Endotoxemia increases the clearance of mPEGylated 5000-MW quantum dots as revealed by multiphoton microvascular imaging

Bateman, Ryon M.; Hodgson, Kevin; Kohli, K. L.; Knight, Darryl A.; Walley, Keith R.

doi:10.1117/1.2822882

Cited by 12 publications

(8 citation statements)

References 20 publications

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“…Solid lines indicate perfused capillaries, whereas broken lines indicate stopped-flow capillaries. Capillaries were pseudo colored for depth below the surface: brown (surface), green (75 µm), blue (150 µm) (Bateman et al [ 35 ]). ( C , D ) Blood smears from a healthy volunteer with normal red blood cell (RBC) discocyte morphology and a septic shock patient with abnormal RBC morphology, respectively.…”

Section: Figurementioning

confidence: 99%

The Effect of Sepsis on the Erythrocyte

Bateman

Sharpe

Singer

et al. 2017

IJMS

134

135

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Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin’s affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O2-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction.

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Section: Figurementioning

confidence: 99%

The Effect of Sepsis on the Erythrocyte

Bateman

Sharpe

Singer

et al. 2017

IJMS

134

135

View full text Add to dashboard Cite

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“…This mode can also be realized in QDs, exhibiting two-and multiphoton effects. 15,16 PA spectroscopy revealed (Figure 5) that the optimal spectral range with high PA responses from the used QDs lies in the wavelength range of 620-645 nm, which is close to the NIR window transparency of biological tissues (650-950 nm), where interference with blood absorption is minimal. 17 Progress in the development of NIR fluorescent QDs with absorption in the range of 750 nm and even 850 nm 2,18 opens up opportunities to use them also with PA/PT techniques.…”

mentioning

confidence: 93%

Quantum Dots as Multimodal Photoacoustic and Photothermal Contrast Agents

et al. 2008

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Quantum dots (QDs) have primarily been developed as fluorescent probes with unique optical properties. We herein demonstrate an extension of these QD utilities to photoacoustic (PA) and photothermal (PT) microscopy, using a nanosecond pulse laser excitation (420–900 nm, 8 ns, 10−3-10 J/cm2). The laser-induced PA, PT and accompanying bubble formation phenomena were studied with an advanced multifunctional microscope, which integrates fluorescence, PA, PT imaging, and PT thermolens modules. It was demonstrated that QDs, in addition to being excellent fluorescent probes, can be used as PA and PT contrast agents and sensitizers, thereby providing an opportunity for multimodal PA-PT-fluorescent imaging as well as PT therapy. Further improvements for this technology are suggested by increasing the conversion of laser energy in PT, PA, and bubble phenomena in hybrid multilayer QDs that have optimized absorption, thermal, and acoustic properties.

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“…In contrast to fluorescent confocal microscopy or spinning-disc microscopy where a single photon is used to excite a given fluorophore, in multiphoton microscopy (MPM), two photons of longer wavelength are used to simultaneously excite a sample fluorophore [33]. The advantage of MPM is that longer wavelengths allow for deeper sample penetration of both tissues [34] and fluids with less light scattering, less photobleaching and loss of fluorescent signal, as may occur with confocal microscopy. This occurs because multiphoton excitation is non-linear and limited to a small femtoliter focal volume at the focal point of the laser beam; whereas, one photon imaging creates a large cone of excitation within the sample.…”

Section: Methodsmentioning

confidence: 99%

S-Nitrosoglutathione Acts as a Small Molecule Modulator of Human Fibrin Clot Architecture

et al. 2012

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BackgroundAltered fibrin clot architecture is increasingly associated with cardiovascular diseases; yet, little is known about how fibrin networks are affected by small molecules that alter fibrinogen structure. Based on previous evidence that S-nitrosoglutathione (GSNO) alters fibrinogen secondary structure and fibrin polymerization kinetics, we hypothesized that GSNO would alter fibrin microstructure.Methodology/Principal FindingsAccordingly, we treated human platelet-poor plasma with GSNO (0.01–3.75 mM) and imaged thrombin induced fibrin networks using multiphoton microscopy. Using custom designed computer software, we analyzed fibrin microstructure for changes in structural features including fiber density, diameter, branch point density, crossing fibers and void area. We report for the first time that GSNO dose-dependently decreased fibrin density until complete network inhibition was achieved. At low dose GSNO, fiber diameter increased 25%, maintaining clot void volume at approximately 70%. However, at high dose GSNO, abnormal irregularly shaped fibrin clusters with high fluorescence intensity cores were detected and clot void volume increased dramatically. Notwithstanding fibrin clusters, the clot remained stable, as fiber branching was insensitive to GSNO and there was no evidence of fiber motion within the network. Moreover, at the highest GSNO dose tested, we observed for the first time, that GSNO induced formation of fibrin agglomerates.Conclusions/SignificanceTaken together, low dose GSNO modulated fibrin microstructure generating coarse fibrin networks with thicker fibers; however, higher doses of GSNO induced abnormal fibrin structures and fibrin agglomerates. Since GSNO maintained clot void volume, while altering fiber diameter it suggests that GSNO may modulate the remodeling or inhibition of fibrin networks over an optimal concentration range.

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Endotoxemia increases the clearance of mPEGylated 5000-MW quantum dots as revealed by multiphoton microvascular imaging

Cited by 12 publications

References 20 publications

The Effect of Sepsis on the Erythrocyte

The Effect of Sepsis on the Erythrocyte

Quantum Dots as Multimodal Photoacoustic and Photothermal Contrast Agents

S-Nitrosoglutathione Acts as a Small Molecule Modulator of Human Fibrin Clot Architecture

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