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In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study.

ABSTRACT: To establish that a magnetic device designed for intravascular use can bind small iron particles in physiologic flow models.Uncoated iron oxide particles 50-100 nm and 1-5 µm in size were tested in a water flow chamber over a period of 10 minutes without a magnet (ie, control) and with large and small prototype magnets. These same particles and 1-µm carboxylic acid-coated iron oxide beads were likewise tested in a serum flow chamber model without a magnet (ie, control) and with the small prototype magnet.Particles were successfully captured from solution. Particle concentrations in solution decreased in all experiments (P < .05 vs matched control runs). At 10 minutes, concentrations were 98% (50-100-nm particles in water with a large magnet), 97% (50-100-nm particles in water with a small magnet), 99% (1-5-µm particles in water with a large magnet), 99% (1-5-µm particles in water with a small magnet), 95% (50-100-nm particles in serum with a small magnet), 92% (1-5-µm particles in serum with a small magnet), and 75% (1-µm coated beads in serum with a small magnet) lower compared with matched control runs.This study demonstrates the concept of magnetic capture of small iron oxide particles in physiologic flow models by using a small wire-mounted magnetic filter designed for intravascular use.

SUBMITTER: Mabray MC

PROVIDER: S-EPMC4769113 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study.

Mabray Marc C MC Lillaney Prasheel P Sze Chia-Hung CH Losey Aaron D AD Yang Jeffrey J Kondapavulur Sravani S Liu Derek D Saeed Maythem M Patel Anand A Cooke Daniel D Jun Young-Wook YW El-Sayed Ivan I Wilson Mark M Hetts Steven W SW

Journal of vascular and interventional radiology : JVIR 20151222 3

<h4>Purpose</h4>To establish that a magnetic device designed for intravascular use can bind small iron particles in physiologic flow models.<h4>Materials and methods</h4>Uncoated iron oxide particles 50-100 nm and 1-5 µm in size were tested in a water flow chamber over a period of 10 minutes without a magnet (ie, control) and with large and small prototype magnets. These same particles and 1-µm carboxylic acid-coated iron oxide beads were likewise tested in a serum flow chamber model without a m ...[more]

PMID: 26706187

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Project description:UNLABELLED:Intraarterial microdosing (IAM) is a novel drug development approach combining intraarterial drug delivery and microdosing. We aimed to demonstrate that IAM leads to target exposure similar to that of systemic full-dose administration but with minimal systemic exposure. IAM could enable the safe, inexpensive, and early study of novel drugs at the first-in-human stage and the study of established drugs in vulnerable populations. METHODS:Insulin was administered intraarterially (ipsilateral femoral artery) or systemically to 8 CD IGS rats just before blood sampling or 60-min (18)F-FDG uptake PET imaging of ipsilateral and contralateral leg muscles (lateral gastrocnemius) and systemic muscles (spinotrapezius). The (18)F-FDG uptake slope analysis was used to compare the interventions. Plasma levels of insulin and glucose were compared using area under the curve calculated by the linear trapezoidal method. A physiologically based computational pharmacokinetics/pharmacodynamics model was constructed to simulate the relationship between the administered dose and response over time. RESULTS:(18)F-FDG slope analysis found no difference between IAM and systemic full-dose slopes (0.0066 and 0.0061, respectively; 95% confidence interval [CI], -0.024 to 0.029; P = 0.7895), but IAM slope was statistically significantly greater than systemic microdose (0.0018; 95% CI, -0.045 to -0.007; P = 0.0147) and sham intervention (-0.0015; 95% CI, 0.023-0.058; P = 0.0052). The pharmacokinetics/pharmacodynamics data were used to identify model parameters that describe membrane insulin binding and glucose-insulin dynamics. CONCLUSION:Target exposure after IAM was similar to systemic full dose administration but with minimal systemic effects. The computational pharmacokinetics/pharmacodynamics model can be generalized to predict whole-body response. Findings should be validated in larger, controlled studies in animals and humans using a range of targets and classes of drugs.

Project description:BackgroundEstimation of glomerular filtration rate (GFR) using estimated glomerular filtration rate creatinine (eGFRcr) is central to clinical practice but has limitations. We tested the hypothesis that serum metabolomic profiling can identify novel markers that in combination can provide more accurate GFR estimates.MethodsWe performed a cross-sectional study of 200 African American Study of Kidney Disease and Hypertension (AASK) and 265 Multi-Ethnic Study of Atherosclerosis (MESA) participants with measured GFR (mGFR). Untargeted gas chromatography/dual mass spectrometry- and liquid chromatography/dual mass spectrometry-based quantification was followed by the development of targeted assays for 15 metabolites. On the log scale, GFR was estimated from single- and multiple-metabolite panels and compared with eGFR using the Chronic Kidney Disease Epidemiology equations with creatinine and/or cystatin C using established metrics, including the proportion of errors >30% of mGFR (1-P30), before and after bias correction.ResultsOf untargeted metabolites in the AASK and MESA, 283 of 780 (36%) and 387 of 1447 (27%), respectively, were significantly correlated (P ≤ 0.001) with mGFR. A targeted metabolite panel eGFR developed in the AASK and validated in the MESA was more accurate (1-P30 3.7 and 1.9%, respectively) than eGFRcr [11.2 and 18.5%, respectively (P < 0.001 for both)] and estimating GFR using cystatin C (eGFRcys) [10.6% (P = 0.02) and 9.1% (P < 0.05), respectively] but was not consistently better than eGFR using both creatinine and cystatin C [3.7% (P > 0.05) and 9.1% (P < 0.05), respectively]. A panel excluding creatinine and demographics still performed well [1-P30 6.4% (P = 0.11) and 3.4% (P < 0.001) in the AASK and MESA] versus eGFRcr.ConclusionsMultimetabolite panels can enable accurate GFR estimation. Metabolomic equations, preferably excluding creatinine and demographic characteristics, should be tested for robustness and generalizability as a potential confirmatory test when eGFRcr is unreliable.

Project description:Background and objectivesRed blood cell (RBC) units in hypothermic storage degrade over time, commonly known as the RBC storage lesion. These older RBC units can cause adverse clinical effects when transfused, as older RBCs in the unit lyse and release cell-free haemoglobin (Hb), a potent vasodilator that can elicit vasoconstriction, systemic hypertension and oxidative tissue injury after transfusion. In this study, we examined a novel method of washing ex vivo stored single RBC units to remove accumulated cellular waste, specifically cell-free Hb, using tangential flow filtration (TFF) driven by a centrifugal pump.Materials and methodsThe TFF RBC washing system was run under hypothermic conditions at 4°C, at a constant system volume with 0.9 wt% saline as the wash solution. The RBC washing process was conducted on 10 separate RBC units. For this proof-of-concept study, RBC units were expired at the time of washing (60-70 days old). Cell-free Hb was quantified by UV-visible absorbance spectroscopy and analysed via the Winterbourn equations. Pre- and post-wash RBC samples were analysed by Hemox Analyser, Coulter counter and Brookfield rheometer. The RBC volume fraction in solution was measured throughout the wash process by standard haematocrit (HCT) analysis.ResultsNo substantial decrease in the HCT was observed during the TFF RBC washing process. However, there was a significant decrease in RBC concentration in the first half of the TFF RBC wash process, with no significant change in RBC concentration during the second half of the TFF cell wash process with an 87% overall cell recovery compared with the total number of cells before initiation of cell washing. Utilization of the extinction coefficients and characteristic peaks of each Hb species potentially present in solution was quantified by Winterbourn analysis on retentate and permeate samples for each diacycle to quantify Hb concentration during the washing process. Significant cell-free Hb reduction was observed within the first four diacycles with a starting cell-free Hb concentration in the RBC unit of 0.105 mM, which plateaus to a constant Hb concentration of 0.01 mM or a total extracellular Hb mass of 0.2 g in the resultant washed unit. The oxygen equilibrium curve showed a significant decrease in P50 between the initial and final RBC sample cell wash with an initial P50 of 15.6 ± 1.8 mm Hg and a final P50 of 14 ± 1.62 mm Hg. Cooperativity increased after washing from an initial Hill coefficient of 2.37 ± 0.19 compared with a final value of 2.52 ± 0.12.ConclusionOverall, this study investigated the proof-of-concept use of TFF for washing single RBC units with an emphasis on the removal of cell-free Hb from the unit. Compared with traditional cell washing procedures, the designed system was able to more efficiently remove extracellular Hb but resulted in longer wash times. For a more complete investigation of the TFF RBC washing process, further work should be done to investigate the effects of RBC unit storage after washing. The designed system is lightweight and transportable with the ability to maintain sterility between uses, providing a potential option for bedside ex vivo transfusion in clinical applications.

Project description:Background: Significant progress toward the recovery of useful vision in blind patients with severe degenerative retinal diseases caused by photoreceptor death has been achieved with the development of visual prostheses that stimulate the retina electrically. However, currently used prostheses do not provide feedback about the retinal activity before and upon stimulation and do not adjust to changes during the remodeling processes in the retina. Both features are desirable to improve the efficiency of the electrical stimulation (ES) therapy offered by these devices. Accordingly, devices that not only enable ES but at the same time provide information about the retinal activity are beneficial. Given the above, a bidirectional communication strategy, in which inner retinal cells are stimulated and the output neurons of the retina, the ganglion cells, are recorded using penetrating microelectrode arrays (MEAs) is proposed. Methods: Custom-made penetrating MEAs with four silicon-based shanks, each one with three or four iridium oxide electrodes specifically designed to match retinal dimensions were used to record the activity of light-adapted wildtype mice retinas and degenerated retinas from rd10 mice in vitro. In addition, responses to high potassium concentration and to light stimulation in wildtype retinas were examined. Furthermore, voltage-controlled ES was performed. Results: The spiking activity of retinal ganglion cells (RGCs) was recorded at different depths of penetration inside the retina. Physiological responses during an increase of the extracellular potassium concentration and phasic and tonic responses during light stimulation were captured. Moreover, pathologic rhythmic activity was recorded from degenerated retinas. Finally, ES of the inner retina and simultaneous recording of the activity of RGCs was accomplished. Conclusion: The access to different layers of the retina with penetrating electrodes while recording at the same time the spiking activity of RGCs broadens the use and the field of action of multi-shank and multi-site penetrating MEAs for retinal applications. It enables a bidirectional strategy to stimulate inner retinal cells electrically and to record from the spiking RGCs simultaneously (BiMEA). This opens the possibility of a feedback loop system to acknowledge the success of ES carried out by retinal prostheses.

Project description:BackgroundFor patients with post-stroke upper limb impairments, the currently available clinical measurement instruments are inadequate for reliable quantification of multiple impairments, such as muscle weakness, abnormal synergy, changes in elastic joint properties and spasticity. Robotic devices to date have successfully achieved precise and accurate quantification but are often limited to the measurement of one or two impairments. Our primary aim is to develop a robotic device that can effectively quantify four main motor impairments of the elbow.Methods The robotic device, Shoulder Elbow Perturbator, is a one-degree-of-freedom device that can simultaneously manipulate the elbow joint and support the (partial) weight of the human arm. Upper limb impairments of the elbow were quantified based on four experiments on the paretic arm in ten stroke patients (mean age 65 ± 10 yrs, 9 males, post-stroke) and the non-dominant arm in 20 healthy controls (mean age 65 ± 14 yrs, 6 males). The maximum strength of elbow flexor and elbow extensor muscles was measured isometrically at 90-degree elbow flexion. The maximal active extension angle of the elbow was measured under different arm weight support levels to assess abnormal synergy. Torque resistance was analyzed during a slow (6°/s) passive elbow rotation, where the elbow moved from the maximal flexion to maximal extension angle and back, to assess elastic joint properties. The torque profile was evaluated during fast (100°/s) passive extension rotation of the elbow to estimate spasticity.ResultsThe ten chronic stroke patients successfully completed the measurement protocol. The results showed impairment values outside the 10th and 90th percentile reference intervals of healthy controls. Individual patient profiles were determined and illustrated in a radar figure, to support clinicians in developing targeted treatment plans.ConclusionThe Shoulder Elbow Perturbator can effectively quantify the four most important impairments of the elbow in stroke patients and distinguish impairment scores of patients from healthy controls. These results are promising for objective and complete quantification of motor impairments of the elbow and monitoring patient prognosis. Our newly developed Shoulder Elbow Perturbator can therefore in the future be employed to evaluate treatment effects by comparing pre- and post-treatment assessments.

Dataset Information

In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study.

Publications

In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study.

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