INT251459
From wiki-pain
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
We have previously characterized the sensitizing effect of LPS exposure on neuronal damage following OGD in juvenile murine hippocampal slice cultures and showed that time separation between the respective insults was decisive for resulting neuronal damage, ie for a sensitizing, or with an increased time separation, a protective effect [17]. | |||||||||||||||
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Still considering that transient changes in H3K4me2 marks associated with the IE lytic promoter ICP0 may have been missed due to experimental constraints, we assessed whether we could detect changes in the accumulation of ICP0 transcript abundance at early times post-TCIE. | |||||||||||||||
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These processes obviously have the potential to influence the interaction between IE and platelets, and it is possible that clumping could be an artefact of in vitro platelet activation. | |||||||||||||||
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However, it does seem plausible that, as suggested by Wassmer et al [17], platelet-binding to IE might promote cytoadherence and sequestration in vivo, and could target binding to endothelial beds not expressing adhesion receptors, such as CD36 [17]. | |||||||||||||||
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The marked effect of assay conditions on clumping frequency is in contrast to another P. falciparum adhesion phenotype studied in suspension assays the formation of rosettes by uninfected erythrocytes binding to IE. | |||||||||||||||
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This limitation of the suspension assay suggests that it may be worthwhile to pursue alternative approaches to analysing the ability of IE to interact with platelets, such as the use of plate binding assays under static or flow conditions [14-16]. | |||||||||||||||
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These results indicate that platelet binding to IE is a property of fresh platelets that is retained by old platelets, and is not merely an artefact resulting from platelet storage. | |||||||||||||||
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Two or more platelets could be seen binding between IE (Figure 1B, left and upper and middle right) and, occasionally, large platelet aggregates were seen within clumps (Figure 1B, bottom right). | |||||||||||||||
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One of the most recent P. falciparum cytoadherence phenotypes to be described is the ability of IE to bind to platelets in suspension assays in vitro to form platelet-mediated clumps of infected cells [6] (Figure 1). | |||||||||||||||
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Assays with stored and fresh PPP were also performed in order to exclude the possibility of IE aggregation occurring without platelet-binding.
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Although cytoadherence and sequestration of mature IE to the microvascular endothelium occurs in all infections, several adhesive phenotypes have been associated with severe pathological outcomes of malaria, such as the formation of rosettes (binding of IE to uninfected erythrocytes) [5], and the sequestration of IE in the microvasculature of the brain and the placenta [4]. | |||||||||||||||
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It is currently unclear whether platelet-mediated clumping measured in suspension assays and platelet-binding by IE measured in plate assays are identical phenotypes. | |||||||||||||||
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Clumping frequency was expressed as the percentage of IE in clumps out of the total number of IE counted. | |||||||||||||||
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This case shows that IE can present with late embolic episodes, even after the completion of appropriate antibiotic therapy. | |||||||||||||||
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The results indicated lack of binding of IE to any of the four receptors during the first eight days of cultivation. | |||||||||||||||
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The ex vivo and subsequent in vitro analysis of IE presented here, indicates a correlation between transcription of particular parasite multicopy gene families and binding of IE to endothelial receptors. | |||||||||||||||
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This latter explanation would be fully consistent with our finding that the ex vivo parasites from the splenectomized patient do not express genes coding for proteins that are targeted to the erythrocyte surface and consequently these IE do not bind to common endothelial receptors as shown by our in vitro analyses. | |||||||||||||||
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However, on the two following time points (day 15 and 30) a gradual increase of IE binding was observed to CD36 and ICAM-1, which reached a maximum on day 30 of cultivation (Fig. 3) and did not further change during the following weeks (data not shown). | |||||||||||||||
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To avoid spleen-dependent killing mechanisms parasite-infected erythrocytes (IE) of Plasmodium falciparum malaria patients have the capacity to bind to endothelial receptors. | |||||||||||||||
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General Comments
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