi and extensive vascular damage with multifaceted prothrombotic local imbalance are characteristics of purpura fulminans. A "vascular wall infection" hypothesis, responsible for endothelial damage and subsequent skin lesions, can be put forward
Comparative overwiew of brain perfusion imaging techniques
Background and Purpose - Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are positron emission tomography, single photon emission computed tomography, Xenon-enhanced computed tomography, dynamic perfusion computed tomography, MRI dynamic susceptibility contrast, arterial spin labeling, and Doppler ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow or cerebral blood volume. All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks.
Summary of Review - This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview established by consensus among specialists of the various techniques.
Conclusions - For clinicians, this article should offer a clearer picture of the pros and cons of currently available brain perfusion imaging techniques and assist them in choosing the proper method for every specific clinical setting
Comparative overview of brain perfusion imaging techniques Epub
Background and Purpose - Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are positron emission tomography, single photon emission computed tomography, Xenon-enhanced computed tomography, dynamic perfusion computed tomography, MRI dynamic susceptibility contrast, arterial spin labeling, and Doppler ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow or cerebral blood volume. All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks.
Summary of Review - This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview established by consensus among specialists of the various techniques.
Conclusions - For clinicians, this article should offer a clearer picture of the pros and cons of currently available brain perfusion imaging techniques and assist them in choosing the proper method for every specific clinical setting
Template-free 13-protofilament microtubule–MAP assembly visualized at 8 A resolution
Microtubule-associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy and single particle algorithms, we solved the 8 Å structure of doublecortin (DCX)-stabilized MTs. Because of DCX’s unusual ability to specifically nucleate and stabilize 13-protofilament MTs, our reconstruction provides unprecedented insight into the structure of MTs with an in vivo architecture, and in the absence of a stabilizing drug. DCX specifically recognizes the corner of four tubulin dimers, a binding mode ideally suited to stabilizing both lateral and longitudinal lattice contacts. A striking consequence of this is that DCX does not bind the MT seam. DCX binding on the MT surface indirectly stabilizes conserved tubulin–tubulin lateral contacts in the MT lumen, operating independently of the nucleotide bound to tubulin. DCX’s exquisite binding selectivity uncovers important insights into regulation of cellular MTs
The importance of diastolic dysfunction in the development of weaning-induced pulmonary oedema
Gold/Silica biochips: applications to Surface Plasmon Resonance and fluorescence quenching
We report Gold/Silica biochips for low cost biosensor devices. Firstly, the
study of biochemical interactions on silica by means of Surface Plasmon
Resonance (SPR) is presented. Secondly, Gold/Silica biochips are employed to
reduce the strong quenching that occurs when a fluorophore is close to the gold
surface. Furthermore, the control of the Silica-like thickness allows
optimizing the distance between the metallic surface and the fluorophore in
order to enhance the fluorescent signal. These results represent the first
steps towards highly sensitive, specific and low cost biosensors based, for
example, on Surface Plasmon Coupled Emission (SPCE) techniques
Comparison of monocyte human leukocyte antigen-DR expression and stimulated tumor necrosis factor alpha production as outcome predictors in severe sepsis: a prospective observational study
Mechanochemical modeling of dynamic microtubule growth involving sheet-to-tube transition
Microtubule dynamics is largely influenced by nucleotide hydrolysis and the
resultant tubulin configuration changes. The GTP cap model has been proposed to
interpret the stabilizing mechanism of microtubule growth from the view of
hydrolysis effects. Besides, the microtubule growth involves the closure of a
curved sheet at its growing end. The curvature conversion also helps to
stabilize the successive growth, and the curved sheet is referred to as the
conformational cap. However, there still lacks theoretical investigation on the
mechanical-chemical coupling growth process of microtubules. In this paper, we
study the growth mechanisms of microtubules by using a coarse-grained molecular
method. Firstly, the closure process involving a sheet-to-tube transition is
simulated. The results verify the stabilizing effect of the sheet structure,
and the minimum conformational cap length that can stabilize the growth is
demonstrated to be two dimers. Then, we show that the conformational cap can
function independently of the GTP cap, signifying the pivotal role of
mechanical factors. Furthermore, based on our theoretical results, we describe
a Tetris-like growth style of microtubules: the stochastic tubulin assembly is
regulated by energy and harmonized with the seam zipping such that the sheet
keeps a practically constant length during growth.Comment: 23 pages, 7 figures. 2 supporting movies have not been uploaded due
to the file type restriction
Dissociable roles of mGlu5 and dopamine receptors in the rewarding and sensitizing properties of morphine and cocaine
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