Spectroscopic evaluation of the effect of the microparticles on radiofrequency argon plasma

International Nuclear Information System (INIS)

Mitic, S; Pustylnik, M Y; Morfill, G E

2009-01-01

Axial distributions of 1s excited states of argon were measured in a radiofrequency (RF) discharge by a self-absorption method. Experiments were performed in the PK-3+ chamber, designed for microgravity experiments in complex (dusty) plasmas on board the International Space Station. A correction of a standard self-absorption method for the extinction of the light by the levitating microparticles is proposed. Distributions, measured at the same discharge conditions in a microparticle-free discharge and a discharge containing a cloud of levitating microparticles, revealed the non-local influence of the microparticle cloud on the discharge plasma. The most probable cause of this influence is the disturbance of the ionization balance by the levitating microparticles.

Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots.

Science.gov (United States)

Zubairova, Laily D; Nabiullina, Roza M; Nagaswami, Chandrasekaran; Zuev, Yuriy F; Mustafin, Ilshat G; Litvinov, Rustem I; Weisel, John W

2015-12-04

Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1-0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis.

Increased IgG on cell-derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation

DEFF Research Database (Denmark)

Nielsen, Christoffer T; Østergaard, Ole; Stener, Line

2012-01-01

To quantify immunoglobulin and C1q on circulating cell-derived microparticles (MPs) in patients with systemic lupus erythematosus (SLE) and to determine whether immunoglobulin and C1q levels are correlated with clinical and serologic parameters.......To quantify immunoglobulin and C1q on circulating cell-derived microparticles (MPs) in patients with systemic lupus erythematosus (SLE) and to determine whether immunoglobulin and C1q levels are correlated with clinical and serologic parameters....

Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube.

Science.gov (United States)

György, Bence; Pálóczi, Krisztina; Kovács, Alexandra; Barabás, Eszter; Bekő, Gabriella; Várnai, Katalin; Pállinger, Éva; Szabó-Taylor, Katalin; Szabó, Tamás G; Kiss, Attila A; Falus, András; Buzás, Edit I

2014-02-01

Recently extracellular vesicles (exosomes, microparticles also referred to as microvesicles and apoptotic bodies) have attracted substantial interest as potential biomarkers and therapeutic vehicles. However, analysis of microparticles in biological fluids is confounded by many factors such as the activation of cells in the blood collection tube that leads to in vitro vesiculation. In this study we aimed at identifying an anticoagulant that prevents in vitro vesiculation in blood plasma samples. We compared the levels of platelet microparticles and non-platelet-derived microparticles in platelet-free plasma samples of healthy donors. Platelet-free plasma samples were isolated using different anticoagulant tubes, and were analyzed by flow cytometry and Zymuphen assay. The extent of in vitro vesiculation was compared in citrate and acid-citrate-dextrose (ACD) tubes. Agitation and storage of blood samples at 37 °C for 1 hour induced a strong release of both platelet microparticles and non-platelet-derived microparticles. Strikingly, in vitro vesiculation related to blood sample handling and storage was prevented in samples in ACD tubes. Importantly, microparticle levels elevated in vivo remained detectable in ACD tubes. We propose the general use of the ACD tube instead of other conventional anticoagulant tubes for the assessment of plasma microparticles since it gives a more realistic picture of the in vivo levels of circulating microparticles and does not interfere with downstream protein or RNA analyses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microparticle counts in platelet-rich and platelet-free plasma, effect of centrifugation and sample-processing protocols.

Science.gov (United States)

Chandler, Wayne L

2013-03-01

This study provides the first estimates of microparticle numbers in platelet-rich plasma (PRP) from normal individuals, closer to in-vivo levels, using higher-resolution flow cytometry. We measured platelet (CD41+) and annexin V+ microparticles in fresh and frozen aliquots of PRP, platelet-poor plasma, platelet-free plasma (PFP), and microparticles isolated by high-speed centrifugation. PRP from healthy individuals contained 730,000/μl total microparticles based on light-scattering measurements. A median of 27,000/μl microparticles in PRP were of platelet origin and 120,000/μl annexin V+, and of these, 24,000/μl were dual-positive procoagulant platelet microparticles. Double centrifugation of PRP removed 99% of platelets, but also 80% of annexin V+ CD41+, 93% of annexin V+ CD41-, and 58% of annexin V- CD41+ microparticles. Loss of microparticles with centrifugation varied from individual to individual. Microparticle counts after isolation by centrifugation and double washing were not significantly different than counts in the original PFP sample, but lower than in PRP. Freeze-thawing of PFP had no effect on platelet microparticle counts, but slightly increased annexin V+, CD41- counts. Freeze-thawing of isolated washed microparticles resulted in a 30-50% increase in annexin V+ microparticles. PRP contains large numbers of cellular microparticles, including platelet and annexin V+ microparticles, which are lost to varying degrees when PRP is double centrifuged to remove platelets. Microparticles remaining in PFP can be recovered by high-speed centrifugation without loss compared to the original PFP sample. Freeze-thawing has variable effects on microparticle counts depending on the sample preparation used.

Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea.

Science.gov (United States)

Ayers, L; Ferry, B; Craig, S; Nicoll, D; Stradling, J R; Kohler, M

2009-03-01

Moderate-severe obstructive sleep apnoea (OSA) has been associated with several pro-atherogenic mechanisms and increased cardiovascular risk, but it is not known if minimally symptomatic OSA has similar effects. Circulating cell-derived microparticles have been shown to have pro-inflammatory, pro-coagulant and endothelial function-impairing effects, as well as to predict subclinical atherosclerosis and cardiovascular risk. In 57 patients with minimally symptomatic OSA, and 15 closely matched control subjects without OSA, AnnexinV-positive, platelet-, leukocyte- and endothelial cell-derived microparticles were measured by flow cytometry. In patients with OSA, median (interquartile range) levels of AnnexinV-positive microparticles were significantly elevated compared with control subjects: 2,586 (1,566-3,964) microL(-1) versus 1,206 (474-2,501) microL(-1), respectively. Levels of platelet-derived and leukocyte-derived microparticles were also significantly higher in patients with OSA (2,267 (1,102-3,592) microL(-1) and 20 (14-31) microL(-1), respectively) compared with control subjects (925 (328-2,068) microL(-1) and 15 (5-23) microL(-1), respectively). Endothelial cell-derived microparticle levels were similar in patients with OSA compared with control subjects (13 (8-25) microL(-1) versus 11 (6-17) microL(-1)). In patients with minimally symptomatic obstructive sleep apnoea, levels of AnnexinV-positive, platelet- and leukocyte-derived microparticles are elevated when compared with closely matched control subjects without obstructive sleep apnoea. These findings suggest that these patients may be at increased cardiovascular risk, despite being minimally symptomatic.

Early results of microwave transmission experiments through an overly dense rectangular plasma sheet with microparticle injection

Energy Technology Data Exchange (ETDEWEB)

Gillman, Eric D., E-mail: eric.gillman.ctr@nrl.navy.mil [National Research Council Postdoctoral Associate at the U.S. Naval Research Laboratory, Washington, DC 20375 (United States); Amatucci, W. E. [U.S. Naval Research Laboratory, Washington, DC 20375 (United States)

2014-06-15

These experiments utilize a linear hollow cathode to create a dense, rectangular plasma sheet to simulate the plasma layer surrounding vehicles traveling at hypersonic velocities within the Earth's atmosphere. Injection of fine dielectric microparticles significantly reduces the electron density and therefore lowers the electron plasma frequency by binding a significant portion of the bulk free electrons to the relatively massive microparticles. Measurements show that microwave transmission through this previously overly dense, impenetrable plasma layer increases with the injection of alumina microparticles approximately 60 μm in diameter. This method of electron depletion is a potential means of mitigating the radio communications blackout experienced by hypersonic vehicles.

Phospholipid Binding Protein C Inhibitor (PCI) Is Present on Microparticles Generated In Vitro and In Vivo

Science.gov (United States)

Einfinger, Katrin; Badrnya, Sigrun; Furtmüller, Margareta; Handschuh, Daniela; Lindner, Herbert; Geiger, Margarethe

2015-01-01

Protein C inhibitor is a secreted, non-specific serine protease inhibitor with broad protease reactivity. It binds glycosaminoglycans and anionic phospholipids, which can modulate its activity. Anionic phospholipids, such as phosphatidylserine are normally localized to the inner leaflet of the plasma membrane, but are exposed on activated and apoptotic cells and on plasma membrane-derived microparticles. In this report we show by flow cytometry that microparticles derived from cultured cells and activated platelets incorporated protein C inhibitor during membrane blebbing. Moreover, protein C inhibitor is present in/on microparticles circulating in normal human plasma as judged from Western blots, ELISAs, flow cytometry, and mass spectrometry. These plasma microparticles are mainly derived from megakaryocytes. They seem to be saturated with protein C inhibitor, since they do not bind added fluorescence-labeled protein C inhibitor. Heparin partially removed microparticle-bound protein C inhibitor, supporting our assumption that protein C inhibitor is bound via phospholipids. To assess the biological role of microparticle-bound protein C inhibitor we performed protease inhibition assays and co-precipitated putative binding partners on microparticles with anti-protein C inhibitor IgG. As judged from amidolytic assays microparticle-bound protein C inhibitor did not inhibit activated protein C or thrombin, nor did microparticles modulate the activity of exogenous protein C inhibitor. Among the proteins co-precipitating with protein C inhibitor, complement factors, especially complement factor 3, were most striking. Taken together, our data do not support a major role of microparticle-associated protein C inhibitor in coagulation, but rather suggest an interaction with proteins of the complement system present on these phospholipid vesicles. PMID:26580551

Microparticles as Potential Biomarkers of Cardiovascular Disease

International Nuclear Information System (INIS)

França, Carolina Nunes; Izar, Maria Cristina de Oliveira; Amaral, Jônatas Bussador do; Tegani, Daniela Melo; Fonseca, Francisco Antonio Helfenstein

2015-01-01

Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice

Microparticles as Potential Biomarkers of Cardiovascular Disease

Energy Technology Data Exchange (ETDEWEB)

França, Carolina Nunes, E-mail: carolufscar24@gmail.com [Universidade Federal de São Paulo - UNIFESP - UNISA, SP, São Paulo (Brazil); Universidade de Santo Amaro - UNISA, SP, São Paulo (Brazil); Izar, Maria Cristina de Oliveira; Amaral, Jônatas Bussador do; Tegani, Daniela Melo; Fonseca, Francisco Antonio Helfenstein [Universidade Federal de São Paulo - UNIFESP - UNISA, SP, São Paulo (Brazil)

2015-02-15

Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice.

Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation.

Science.gov (United States)

Rubin, Olivier; Delobel, Julien; Prudent, Michel; Lion, Niels; Kohl, Kid; Tucker, Erik I; Tissot, Jean-Daniel; Angelillo-Scherrer, Anne

2013-08-01

Red blood cell-derived microparticles (RMPs) are small phospholipid vesicles shed from RBCs in blood units, where they accumulate during storage. Because microparticles are bioactive, it could be suggested that RMPs are mediators of posttransfusion complications or, on the contrary, constitute a potential hemostatic agent. This study was performed to establish the impact on coagulation of RMPs isolated from blood units. Using calibrated automated thrombography, we investigated whether RMPs affect thrombin generation (TG) in plasma. We found that RMPs were not only able to increase TG in plasma in the presence of a low exogenous tissue factor (TF) concentration, but also to initiate TG in plasma in absence of exogenous TF. TG induced by RMPs in the absence of exogenous TF was neither affected by the presence of blocking anti-TF nor by the absence of Factor (F)VII. It was significantly reduced in plasma deficient in FVIII or F IX and abolished in FII-, FV-, FX-, or FXI-deficient plasma. TG was also totally abolished when anti-XI 01A6 was added in the sample. Finally, neither Western blotting, flow cytometry, nor immunogold labeling allowed the detection of traces of TF antigen. In addition, RMPs did not comprise polyphosphate, an important modulator of coagulation. Taken together, our data show that RMPs have FXI-dependent procoagulant properties and are able to initiate and propagate TG. The anionic surface of RMPs might be the site of FXI-mediated TG amplification and intrinsic tenase and prothrombinase complex assembly. © 2012 American Association of Blood Banks.

CIRCULATING MICROPARTICLES IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES: CHARACTERIZATION AND ASSOCIATIONS

Science.gov (United States)

Chaturvedi, Shruti; Cockrell, Erin; Espinola, Ricardo; Hsi, Linda; Fulton, Stacey; Khan, Mohammad; Li, Liang; Fonseca, Fabio; Kundu, Suman; McCrae, Keith R.

2014-01-01

The antiphospholipid syndrome is characterized by venous or arterial thrombosis and/or recurrent fetal loss in the presence of circulating antiphospholipid antibodies. These antibodies cause activation of endothelial and other cell types leading to the release of microparticles with procoagulant and pro-inflammatory properties. The aims of this study were to characterize the levels of endothelial cell, monocyte, platelet derived, and tissue factor-bearing microparticles in patients with antiphospholipid antibodies, to determine the association of circulating microparticles with anticardiolipin and anti-β2-glycoprotein antibodies, and to define the cellular origin of microparticles that express tissue factor. Microparticle content within citrated blood from 47 patients with antiphospholipid antibodies and 144 healthy controls was analyzed within 2 hours of venipuncture. Levels of Annexin-V, CD105 and CD144 (endothelial derived), CD41 (platelet derived) and tissue factor positive microparticles were significantly higher in patients than controls. Though levels of CD14 (monocyte-derived) microparticles in patient plasma were not significantly increased, increased levels of CD14 and tissue factor positive microparticles were observed in patients. Levels of microparticles that stained for CD105 and CD144 showed a positive correlation with IgG (R = 0.60, p=0.006) and IgM anti-beta2-glycoprotein I antibodies (R=0.58, p=0.006). The elevation of endothelial and platelet derived microparticles in patients with APS and their correlation with anti-β2-glycoprotein I antibodies suggests a chronic state of vascular cell activation in these individuals and an important role for β2-glycoprotein I in development of the pro-thrombotic state associated with antiphospholipid antibodies. PMID:25467081

Pre-analytical and Analytical Variables Affecting the Measurement of Plasma-Derived Microparticle Tissue Factor Activity

Science.gov (United States)

Lee, RD; Barcel, DA; Williams, JC; Wang, JG; Boles, JC; Manly, DA; Key, NS; Mackman, N

2011-01-01

Introduction Elevated levels of tissue factor positive (TF+) microparticles (MPs) are observed in plasma from a variety of patients with an increased risk of thrombosis. We and others have described the measurement of TF activity in MPs isolated from plasma. The aim of this study was to investigate the effects of pre-analytical and analytical variables on TF activity of MPs isolated from blood of healthy volunteers treated ex vivo with or without bacterial lipopolysaccharide. Materials and Methods We evaluated the following parameters: use of different centrifugation speeds to isolate the MPs; comparison of TF activity of MPs isolated from platelet poor plasma versus platelet free plasma; effect of freeze/thaw on MP TF activity; and comparison of the MP TF activity assay with the measurement of TF protein by ELISA or flow cytometry. Results MPs prepared from platelet poor plasma by centrifugation at 20,000 × g or 100,000 × g for 15 minutes had similar levels of TF activity. However, significantly less TF activity was found in MPs isolated from platelet free plasma compared with platelet poor plasma. Interestingly, freeze/thawing of the plasma showed donor to donor variation in MP TF activity, with a moderate increase in some individuals. Conclusion TF+ MPs can be quantitatively isolated from platelet poor or platelet free plasma by centrifugation at 20,000 × g for 15 minutes. Measurement of MP TF activity in plasma can be used to detect a prothrombotic state in patients with various diseases. PMID:21737126

Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases.

Science.gov (United States)

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

2009-11-01

Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-alpha) and also induced allogeneic naive CD4(+) T cells to proliferate and to produce type 1 cytokines such as interferon-gamma and tumor necrosis factor-alpha. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and

Four-dimensional (4D) tracking of high-temperature microparticles

International Nuclear Information System (INIS)

Wang, Zhehui; Liu, Q.; Waganaar, W.; Fontanese, J.; James, D.; Munsat, T.

2016-01-01

High-speed tracking of hot and molten microparticles in motion provides rich information about burning plasmas in magnetic fusion. An exploding-wire apparatus is used to produce moving high-temperature metallic microparticles and to develop four-dimensional (4D) or time-resolved 3D particle tracking techniques. The pinhole camera model and algorithms developed for computer vision are used for scene calibration and 4D reconstructions. 3D positions and velocities are then derived for different microparticles. Velocity resolution approaches 0.1 m/s by using the local constant velocity approximation.

Influence of red blood cell-derived microparticles upon vasoregulation.

Science.gov (United States)

Said, Ahmed S; Doctor, Allan

2017-10-01

Here we review recent data and the evolving understanding of the role of red blood cell-derived microparticles (RMPs) in normal physiology and in disease progression. Microparticles (MPs) are small membrane vesicles derived from various parent cell types. MPs are produced in response to a variety of stimuli through several cytoskeletal and membrane phospholipid changes. MPs have been investigated as potential biomarkers for multiple disease processes and are thought to have biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in apoptosis. Specifically, RMPs are produced normally during RBC maturation and their production is accelerated during processing and storage for transfusion. Several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs from that of intact RBCs, and the nature and composition of RMP components are affected by both storage duration and the character of storage solutions. Recognised RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion, as well as influence upon vasoregulation via nitric oxide (NO) scavenging. Of particular relevance, RMPs are more avid NO scavengers than intact RBCs and this feature has been proposed as a mechanism for the impaired oxygen delivery homeostasis that has been observed following transfusion. Preliminary human studies demonstrate that circulating RMP abundance increases with RBC transfusion and is associated with altered plasma vasoactivity and abnormal vasoregulation. In summary, RMPs are submicron particles released from stored RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in transfusion recipients is an area of continued

Laser plasma jet driven microparticles for DNA/drug delivery.

Directory of Open Access Journals (Sweden)

Viren Menezes

Full Text Available This paper describes a microparticle delivery device that generates a plasma jet through laser ablation of a thin metal foil and uses the jet to accomplish particle delivery into soft living targets for transferring biological agents. Pure gold microparticles of 1 µm size were coated with a plasmid DNA, pIG121Hm, and were deposited as a thin layer on one surface of an aluminum foil. The laser (Nd:YAG, 1064 nm wavelength ablation of the foil generated a plasma jet that carried the DNA coated particles into the living onion cells. The particles could effectively penetrate the target cells and disseminate the DNA, effecting the transfection of the cells. Generation of the plasma jet on laser ablation of the foil and its role as a carrier of microparticles was visualized using a high-speed video camera, Shimadzu HPV-1, at a frame rate of 500 kfps (2 µs interframe interval in a shadowgraph optical set-up. The particle speed could be measured from the visualized images, which was about 770 m/s initially, increased to a magnitude of 1320 m/s, and after a quasi-steady state over a distance of 10 mm with an average magnitude of 1100 m/s, started declining, which typically is the trend of a high-speed, pulsed, compressible jet. Aluminum launch pad (for the particles was used in the present study to make the procedure cost-effective, whereas the guided, biocompatible launch pads made of gold, silver or titanium can be used in the device during the actual clinical operations. The particle delivery device has a potential to have a miniature form and can be an effective, hand-held drug/DNA delivery device for biological applications.

Association between cell-derived microparticles and adverse events in patients with nonpulsatile left ventricular assist devices.

Science.gov (United States)

Nascimbene, Angelo; Hernandez, Ruben; George, Joggy K; Parker, Anita; Bergeron, Angela L; Pradhan, Subhashree; Vijayan, K Vinod; Civitello, Andrew; Simpson, Leo; Nawrot, Maria; Lee, Vei-Vei; Mallidi, Hari R; Delgado, Reynolds M; Dong, Jing Fei; Frazier, O H

2014-05-01

Continuous-flow left ventricular assist devices (LVADs) expose blood cells to high shear stress, potentially resulting in the production of microparticles that express phosphatidylserine (PS+) and promote coagulation and inflammation. In this prospective study, we attempted to determine whether PS+ microparticle levels correlate with clinical outcomes in LVAD-supported patients. We enrolled 20 patients undergoing implantation of the HeartMate II LVAD (Thoratec Corp, Pleasanton, CA) and 10 healthy controls who provided reference values for the microparticle assays. Plasma was collected before LVAD implantation, at discharge, at the 3-month follow-up, and when an adverse clinical event occurred. We quantified PS+ microparticles in the plasma using flow cytometry. During the study period, 8 patients developed adverse clinical events: ventricular tachycardia storm in 1, non-ST-elevation myocardial infarction in 2, arterial thrombosis in 2, gastrointestinal bleeding in 2, and stroke in 3. Levels of PS+ microparticles were higher in patients at baseline than in healthy controls (2.11% ± 1.26% vs 0.69% ± 0.46%, p = 0.007). After LVAD implantation, patient PS+ microparticle levels increased to 2.39% ± 1.22% at discharge and then leveled to 1.97% ± 1.25% at the 3-month follow-up. Importantly, levels of PS+ microparticles were significantly higher in patients who developed an adverse event than in patients with no events (3.82% ± 1.17% vs 1.57% ± 0.59%, p microparticle levels may be associated with adverse clinical events. Thus, measuring PS+ microparticle levels in LVAD-supported patients may help identify patients at increased risk for adverse events. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Restructuring of microparticles in nuclear ceramic materials. Part II. Analytical derivation of the steady-state size distribution

International Nuclear Information System (INIS)

Lameiras, F.S.

1991-01-01

Two fundamental principles were assumed to govern the restructuring of microparticles: minimization and uniformization in space of the interface energy. Five fundamental ways, independent of each other and acting simultaneously, were identified, through which a microparticle set can be restructured according to the fundamental principles: a) decrease of the number of microparticles; b) modification of the microparticle size distribution; c) modification of the microparticles from tending to an equiaxial one; d) tendency to the distribution of microparticles uniform in space; e) tendency to the distribution of the interface energy uniform per microparticle. This presents an analytical derivation of the steady-state microparticle size distribution due to the simultaneous action of the fundamental ways b) and e). (author)

Fast nanostructured carbon microparticle synthesis by one-step high-flux plasma processing

NARCIS (Netherlands)

Aussems, D. U. B.; Bystrov, K.; Dogan, I.; Arnas, C.; Cabié, M.; Neisius, T.; Rasinski, M.; Zoethout, E.; Lipman, P.; van de Sanden, M. C. M.; Morgan, T. W.

2017-01-01

This study demonstrates a fast one-step synthesis method for nanostructured carbon microparticles on graphite samples using high-flux plasma exposure. These structures are considered as potential candidates for energy applications such as Li-ion batteries and supercapacitors. The samples were

Fast nanostructured carbon microparticle synthesis by one-step high-flux plasma processing

NARCIS (Netherlands)

Aussems, D.U.B.; Bystrov, K.E.; Doǧan, I.; Arnas, C.; Cabié, M.; Neisius, T.; Rasinski, M.; Lipman, P.J.L.; van de Sanden, M.C.M.; Morgan, T.W.

This study demonstrates a fast one-step synthesis method for nanostructured carbon microparticles on graphite samples using high-flux plasma exposure. These structures are considered as potential candidates for energy applications such as Li-ion batteries and supercapacitors. The samples were

Cell-derived microparticles promote coagulation after moderate exercise.

Science.gov (United States)

Sossdorf, Maik; Otto, Gordon P; Claus, Ralf A; Gabriel, Holger H W; Lösche, Wolfgang

2011-07-01

Cell-derived procoagulant microparticles (MP) might be able to contribute to exercise-induced changes in blood hemostasis. This study aimed to examine (i) the concentration and procoagulant activity of cell-derived MP after a moderate endurance exercise and (ii) the differences in the release, clearance, and activity of MP before and after exercise between trained and untrained individuals. All subjects performed a single bout of physical exercise on a bicycle ergometer for 90 min at 80% of their individual anaerobic threshold. MP were identified and quantified by flow cytometry measurements. Procoagulant activity of MP was measured by a prothrombinase activity assay as well as tissue factor-induced fibrin formation in MP-containing plasma. At baseline, no differences were observed for the absolute number and procoagulant activities of MP between trained and untrained subjects. However, trained individuals had a lower number of tissue factor-positive monocyte-derived MP compared with untrained individuals. In trained subjects, exercise induced a significant increase in the number of MP derived from platelets, monocytes, and endothelial cells, with maximum values at 45 min after exercise and returned to basal levels at 2 h after exercise. Untrained subjects revealed a similar increase in platelet-derived MP, but their level was still increased at 2 h after exercise, indicating a reduced clearance compared with trained individuals. Procoagulant activities of MP were increased immediately after exercise and remained elevated up to 2 h after exercise. We conclude that increased levels of MP were found in healthy individuals after an acute bout of exercise, that the amount of circulating MP contributes to an exercise-induced increase of hemostatic potential, and that there were differences in kinetic and dynamic characteristics between trained and untrained individuals.

Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood, with and without leucofiltration, with and without ionising radiation.

Science.gov (United States)

Saito, Shunnichi; Nollet, Kenneth E; Ngoma, Alain M; Ono, Takako; Ohto, Hitoshi

2018-02-01

Storage lesion, including microparticle formation, has been partially characterised in whole blood, but not in all combinations of pre-storage leucofiltration and/or irradiation. Single-donor whole blood products were processed into four subunits: with and without leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-, and erythrocyte-derived microparticles and free haemoglobin were measured periodically throughout 42 days of storage. Pre-storage leucofiltration substantially reduced platelet- and leucocyte-derived microparticle counts throughout storage. Irradiation, in contrast, had no significant effect on microparticle counts. A gate for all microparticles showed a substantial time-dependent increase in unfiltered whole blood. A time-dependent increase in free haemoglobin was greatest in unfiltered, irradiated whole blood. This study indicates that leucofiltration can prevent the formation of leucocyte- and platelet-derived microparticles, and might reduce haemolysis in irradiated whole blood, either by removing factors that provoke haemolysis, or by selective retention of senescent or effete red cells most prone to haemolysis.

Analysis of Cell-Derived Microparticles with Highly Precise Nanotechnological Methods

DEFF Research Database (Denmark)

Cherré, Solène; Østergaard, Ole; Heegaard, Niels H.H.

2014-01-01

Cell-derived microparticles have gained a broad interest in the past years. Being released by blood cells upon activation or induction of apoptosis, they have a great potential as novel diagnostic markers and their investigation can bring new knowledge into the pathogenesis of various diseases. H...

A concept of ferroelectric microparticle propulsion thruster

International Nuclear Information System (INIS)

Yarmolich, D.; Vekselman, V.; Krasik, Ya. E.

2008-01-01

A space propulsion concept using charged ferroelectric microparticles as a propellant is suggested. The measured ferroelectric plasma source thrust, produced mainly by microparticles emission, reaches ∼9x10 -4 N. The obtained trajectories of microparticles demonstrate that the majority of the microparticles are positively charged, which permits further improvement of the thruster

A flow cytometric method for characterization of circulating cell-derived microparticles in plasma

DEFF Research Database (Denmark)

Nielsen, Morten Hjuler; Beck-Nielsen, Henning; Andersen, Morten Nørgaard

2014-01-01

BACKGROUND AND AIM: Previous studies on circulating microparticles (MPs) indicate that the majority of MPs are of a size below the detection limit of most standard flow cytometers. The objective of the present study was to establish a method to analyze MP subpopulations above the threshold...

Tumor cell-derived microparticles: a new form of cancer vaccine.

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Zhang, Huafeng; Huang, Bo

2015-08-01

For cancer vaccines, tumor antigen availability is currently not an issue due to technical advances. However, the generation of optimal immune stimulation during vaccination is challenging. We have recently demonstrated that tumor cell-derived microparticles (MP) can function as a new form of potent cancer vaccine by efficiently activating type I interferon pathway in a cGAS/STING dependent manner.

Detection of circulating parasite-derived microRNAs in filarial infections.

Directory of Open Access Journals (Sweden)

Lucienne Tritten

2014-07-01

Full Text Available Filarial nematodes cause chronic and profoundly debilitating diseases in both humans and animals. Applications of novel technology are providing unprecedented opportunities to improve diagnosis and our understanding of the molecular basis for host-parasite interactions. As a first step, we investigated the presence of circulating miRNAs released by filarial nematodes into the host bloodstream. miRNA deep-sequencing combined with bioinformatics revealed over 200 mature miRNA sequences of potential nematode origin in Dirofilaria immitis-infected dog plasma in two independent analyses, and 21 in Onchocerca volvulus-infected human serum. Total RNA obtained from D. immitis-infected dog plasma was subjected to stem-loop RT-qPCR assays targeting two detected miRNA candidates, miR-71 and miR-34. Additionally, Brugia pahangi-infected dog samples were included in the analysis, as these miRNAs were previously detected in extracts prepared from this species. The presence of miR-71 and miR-34 discriminated infected samples (both species from uninfected samples, in which no specific miRNA amplification occurred. However, absolute miRNA copy numbers were not significantly correlated with microfilaraemia for either parasite. This may be due to the imprecision of mf counts to estimate infection intensity or to miRNA contributions from the unknown number of adult worms present. Nonetheless, parasite-derived circulating miRNAs are found in plasma or serum even for those species that do not live in the bloodstream.

A simple clot based assay for detection of procoagulant cell-derived microparticles.

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Patil, Rucha; Ghosh, Kanjaksha; Shetty, Shrimati

2016-05-01

Cell-derived microparticles (MPs) are important biomarkers in many facets of medicine. However, the MP detection methods used till date are costly and time consuming. The main aim of this study was to standardize an in-house clot based screening method for MP detection which would not only be specific and sensitive, but also inexpensive. Four different methods of MP assessment were performed and the results correlated. Using the flow cytometry technique as the gold standard, 25 samples with normal phosphatidylserine (PS) expressing MP levels and 25 samples with elevated levels were selected, which was cross checked by the commercial STA Procoag PPL clotting time (CT) assay. A simple recalcification time and an in-house clot assay were the remaining two tests. The in-house test measures the CT after the addition of calcium chloride to MP rich plasma, following incubation with Russell viper venom and phospholipid free plasma. The CT obtained by the in-house assay significantly correlated with the results obtained by flow cytometry (R2=0.87, p<0.01). Though preliminary, the in-house assay seems to be efficient, inexpensive and promising. It could definitely be utilized routinely for procoagulant MP assessment in various clinical settings.

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

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Renner, Brandon; Klawitter, Jelena; Goldberg, Ryan; McCullough, James W.; Ferreira, Viviana P.; Cooper, James E.; Christians, Uwe

2013-01-01

Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases. PMID:24092930

Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

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Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

2013-01-01

Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

A heparin-based method for flow cytometric analysis of microparticles directly from platelet-poor plasma in calcium containing buffer

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Iversen, Line V; Ostergaard, Ole; Nielsen, Christoffer

2013-01-01

Characterization of circulating microparticles (MPs) is usually performed by flow cytometry. Annexin V, a protein that Ca(2+)-dependently binds to phosphatidylserine, has been used to define entire microparticle (MP) populations, but not all MPs bind AnxV. Recent reports have correlated Anx...... for comprehensive assessment of circulating MPs directly from platelet-poor plasma with characterization of AnxV-binding and of cellular origin of MPs....

Platelet-derived microparticles regulates thrombin generation via phophatidylserine in abdominal sepsis.

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Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Norström, Eva; Braun, Oscar Ö; Mörgelin, Matthias; Thorlacius, Henrik

2018-02-01

Sepsis is associated with dysfunctional coagulation. Recent data suggest that platelets play a role in sepsis by promoting neutrophil accumulation. Herein, we show that cecal ligation and puncture (CLP) triggered systemic inflammation, which is characterized by formation of IL-6 and CXC chemokines as well as neutrophil accumulation in the lung. Platelet depletion decreased neutrophil accumulation, IL-6, and CXC chemokines formation in septic lungs. Depletion of platelets increased peak thrombin formation and total thrombin generation (TG) in plasma from septic animals. CLP elevated circulating levels of platelet-derived microparticles (PMPs). In vitro generated PMPs were a potent inducer of TG. Interestingly, in vitro wild-type recombinant annexin V abolished PMP-induced thrombin formation whereas a mutant annexin V protein, which does not bind to phosphatidylserine (PS), had no effect. Administration of wild-type, but not mutant annexin V, significantly inhibited thrombin formation in septic animals. Moreover, CLP-induced formation of thrombin-antithrombin complexes were reduced in platelet-depleted mice and in animals pretreated with annexin V. PMP-induced TG attenuated in FXII- and FVII-deficient plasma. These findings suggest that sepsis-induced TG is dependent on platelets. Moreover, PMPs formed in sepsis are a potent inducer of TG via PS exposure, and activation of both the intrinsic and extrinsic pathway of coagulation. In conclusion, these observations suggest that PMPs and PS play an important role in dysfunctional coagulation in abdominal sepsis. © 2017 Wiley Periodicals, Inc.

Nano-zymography Using Laser-Scanning Confocal Microscopy Unmasks Proteolytic Activity of Cell-Derived Microparticles.

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Briens, Aurélien; Gauberti, Maxime; Parcq, Jérôme; Montaner, Joan; Vivien, Denis; Martinez de Lizarrondo, Sara

2016-01-01

Cell-derived microparticles (MPs) are nano-sized vesicles released by activated cells in the extracellular milieu. They act as vectors of biological activity by carrying membrane-anchored and cytoplasmic constituents of the parental cells. Although detection and characterization of cell-derived MPs may be of high diagnostic and prognostic values in a number of human diseases, reliable measurement of their size, number and biological activity still remains challenging using currently available methods. In the present study, we developed a protocol to directly image and functionally characterize MPs using high-resolution laser-scanning confocal microscopy. Once trapped on annexin-V coated micro-wells, we developed several assays using fluorescent reporters to measure their size, detect membrane antigens and evaluate proteolytic activity (nano-zymography). In particular, we demonstrated the applicability and specificity of this method to detect antigens and proteolytic activities of tissue-type plasminogen activator (tPA), urokinase and plasmin at the surface of engineered MPs from transfected cell-lines. Furthermore, we were able to identify a subset of tPA-bearing fibrinolytic MPs using plasma samples from a cohort of ischemic stroke patients who received thrombolytic therapy and in an experimental model of thrombin-induced ischemic stroke in mice. Overall, this method is promising for functional characterization of cell-derived MPs.

On melting criteria for complex plasma

International Nuclear Information System (INIS)

Klumov, Boris A

2011-01-01

The present paper considers melting criteria for a plasma crystal discovered in dust plasma in 1994. Separate discussions are devoted to three-dimensional (3D) and two-dimensional (2D) systems. In the 3D case, melting criteria are derived based on the properties of local order in a system of microparticles. The order parameters are constructed from the cumulative distributions of the microparticle probability distributions as functions of various rotational invariants. The melting criteria proposed are constructed using static information on microparticle positions: a few snapshots of the system that allow for the determination of particle coordinates are enough to determine the phase state of the system. It is shown that criteria obtained in this way describe well the melting and premelting of 3D complex plasmas. In 2D systems, a system of microparticles interacting via a screened Coulomb (i.e., Debye-Hueckel or Yukawa) potential is considered as an example, using molecular dynamics simulations. A number of new order parameters characterizing the melting of 2D complex plasmas are proposed. The order parameters and melting criteria proposed for 2D and 3D complex plasmas can be applied to other systems as well. (methodological notes)

Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation?

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Baron, Morgane; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne

2012-07-01

Cardiovascular diseases remain an important cause of morbi-mortality. Atherosclerosis, which predisposes to cardiovascular disorders such as myocardial infarction and stroke, develops silently over several decades. Identification of circulating biomarkers to evaluate cardiovascular event risk and pathology prognosis is of particular importance. Microparticles (MPs) are small vesicles released from cells upon apoptosis or activation. Microparticles are present in blood of healthy individuals. Studies showing a modification of their concentrations in patients with cardiovascular risk factors and after cardiovascular events identify MPs as potential biomarkers of disease. Moreover, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological compounds, used in the treatment of cardiovascular disease, can reduce plasma MP concentrations. Nevertheless, numerous issues remain to be solved before MP measurement can be applied as routine biological tests to improve cardiovascular risk prediction. In particular, prospective studies to identify the predictive values of MPs in pathologies such as cardiovascular diseases are needed to demonstrate whether MPs are useful biomarkers for the early detection of the disease and its progression. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Membrane microparticles and diseases.

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Wu, Z-H; Ji, C-L; Li, H; Qiu, G-X; Gao, C-J; Weng, X-S

2013-09-01

Membrane microparticles (MPs) are plasma membrane-derived vesicles shed by various types of activated or apoptotic cells including platelets, monocytes, endothelial cells, red blood cells, and granulocytes. MPs are being increasingly recognized as important regulators of cell-to-cell interactions. Recent evidences suggest they may play important functions not only in homeostasis but also in the pathogenesis of a number of diseases such as vascular diseases, cancer, infectious diseases and diabetes mellitus. Accordingly, inhibiting the production of MPs may serve as a novel therapeutic strategy for these diseases. Here we review recent advances on the mechanism underlying the generation of MPs and the role of MPs in vascular diseases, cancer, diabetes, inflammation, and pathogen infection.

Development of a NanoBioAnalytical platform for "on-chip" qualification and quantification of platelet-derived microparticles.

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Obeid, Sameh; Ceroi, Adam; Mourey, Guillaume; Saas, Philippe; Elie-Caille, Celine; Boireau, Wilfrid

2017-07-15

Blood microparticles (MPs) are small membrane vesicles (50-1000nm), derived from different cell types. They are known to play important roles in various biological processes and also recognized as potential biomarkers of various health disorders. Different methods are currently used for the detection and characterization of MPs, but none of these methods is capable to quantify and qualify total MPs at the same time, hence, there is a need to develop a new approach for simultaneous detection, characterization and quantification of microparticles. Here we show the potential of surface plasmon resonance (SPR) method coupled to atomic force microscopy (AFM) to quantify and qualify platelet-derived microparticles (PMPs), on the whole nano-to micro-meter scale. The different subpopulations of microparticles could be determined via their capture onto the surface using specific ligands. In order to verify the correlation between the capture level and the microparticles concentration in solution, two calibration standards were used: Virus-Like Particles (VLPs) and synthetic beads with a mean diameter of 53nm and 920nm respectively. The AFM analysis of the biochip surface allowed metrological analysis of captured PMPs and revealed that more than 95% of PMPs were smaller than 300nm. Our results suggest that our NanoBioAnalytical platform, combining SPR and AFM, is a suitable method for a sensitive, reproducible, label-free characterization and quantification of MPs over a wide concentration range (≈10 7 to 10 12 particles/mL; with a limit of detection (LOD) in the lowest ng/µL range) which matches with their typical concentrations in blood. Copyright © 2016 Elsevier B.V. All rights reserved.

Exacerbation of oxidative stress during sickle vaso-occlusive crisis is associated with decreased anti-band 3 autoantibodies rate and increased red blood cell-derived microparticle level: a prospective study.

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Hierso, Régine; Lemonne, Nathalie; Villaescusa, Rinaldo; Lalanne-Mistrih, Marie-Laure; Charlot, Keyne; Etienne-Julan, Maryse; Tressières, Benoit; Lamarre, Yann; Tarer, Vanessa; Garnier, Yohann; Hernandez, Ada Arce; Ferracci, Serge; Connes, Philippe; Romana, Marc; Hardy-Dessources, Marie-Dominique

2017-03-01

Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates. © 2016 John Wiley & Sons Ltd.

Measurements of electric charge and screening length of microparticles in a plasma sheath

International Nuclear Information System (INIS)

Nakamura, Y.; Ishihara, O.

2009-01-01

An experiment is described in which microparticles are levitated within a rf sheath above a conducting plate in argon plasma. The microparticles forming a two-dimensional crystal structure are considered to possess Debye screening Coulomb potential φ(r)=(Q/4πε 0 r)exp(-r/λ), where Q is the electric charge, r is distance, and λ is the screening length. When the crystal structure is slanted with an angle θ, a particle experiences a force Mg sin θ, where M is the mass of the particle and g is acceleration due to gravity, which must be equal to the Debye screened Coulomb force from other particles. By changing θ, relations for λ(Q) are measured. The screening length λ and Q are determined uniquely from the crossing points of several relations. The electric charge Q is also estimated from a floating potential measured with a probe. The measured λ is nearly equal to an ion Debye length.

Energy losses in magnetically insulated transmission lines due to microparticles

International Nuclear Information System (INIS)

Gray, E.W.; Stinnett, R.W.

1987-01-01

We discuss the effects of high-velocity and hypervelocity microparticles in the magnetically insulated transmission lines of multiterawatt accelerators used for particle beam fusion and radiation effects simulation. These microparticles may be a possible source for plasma production near the anode and cathode in early stages of the voltage pulse, and current carriers during and after the power pulse, resulting in power flow losses. Losses in the current pulse, due to microparticles, are estimated to be approximately 12 mA/cm 2 (0.3 kA) as a lower limit, and --0.3 A/cm 2 (7.2 kA) for microparticle initiated, anode plasma positive ion transport. We have calculated the velocities reached by these microparticles and the effects on them of Van der Waals forces. Field emission from the particles and their effects on cathode and anode plasma formation have been examined. Particle collision with the electrodes is also examined in terms of plasma production, as in the electron deposition in the particles in transit across the anode-cathode gap. Blistering of the electrode surface, thought to be due to H - bombardment was also observed and appears to be consistent with losses due to negative ions previously reported by J. P. VanDevender, R. W. Stinnett, and R. J. Anderson [App. Phys. Lett. 38, 229 (1981)

Elevated levels of endothelial cell-derived microparticles following short-term withdrawal of continuous positive airway pressure in patients with obstructive sleep apnea: data from a randomized controlled trial.

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Ayers, Lisa; Stoewhas, Anne-Christin; Ferry, Berne; Stradling, John; Kohler, Malcolm

2013-01-01

Obstructive sleep apnea has been associated with impaired endothelial function; however, the mechanisms underlying this association are not completely understood. Cell-derived microparticles may provide a link between obstructive sleep apnea and endothelial dysfunction. This randomized controlled trial aimed to examine the effect of a 2-week withdrawal of continuous positive airway pressure (CPAP) therapy on levels of circulating microparticles. Forty-one obstructive sleep apnea patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continuing therapeutic CPAP, for 2 weeks. Polysomnography was performed and circulating levels of microparticles were analyzed by flow cytometry at baseline and 2 weeks. CPAP withdrawal led to a recurrence of obstructive sleep apnea. Levels of CD62E+ endothelium-derived microparticles increased significantly in the CPAP withdrawal group compared to the continuing therapeutic CPAP group (median difference in change +32.4 per µl; 95% CI +7.3 to +64.1 per µl, p = 0.010). CPAP withdrawal was not associated with a statistically significant increase in granulocyte, leukocyte, and platelet-derived microparticles when compared with therapeutic CPAP. Short-term withdrawal of CPAP therapy leads to a significant increase in endothelium-derived microparticles, suggesting that microparticle formation may be causally linked to obstructive sleep apnea and may promote endothelial activation. Copyright © 2012 S. Karger AG, Basel.

Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System

Directory of Open Access Journals (Sweden)

Hiraku Onishi

2016-09-01

Full Text Available Background: The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention. Methods: Microparticles (MP were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA, trimethyl-chitosan (TMC, and chitosan (Ch. Using salmon calcitonin (sCT as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1-, and Ch-based MP were produced, and their Eudragit L100 (Eud-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo. Results: All microparticles before and after enteric coating had a submicron size (600–800 nm and micrometer size (1300–1500 nm, respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness. Conclusion: The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs.

Cell-derived microparticles in the pathogenesis of cardiovascular disease: friend or foe?

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Tushuizen, Maarten E; Diamant, Michaela; Sturk, Augueste; Nieuwland, Rienk

2011-01-01

Microparticles are ascribed important roles in coagulation, inflammation, and endothelial function. These processes are mandatory to safeguard the integrity of the organism, and their derangements contribute to the development of atherosclerosis and cardiovascular disease. More recently, the presumed solely harmful role of microparticles has been challenged because microparticles may also be involved in the maintenance and preservation of cellular homeostasis and in promoting defense mechanisms. Here, we summarize recent studies revealing these 2 faces of microparticles in cardiovascular disease.

Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.

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Nielsen, C T; Østergaard, O; Rekvig, O P; Sturfelt, G; Jacobsen, S; Heegaard, N H H

2015-10-01

A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major autoantigen source and provides a new understanding of the origin of

Dynamic release and clearance of circulating microparticles during cardiac stress.

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Augustine, Daniel; Ayers, Lisa V; Lima, Eduardo; Newton, Laura; Lewandowski, Adam J; Davis, Esther F; Ferry, Berne; Leeson, Paul

2014-01-03

Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

Increased plasma levels of microparticles expressing CD39 and CD133 in acute liver injury

DEFF Research Database (Denmark)

Schmelzle, Moritz; Splith, Katrin; Wiuff Andersen, Lars

2013-01-01

BACKGROUND: We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block...... sacrificed and plasma MP were isolated by ultracentrifugation. HSC and CD133 MP levels were analyzed by fluorescence-activated cell sorting. Patients were enrolled with acute (n=5) and acute on chronic (n=5) liver injury with matched controls (n=7). Blood was collected at admission and plasma CD133 and CD39...... MP subsets were analyzed by fluorescence-activated cell sorting. RESULTS: HSC and CD133 MP levels were significantly increased only in the plasma of wild-type mice with acetaminophen hepatotoxicity (P

Measurement of plasma-surface energy fluxes in an argon rf-discharge by means of calorimetric probes and fluorescent microparticles

International Nuclear Information System (INIS)

Maurer, H. R.; Kersten, H.; Hannemann, M.; Basner, R.

2010-01-01

Measured energy influx densities toward a tungsten dummy substrate in an argon rf-plasma are presented and a model for the description of the energy influx density based on plasma parameters, which have been obtained by Langmuir probe measurements, is applied. Furthermore, temperature measurements of microparticles are presented, which are confined in the plasma sheath. An extension of the model is developed for the description of the energy influx density to the particles. The comparison of model and experimental results offer the possibility to obtain an improved understanding of plasma-surface interactions.

Membrane Protected Apoptotic Trophoblast Microparticles Contain Nucleic Acids

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Orozco, Aaron F.; Jorgez, Carolina J.; Horne, Cassandra; Marquez-Do, Deborah A.; Chapman, Matthew R.; Rodgers, John R.; Bischoff, Farideh Z.; Lewis, Dorothy E.

2008-01-01

Microparticles (MPs) that circulate in blood may be a source of DNA for molecular analyses, including prenatal genetic diagnoses. Because MPs are heterogeneous in nature, however, further characterization is important before use in clinical settings. One key question is whether DNA is either bound to aggregates of blood proteins and lipid micelles or intrinsically associated with MPs from dying cells. To test the latter hypothesis, we asked whether MPs derived in vitro from dying cells were similar to those in maternal plasma. JEG-3 cells model extravillous trophoblasts, which predominate during the first trimester of pregnancy when prenatal diagnosis is most relevant. MPs were derived from apoptosis and increased over 48 hours. Compared with necrotic MPs, DNA in apoptotic MPs was more fragmented and resistant to plasma DNases. Membrane-specific dyes indicated that apoptotic MPs had more membranous material, which protects nucleic acids, including RNA. Flow cytometry showed that MPs derived from dying cells displayed light scatter and DNA staining similar to MPs found in maternal plasma. Quantification of maternal MPs using characteristics defined by MPs generated in vitro revealed a significant increase of DNA+ MPs in the plasma of women with preeclampsia compared with plasma from women with normal pregnancies. Apoptotic MPs are therefore a likely source of stable DNA that could be enriched for both early genetic diagnosis and monitoring of pathological pregnancies. PMID:18974299

Cell-derived microparticles and vascular pregnancy complications: a systematic and comprehensive review.

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Alijotas-Reig, Jaume; Palacio-Garcia, Carles; Llurba, Elisa; Vilardell-Tarres, Miquel

2013-02-01

To assess current studies on the relationship between cell-derived microparticles (cMP) and recurrent miscarriages (RM) and pre-eclampsia (PE), and review the relationships between cMP and inflammatory and clot pathways, antiphospholipid antibodies (aPL), cytokines, and pregnancy complications. Systematic and comprehensive review of the literature from January 2000 to January 2012. Vall d'Hebron University Hospital. Women with recurrent miscarriages or PE, healthy nonpregnant women, and healthy pregnant women. None. Comparison of cMP numbers and types among groups. Platelet and endothelial cMP are increased in women with normal pregnancies compared with nonpregnant healthy women. Only five case-control studies regarding cMP and RM and 16 on cMP and PE were found to match our objective. Three of five articles referring to RM showed differences in cMP numbering, and 13 of 16 on cMP and PE showed differences in some type of cMP compared with controls. Cell-derived microparticles were raised in normal pregnancy. Recurrent miscarriage seems to be related to endothelial and platelet cell activation and/or consumption. An increase in almost all cMP types was observed in PE. A relationship between cMP and endothelial activation and proinflammatory status seems to exist. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Circulating cell-derived microparticles in severe preeclampsia and in fetal growth restriction.

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Alijotas-Reig, Jaume; Palacio-Garcia, Carles; Farran-Codina, Immaculada; Ruiz-Romance, Mar; Llurba, Elisa; Vilardell-Tarres, Miquel

2012-02-01

The behavior of the circulating microparticles (cMP) in severe preeclampsia (PE) and fetal growth restriction (FGR) is disputed. METHOD OF STUDY  Non-matched case-control study. Seventy cases of severe PE/HELLP/FGR were compared to 38 healthy pregnant women. Twenty healthy non-pregnant women acted as a control. cMP were analyzed using flow cytometry. Results are given as total (annexin-A5-ANXA5+), platelet (CD41+), leukocyte (CD45+), endothelial (CD144+CD31+//CD41-), and CD41-negative cMP/μL of plasma. Antiphospholipid antibodies (aPL) were analyzed through usual methods. Platelet and endothelial cMP increased in healthy pregnant women. PE whole group (PE±FGR) showed an increase in endothelial and CD41-negative, but not in platelet-derived, cMP. Comparing PE whole group versus healthy pregnant, we found cMP levels of endothelial and CD41- had increased. The cMP results obtained in PE group were similar to those of the PE whole group. Comparing PE group to isolated FGR, significant CD41-negative cMP increase was found in PE. According to its aPL positivity, a trend to decrease in leukocyte and endothelial-derived cMP was found in PE group. Normal pregnancy is accompanied by endothelial and platelet cell activation. Endothelial cell activation has been shown in PE but not in isolated FGR. In PE, aPL may contribute to endothelial and possibly to leukocyte cell activation. © 2011 John Wiley & Sons A/S.

"Thunderstruck": Plasma-Polymer-Coated Porous Silicon Microparticles As a Controlled Drug Delivery System.

Science.gov (United States)

McInnes, Steven J P; Michl, Thomas D; Delalat, Bahman; Al-Bataineh, Sameer A; Coad, Bryan R; Vasilev, Krasimir; Griesser, Hans J; Voelcker, Nicolas H

2016-02-01

Controlling the release kinetics from a drug carrier is crucial to maintain a drug's therapeutic window. We report the use of biodegradable porous silicon microparticles (pSi MPs) loaded with the anticancer drug camphothecin, followed by a plasma polymer overcoating using a loudspeaker plasma reactor. Homogenous "Teflon-like" coatings were achieved by tumbling the particles by playing AC/DC's song "Thunderstruck". The overcoating resulted in a markedly slower release of the cytotoxic drug, and this effect correlated positively with the plasma polymer coating times, ranging from 2-fold up to more than 100-fold. Ultimately, upon characterizing and verifying pSi MP production, loading, and coating with analytical methods such as time-of-flight secondary ion mass spectrometry, scanning electron microscopy, thermal gravimetry, water contact angle measurements, and fluorescence microscopy, human neuroblastoma cells were challenged with pSi MPs in an in vitro assay, revealing a significant time delay in cell death onset.

Complement activation on the surface of cell-derived microparticles during cardiac surgery with cardiopulmonary bypass - is retransfusion of pericardial blood harmful?

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Biró, E; van den Goor, J M; de Mol, B A; Schaap, M C; Ko, L-Y; Sturk, A; Hack, C E; Nieuwland, R

2011-01-01

To investigate whether cell-derived microparticles play a role in complement activation in pericardial blood of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and whether microparticles in pericardial blood contribute to systemic complement activation upon retransfusion. Pericardial blood of 13 patients was retransfused in 9 and discarded in 4 cases. Microparticles were isolated from systemic blood collected before anesthesia (T1) and at the end of CPB (T2), and from pericardial blood. The microparticles were analyzed by flow cytometry for bound complement components C1q, C4 and C3, and bound complement activator molecules C-reactive protein (CRP), serum amyloid P-component (SAP), immunoglobulin (Ig)M and IgG. Fluid-phase complement activation products (C4b/c, C3b/c) and activator molecules were determined by ELISA. Compared with systemic T1 blood, pericardial blood contained increased C4b/c and C3b/c, and increased levels of microparticles with bound complement components. In systemic T1 samples, microparticle-bound CRP, whereas in pericardial blood, microparticle-bound SAP and IgM were associated with complement activation. At the end of CPB, increased C3b/c (but not C4b/c) was present in systemic T2 blood compared with T1, while concentrations of microparticles binding complement components and of those binding complement activator molecules were similar. Concentrations of fluid-phase complement activation products and microparticles were similar in patients whether or not retransfused with pericardial blood. In pericardial blood of patients undergoing cardiac surgery with CPB, microparticles contribute to activation of the complement system via bound SAP and IgM. Retransfusion of pericardial blood, however, does not contribute to systemic complement activation.

Plasma centrifugation does not influence thrombin-antithrombin and plasmin-antiplasmin levels but determines platelet microparticles count.

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Stępień, Ewa; Gruszczyński, Krzysztof; Kapusta, Przemysław; Kowalik, Artur; Wybrańska, Iwona

2015-01-01

Centrifugation is an essential step for plasma preparation to remove residual elements in plasma, especially platelets and platelet-derived microparticles (PMPs). Our working hypothesis was that centrifugation as a preanalytical step may influence some coagulation parameters. Healthy young men were recruited (N=17). For centrifugation, two protocols were applied: (A) the first centrifugation at 2500xg for 15 min and (B) at 2500xg for 20 min at room temperature with a light brake. In protocol (A), the second centrifugation was carried out at 2500xg for 15 min, whereas in protocol (B), the second centrifugation involved a 10 min spin at 13,000 x g. Thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes concentrations were determined by enzyme-linked immunosorbent assays. PMPs were stained with CD41 antibody and annexin V, and analyzed by flow cytometry method. Procoagulant activity was assayed by the Calibrated Automated Thrombogram method as a slope of thrombin formation (CAT velocity). Median TAT and PAP concentrations did not differ between the centrifugation protocols. The high speed centrifugation reduced the median (IQR) PMP count in plasma from 1291 (841-1975) to 573 (391-1010) PMP/µL (P=0.001), and CAT velocity from 2.01 (1.31-2.88) to 0.97 (0.82-1.73) nM/min (P=0.049). Spearman's rank correlation analysis showed correlation between TAT and PMPs in the protocol A plasma which was (rho=0.52, PCentrifugation protocols do not influence the markers of plasminogen (PAP) and thrombin (TAT) generation but they do affect the PMP count and procoagulant activity.

Proteome analysis of multidrug-resistant, breast cancer–derived microparticles

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Deep Pokharel

2014-08-01

Full Text Available Cancer multidrug resistance (MDR occurs when cancer cells evade the cytotoxic actions of chemotherapeutics through the active efflux of drugs from within the cells. Our group have previously demonstrated that multidrug-resistant breast cancer cells spontaneously shed microparticles (MPs and that these MPs can transfer resistance to drug-responsive cells and confer MDR on those cells in as little as 4 h. Furthermore, we also showed that, unlike MPs derived from leukaemia cells, breast cancer–derived MPs display a tissue selectivity in the transfer of P-glycoprotein (P-gp, transferring the resistance protein only to malignant breast cells. This study aims to define the proteome of breast cancer–derived MPs in order to understand the differences in protein profiles between those shed from drug-resistant versus drug-sensitive breast cancer cells. In doing so, we detail the protein cargo required for the intercellular transfer of MDR to drug-sensitive recipient cells and the factors governing the transfer selectivity to malignant breast cells. We describe the first proteomic analysis of MPs derived from human breast cancer cells using SDS PAGE and liquid chromatography–tandem mass spectrometry (LC/MS/MS, in which we identify 120 unique proteins found only in drug-resistant, breast cancer–derived MPs. Our results demonstrate that the MP-mediated transfer of P-gp to recipient cells occurs alongside CD44; the Ezrin, Radixin and Moesin protein family (ERM; and cytoskeleton motor proteins within the MP cargo.

Apheresis platelet concentrates contain platelet-derived and endothelial cell-derived microparticles

NARCIS (Netherlands)

Rank, A.; Nieuwland, R.; Liebhardt, S.; Iberer, M.; Grützner, S.; Toth, B.; Pihusch, R.

2011-01-01

Background and Objectives Microparticles (MP) are membrane vesicles with thrombogenic and immunomodulatory properties. We determined MP subgroups from resting platelets, activated platelets and endothelial cells in donors and apheresis platelet concentrates (PC). Material and Methods MP were double

The Volatile Anesthetic Isoflurane Increases Endothelial Adenosine Generation via Microparticle Ecto-5′-Nucleotidase (CD73) Release

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Kim, Mihwa; Ham, Ahrom; Kim, Katelyn Yu-Mi; Brown, Kevin M.; Lee, H. Thomas

2014-01-01

Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether isoflurane induces endothelial ecto-5′-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, isoflurane-induced release of CD73 containing microparticles was significantly attenuated by a selective Rho kinase inhibitor (Y27632). Taken together, we conclude that the volatile anesthetic isoflurane causes Rho kinase-mediated release of endothelial microparticles containing preformed CD73 and increase adenosine generation to protect against endothelial apoptosis and inflammation. PMID:24945528

Effects of a novel β–lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis

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Danielle Oliveira dos Anjos

2016-12-01

Full Text Available Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β–lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β–lapachone derivative affected the T. cruzi morphology and surface topography. General plasma membrane waving and blebbing particularly on the cytostome region were observed in the R72-treated parasites. Transmission electron microscopy observations confirmed the surface damage at the cytostome opening vicinity. We also observed ultrastructural evidence of the autophagic mechanism termed macroautophagy. Some of the autophagosomes involved large portions of the parasite cytoplasm and their fusion/confluence may lead to necrotic parasite death. The remarkably enhanced frequency of autophagy triggering was confirmed by quantitating monodansylcadaverine labeling. Some cells displayed evidence of chromatin pycnosis and nuclear fragmentation were detected. This latter phenomenon was also indicated by DAPI staining of R72-treated cells. The apoptotis induction was suggested to take place in circa one-third of the parasites assessed by annexin V labeling measured by flow cytometry. TUNEL staining corroborated the apoptosis induction. Propidium iodide labeling indicate that at least 10% of the R72-treated parasites suffered necrosis within 24 h. The present data indicate that the β–lapachone derivative R72 selectively triggers T. cruzi cell death, involving both apoptosis and autophagy-induced necrosis.

Detection and quantification of microparticles from different cellular lineages using flow cytometry. Evaluation of the impact of secreted phospholipase A2 on microparticle assessment.

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Rousseau, Matthieu; Belleannee, Clemence; Duchez, Anne-Claire; Cloutier, Nathalie; Levesque, Tania; Jacques, Frederic; Perron, Jean; Nigrovic, Peter A; Dieude, Melanie; Hebert, Marie-Josee; Gelb, Michael H; Boilard, Eric

2015-01-01

Microparticles, also called microvesicles, are submicron extracellular vesicles produced by plasma membrane budding and shedding recognized as key actors in numerous physio(patho)logical processes. Since they can be released by virtually any cell lineages and are retrieved in biological fluids, microparticles appear as potent biomarkers. However, the small dimensions of microparticles and soluble factors present in body fluids can considerably impede their quantification. Here, flow cytometry with improved methodology for microparticle resolution was used to detect microparticles of human and mouse species generated from platelets, red blood cells, endothelial cells, apoptotic thymocytes and cells from the male reproductive tract. A family of soluble proteins, the secreted phospholipases A2 (sPLA2), comprises enzymes concomitantly expressed with microparticles in biological fluids and that catalyze the hydrolysis of membrane phospholipids. As sPLA2 can hydrolyze phosphatidylserine, a phospholipid frequently used to assess microparticles, and might even clear microparticles, we further considered the impact of relevant sPLA2 enzymes, sPLA2 group IIA, V and X, on microparticle quantification. We observed that if enriched in fluids, certain sPLA2 enzymes impair the quantification of microparticles depending on the species studied, the source of microparticles and the means of detection employed (surface phosphatidylserine or protein antigen detection). This study provides analytical considerations for appropriate interpretation of microparticle cytofluorometric measurements in biological samples containing sPLA2 enzymes.

Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

LENUS (Irish Health Repository)

Hong, Ying

2012-01-01

The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics.

Predicting carotid artery disease and plaque instability from cell-derived microparticles.

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Wekesa, A L; Cross, K S; O'Donovan, O; Dowdall, J F; O'Brien, O; Doyle, M; Byrne, L; Phelan, J P; Ross, M D; Landers, R; Harrison, M

2014-11-01

Cell-derived microparticles (MPs) are small plasma membrane-derived vesicles shed from circulating blood cells and may act as novel biomarkers of vascular disease. We investigated the potential of circulating MPs to predict (a) carotid plaque instability and (b) the presence of advanced carotid disease. This pilot study recruited carotid disease patients (aged 69.3 ± 1.2 years [mean ± SD], 69% male, 90% symptomatic) undergoing endarterectomy (n = 42) and age- and sex-matched controls (n = 73). Plaques were classified as stable (n = 25) or unstable (n = 16) post surgery using immunohistochemistry. Blood samples were analysed for MP subsets and molecular biomarkers. Odds ratios (OR) are expressed per standard deviation biomarker increase. Endothelial MP (EMP) subsets, but not any vascular, inflammatory, or proteolytic molecular biomarker, were higher (p < .05) in the unstable than the stable plaque patients. The area under the receiver operator characteristic curve for CD31(+)41(-) EMP in discriminating an unstable plaque was 0.73 (0.56-0.90, p < .05). CD31(+)41(-) EMP predicted plaque instability (OR = 2.19, 1.08-4.46, p < .05) and remained significant in a multivariable model that included transient ischaemic attack symptom status. Annexin V(+) MP, platelet MP (PMP) subsets, and C-reactive protein were higher (p < .05) in cases than controls. Annexin V(+) MP (OR = 3.15, 1.49-6.68), soluble vascular cell adhesion molecule-1 (OR = 1.64, 1.03-2.59), and previous smoking history (OR = 3.82, 1.38-10.60) independently (p < .05) predicted the presence of carotid disease in a multivariable model. EMP may have utility in predicting plaque instability in carotid patients and annexin V(+) MPs may predict the presence of advanced carotid disease in aging populations, independent of established biomarkers. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Parasite-Derived Proteins for the Treatment of Allergies and Autoimmune Diseases

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Zhenyu Wu

2017-11-01

Full Text Available The morbidity associated with atopic diseases and immune dysregulation disorders such as asthma, food allergies, multiple sclerosis, atopic dermatitis, type 1 diabetes mellitus, and inflammatory bowel disease has been increasing all around the world over the past few decades. Although the roles of non-biological environmental factors and genetic factors in the etiopathology have been particularly emphasized, they do not fully explain the increase; for example, genetic factors in a population change very gradually. Epidemiological investigation has revealed that the increase also parallels a decrease in infectious diseases, especially parasitic infections. Thus, the reduced prevalence of parasitic infections may be another important reason for immune dysregulation. Parasites have co-evolved with the human immune system for a long time. Some parasite-derived immune-evasion molecules have been verified to reduce the incidence and harmfulness of atopic diseases in humans by modulating the immune response. More importantly, some parasite-derived products have been shown to inhibit the progression of inflammatory diseases and consequently alleviate their symptoms. Thus, parasites, and especially their products, may have potential applications in the treatment of autoimmune diseases. In this review, the potential of parasite-derived products and their analogs for use in the treatment of atopic diseases and immune dysregulation is summarized.

Endotoxin-induced monocytic microparticles have contrasting effects on endothelial inflammatory responses.

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Beryl Wen

Full Text Available Septic shock is a severe disease state characterised by the body's life threatening response to infection. Complex interactions between endothelial cells and circulating monocytes are responsible for microvasculature dysfunction contributing to the pathogenesis of this syndrome. Here, we intended to determine whether microparticles derived from activated monocytes contribute towards inflammatory processes and notably vascular permeability. We found that endotoxin stimulation of human monocytes enhances the release of microparticles of varying phenotypes and mRNA contents. Elevated numbers of LPS-induced monocytic microparticles (mMP expressed CD54 and contained higher levels of transcripts for pro-inflammatory cytokines such as TNF, IL-6 and IL-8. Using a prothrombin time assay, a greater reduction in plasma coagulation time was observed with LPS-induced mMP than with non-stimulated mMP. Co-incubation of mMP with the human brain endothelial cell line hCMEC/D3 triggered their time-dependent uptake and significantly enhanced endothelial microparticle release. Unexpectedly, mMP also modified signalling pathways by diminishing pSrc (tyr416 expression and promoted endothelial monolayer tightness, as demonstrated by endothelial impedance and permeability assays. Altogether, these data strongly suggest that LPS-induced mMP have contrasting effects on the intercellular communication network and display a dual potential: enhanced pro-inflammatory and procoagulant properties, together with protective function of the endothelium.

Identification of clam plasma proteins that bind its pathogen Quahog Parasite Unknown.

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Hartman, Rachel; Pales Espinosa, Emmanuelle; Allam, Bassem

2018-06-01

The hard clam (Mercenaria mercenaria) is among the most economically-important marine species along the east coast of the United States, representing the first marine resource in several Northeastern states. The species is rather resilient to infections and the only important disease of hard clams results from an infection caused by Quahog Parasite Unknown (QPX), a protistan parasite that can lead to significant mortality events in wild and aquacultured clam stocks. Though the presence of QPX disease has been documented since the 1960s, little information is available on cellular and molecular interactions between the parasite and the host. This study examined the interactions between the clam immune system and QPX cells. First, the effect of clam plasma on the binding of hemocytes to parasite cells was evaluated. Second, clam plasma proteins that bind QPX cells were identified through proteomic (LC-MS/MS) analyses. Finally, the effect of prior clam exposure to QPX on the abundance of QPX-reactive proteins in the plasma was evaluated. Results showed that plasma factors enhance the attachment of hemocytes to QPX. Among the proteins that specifically bind to QPX cells, several lectins were identified, as well as complement component proteins and proteolytic enzymes. Furthermore, results showed that some of these lectins and complement-related proteins are inducible as their abundance significantly increased following QPX challenge. These results shed light on plasma proteins involved in the recognition and binding of parasite cells and provide molecular targets for future investigations of factors involved in clam resistance to the disease, and ultimately for the selection of resistant clam stocks. Copyright © 2018 Elsevier Ltd. All rights reserved.

Microparticle charging in dry air plasma created by an external ionization source

International Nuclear Information System (INIS)

Derbenev, I N; Filippov, A V

2015-01-01

In the present paper the dust particle charging is studied in a dry air plasma created by an external ionization source. The ionization rate is changed in the range 10 1 -10 20 cm -3 s -1 . It is found that the main positive ion of the plasma is O + 4 and the main negative ones are O − 2 and O − 4 . The point sink model based on the diffusion-drift approach shows that the screening potential distribution around a dust particle is a superposition of four Debye-like exponentials with four different spatial scales. The first scale almost coincides with the Debye radius. The second one is the distance, passed by positive and negative plasma components due to ambipolar diffusion in their recombination time. The third one is defined by the negative ion conversion and diffusion. The fourth scale is described by the electron attachment, recombination and diffusion at low gas ionization rates and by the recombination and diffusion of negative diatomic ions at high ionization rates. It is also shown that the electron flux defines the microparticle charge at high ionization rates, whereas the electron number density is much less than the ion one. (paper)

[Cell-derived microparticles unveil their fibrinolytic and proteolytic function].

Science.gov (United States)

Doeuvre, Loïc; Angles-Cano, Eduardo

2009-01-01

Cell-derived microparticles (MP) are membrane microvesicles, 0.1-1 microm in size, shed by cells following activation or during apoptosis in a variety of pathological conditions. MPs released by blood cells or by vascular endothelial cells display molecular signatures that allow their identification and functional characterization. In addition, they provide tissue factor (TF) and a procoagulant phospholipid surface. Therefore, at present, the most strongly established applied research on MPs is their procoagulant activity as a determinant of thrombotic risk in various clinical conditions. Previous studies have indicated that MPs derived from malignant cells express matrix metalloproteinases, urokinase and its receptor (uPA/uPAR) that, in the presence of plasminogen, may act in concert to degrade extracellular matrix proteins. Recently, it was shown that MPs from TNFa-stimulated endothelial cells served as a surface for interaction with plasminogen and its conversion into plasmin by the uPA/uPAR system expressed at their surface. This capacity of MPs to promote plasmin generation confers them a new profibrinolytic and proteolytic function that may be of relevance in fibrinolysis, cell migration, angiogenesis, dissemination of malignant cells, cell detachment and apoptosis.

Microparticle content of platelet concentrates is predicted by donor microparticles and is altered by production methods and stress

DEFF Research Database (Denmark)

Maurer-Spurej, Elisabeth; Larsen, Rune; Labrie, Audrey

2016-01-01

In circulation, shedding of microparticles from a variety of viable cells can be triggered by pathological activation of inflammatory processes, by activation of coagulation or complement systems, or by physical stress. Elevated microparticle content (MPC) in donor blood might therefore indicate...... a clinical condition of the donor which, upon transfusion, might affect the recipient. In blood products, elevated MPC might also represent product stress. Surprisingly, the MPC in blood collected from normal blood donors is highly variable, which raises the question whether donor microparticles are present...... in-vivo and transfer into the final blood component, and how production methods and post-production processing might affect the MPC. We measured MPC using ThromboLUX in (a) platelet-rich plasma (PRP) of 54 apheresis donors and the corresponding apheresis products, (b) 651 apheresis and 646 pooled...

Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles.

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Lai, Ruenn Chai; Arslan, Fatih; Tan, Soon Sim; Tan, Betty; Choo, Andre; Lee, May May; Chen, Tian Sheng; Teh, Bao Ju; Eng, John Kun Long; Sidik, Harwin; Tanavde, Vivek; Hwang, Wei Sek; Lee, Chuen Neng; El Oakley, Reida Menshawe; Pasterkamp, Gerard; de Kleijn, Dominique P V; Tan, Kok Hian; Lim, Sai Kiang

2010-06-01

The therapeutic effects of mesenchymal stem cells (MSCs) transplantation are increasingly thought to be mediated by MSC secretion. We have previously demonstrated that human ESC-derived MSCs (hESC-MSCs) produce cardioprotective microparticles in pig model of myocardial ischemia/reperfusion (MI/R) injury. As the safety and availability of clinical grade human ESCs remain a concern, MSCs from fetal tissue sources were evaluated as alternatives. Here we derived five MSC cultures from limb, kidney and liver tissues of three first trimester aborted fetuses and like our previously described hESC-derived MSCs; they were highly expandable and had similar telomerase activities. Each line has the potential to generate at least 10(16-19) cells or 10(7-10) doses of cardioprotective secretion for a pig model of MI/R injury. Unlike previously described fetal MSCs, they did not express pluripotency-associated markers such as Oct4, Nanog or Tra1-60. They displayed a typical MSC surface antigen profile and differentiated into adipocytes, osteocytes and chondrocytes in vitro. Global gene expression analysis by microarray and qRT-PCR revealed a typical MSC gene expression profile that was highly correlated among the five fetal MSC cultures and with that of hESC-MSCs (r(2)>0.90). Like hESC-MSCs, they produced secretion that was cardioprotective in a mouse model of MI/R injury. HPLC analysis of the secretion revealed the presence of a population of microparticles with a hydrodynamic radius of 50-65 nm. This purified population of microparticles was cardioprotective at approximately 1/10 dosage of the crude secretion. (c) 2009 Elsevier Ltd. All rights reserved.

Differences in levels of platelet-derived microparticles in platelet components prepared using the platelet rich plasma, buffy coat, and apheresis procedures.

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Noulsri, Egarit; Udomwinijsilp, Prapaporn; Lerdwana, Surada; Chongkolwatana, Viroje; Permpikul, Parichart

2017-04-01

There has been an increased interest in platelet-derived microparticles (PMPs) in transfusion medicine. Little is known about PMP status during the preparation of platelet concentrates for transfusion. The aim of this study is to compare the PMP levels in platelet components prepared using the buffy coat (BC), platelet-rich plasma platelet concentrate (PRP-PC), and apheresis (AP) processes. Platelet components were prepared using the PRP-PC and BC processes. Apheresis platelets were prepared using the Trima Accel and Amicus instruments. The samples were incubated with annexin A5-FITC, CD41-PE, and CD62P-APC. At day 1 after processing, the PMPs and activated platelets were determined using flow cytometry. Both the percentage and number of PMPs were higher in platelet components prepared using the Amicus instrument (2.6±1.8, 32802±19036 particles/μL) than in platelet components prepared using the Trima Accel instrument (0.5±0.4, 7568±5298 particles/μL), BC (1.2±0.6, 12,920±6426 particles/μL), and PRP-PC (0.9±0.6, 10731±5514 particles/μL). Both the percentage and number of activated platelets were higher in platelet components prepared using the Amicus instrument (33.2±13.9, 427553±196965 cells/μL) than in platelet components prepared using the Trima Accel instrument (16.2±6.1, 211209±87706 cells/μL), BC (12.9±3.2, 140624±41003 cells/μL), and PRP-PC (21.1±6.3, 265210±86257 cells/μL). The study suggests high variability of PMPs and activated platelets in platelet components prepared using different processes. This result may be important in validating the instruments involved in platelet blood collection and processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improved flow cytometric assessment reveals distinct microvesicle (cell-derived microparticle signatures in joint diseases.

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Bence György

Full Text Available INTRODUCTION: Microvesicles (MVs, earlier referred to as microparticles, represent a major type of extracellular vesicles currently considered as novel biomarkers in various clinical settings such as autoimmune disorders. However, the analysis of MVs in body fluids has not been fully standardized yet, and there are numerous pitfalls that hinder the correct assessment of these structures. METHODS: In this study, we analyzed synovial fluid (SF samples of patients with osteoarthritis (OA, rheumatoid arthritis (RA and juvenile idiopathic arthritis (JIA. To assess factors that may confound MV detection in joint diseases, we used electron microscopy (EM, Nanoparticle Tracking Analysis (NTA and mass spectrometry (MS. For flow cytometry, a method commonly used for phenotyping and enumeration of MVs, we combined recent advances in the field, and used a novel approach of differential detergent lysis for the exclusion of MV-mimicking non-vesicular signals. RESULTS: EM and NTA showed that substantial amounts of particles other than MVs were present in SF samples. Beyond known MV-associated proteins, MS analysis also revealed abundant plasma- and immune complex-related proteins in MV preparations. Applying improved flow cytometric analysis, we demonstrate for the first time that CD3(+ and CD8(+ T-cell derived SF MVs are highly elevated in patients with RA compared to OA patients (p=0.027 and p=0.009, respectively, after Bonferroni corrections. In JIA, we identified reduced numbers of B cell-derived MVs (p=0.009, after Bonferroni correction. CONCLUSIONS: Our results suggest that improved flow cytometric assessment of MVs facilitates the detection of previously unrecognized disease-associated vesicular signatures.

Leukocyte-derived microparticles and scanning electron microscopic structures in two fractions of fresh cerebrospinal fluid in amyotrophic lateral sclerosis: a case report

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Zachau Anne C

2012-09-01

Full Text Available Abstract Introduction Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder characterized by degeneration of motoneuron cells in anterior spinal horns. There is a need for early and accurate diagnosis with this condition. In this case report we used two complementary methods: scanning electron microscopy and fluorescence-activated cell sorting. This is the first report to our knowledge of microparticles in the cerebrospinal fluid of a patient with amyotrophic lateral sclerosis. Case presentation An 80-year-old Swedish man of Caucasian ethnicity presented to our facility with symptoms of amyotrophic lateral sclerosis starting a year before his first hospital examination, such as muscle weakness and twitching in his right hand progressing to arms, body and leg muscles. Electromyography showed classical neurophysiological findings of amyotrophic lateral sclerosis. Routine blood sample results were normal. A lumbar puncture was performed as a routine investigation and his cerebrospinal fluid was normal with regard to cell count and protein levels, and there were no signs of inflammation. However, scanning electron microscopy and fluorescence-activated cell sorting showed pronounced abnormalities compared to healthy controls. Flow cytometry analysis of two fractions of cerebrospinal fluid from our patient with amyotrophic lateral sclerosis was used to measure the specific binding of antibodies to CD42a, CD144 and CD45, and of phosphatidylserine to lactadherin. Our patient displayed over 100 times more phosphatidylserine-positive microparticles and over 400 times more cell-derived microparticles of leukocyte origin in his cerebrospinal fluid compared to healthy control subjects. The first cerebrospinal fluid fraction contained about 50% more microparticles than the second fraction. The scanning electron microscopy filters used with cerebrospinal fluid from our patient were filled with compact aggregates of spherical particles of

Mesenchymal stem cell-derived microparticles: a promising therapeutic strategy.

Science.gov (United States)

Tan, Xi; Gong, Yong-Zhen; Wu, Ping; Liao, Duan-Fang; Zheng, Xi-Long

2014-08-18

Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on injured and cancerous tissues, MSCs are of great potential in regenerative medicine. MSCs also contribute to reparative processes in different pathological conditions, including cardiovascular diseases and cancer. However, many studies have shown that only a small proportion of transplanted MSCs can actually survive and be incorporated into host tissues. The effects of MSCs cannot be fully explained by their number. Recent discoveries suggest that microparticles (MPs) derived from MSCs may be important for the physiological functions of their parent. Though the physiological role of MSC-MPs is currently not well understood, inspiring results indicate that, in tissue repair and anti-cancer therapy, MSC-MPs have similar pro-regenerative and protective properties as their cellular counterparts. Thus, MSC-MPs represent a promising approach that may overcome the obstacles and risks associated with the use of native or engineered MSCs.

Platelet-, monocyte-derived and tissue factor-carrying circulating microparticles are related to acute myocardial infarction severity.

Directory of Open Access Journals (Sweden)

Gemma Chiva-Blanch

Full Text Available Circulating microparticles (cMPs are phospholipid-rich vesicles released from cells when activated or injured, and contribute to the formation of intracoronary thrombi. Tissue factor (TF, CD142 is the main trigger of fibrin formation and TF-carrying cMPs are considered one of the most procoagulant cMPs. Similar types of atherosclerotic lesions may lead to different types of AMI, although the mechanisms behind are unresolved. Therefore, we aimed to investigate the phenotype of cMPs found in plasma of ACS patients and its relation to AMI severity and thrombotic burden.In a cross-sectional study, two hundred patients aged 75±4 years were included in the study 2-8 weeks after suffering an AMI. Annexin V positive (AV+-cMPs derived from blood and vascular cells were measured by flow cytometry. Plasma procoagulant activity (TF-PCA was measured through a chromogenic assay.STEMI patients (n = 75 showed higher levels of platelet-derived cMPs [CD61+/AV+, CD31+/AV+, CD42b+/AV+ and CD31+/CD42b+/AV+, P = 0.048, 0.038, 0.009 and 0.006, respectively], compared to NSTEMI patients (n = 125. Patients who suffered a heart failure during AMI (n = 17 had increased levels of platelet (CD61+-and monocyte (CD14+-derived cMPs carrying TF (CD142+ (P<0.0001 and 0.004, respectively. Additionally, NYHA class III (n = 23 patients showed higher levels of CD142+/AV+, CD14+/AV+ and CD14+/CD142+/AV+ cMPs than those in class I/II (P = 0.001, 0.015 and 0.014, respectively. The levels of these cMPs positively correlated with TF-PCA (r≥0.166, P≤0.027, all.Platelets and monocytes remain activated in AMI patients treated as per guidelines and release cMPs that discriminate AMI severity. Therefore, TF-MPs, and platelet- and monocyte-MPs may reflect thrombotic burden in AMI patients.

Isolation of Human CD138+ Microparticles from the Plasma of Patients with Multiple Myeloma

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Sabna Rajeev Krishnan

2016-01-01

Full Text Available The confinement of multiple myeloma (MM to the bone marrow microenvironment requires an invasive bone marrow biopsy to monitor the malignant compartment. The existing clinical tools used to determine treatment response and tumor relapse are limited in sensitivity mainly because they indirectly measure tumor burden inside the bone marrow and fail to capture the patchy, multisite tumor infiltrates associated with MM. Microparticles (MPs are 0.1- to 1.0-μm membrane vesicles, which contain the cellular content of their originating cell. MPs are functional mediators and convey prothrombotic, promalignant, proresistance, and proinflammatory messages, establishing intercellular cross talk and bypassing the need for direct cell-cell contact in many pathologies. In this study, we analyzed plasma cell–derived MPs (CD138+ from deidentified MM patients (n = 64 and normal subjects (n = 18 using flow cytometry. The morphology and size of the MPs were further analyzed using scanning electron microscopy. Our study shows the proof of a systemic signature of MPs in MM patients. We observed that the levels of MPs were significantly elevated in MM corresponding to the tumor burden. We provide the first evidence for the presence of MPs in the peripheral blood of MM patients with potential applications in personalized MM clinical monitoring.

Fission product release from HTGR coated microparticles and fuel elements

International Nuclear Information System (INIS)

Gusev, A.A.; Deryugin, A.I.; Lyutikov, R.A.; Chernikov, A.S.

1991-01-01

The article presents the results of the investigation of fission products release from microparticles with UO 2 core and five-layer HII PyC- and SiC base protection layers of TRICO type as well as from spherical fuel elements based thereon. It is shown that relative release of short-lived xenon and crypton from microparticles does not exceed (2-3) 10 -7 . The release of gaseous fission products from fuel elements containing no damaged coated microparticles, is primarily determined by the contamination of matrix graphite with fuel. An analytical dependence is derived, the dependence described the relation between structural parameters of coated microparticles, irradiation conditions and fuel burnup at which depressurization of coated microparticles starts

Absolute measurement of the total ion-drag force on a single plasma-confined microparticle at the void edge under microgravity conditions

NARCIS (Netherlands)

Beckers, J.; Trienekens, D.J.M.; Kroesen, G.M.W.

2013-01-01

We present an absolute measurement of the total ion-drag force on one single microparticle at the edge of the dust free region in low pressure complex plasmas: the void. In order to do so, the particle confinement position was monitored as a function of the gas pressure for two particle sizes under

Physical Characterization of Mouse Deep Vein Thrombosis Derived Microparticles by Differential Filtration with Nanopore Filters

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Antonio Peramo

2011-12-01

Full Text Available With the objective of making advancements in the area of pro-thrombotic microparticle characterization in cardiovascular biology, we present a novel method to separate blood circulating microparticles using a membrane-based, nanopore filtration system. In this qualitative study, electron microscopy observations of these pro-thrombotic mouse microparticles, as well as mouse platelets and leukocytes obtained using a mouse inferior vena cava ligation model of deep-vein thrombosis are presented. In particular, we present mouse microparticle morphology and microstructure using SEM and TEM indicating that they appear to be mostly spherical with diameters in the 100 to 350 nm range. The nanopore filtration technique presented is focused on the development of novel methodologies to isolate and characterize blood circulating microparticles that can be used in conjunction with other methodologies. We believe that determination of microparticle size and structure is a critical step for the development of reliable assays with clinical or research application in thrombosis and it will contribute to the field of nanomedicine in thrombosis.

Microparticle content of platelet concentrates is predicted by donor microparticles and is altered by production methods and stress.

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Maurer-Spurej, Elisabeth; Larsen, Rune; Labrie, Audrey; Heaton, Andrew; Chipperfield, Kate

2016-08-01

In circulation, shedding of microparticles from a variety of viable cells can be triggered by pathological activation of inflammatory processes, by activation of coagulation or complement systems, or by physical stress. Elevated microparticle content (MPC) in donor blood might therefore indicate a clinical condition of the donor which, upon transfusion, might affect the recipient. In blood products, elevated MPC might also represent product stress. Surprisingly, the MPC in blood collected from normal blood donors is highly variable, which raises the question whether donor microparticles are present in-vivo and transfer into the final blood component, and how production methods and post-production processing might affect the MPC. We measured MPC using ThromboLUX in (a) platelet-rich plasma (PRP) of 54 apheresis donors and the corresponding apheresis products, (b) 651 apheresis and 646 pooled platelet concentrates (PCs) with plasma and 414 apheresis PCs in platelet additive solution (PAS), and (c) apheresis PCs before and after transportation, gamma irradiation, and pathogen inactivation (N = 8, 7, and 12 respectively). ThromboLUX-measured MPC in donor PRP and their corresponding apheresis PC samples were highly correlated (r = 0.82, P = .001). The average MPC in pooled PC was slightly lower than that in apheresis PC and substantially lower in apheresis PC stored with PAS rather than plasma. Mirasol Pathogen Reduction treatment significantly increased MPC with age. Thus, MPC measured in donor samples might be a useful predictor of product stability, especially if post-production processes are necessary. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles.

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Bilyy, Rostyslav O; Shkandina, Tanya; Tomin, Andriy; Muñoz, Luis E; Franz, Sandra; Antonyuk, Volodymyr; Kit, Yuriy Ya; Zirngibl, Matthias; Fürnrohr, Barbara G; Janko, Christina; Lauber, Kirsten; Schiller, Martin; Schett, Georg; Stoika, Rostyslav S; Herrmann, Martin

2012-01-02

Inappropriate clearance of apoptotic remnants is considered to be the primary cause of systemic autoimmune diseases, like systemic lupus erythematosus. Here we demonstrate that apoptotic cells release distinct types of subcellular membranous particles (scMP) derived from the endoplasmic reticulum (ER) or the plasma membrane. Both types of scMP exhibit desialylated glycotopes resulting from surface exposure of immature ER-derived glycoproteins or from surface-borne sialidase activity, respectively. Sialidase activity is activated by caspase-dependent mechanisms during apoptosis. Cleavage of sialidase Neu1 by caspase 3 was shown to be directly involved in apoptosis-related increase of surface sialidase activity. ER-derived blebs possess immature mannosidic glycoepitopes and are prioritized by macrophages during clearance. Plasma membrane-derived blebs contain nuclear chromatin (DNA and histones) but not components of the nuclear envelope. Existence of two immunologically distinct types of apoptotic blebs may provide new insights into clearance-related diseases.

Coherent beam combination via microparticle plasma modes

International Nuclear Information System (INIS)

Rogovin, D.; Shen, T.P.

1988-01-01

Recently, there have been interesting observations and calculations on phase conjugation via degenerate four-wave mixing in gold colloids. The generation of phase conjugate radiation in these media arises from and reflects the creation of static index grating imposed on the electronic wave functions within the microparticles. These encouraging findings motivate us to consider the possibility of generating moving index gratings in these media with possible applications to coherent beam combination

Red cell-derived microparticles (RMP) as haemostatic agent.

Science.gov (United States)

Jy, Wenche; Johansen, Max E; Bidot, Carlos; Horstman, Lawrence L; Ahn, Yeon S

2013-10-01

Among circulating cell-derived microparticles, those derived from red cells (RMP) have been least well investigated. To exploit potential haemostatic benefit of RMP, we developed a method of producing them in quantity, and here report on their haemostatic properties. High-pressure extrusion of washed RBC was employed to generate RMP. RMP were identified and enumerated by flow cytometry. Their size distribution was assessed by Doppler electrophoretic light scattering analysis (DELSA). Interaction with platelets was studied by platelet aggregometry, and shear-dependent adhesion by Diamed IMPACT-R. Thrombin generation and tissue factor (TF) expression was also measured. The effect of RMP on blood samples of patients with bleeding disorders was investigated ex vivo by thromboelastography (TEG). Haemostatic efficacy in vivo was assessed by measuring reduction of blood loss and bleeding time in rats and rabbits. RMP have mean diameter of 0.45 µm and 50% of them exhibit annexin V binding, a proxy for procoagulant phospholipids (PL). No TF could be detected by flow cytometry. At saturating concentrations of MPs, RMP generated thrombin robustly but after longer delay compared to PMP and EMP. RMP enhanced platelet adhesion and aggregation induced by low-dose ADP or AA. In TEG study, RMP corrected or improved haemostatic defects in blood of patients with platelet and coagulation disorders. RMP reduced bleeding time and blood loss in thrombocytopenic rabbits (busulfan-treated) and in Plavix-treated rats. In conclusion, RMP has broad haemostatic activity, enhancing both primary (platelet) and secondary (coagulation) haemostasis, suggesting potential use as haemostatic agent for treatment of bleeding.

Plasma protein loss associated with gastrointestinal parasitism in grazing sheep.

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Yakoob, A Y; Holmes, P H; Parkins, J J; Armour, J

1983-01-01

Some pathophysiological effects of parasitic gastroenteritis in two groups of lambs grazing paddocks either heavily or lightly contaminated with trichostrongyle larvae were investigated between July and October 1980. The leak of plasma protein was measured on three occasions at pasture using 51chromic chloride. Total faecal output was measured indirectly using chromic oxide. Losses of 51chromic chloride-labelled plasma protein into the gastrointestinal tract were significantly higher in the lambs grazing the heavily contaminated pasture than in those grazing lightly infected ground in both July and August. The increased plasma losses were associated with high faecal egg counts, hypoalbuminaemia and elevated levels of plasma pepsinogen.

Super-resolved calibration-free flow cytometric characterization of platelets and cell-derived microparticles in platelet-rich plasma.

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Konokhova, Anastasiya I; Chernova, Darya N; Moskalensky, Alexander E; Strokotov, Dmitry I; Yurkin, Maxim A; Chernyshev, Andrei V; Maltsev, Valeri P

2016-02-01

Importance of microparticles (MPs), also regarded as extracellular vesicles, in many physiological processes and clinical conditions motivates one to use the most informative and precise methods for their characterization. Methods based on individual particle analysis provide statistically reliable distributions of MP population over characteristics. Although flow cytometry is one of the most powerful technologies of this type, the standard forward-versus-side-scattering plots of MPs and platelets (PLTs) overlap considerably because of similarity of their morphological characteristics. Moreover, ordinary flow cytometry is not capable of measurement of size and refractive index (RI) of MPs. In this study, we 1) employed the potential of the scanning flow cytometer (SFC) for identification and characterization of MPs from light scattering; 2) suggested the reference method to characterize MP morphology (size and RI) with high precision; and 3) determined the lowest size of a MP that can be characterized from light scattering with the SFC. We equipped the SFC with 405 and 488 nm lasers to measure the light-scattering profiles and side scattering from MPs, respectively. The developed two-stage method allowed accurate separation of PLTs and MPs in platelet-rich plasma. We used two optical models for MPs, a sphere and a bisphere, in the solution of the inverse light-scattering problem. This solution provides unprecedented precision in determination of size and RI of individual spherical MPs-median uncertainties (standard deviations) were 6 nm and 0.003, respectively. The developed method provides instrument-independent quantitative information on MPs, which can be used in studies of various factors affecting MP population. © 2015 International Society for Advancement of Cytometry.

Apheresis platelet concentrates contain platelet-derived and endothelial cell-derived microparticles.

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Rank, A; Nieuwland, R; Liebhardt, S; Iberer, M; Grützner, S; Toth, B; Pihusch, R

2011-02-01

Microparticles (MP) are membrane vesicles with thrombogenic and immunomodulatory properties. We determined MP subgroups from resting platelets, activated platelets and endothelial cells in donors and apheresis platelet concentrates (PC). MP were double stained with annexin V and CD61 (platelet-derived MP; PMP), P-selectin or CD63 (MP from activated platelets) and CD144 plus E-selectin (endothelial cell-derived MP; EMP) and detected by flow cytometry in platelet donors (n=36) and apheresis PC (n=11; Trima™). PC contained MP, mainly from resting platelets [93% (90-95)], and minor fractions of PMP from activated platelets [P-selectin(+) or CD63(+); 4·8% (3·2-7·7) and 2·6% (2·0-4·0)]. Compared to donors, levels of annexin V+ MP, PMP, P-selectin(+) and CD63(+) MP were 1·7-, 2·3-, 8·6- and 3·1-fold higher in PC (all P<0·05). During storage (1-5 days), levels of annexin V+ MP and PMP did not increase, although small increases in the fraction of P-selectin(+) or CD63(+) MP occurred (both P<0·05). PC also contained EMP, which were 2·6- to 3·7-fold enriched in PC compared to donors (P<0·05). Transfusion of apheresis PC also results in transfusion of HLA-carrying PMP and EMP. This might counteract the aim of reducing transfused HLA load by leucodepletion. The increases in PMP exposing P-selectin or CD63 reflect mild platelet activation during storage. We conclude that in leucodepleted platelet apheresis using fluidized particle bed technology, MP are harvested mainly from the donor by apheresis. Improvement in apheresis technology might reduce MP load. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Measurement of circulating cell-derived microparticles by flow cytometry: sources of variability within the assay.

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Ayers, Lisa; Kohler, Malcolm; Harrison, Paul; Sargent, Ian; Dragovic, Rebecca; Schaap, Marianne; Nieuwland, Rienk; Brooks, Susan A; Ferry, Berne

2011-04-01

Circulating cell-derived microparticles (MPs) have been implicated in several disease processes and elevated levels are found in many pathological conditions. The detection and accurate measurement of MPs, although attracting widespread interest, is hampered by a lack of standardisation. The aim of this study was to establish a reliable flow cytometric assay to measure distinct subtypes of MPs in disease and to identify any significant causes of variability in MP quantification. Circulating MPs within plasma were identified by their phenotype (platelet, endothelial, leukocyte and annexin-V positivity (AnnV+). The influence of key variables (i.e. time between venepuncture and centrifugation, washing steps, the number of centrifugation steps, freezing/long-term storage and temperature of thawing) on MP measurement were investigated. Increasing time between venepuncture and centrifugation leads to increased MP levels. Washing samples results in decreased AnnV+MPs (P=0.002) and platelet-derived MPs (PMPs) (P=0.002). Double centrifugation of MPs prior to freezing decreases numbers of AnnV+MPs (P=0.0004) and PMPs (P=0.0004). A single freeze thaw cycle of samples led to an increase in AnnV+MPs (P=0.0020) and PMPs (P=0.0039). Long-term storage of MP samples at -80° resulted in decreased MP levels. This study found that minor protocol changes significantly affected MP levels. This is one of the first studies attempting to standardise a method for obtaining and measuring circulating MPs. Standardisation will be essential for successful development of MP technologies, allowing direct comparison of results between studies and leading to a greater understanding of MPs in disease. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Phospholipid composition of cell-derived microparticles determined by one-dimensional high-performance thin-layer chromatography

NARCIS (Netherlands)

Weerheim, A. M.; Kolb, A. M.; Sturk, A.; Nieuwland, R.

2002-01-01

Microparticles in the circulation activate the coagulation system and may activate the complement system via C-reactive protein upon conversion of membrane phospholipids by phospholipases. We developed a sensitive and reproducible method to determine the phospholipid composition of microparticles.

Observation of metallic sphere–complex plasma interactions in microgravity

International Nuclear Information System (INIS)

Schwabe, M; Zhdanov, S; Hagl, T; Huber, P; Rubin-Zuzic, M; Zaehringer, E; Thomas, H M; Lipaev, A M; Molotkov, V I; Naumkin, V N; Fortov, V E; Vinogradov, P V

2017-01-01

The PK-3 Plus laboratory on board the International Space Station is used to study the interaction between metallic spheres and a complex plasma. We show that the metallic spheres significantly affect both the local plasma environment and the microparticle dynamics. The spheres charge under the influence of the plasma and repel the microparticles, forming cavities surrounding the spheres. The size of the cavity around a sphere is used to study the force balance acting on microparticles at the cavity edge. We show that the ion drag force and pressure force from other microparticles balances with the electric force acting from the sphere to within 20%. At intermediate distances from the sphere surface, the interaction between the microparticles and the metallic spheres is attractive due to the drag force stemming from the ions which are moving towards the highly charged spheres. The spheres thus strongly affect the plasma fluxes. This modification of the plasma flux can lead to an effective surface tension acting on the microparticles, and to the excitation of dust-density waves near the spheres, as the local electric field crosses a threshold. (paper)

Cutting-edge analysis of extracellular microparticles using ImageStream(X) imaging flow cytometry.

Science.gov (United States)

Headland, Sarah E; Jones, Hefin R; D'Sa, Adelina S V; Perretti, Mauro; Norling, Lucy V

2014-06-10

Interest in extracellular vesicle biology has exploded in the past decade, since these microstructures seem endowed with multiple roles, from blood coagulation to inter-cellular communication in pathophysiology. In order for microparticle research to evolve as a preclinical and clinical tool, accurate quantification of microparticle levels is a fundamental requirement, but their size and the complexity of sample fluids present major technical challenges. Flow cytometry is commonly used, but suffers from low sensitivity and accuracy. Use of Amnis ImageStream(X) Mk II imaging flow cytometer afforded accurate analysis of calibration beads ranging from 1 μm to 20 nm; and microparticles, which could be observed and quantified in whole blood, platelet-rich and platelet-free plasma and in leukocyte supernatants. Another advantage was the minimal sample preparation and volume required. Use of this high throughput analyzer allowed simultaneous phenotypic definition of the parent cells and offspring microparticles along with real time microparticle generation kinetics. With the current paucity of reliable techniques for the analysis of microparticles, we propose that the ImageStream(X) could be used effectively to advance this scientific field.

Post-Effect of Air Quality Improvement on Biomarkers for Systemic Inflammation and Microparticles in Asthma Patients After the 2008 Beijing Olympic Games: a Pilot Study.

Science.gov (United States)

Gao, Jinming; Xu, Xiaohua; Ying, Zhekang; Jiang, Lei; Zhong, Mianhua; Wang, Aixia; Chen, Lung-Chi; Lu, Bo; Sun, Qinghua

2017-08-01

This study's aim was to investigate the post-effect of an air quality improvement on systemic inflammation and circulating microparticles in asthmatic patients during, and 2 months after, the Beijing Olympics 2008. We measured the levels of circulating inflammatory cytokines and microparticles in the peripheral blood from asthma patients and healthy controls during (phase 1), and 2 months after (phase 2) the Beijing 2008 Olympic Games. The concentrations of circulating cytokines (including TNFα, IL-6, IL-8, and IL-10) were still seen reduced in phase 2 when compared with those in phase 1. The number of circulating endothelial cell-derived microparticles was significantly lower during the phase 2 than that during phase 1 in asthma patients. The level of plasma lipopolysaccharide-binding protein (LBP) was significantly decreased in asthmatics in phase 2. The level of norepinephrine was significantly higher in phase 2 than that in phase 1 in plasma from both asthma patients and healthy subjects. There were no significant differences in the gene profile for the toll-like receptor (TLR) signaling from peripheral blood mononuclear cells. In vitro, microvesicles from patients with asthma impaired the relaxation to bradykinin and contraction to acetylcholine, whereas microparticles from healthy subjects did not. These data suggested that reduction in systemic pro-inflammatory responses and circulating LBP and increased level of norepinephrine in asthma patients persisted even after 2 months of the air pollution intervention. These changes were independent of the TLR signaling pathway. Circulating microparticles might be associated with airway smooth muscle dysfunction.

Circulating Endothelial Microparticles: A Key Hallmark of Atherosclerosis Progression

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Keshav Raj Paudel

2016-01-01

Full Text Available The levels of circulating microparticles (MPs are raised in various cardiovascular diseases. Their increased level in plasma is regarded as a biomarker of alteration in vascular function. The prominent MPs present in blood are endothelial microparticles (EMPs described as complex submicron (0.1 to 1.0 μm vesicles like structure, released in response to endothelium cell activation or apoptosis. EMPs possess both physiological and pathological effects and may promote oxidative stress and vascular inflammation. EMPs release is triggered by inducer like angiotensin II, lipopolysaccharide, and hydrogen peroxide leading to the progression of atherosclerosis. However, there are multiple physiological pathways for EMPs generation like NADPH oxidase derived endothelial ROS formation, Rho kinase pathway, and mitogen-activated protein kinases. Endothelial dysfunction is a key initiating event in atherosclerotic plaque formation. Atheroemboli, resulting from ruptured carotid plaques, is a major cause of stroke. Increasing evidence suggests that EMPs play an important role in the pathogenesis of cardiovascular disease, acting as a marker of damage, either exacerbating disease progression or triggering a repair response. In this regard, it has been suggested that EMPs have the potential to act as biomarkers of disease status. This review aims to provide updated information of EMPs in relation to atherosclerosis pathogenesis.

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

Science.gov (United States)

Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

2016-01-01

Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

Directory of Open Access Journals (Sweden)

Gemma Chiva-Blanch

Full Text Available Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke.Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls.Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions.Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger

Cell-derived microparticles: new targets in the therapeutic management of disease.

Science.gov (United States)

Roseblade, Ariane; Luk, Frederick; Rawling, Tristan; Ung, Alison; Grau, Georges E R; Bebawy, Mary

2013-01-01

Intercellular communication is essential to maintain vital physiological activities and to regulate the organism's phenotype. There are a number of ways in which cells communicate with one another. This can occur via autocrine signaling, endocrine signaling or by the transfer of molecular mediators across gap junctions. More recently communication via microvesicular shedding has gained important recognition as a significant pathway by which cells can coordinate the spread and dominance of selective traits within a population. Through this communication apparatus, cells can now acquire and secure a survival advantage, particularly in the context of malignant disease. This review aims to highlight some of the functions and implications of microparticles in physiology of various disease states, and present a novel therapeutic strategy through the regulation of microparticle production.

Microparticle Shedding by Erythrocytes, Monocytes and Vascular Smooth Muscular Cells Is Reduced by Aspirin in Diabetic Patients.

Science.gov (United States)

Chiva-Blanch, Gemma; Suades, Rosa; Padró, Teresa; Vilahur, Gemma; Peña, Esther; Ybarra, Juan; Pou, Jose M; Badimon, Lina

2016-07-01

Diabetes mellitus is associated with an enhanced risk for cardiovascular disease and its prevalence is increasing. Diabetes induces metabolic stress on blood and vascular cells, promoting platelet activation and vascular dysfunction. The level of vascular cell activation can be measured by the number and phenotype of microparticles found in the circulation. The aim of this study was to investigate the effect of a platelet-inhibitory dose of aspirin on the number and type of microparticles shed to the circulation. Forty-three diabetic patients were enrolled in the study and received a daily dose of 100mg of aspirin for 10 days to cover the average platelet life-span in the circulation. Before and after the intervention period, circulating microparticles were characterized and quantified by flow cytometry. Type 1 diabetic patients had about twice the number of tissue factor-positive circulating microparticles (derived both from platelets and monocytes) and endothelial-derived E-selectin positive microparticles than type 2 diabetic patients. Aspirin therapy significantly inhibited platelets since cyclooxygenase 1 derived thromboxane generation levels were reduced by 99%. Microparticles derived from erythrocytes, activated monocytes, and smooth muscle cells were significantly reduced after 10 days of aspirin administration. These results indicate that: a) vascular and blood cells in type 1 diabetic patients are exposed to more sustained stress shown by their specific microparticle origin and levels; b) aspirin therapy inhibits vascular wall cell activation and microparticle shedding, and c) the effects of aspirin are similar in type 1 and 2 diabetes. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The effect of a direct current field on the microparticle charge in the plasma afterglow

Energy Technology Data Exchange (ETDEWEB)

Wörner, L. [Max Planck Institute for extraterrestrial Physics, P.O. Box 1312, Giessenbachstr., 85741 Garching (Germany); Groupe de Recherches sur l' Energétique des Milieux Ionisés, UMR7344, CNRS, Univ. Orléans, F-45067 Orléans (France); Ivlev, A. V.; Huber, P.; Hagl, T.; Thomas, H. M.; Morfill, G. E. [Max Planck Institute for extraterrestrial Physics, P.O. Box 1312, Giessenbachstr., 85741 Garching (Germany); Couëdel, L. [Centre National de la Recherche Scientifique, Aix-Marseille-Université, Laboiratoire de Physique des Intéractions Ioniques et Moléculaires, UMR 7345, 13397 Marseille cedex 20 (France); Schwabe, M. [Max Planck Institute for extraterrestrial Physics, P.O. Box 1312, Giessenbachstr., 85741 Garching (Germany); Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California 94720 (United States); Mikikian, M.; Boufendi, L. [Groupe de Recherches sur l' Energétique des Milieux Ionisés, UMR7344, CNRS, Univ. Orléans, F-45067 Orléans (France); Skvortsov, A. [Yuri Gagarin Cosmonauts Training Center, RU-141160 Star City (Russian Federation); Lipaev, A. M.; Molotkov, V. I.; Petrov, O. F.; Fortov, V. E. [Joint Institute for High Temperatures, RU-125412 Moscow (Russian Federation)

2013-12-15

Residual charges of individual microparticles forming dense clouds were measured in a RF discharge afterglow. Experiments were performed under microgravity conditions on board the International Space Station, which ensured particle levitation inside the gas volume after the plasma switch-off. The distribution of residual charges as well as the spatial distribution of charged particles across the cloud were analyzed by applying a low-frequency voltage to the electrodes and measuring amplitudes of the resulting particle oscillations. Upon “free decharging” conditions, the charge distribution had a sharp peak at zero and was rather symmetric (with charges concentrated between −10e and +10e), yet positively and negatively charged particles were homogeneously distributed over the cloud. However, when decharging evolved in the presence of an external DC field (applied shortly before the plasma switch-off) practically all residual charges were positive. In this case, the overall charge distribution had a sharp peak at about +15e and was highly asymmetric, while the spatial distribution exhibited a significant charge gradient along the direction of the applied DC field.

The signature of circulating microparticles in heart failure patients with metabolic syndrome

Directory of Open Access Journals (Sweden)

Alexander E Berezin

2016-11-01

Full Text Available The role of pattern of circulating endothelial cell-derived microparticles, platelet-derived microparticles (PMPs, and monocyte-derived microparticles (MMPs in metabolic syndrome (MetS patients with chronic heart failure (CHF is not still understood. The aim of the study was to investigate a pattern of circulating microparticles (MPs in MetS patients with CHF in relation to neurohumoral and inflammatory activation. The study retrospectively involved 101 patients with MetS and 35 healthy volunteers. Biomarkers were measured at baseline of the study. The results of the study have shown that numerous circulating PMPs- and MMPs in subjects with MetS (with or without CHF insufficiently distinguished from level obtained in healthy volunteers. We found elevated level of CD31+/annexin V+ MPs in association with lower level of CD62E+ MPs. Therefore, we found that biomarkers of biomechanical stress serum N-terminal brain natriuretic peptide and inflammation (high-sensitive C-reactive protein ,osteoprotegerin remain statistically significant predictors for decreased CD62E+ to CD31+/annexin V+ ratio in MetS patients with CHF. In conclusion, decreased CD62E+ to CD31+/annexin V+ ratio reflected that impaired immune phenotype of MPs may be discussed as a surrogate marker of CHF development in MetS population.

Circulating procoagulant microparticles in cancer patients

OpenAIRE

Thaler, Johannes; Ay, Cihan; Weinstabl, Harald; Dunkler, Daniela; Simanek, Ralph; Vormittag, Rainer; Freyssinet, Jean-Marie; Zielinski, Christoph; Pabinger, Ingrid

2010-01-01

Abstract Accumulating evidence indicates that microparticles (MPs) are important mediators of the interaction between cancer and the hemostatic system. We conducted a large prospective cohort study to determine whether the number of circulating procoagulant MPs is elevated in cancer patients and whether the elevated MP levels are predictive of occurrence of venous thrombembolism (VTE). We analyzed plasma samples of 728 cancer patients from the ongoing prospective observational Vien...

Novel cryomilled physically cross-linked biodegradable hydrogel microparticles as carriers for inhalation therapy.

Science.gov (United States)

El-Sherbiny, I M; Smyth, H D C

2010-01-01

In this study, novel biodegradable physically cross-linked hydrogel microparticles were developed and evaluated in-vitro as potential carriers for inhalation therapy. These hydrogel microparticles were prepared to be respirable (desired aerodynamic size) when dry and also designed to avoid the macrophage uptake (attain large swollen size once deposited in lung). The swellable microparticles, prepared using cryomilling, were based on Pluronic® F-108 in combination with PEG grafted onto both chitosan (Cs) and its N-phthaloyl derivative (NPHCs). Polymers synthesized in the study were characterized using EA, FTIR, 2D-XRD and DSC. Morphology, particle size, density, biodegradation and moisture content of the microparticles were quantified. Swelling characteristics for both drug-free and drug-loaded microparticles showed excellent size increases (between 700-1300%) and the release profiles indicated sustained release could be achieved for up to 20 days. The respirable microparticles showed drug loading efficiency up to 92%. The enzymatic degradation of developed microparticles started within the first hour and only ∼10% weights were remaining after 10 days. In conclusion, these respirable microparticles demonstrated promising in-vitro performance for potential sustained release vectors in pulmonary drug delivery.

Innovation in detection of microparticles and exosomes

NARCIS (Netherlands)

van der Pol, E.; Coumans, F.; Varga, Z.; Krumrey, M.; Nieuwland, R.

2013-01-01

Cell-derived or extracellular vesicles, including microparticles and exosomes, are abundantly present in body fluids such as blood. Although such vesicles have gained strong clinical and scientific interest, their detection is difficult because many vesicles are extremely small with a diameter of

Measurement of the speed of sound by observation of the Mach cones in a complex plasma under microgravity conditions

Energy Technology Data Exchange (ETDEWEB)

Zhukhovitskii, D. I., E-mail: dmr@ihed.ras.ru; Fortov, V. E.; Molotkov, V. I.; Lipaev, A. M.; Naumkin, V. N. [Joint Institute of High Temperatures, Russian Academy of Sciences, Izhorskaya 13, Bd. 2, 125412 Moscow (Russian Federation); Thomas, H. M. [Research Group Complex Plasma, DLR, Oberpfaffenhofen, 82234 Wessling (Germany); Ivlev, A. V.; Morfill, G. E. [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse, 85748 Garching (Germany); Schwabe, M. [Department of Chemical and Biomolecular Engineering, Graves Lab, D75 Tan Hall, University of California, Berkeley, CA 94720 (United States)

2015-02-15

We report the first observation of the Mach cones excited by a larger microparticle (projectile) moving through a cloud of smaller microparticles (dust) in a complex plasma with neon as a buffer gas under microgravity conditions. A collective motion of the dust particles occurs as propagation of the contact discontinuity. The corresponding speed of sound was measured by a special method of the Mach cone visualization. The measurement results are incompatible with the theory of ion acoustic waves. The estimate for the pressure in a strongly coupled Coulomb system and a scaling law for the complex plasma make it possible to derive an evaluation for the speed of sound, which is in a reasonable agreement with the experiments in complex plasmas.

Measurement of the speed of sound by observation of the Mach cones in a complex plasma under microgravity conditions

International Nuclear Information System (INIS)

Zhukhovitskii, D. I.; Fortov, V. E.; Molotkov, V. I.; Lipaev, A. M.; Naumkin, V. N.; Thomas, H. M.; Ivlev, A. V.; Morfill, G. E.; Schwabe, M.

2015-01-01

We report the first observation of the Mach cones excited by a larger microparticle (projectile) moving through a cloud of smaller microparticles (dust) in a complex plasma with neon as a buffer gas under microgravity conditions. A collective motion of the dust particles occurs as propagation of the contact discontinuity. The corresponding speed of sound was measured by a special method of the Mach cone visualization. The measurement results are incompatible with the theory of ion acoustic waves. The estimate for the pressure in a strongly coupled Coulomb system and a scaling law for the complex plasma make it possible to derive an evaluation for the speed of sound, which is in a reasonable agreement with the experiments in complex plasmas

Microparticles in cardiovascular diseases

NARCIS (Netherlands)

VanWijk, Marja J.; VanBavel, E.; Sturk, A.; Nieuwland, R.

2003-01-01

Microparticles are membrane vesicles released from many different cell types. There are two mechanisms that can result in their formation, cell activation and apoptosis. In these two mechanisms, different pathways are involved in microparticle generation. Microparticle generation seems to be a well

Restructuring of microparticles

International Nuclear Information System (INIS)

Lameiras, F.S.; Santos, A.M.M. dos

1992-01-01

Experimental grain sizes distribution of sintered (U,Gd)O 2 pellets were analysed according to the model of Lameiras for microparticles restructuring. This model, which includes the grain growth and Ostwald ripening phenomena, assumes that the microparticles restructuring is governed by two fundamental principles: minimization of the interface energy and uniformization of its distribution in space. It is also, assumed that the interface energy is stored in the grain boundaries, triple lines and quadruple points. The minimization of the interface energy can be done through three ways independent of each other: diminishing of the number of microparticles, alteration of the size distribution and alteration of the form distribution. The uniformization of the spatial distribution of the interface energy can be done through two ways also independent of each other: tendency to an uniform spatial distribution of microparticles and tendency to an uniform distribution of the interface energy per microparticle. The model accords well with these experimental data. (author)

Neurokinin 1 Receptor Mediates Membrane Blebbing and Sheer Stress-Induced Microparticle Formation in HEK293 Cells

Science.gov (United States)

Chen, Panpan; Douglas, Steven D.; Meshki, John; Tuluc, Florin

2012-01-01

Cell-derived microparticles participate in intercellular communication similar to the classical messenger systems of small and macro-molecules that bind to specialized membrane receptors. Microparticles have been implicated in the regulation of a variety of complex physiopathologic processes, such as thrombosis, the control of innate and adaptive immunity, and cancer. The neurokinin 1 receptor (NK1R) is a Gq-coupled receptor present on the membrane of a variety of tissues, including neurons in the central and peripheral nervous system, immune cells, endocrine and exocrine glands, and smooth muscle. The endogenous agonist of NK1R is the undecapeptide substance P (SP). We have previously described intracellular signaling mechanisms that regulate NK1R-mediated rapid cell shape changes in HEK293 cells and U373MG cells. In the present study, we show that the activation of NK1R in HEK293 cells, but not in U373MG cells, leads to formation of sheer-stress induced microparticles that stain positive with the membrane-selective fluorescent dye FM 2–10. SP-induced microparticle formation is independent of elevated intracellular calcium concentrations and activation of NK1R present on HEK293-derived microparticles triggers detectable calcium increase in SP-induced microparticles. The ROCK inhibitor Y27632 and the dynamin inhibitor dynasore inhibited membrane blebbing and microparticle formation in HEK293 cells, strongly suggesting that microparticle formation in this cell type is dependent on membrane blebbing. PMID:23024816

Neurokinin 1 receptor mediates membrane blebbing and sheer stress-induced microparticle formation in HEK293 cells.

Directory of Open Access Journals (Sweden)

Panpan Chen

Full Text Available Cell-derived microparticles participate in intercellular communication similar to the classical messenger systems of small and macro-molecules that bind to specialized membrane receptors. Microparticles have been implicated in the regulation of a variety of complex physiopathologic processes, such as thrombosis, the control of innate and adaptive immunity, and cancer. The neurokinin 1 receptor (NK1R is a Gq-coupled receptor present on the membrane of a variety of tissues, including neurons in the central and peripheral nervous system, immune cells, endocrine and exocrine glands, and smooth muscle. The endogenous agonist of NK1R is the undecapeptide substance P (SP. We have previously described intracellular signaling mechanisms that regulate NK1R-mediated rapid cell shape changes in HEK293 cells and U373MG cells. In the present study, we show that the activation of NK1R in HEK293 cells, but not in U373MG cells, leads to formation of sheer-stress induced microparticles that stain positive with the membrane-selective fluorescent dye FM 2-10. SP-induced microparticle formation is independent of elevated intracellular calcium concentrations and activation of NK1R present on HEK293-derived microparticles triggers detectable calcium increase in SP-induced microparticles. The ROCK inhibitor Y27632 and the dynamin inhibitor dynasore inhibited membrane blebbing and microparticle formation in HEK293 cells, strongly suggesting that microparticle formation in this cell type is dependent on membrane blebbing.

Membrane properties involved in calcium-stimulated microparticle release from the plasma membranes of S49 lymphoma cells.

Science.gov (United States)

Campbell, Lauryl E; Nelson, Jennifer; Gibbons, Elizabeth; Judd, Allan M; Bell, John D

2014-01-01

This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32-42°C). A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.

Cell-Derived Microparticles in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-Analysis

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Sheyu Li

2016-11-01

Full Text Available Background/Aims: The aim of this study was to assess the association between circulating cell-derived microparticles (MPs and type 2 diabetes mellitus (T2DM. Methods: A literature search was performed systematically in PubMed and Embase to identify available case-control or cross-sectional studies that compared different types of cell-derived MPs in patients with T2DM and non-diabetic controls. Pooled standardized mean differences (SMDs of each MP type were pooled using meta-analysis. Results: Forty-eight studies involving 2,460 patients with T2DM and 1,880 non-diabetic controls were included for systematic review and 34 of which were included for quantitative study by meta-analysis. In the overall analysis, the levels of circulating total MPs (TMPs, platelet-derived MPs (PMPs, monocyte-derived MPs (MMPs and endothelium-derived MPs (EMPs were significantly higher in T2DM patients than those in controls (TMPs: SMD, 0.64; 95%CI, 0.12∼1.15; P=0.02; PMPs: SMD, 1.19; 95%CI, 0.88∼1.50; P Conclusions: The counts of TMPs, PMPs, MMPs and EMPs elevated in patients with T2DM. And cell-derived MPs may play a role in the pathogenesis of T2DM.

Microparticle analysis system and method

Science.gov (United States)

Morrison, Dennis R. (Inventor)

2007-01-01

A device for analyzing microparticles is provided which includes a chamber with an inlet and an outlet for respectively introducing and dispensing a flowing fluid comprising microparticles, a light source for providing light through the chamber and a photometer for measuring the intensity of light transmitted through individual microparticles. The device further includes an imaging system for acquiring images of the fluid. In some cases, the device may be configured to identify and determine a quantity of the microparticles within the fluid. Consequently, a method for identifying and tracking microparticles in motion is contemplated herein. The method involves flowing a fluid comprising microparticles in laminar motion through a chamber, transmitting light through the fluid, measuring the intensities of the light transmitted through the microparticles, imaging the fluid a plurality of times and comparing at least some of the intensities of light between different images of the fluid.

Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo

Science.gov (United States)

Thomas, Grace M.; Panicot-Dubois, Laurence; Lacroix, Romaric; Dignat-George, Françoise; Lombardo, Dominique

2009-01-01

Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active TF and P-selectin glycoprotein ligand 1 (PSGL-1). Cancer cell–derived MPs aggregate platelets via a TF-dependent pathway. In vivo, cancer cell–derived MPs, but not their parent cells, infused into a living mouse accumulate at the site of injury and reduce tail bleeding time and the time to occlusion of venules and arterioles. This thrombotic state is also observed in mice developing tumors. In such mice, the amount of circulating platelet-, endothelial cell–, and cancer cell–derived MPs is increased. Endogenous cancer cell–derived MPs shed from the growing tumor are able to accumulate at the site of injury. Infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor. Collectively, our results indicate that cancer cell–derived MPs bearing PSGL-1 and TF play a key role in thrombus formation in vivo. Targeting these MPs could be of clinical interest in the prevention of thrombosis and to limit formation of metastasis in cancer patients. PMID:19667060

A method to assess the migration properties of cell-derived microparticles within a living tissue.

Science.gov (United States)

Hoang, Thang Q; Rampon, Christine; Freyssinet, Jean-Marie; Vriz, Sophie; Kerbiriou-Nabias, Danièle

2011-09-01

Cells undergoing activation or apoptosis exhibit plasma membrane changes, leading to the formation of shed vesicles (microparticles, MP). Although their effects on recipient cells in vitro, and their ability to support inflammatory or thrombotic events in the circulation have been studied, the spreading of such vesicles in tissues is still elusive. Our aim was to set up a method to examine the behavior of these vesicles in vivo. We examined the persistence of green-fluorescent microparticles (fMP), prepared after Ca2+ ionophore activation (iono-fMP) or apoptogenic treatment (eto-fMP) of human Jurkat T lymphoblastic or non-hematopoietic embryonic kidney (HEK) cell lines, following injection in zebrafish embryos 2h after egg fertilization. One hour post-injection, iono-fMP issued from both cell types formed a fluorescent dispersal in the intercellular space of embryos. In contrast, eto-fMP or MP deprived of sialic acid at their membrane, gathered together at the site of injection. We propose a method characterizing the abilities of MP to spread in the intercellular space. We showed that MP produced by apoptosis of T cells and those deprived of sialic acid at their membrane do not diffuse within the living cells. On the contrary, MP shed upon calcium induced activation of T and HEK cells, diffuse at a distance and spread in the intercellular space. The fate of injected MP relies on the type of induction rather than the cell species and results provide a model to test the ability of vesicles to interact locally or to spread outside of the site of production. Copyright © 2011 Elsevier B.V. All rights reserved.

Microparticle subpopulations are increased in preeclampsia: Possible involvement in vascular dysfunction?

NARCIS (Netherlands)

VanWijk, Marja J.; Nieuwland, Rienk; Boer, Kees; van der Post, Joris A. M.; VanBavel, Ed; Sturk, Augueste

2002-01-01

OBJECTIVE: The purpose of this study was to investigate the cellular origin and numbers of circulating microparticles in normal pregnancy and preeclampsia. STUDY DESIGN: Plasma samples from 10 women with preeclampsia, from 10 normal pregnant women, and from 10 nonpregnant women matched for age and

Electric field measurements in the sheath of an argon RF discharge by probing with microparticles under varying gravity conditions

NARCIS (Netherlands)

Beckers, J.; Stoffels, W.W.; Kroesen, G.M.W.; Ockenga, T.; Wolter, M.; Kersten, H.

2010-01-01

The electric field profile in the plasma sheath of an argon rf plasma has been determined by measuring the equilibrium height and the resonance frequency of plasma-confined microparticles. In order to determine the electric field structure at any position in the plasma sheath without the discharge

Detection of circulating microparticles by flow cytometry: influence of centrifugation, filtration of buffer, and freezing.

Science.gov (United States)

Dey-Hazra, Emily; Hertel, Barbara; Kirsch, Torsten; Woywodt, Alexander; Lovric, Svjetlana; Haller, Hermann; Haubitz, Marion; Erdbruegger, Uta

2010-12-06

The clinical importance of microparticles resulting from vesiculation of platelets and other blood cells is increasingly recognized, although no standardized method exists for their measurement. Only a few studies have examined the analytical and preanalytical steps and variables affecting microparticle detection. We focused our analysis on microparticle detection by flow cytometry. The goal of our study was to analyze the effects of different centrifugation protocols looking at different durations of high and low centrifugation speeds. We also analyzed the effect of filtration of buffer and long-term freezing on microparticle quantification, as well as the role of Annexin V in the detection of microparticles. Absolute and platelet-derived microparticles were 10- to 15-fold higher using initial lower centrifugation speeds at 1500 × g compared with protocols using centrifugation speeds at 5000 × g (P centrifugation speeds. Filtration of buffer with a 0.2 μm filter reduced a significant amount of background noise. Storing samples for microparticle detection at -80°C decreased microparticle levels at days 28, 42, and 56 (P centrifugation speeds should be used to minimize contamination by smaller size platelets.

Influence of sex on the number of circulating endothelial microparticles and microRNA expression in middle-aged adults.

Science.gov (United States)

Bammert, Tyler D; Hijmans, Jamie G; Kavlich, Philip J; Lincenberg, Grace M; Reiakvam, Whitney R; Fay, Ryan T; Greiner, Jared J; Stauffer, Brian L; DeSouza, Christopher A

2017-08-01

What is the central question of this study? Are there sex-related differences in the number of circulating endothelial microparticles (EMPs) and microparticle microRNA expression in middle-aged adult humans? What is the main finding and its importance? Although the numbers of circulating endothelial microparticles do not differ between middle-aged men and women, there are sex-related differences in the expression of miR-125a in activation-derived EMPs and miR-34a in apoptosis-derived EMPs. Differences in circulating endothelial microparticle microRNA content may provide new insight into the sex-related disparity in the risk and prevalence of vascular disease in middle-aged adults. The aims of this study were to determine: (i) whether circulating concentrations of endothelial microparticles (EMPs) differ in middle-aged men compared with women; and (ii) whether there are sex-related differences in microRNA expression in EMPs. Peripheral blood was collected from 30 sedentary adults: 15 men (56 ± 6 years old) and 15 women (56 ± 5 years old). Endothelial microparticles were defined by markers of activation (CD62e + ) or apoptosis (CD31 + /CD42b - ) by flow cytometry. Expression of microRNA (miR-34a, 92a, 125a and 126) in activation- and apoptosis-derived EMPs was measured by RT-PCR. Circulating activation- (33 ± 31 versus 39 ± 35 microparticles μl -1 ) and apoptosis-derived EMPs (49 ± 54 versus 42 ± 43 microparticles μl -1 ) were not significantly different between men and women. Expression of miR-125a (2.23 ± 2.01 versus 6.95 ± 3.99 a.u.) was lower (∼215%; P < 0.05) in activation-derived EMPs, whereas expression of miR-34a (1.17 ± 1.43 versus 0.38 ± 0.35 a.u.) was higher (∼210%; P < 0.05) in apoptosis-derived EMPs from men compared with women. Expression of microRNA in circulating EMPs may provide new insight into sex-related differences in cardiovascular disease. © 2017 The Authors. Experimental Physiology © 2017 The

Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma.

Science.gov (United States)

Frelinger, Andrew L; Gerrits, Anja J; Garner, Allen L; Torres, Andrew S; Caiafa, Antonio; Morton, Christine A; Berny-Lang, Michelle A; Carmichael, Sabrina L; Neculaes, V Bogdan; Michelson, Alan D

2016-01-01

Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma. To determine whether sub-microsecond duration, low electric field (SMLEF) bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity. PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and platelet factor 4 (PF4), and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin. PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the presence of platelet-derived

Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma.

Directory of Open Access Journals (Sweden)

Andrew L Frelinger

Full Text Available Activated autologous platelet-rich plasma (PRP used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma.To determine whether sub-microsecond duration, low electric field (SMLEF bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity.PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF, vascular endothelial growth factor (VEGF, endothelial growth factor (EGF and platelet factor 4 (PF4, and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin.PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the presence of platelet-derived

Latest Results on Complex Plasmas with the PK-3 Plus Laboratory on Board the International Space Station

Science.gov (United States)

Schwabe, M.; Du, C.-R.; Huber, P.; Lipaev, A. M.; Molotkov, V. I.; Naumkin, V. N.; Zhdanov, S. K.; Zhukhovitskii, D. I.; Fortov, V. E.; Thomas, H. M.

2018-03-01

Complex plasmas are low temperature plasmas that contain microparticles in addition to ions, electrons, and neutral particles. The microparticles acquire high charges, interact with each other and can be considered as model particles for effects in classical condensed matter systems, such as crystallization and fluid dynamics. In contrast to atoms in ordinary systems, their movement can be traced on the most basic level, that of individual particles. In order to avoid disturbances caused by gravity, experiments on complex plasmas are often performed under microgravity conditions. The PK-3 Plus Laboratory was operated on board the International Space Station from 2006 - 2013. Its heart consisted of a capacitively coupled radio-frequency plasma chamber. Microparticles were inserted into the low-temperature plasma, forming large, homogeneous complex plasma clouds. Here, we review the results obtained with recent analyzes of PK-3 Plus data: We study the formation of crystallization fronts, as well as the microparticle motion in, and structure of crystalline complex plasmas. We investigate fluid effects such as wave transmission across an interface, and the development of the energy spectra during the onset of turbulent microparticle movement. We explore how abnormal particles move through, and how macroscopic spheres interact with the microparticle cloud. These examples demonstrate the versatility of the PK-3 Plus Laboratory.

Placental release of distinct DNA-associated microparticles into maternal circulation: reflective of gestation time and preeclampsia

Science.gov (United States)

Orozco, Aaron F.; Jorgez, Carolina J.; Ramos-Perez, William D.; Popek, Edwina J.; Yu, Xiaoying; Kozinetz, Claudia A.; Bischoff, Farideh Z.; Lewis, Dorothy E.

2009-01-01

Background The aim of this study was to determine whether DNA-associated micro-particles (MPs) in maternal plasma express fetal-derived human leukocyte antigen-G (HLA-G) or placental alkaline phosphatase (PLAP) and whether the levels differ between women with normotensive pregnancies and preeclampsia. Methods DNA-associated MPs expressing HLA-G or PLAP were examined in the plasma of normal pregnant women and preeclamptic patients using flow cytometric analysis. Results DNA-associated HLA-G+ MPs were significantly increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.005), with highest levels found in first and second trimesters. DNA-associated PLAP+ MPs were also increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.006), with highest levels in second and third trimesters. Term preeclamptic women had higher levels of DNA-associated MPs than control pregnant women. HLA-G+ MPs from the plasma of preeclamptic women had more DNA per MP than HLA-G+ MPs from the plasma of normal pregnant women (p < 0.03). Conclusions HLA-G and PLAP MPs increase in maternal circulation at different times during gestation. DNA amounts per HLA-G+ MP increase in preeclamptic women which might indicate dysfunctional extravillous cytotrophoblasts. PMID:19692120

Low level of procoagulant platelet microparticles is associated with impaired coagulation and transfusion requirements in trauma patients

DEFF Research Database (Denmark)

Windeløv, Nis Agerlin; Johansson, Pär Ingemar; Sørensen, Anne Marie

2014-01-01

BACKGROUND: Following activation, platelets release small vesicles called platelet-derived microparticles (PMPs). PMPs accelerate thrombin generation and thus clot formation at sites of injury by exposing the procoagulant membrane phospholipid phosphatidylserine (PS). The role of PMPs in coagulop......BACKGROUND: Following activation, platelets release small vesicles called platelet-derived microparticles (PMPs). PMPs accelerate thrombin generation and thus clot formation at sites of injury by exposing the procoagulant membrane phospholipid phosphatidylserine (PS). The role of PMPs...

Microparticles generated during chronic cerebral ischemia deliver proapoptotic signals to cultured endothelial cells

International Nuclear Information System (INIS)

Schock, Sarah C.; Edrissi, Hamidreza; Burger, Dylan; Cadonic, Robert; Hakim, Antoine; Thompson, Charlie

2014-01-01

Highlights: • Microparticles are elevated in the plasma in a rodent model of chronic cerebral ischemia. • These microparticles initiate apoptosis in cultured cells. • Microparticles contain caspase 3 and they activate receptors for TNF-α and TRAIL. - Abstract: Circulating microparticles (MPs) are involved in many physiological processes and numbers are increased in a variety of cardiovascular disorders. The present aims were to characterize levels of MPs in a rodent model of chronic cerebral hypoperfusion (CCH) and to determine their signaling properties. MPs were isolated from the plasma of rats exposed to CCH and quantified by flow cytometry. When MPs were added to cultured endothelial cells or normal rat kidney cells they induced cell death in a time and dose dependent manner. Analysis of pellets by electron microscopy indicates that cell death signals are carried by particles in the range of 400 nm in diameter or less. Cell death involved the activation of caspase 3 and was not a consequence of oxidative stress. Inhibition of the Fas/FasL signaling pathway also did not improve cell survival. MPs were found to contain caspase 3 and treating the MPs with a caspase 3 inhibitor significantly reduced cell death. A TNF-α receptor blocker and a TRAIL neutralizing antibody also significantly reduced cell death. Levels of circulating MPs are elevated in a rodent model of chronic cerebral ischemia. MPs with a diameter of 400 nm or less activate the TNF-α and TRAIL signaling pathways and may deliver caspase 3 to cultured cells

Microparticles generated during chronic cerebral ischemia deliver proapoptotic signals to cultured endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Schock, Sarah C. [Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Edrissi, Hamidreza [University of Ottawa, Neuroscience Graduate Program, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Burger, Dylan [Ottawa Hospital Research Institute, Kidney Centre, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Cadonic, Robert; Hakim, Antoine [Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Thompson, Charlie, E-mail: charliet@uottawa.ca [Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada)

2014-07-18

Highlights: • Microparticles are elevated in the plasma in a rodent model of chronic cerebral ischemia. • These microparticles initiate apoptosis in cultured cells. • Microparticles contain caspase 3 and they activate receptors for TNF-α and TRAIL. - Abstract: Circulating microparticles (MPs) are involved in many physiological processes and numbers are increased in a variety of cardiovascular disorders. The present aims were to characterize levels of MPs in a rodent model of chronic cerebral hypoperfusion (CCH) and to determine their signaling properties. MPs were isolated from the plasma of rats exposed to CCH and quantified by flow cytometry. When MPs were added to cultured endothelial cells or normal rat kidney cells they induced cell death in a time and dose dependent manner. Analysis of pellets by electron microscopy indicates that cell death signals are carried by particles in the range of 400 nm in diameter or less. Cell death involved the activation of caspase 3 and was not a consequence of oxidative stress. Inhibition of the Fas/FasL signaling pathway also did not improve cell survival. MPs were found to contain caspase 3 and treating the MPs with a caspase 3 inhibitor significantly reduced cell death. A TNF-α receptor blocker and a TRAIL neutralizing antibody also significantly reduced cell death. Levels of circulating MPs are elevated in a rodent model of chronic cerebral ischemia. MPs with a diameter of 400 nm or less activate the TNF-α and TRAIL signaling pathways and may deliver caspase 3 to cultured cells.

Ultrasound-induced acoustophoretic motion of microparticles in three dimensions

DEFF Research Database (Denmark)

Muller, Peter Barkholt; Rossi, M.; Marín, Á. G.

2013-01-01

We derive analytical expressions for the three-dimensional (3D) acoustophoretic motion of spherical microparticles in rectangular microchannels. The motion is generated by the acoustic radiation force and the acoustic streaming-induced drag force. In contrast to the classical theory of Rayleigh...

Cell behavior on microparticles with different surface morphology

International Nuclear Information System (INIS)

Huang Sha; Fu Xiaobing

2010-01-01

Microparticles can serve as substrates for cell amplification and deliver the cell aggregation to the site of the defect for tissue regeneration. To develop favorable microparticles for cell delivery application, we fabricated and evaluated three types of microparticles that differ in surface properties. The microparticles with varied surface morphology (smooth, pitted and multicavity) were created from chemically crosslinked gelatin particles that underwent various drying treatments. Three types of microparticles were characterized and assessed in terms of the cell behavior of human keratinocytes and fibroblasts seeded on them. The cells could attach, spread and proliferate on all types of microparticles but spread and populated more slowly on the microparticles with smooth surfaces than on those with pitted or multicavity surfaces. Microparticles with a multicavity surface demonstrated the highest cell attachment and growth rate. Furthermore, cells tested on microparticles with a multicavity surface exhibited better morphology and induced the earlier formation of extracellular-based cell-microparticle aggregation than those on microparticles with other surface morphology (smooth and pitted). Thus, microparticles with a multicavity surface show promise for attachment and proliferation of cells in tissue engineering.

Formation of monodisperse mesoporous silica microparticles via spray-drying.

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Waldron, Kathryn; Wu, Winston Duo; Wu, Zhangxiong; Liu, Wenjie; Selomulya, Cordelia; Zhao, Dongyuan; Chen, Xiao Dong

2014-03-15

In this work, a protocol to synthesize monodisperse mesoporous silica microparticles via a unique microfluidic jet spray-drying route is reported for the first time. The microparticles demonstrated highly ordered hexagonal mesostructures with surface areas ranging from ~900 up to 1500 m(2)/g and pore volumes from ~0.6 to 0.8 cm(3)/g. The particle size could be easily controlled from ~50 to 100 μm from the same diameter nozzle via changing the initial solute content, or changing the drying temperature. The ratio of the surfactant (CTAB) and silica (TEOS), and the amount of water in the precursor were found to affect the degree of ordering of mesopores by promoting either the self-assembly of the surfactant-silica micelles or the condensation of the silica as two competing processes in evaporation induced self-assembly. The drying rate and the curvature of particles also affected the self-assembly of the mesostructure. The particle mesostructure is not influenced by the inlet drying temperature in the range of 92-160 °C, with even a relatively low temperature of 92 °C producing highly ordered mesoporous microparticles. The spray-drying derived mesoporous silica microparticles, while of larger sizes and more rapidly synthesized, showed a comparable performance with the conventional mesoporous silica MCM-41 in controlled release of a dye, Rhodamine B, indicating that these spray dried microparticles could be used for the immobilisation and controlled release of small molecules. Copyright © 2013 Elsevier Inc. All rights reserved.

Sustained release nimesulide microparticles: evaluation of release modifying property of ethy

International Nuclear Information System (INIS)

Khan, S.A.; Ahmed, M.; Nisar-ur-Rehman; Madni, A.U.; Aamir, M.N.; Murtaza, G.

2011-01-01

Microencapsulated controlled-release preparations of nimesulide were formulated. Microparticles were prepared by modified phase separation (non-solvent addition) technique using different ratios of ethylcellulose. The microparticles (M/sub 1/, M/sub 2/, and M/sub 3/) were yellow, free flowing and spherical in shape with the particle size varying from 93.62 +- 14.15 to 104.19 +- 18.15 mu m. The t/sub 60%/of nimesulide release from microparticles was found to be 3 +- 0.6, 5 +- 0.6 and 8 +- 0.8 h for formulations M/sub 1/, M/sub 2/, and M/sub 3/, respectively. FT-IR, XRD, and thermal analysis were done which showed that there is no interaction between the polymer and drug. The mechanism of drug release from nimesulide microparticles was studied by using Higuchi and Korsmeyer-Peppas models. The value of coefficient of determination (R/sup 2/) for M/sub 1/, M/sub 2/, and M/sub 3/ indicates anomalous and case-II transport release mechanism. The dissolution data of designed system verified its ability to maintain plasma concentration without the need of frequent dosing. The Nimesulide microparticles prolonged drug release for 12 hours or longer. Based on the results of release studies, M/sub 3/ was opted as a suitable microparticulate formulation allowing the controlled release of nimesulide over a prolonged period of time. Moreover, its encapsulation efficiency was also comparable to the other two formulations (M/sub 1/ and M/sub 2/). In conclusion, the influence of polymer concentration should be considered during formulation development. (author)

Transformation of cell-derived microparticles into quantum-dot-labeled nanovectors for antitumor siRNA delivery.

Science.gov (United States)

Chen, Gang; Zhu, Jun-Yi; Zhang, Zhi-Ling; Zhang, Wei; Ren, Jian-Gang; Wu, Min; Hong, Zheng-Yuan; Lv, Cheng; Pang, Dai-Wen; Zhao, Yi-Fang

2015-01-12

Cell-derived microparticles (MPs) have been recently recognized as critical intercellular information conveyors. However, further understanding of their biological behavior and potential application has been hampered by the limitations of current labeling techniques. Herein, a universal donor-cell-assisted membrane biotinylation strategy was proposed for labeling MPs by skillfully utilizing the natural membrane phospholipid exchange of their donor cells. This innovative strategy conveniently led to specific, efficient, reproducible, and biocompatible quantum dot (QD) labeling of MPs, thereby reliably conferring valuable traceability on MPs. By further loading with small interference RNA, QD-labeled MPs that had inherent cell-targeting and biomolecule-conveying ability were successfully employed for combined bioimaging and tumor-targeted therapy. This study provides the first reliable and biofriendly strategy for transforming biogenic MPs into functionalized nanovectors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii.

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Erica S Martins-Duarte

Full Text Available Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound. Cipro derivatives are expected to target the parasite's DNA gyrase complex in the apicoplast. The activity of these compounds in vivo, as well as their mode of action, remained thus far uncharacterized. Here, we examined the activity of the Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition, we investigated the cellular effects T. gondii tachyzoites in vitro, by immunofluorescence and transmission electron microscopy (TEM. When compared with Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival significantly, with 13-25% of mice surviving for up to 60 days post-infection (vs. complete lethality 10 days post-infection, with Cipro treatment. Light microscopy examination early (6 and 24h post-infection revealed that 6-h treatments with Cipro derivatives inhibited the initial event of parasite cell division inside host cells, in an irreversible manner. By TEM and immunofluorescence, the main cellular effects observed after treatment with Cipro derivatives and Cipro were cell scission inhibition--with the appearance of 'tethered' parasites--malformation of the inner membrane complex, and apicoplast enlargement and missegregation. Interestingly, tethered daughter cells resulting from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or centrocone localization. The biological activity of Cipro derivatives against C. parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50 fold lower than that in T. gondii tachyzoites, supporting that these compounds targets the apicoplast. Our results

Host-Parasite Interaction: Parasite-Derived and -Induced Proteases That Degrade Human Extracellular Matrix

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Carolina Piña-Vázquez

2012-01-01

Full Text Available Parasitic protozoa are among the most important pathogens worldwide. Diseases such as malaria, leishmaniasis, amoebiasis, giardiasis, trichomoniasis, and trypanosomiasis affect millions of people. Humans are constantly threatened by infections caused by these pathogens. Parasites engage a plethora of surface and secreted molecules to attach to and enter mammalian cells. The secretion of lytic enzymes by parasites into host organs mediates critical interactions because of the invasion and destruction of interstitial tissues, enabling parasite migration to other sites within the hosts. Extracellular matrix is a complex, cross-linked structure that holds cells together in an organized assembly and that forms the basement membrane lining (basal lamina. The extracellular matrix represents a major barrier to parasites. Therefore, the evolution of mechanisms for connective-tissue degradation may be of great importance for parasite survival. Recent advances have been achieved in our understanding of the biochemistry and molecular biology of proteases from parasitic protozoa. The focus of this paper is to discuss the role of protozoan parasitic proteases in the degradation of host ECM proteins and the participation of these molecules as virulence factors. We divide the paper into two sections, extracellular and intracellular protozoa.

Effects of parasitic infection and reproduction on corticosterone plasma levels in Galápagos land iguanas, Conolophus marthae and C. subcristatus.

Science.gov (United States)

Onorati, Michela; Sancesario, Giulia; Pastore, Donatella; Bernardini, Sergio; Cruz, Marilyn; Carrión, Jorge E; Carosi, Monica; Vignoli, Leonardo; Lauro, Davide; Gentile, Gabriele

2017-08-01

In vertebrates, one main feature of stress response is the release of glucocorticoids (corticosterone in reptiles), steroid hormones whose synthesis is regulated by the hypothalamic-pituitary-adrenal axis (HPA). In the Galápagos Islands, populations of land iguanas are differentially impacted by a tick-transmitted apicomplexan hemoparasite of genus Hepatozoon , which could cause diseases and ultimately reduce fitness. Using competitive enzyme-linked immunosorbent assays (ELISA), we examined baseline plasma corticosterone levels of two syntopic and highly parasitized populations of the land iguana species Conolophus marthae and C. subcristatus in Wolf volcano (Isabela Island). We also used a poorly parasitized population of C. subcristatus from the same island (Bahia Urbina) as a reference. To better interpret the observed glucocorticoids patterns, we simultaneously performed the count of white blood cells (WBCs) in all individuals and investigated the reproductive status of females. We did not find evidence in support of either a positive or negative relationship between the tick load, hemoparasite infection, and glucocorticoid plasma concentration in C. marthae and C. subcristatus at Wolf volcano. The comparison between parasitized and non-parasitized sites (V. Wolf and Bahia Urbina) would instead suggest an inverse relationship between corticosterone and parasites. Our findings support association between corticosterone plasma levels and reproduction.

The appearance of microparticles in accelerator tubes

International Nuclear Information System (INIS)

Griffiths, G.L.; Eastham, D.A.; Kivlin, F.J.

1978-07-01

Microparticles have been found in submodules of accelerator tubes during the voltage conditioning process. The microparticle detector uses electrostatic induction and time-of-flight measurements to determine the charge and velocity of microparticles. Preliminary measurements with a charge sensitive limit of about 5 x 10 -15 C proves the presence of microparticles at a threshold voltage well below the onset of microdischarges or voltage breakdown. No direct evidence relating microparticles to the initiation of electrical breakdown has been found in this experiment. (author)

Pleomorphic Structures in Human Blood Are Red Blood Cell-Derived Microparticles, Not Bacteria.

Science.gov (United States)

Mitchell, Adam J; Gray, Warren D; Schroeder, Max; Yi, Hong; Taylor, Jeannette V; Dillard, Rebecca S; Ke, Zunlong; Wright, Elizabeth R; Stephens, David; Roback, John D; Searles, Charles D

2016-01-01

Red blood cell (RBC) transfusions are a common, life-saving therapy for many patients, but they have also been associated with poor clinical outcomes. We identified unusual, pleomorphic structures in human RBC transfusion units by negative-stain electron microscopy that appeared identical to those previously reported to be bacteria in healthy human blood samples. The presence of viable, replicating bacteria in stored blood could explain poor outcomes in transfusion recipients and have major implications for transfusion medicine. Here, we investigated the possibility that these structures were bacteria. Flow cytometry, miRNA analysis, protein analysis, and additional electron microscopy studies strongly indicated that the pleomorphic structures in the supernatant of stored RBCs were RBC-derived microparticles (RMPs). Bacterial 16S rDNA PCR amplified from these samples were sequenced and was found to be highly similar to species that are known to commonly contaminate laboratory reagents. These studies suggest that pleomorphic structures identified in human blood are RMPs and not bacteria, and they provide an example in which laboratory contaminants may can mislead investigators.

Complex (dusty) plasmas: Current status, open issues, perspectives

International Nuclear Information System (INIS)

Fortov, V.E.; Ivlev, A.V.; Khrapak, S.A.; Khrapak, A.G.; Morfill, G.E.

2005-01-01

The field of complex (dusty) plasmas-low-temperature plasmas containing charged microparticles-is reviewed: The major types of experimental complex plasmas are briefly discussed. Various elementary processes, including grain charging in different regimes, interaction between charged particles, and momentum exchange between different species are investigated. The major forces on microparticles and features of the particle dynamics in complex plasmas are highlighted. An overview of the wave properties in different phase states, as well as recent results on the phase transitions between different crystalline and liquid states are presented. Fluid behaviour of complex plasmas and the onset of cooperative phenomena are discussed. Properties of the magnetized complex plasmas and plasmas with nonspherical particles are briefly mentioned. In conclusion, possible applications of complex plasmas, interdisciplinary aspects, and perspectives are discussed

Laser ablation of microparticles for nanostructure generation

International Nuclear Information System (INIS)

Waraich, Palneet Singh; Tan, Bo; Venkatakrishnan, Krishnan

2011-01-01

The process of laser ablation of microparticles has been shown to generate nanoparticles from microparticles; but the generation of nanoparticle networks from microparticles has never been reported before. We report a unique approach for the generation of nanoparticle networks through ablation of microparticles. Using this approach, two samples containing microparticles of lead oxide (Pb 3 O 4 ) and nickel oxide (NiO), respectively, were ablated under ambient conditions using a femtosecond laser operating in the MHz repetition rate regime. Nanoparticle networks with particle diameter ranging from 60 to 90 nm were obtained by ablation of microparticles without use of any specialized equipment, catalysts or external stimulants. The formation of finer nanoparticle networks has been explained by considering the low pressure region created by the shockwave, causing rapid condensation of microparticles into finer nanoparticles. A comparison between the nanostructures generated by ablating microparticle and those by ablating bulk substrate was carried out; and a considerable reduction in size and narrowed size distribution was observed. Our nanostructure fabrication technique will be a unique process for nanoparticle network generation from a vast array of materials.

Role of receptor-mediated endocytosis in the antiangiogenic effects of human T lymphoblastic cell-derived microparticles.

Science.gov (United States)

Yang, Chun; Xiong, Wei; Qiu, Qian; Shao, Zhuo; Shao, Zuo; Hamel, David; Tahiri, Houda; Leclair, Grégoire; Lachapelle, Pierre; Chemtob, Sylvain; Hardy, Pierre

2012-04-15

Microparticles possess therapeutic potential regarding angiogenesis. We have demonstrated the contribution of apoptotic human CEM T lymphocyte-derived microparticles (LMPs) as inhibitors of angiogenic responses in animal models of inflammation and tumor growth. In the present study, we characterized the antivascular endothelial growth factor (VEGF) effects of LMPs on pathological angiogenesis in an animal model of oxygen-induced retinopathy and explored the role of receptor-mediated endocytosis in the effects of LMPs on human retinal endothelial cells (HRECs). LMPs dramatically inhibited cell growth of HRECs, suppressed VEGF-induced cell migration in vitro experiments, and attenuated VEGF-induced retinal vascular leakage in vivo. Intravitreal injections of fluorescently labeled LMPs revealed accumulation of LMPs in retinal tissue, with more than 60% reductions of the vascular density in retinas of rats with oxygen-induced neovascularization. LMP uptake experiments demonstrated that the interaction between LMPs and HRECs is dependent on temperature. In addition, endocytosis is partially dependent on extracellular calcium. RNAi-mediated knockdown of low-density lipoprotein receptor (LDLR) reduced the uptake of LMPs and attenuated the inhibitory effects of LMPs on VEGF-A protein expression and HRECs cell growth. Intravitreal injection of lentivirus-mediated RNA interference reduced LDLR protein expression in retina by 53% and significantly blocked the antiangiogenic effects of LMPs on pathological vascularization. In summary, the potent antiangiogenic LMPs lead to a significant reduction of pathological retinal angiogenesis through modulation of VEGF signaling, whereas LDLR-mediated endocytosis plays a partial, but pivotal, role in the uptake of LMPs in HRECs.

Physics of microparticle acoustophoresis

DEFF Research Database (Denmark)

Barnkob, Rune

2012-01-01

of microparticle acoustophoresis and to develop methods for future advancement of its use. Throughout the work on this thesis the author and co-workers1 have studied the physics of microparticle acoustophoresis by comparing quantitative measurements to a theoretical framework consisting of existing hydrodynamic...

Processing and characterization of diatom nanoparticles and microparticles as potential source of silicon for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Le, Thi Duy Hanh [Department of Industrial Engineering, University of Trento, Trento (Italy); BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Trento (Italy); Bonani, Walter [Department of Industrial Engineering, University of Trento, Trento (Italy); BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Trento (Italy); Interuniversity Consortium for Science and Technology of Materials, Trento Research Unit, Trento (Italy); Speranza, Giorgio [Center for Materials and Microsystems, PAM-SE, Fondazione Bruno Kessler, Trento (Italy); Sglavo, Vincenzo; Ceccato, Riccardo [Department of Industrial Engineering, University of Trento, Trento (Italy); Maniglio, Devid; Motta, Antonella [Department of Industrial Engineering, University of Trento, Trento (Italy); BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Trento (Italy); Interuniversity Consortium for Science and Technology of Materials, Trento Research Unit, Trento (Italy); Migliaresi, Claudio, E-mail: claudio.migliaresi@unitn.it [Department of Industrial Engineering, University of Trento, Trento (Italy); BIOtech Research Center and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Trento (Italy); Interuniversity Consortium for Science and Technology of Materials, Trento Research Unit, Trento (Italy)

2016-02-01

Silicon plays an important role in bone formation and maintenance, improving osteoblast cell function and inducing mineralization. Often, bone deformation and long bone abnormalities have been associated with silica/silicon deficiency. Diatomite, a natural deposit of diatom skeleton, is a cheap and abundant source of biogenic silica. The aim of the present study is to validate the potential of diatom particles derived from diatom skeletons as silicon-donor materials for bone tissue engineering applications. Raw diatomite (RD) and calcined diatomite (CD) powders were purified by acid treatments, and diatom microparticles (MPs) and nanoparticles (NPs) were produced by fragmentation of purified diatoms under alkaline conditions. The influence of processing on the surface chemical composition of purified diatomites was evaluated by X-ray photoelectron spectroscopy (XPS). Diatoms NPs were also characterized in terms of morphology and size distribution by transmission electron microscopy (TEM) and Dynamic light scattering (DLS), while diatom MPs morphology was analyzed by scanning electron microscopy (SEM). Surface area and microporosity of the diatom particles were evaluated by nitrogen physisorption methods. Release of silicon ions from diatom-derived particles was demonstrated using inductively coupled plasma optical emission spectrometry (ICP/OES); furthermore, silicon release kinetic was found to be influenced by diatomite purification method and particle size. Diatom-derived microparticles (MPs) and nanoparticles (NPs) showed limited or no cytotoxic effect in vitro depending on the administration conditions. - Highlights: • Diatomite is a natural source of silica and has a potential as silicon-donor for bone regenerative applications. • Diatom particles derived from purified diatom skeletons were prepared by fragmentation under extreme alkaline condition. • Dissolution of diatom particles derived from diatom skeletons in DI water depend on purification method

Microfluidic production of polymeric functional microparticles

Science.gov (United States)

Jiang, Kunqiang

This dissertation focuses on applying droplet-based microfluidics to fabricate new classes of polymeric microparticles with customized properties for various applications. The integration of microfluidic techniques with microparticle engineering allows for unprecedented control over particle size, shape, and functional properties. Specifically, three types of microparticles are discussed here: (1) Magnetic and fluorescent chitosan hydrogel microparticles and their in-situ assembly into higher-order microstructures; (2) Polydimethylsiloxane (PDMS) microbeads with phosphorescent properties for oxygen sensing; (3) Macroporous microparticles as biological immunosensors. First, we describe a microfluidic approach to generate monodisperse chitosan hydrogel microparticles that can be further connected in-situ into higher-order microstructures. Microparticles of the biopolymer chitosan are created continuously by contacting an aqueous solution of chitosan at a microfluidic T-junction with a stream of hexadecane containing a nonionic detergent, followed by downstream crosslinking of the generated droplets by a ternary flow of glutaraldehyde. Functional properties of the microparticles can be easily varied by introducing payloads such as magnetic nanoparticles and/or fluorescent dyes into the chitosan solution. We then use these prepared microparticles as "building blocks" and assemble them into high ordered microstructures, i.e. microchains with controlled geometry and flexibility. Next, we describe a new approach to produce monodisperse microbeads of PDMS using microfluidics. Using a flow-focusing configuration, a PDMS precursor solution is dispersed into microdroplets within an aqueous continuous phase. These droplets are collected and thermally cured off-chip into soft, solid microbeads. In addition, our technique allows for direct integration of payloads, such as an oxygen-sensitive porphyrin dye, into the PDMS microbeads. We then show that the resulting dye

Microparticles engineered to highly express peroxisome proliferator-activated receptor-γ decreased inflammatory mediator production and increased adhesion of recipient monocytes.

Science.gov (United States)

Sahler, Julie; Woeller, Collynn F; Phipps, Richard P

2014-01-01

Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particularly during inflammatory provocation. We therefore engineered the composition of megakaryocyte culture-derived microparticles to generate distinct microparticle populations that were given to human monocytes to assay for influences recipient cell function. Herein, we tested the responses of monocytes exposed to either control microparticles or microparticles that contain the anti-inflammatory transcription factor, peroxisome proliferator-activated receptor-γ (PPARγ). In order to normalize relative microparticle abundance from two microparticle populations, we implemented a novel approach that utilizes a Nanodrop Spectrophotometer to assay for microparticle density rather than concentration. We found that when given to peripheral blood mononuclear cells, microparticles were preferentially internalized by CD11b+ cells, and furthermore, microparticle composition had a profound functional impact on recipient monocytes. Specifically, microparticles containing PPARγ reduced activated monocyte production of the proinflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared to activated monocytes exposed to control microparticles. Additionally, treatment with PPARγ microparticles greatly increased monocyte cell adherence. This change in morphology occurred simultaneously with increased production of the key extracellular matrix protein, fibronectin and increased expression of the fibronectin-binding integrin, ITGA5. PPARγ microparticles also changed monocyte

On the heterogeneous character of the heartbeat instability in complex (dusty) plasmas

Energy Technology Data Exchange (ETDEWEB)

Pustylnik, M. Y.; Ivlev, A. V.; Heidemann, R.; Mitic, S.; Thomas, H. M.; Morfill, G. E. [Max-Planck-Institut fuer Extraterrestrische Physik, Giessenbachstrasse, 85741 Garching (Germany); Sadeghi, N. [LIPhy, Universite de Grenoble 1/CNRS, UMR 5588, Grenoble 38401 (France)

2012-10-15

A hypothesis on the physical mechanism generating the heartbeat instability in complex (dusty) plasmas is presented. It is suggested that the instability occurs due to the periodically repeated critical transformation on the boundary between the microparticle-free area (void) and the complex plasma. The critical transformation is supposed to be analogous to the formation of the sheath in the vicinity of an electrode. The origin of the transformation is the loss of the electrons and ions on microparticles surrounding the void. We have shown that this hypothesis is consistent with the experimentally measured stability parameter range, with the evolution of the plasma glow intensity and microparticle dynamics during the instability, as well as with the observed excitation of the heartbeat instability by an intensity-modulated laser beam (inducing the modulation of plasma density).

Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives

Directory of Open Access Journals (Sweden)

C.S. Carvalho

2010-02-01

Full Text Available Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM. The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1 These new derivatives decreased T. gondii infection with an in vitro parasite IC50% of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives and 4 (thiazolidinone derivative; 2 The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3 Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4 Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5 The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.

Cell-Derived Microparticles in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-Analysis.

Science.gov (United States)

Li, Sheyu; Wei, Jia; Zhang, Chenghui; Li, Xiaodan; Meng, Wentong; Mo, Xianming; Zhang, Qianying; Liu, Qilin; Ren, Kaiyun; Du, Rong; Tian, Haoming; Li, Jianwei

2016-01-01

The aim of this study was to assess the association between circulating cell-derived microparticles (MPs) and type 2 diabetes mellitus (T2DM). A literature search was performed systematically in PubMed and Embase to identify available case-control or cross-sectional studies that compared different types of cell-derived MPs in patients with T2DM and non-diabetic controls. Pooled standardized mean differences (SMDs) of each MP type were pooled using meta-analysis. Forty-eight studies involving 2,460 patients with T2DM and 1,880 non-diabetic controls were included for systematic review and 34 of which were included for quantitative study by meta-analysis. In the overall analysis, the levels of circulating total MPs (TMPs), platelet-derived MPs (PMPs), monocyte-derived MPs (MMPs) and endothelium-derived MPs (EMPs) were significantly higher in T2DM patients than those in controls (TMPs: SMD, 0.64; 95%CI, 0.12∼1.15; P=0.02; PMPs: SMD, 1.19; 95%CI, 0.88∼1.50; P <0.00001; MMPs: SMD, 0.92; 95%CI, 0.66∼1.17; P <0.00001; EMPs: SMD, 0.73; 95%CI, 0.50∼0.96; P <0.00001). Meanwhile, no significant difference was shown in leukocyte-derived MPs (LMPs) level between diabetic and non-diabetic groups (SMD, 0.37; 95%CI, -0.15∼0.89; P=0.17). The counts of TMPs, PMPs, MMPs and EMPs elevated in patients with T2DM. And cell-derived MPs may play a role in the pathogenesis of T2DM. © 2016 The Author(s) Published by S. Karger AG, Basel.

The Influence of Chitosan Cross-linking on the Properties of Alginate Microparticles with Metformin Hydrochloride—In Vitro and In Vivo Evaluation

Directory of Open Access Journals (Sweden)

Marta Szekalska

2017-01-01

Full Text Available Sodium alginate is a polymer with unique ability to gel with different cross-linking agents in result of ionic and electrostatic interactions. Chitosan cross-linked alginate provides improvement of swelling and mucoadhesive properties and might be used to design sustained release dosage forms. Therefore, the aim of this research was to develop and evaluate possibility of preparing chitosan cross-linked alginate microparticles containing metformin hydrochloride by the spray-drying method. In addition, influence of cross-linking agent on the properties of microparticles was evaluated. Formulation of microparticles prepared by the spray drying of 2% alginate solution cross-linked by 0.1% chitosan was characterized by good mucoadhesive properties, high drug loading and prolonged metformin hydrochloride release. It was shown that designed microparticles reduced rat glucose blood level, delayed absorption of metformin hydrochloride and provided stable plasma drug concentration. Additionally, histopathological studies of pancreas, liver and kidneys indicated that all prepared microparticles improved degenerative changes in organs of diabetic rats. Moreover, no toxicity effect and no changes in rats behavior after oral administration of chitosan cross-linked alginate microparticles were noted.

Acceleration of microparticle

CERN Document Server

Shibata, H

2002-01-01

A microparticle (dust) ion source has been installed at the high voltage terminal of the 3.75 MV single ended Van de Graaff electrostatic accelerator and a beam line for microparticle experiments has been build at High Fluence Irradiation Facility (HIT) of Research Center for Nuclear Science and Technology, the University of Tokyo. Microparticle acceleration has been successful in obtaining expected velocities of 1-20 km/s or more for micron or submicron sized particles. Development of in situ dust detectors and analyzers on board satellites and spacecraft in the expected mass and velocity range of micrometeoroids and investigation of hypervelocity impact phenomena by using time of flight mass spectrometry, impact flash or luminescence measurement and scanning electron or laser microscope observation for metals, ceramics, polymers and semiconductors bombarded by micron-sized particles were started three years ago. (author)

Effect of exercise intensity on circulating microparticles in men and women.

Science.gov (United States)

Shill, Daniel D; Lansford, Kasey A; Hempel, Hannah K; Call, Jarrod A; Murrow, Jonathan R; Jenkins, Nathan T

2018-05-01

What is the central question of this study? What is the effect of exercise intensity on circulating microparticle populations in young, healthy men and women? What is the main finding and its importance? Acute, moderate-intensity continuous exercise and high-intensity interval exercise altered distinct microparticle populations during and after exercise in addition to a sex-specific response in CD62E + microparticles. The microparticles studied contribute to cardiovascular disease progression, regulate vascular function and facilitate new blood vessel formation. Thus, characterizing the impact of intensity on exercise-induced microparticle responses advances our understanding of potential mechanisms underlying the beneficial vascular adaptations to exercise. Circulating microparticles (MPs) are biological vectors of information within the cardiovascular system that elicit both deleterious and beneficial effects on the vasculature. Acute exercise has been shown to alter MP concentrations, probably through a shear stress-dependent mechanism, but evidence is limited. Therefore, we investigated the effect of exercise intensity on plasma levels of CD34 + and CD62E + MPs in young, healthy men and women. Blood samples were collected before, during and after two energy-matched bouts of acute treadmill exercise: interval exercise (10 × 1 min intervals at ∼95% of maximal oxygen uptake V̇O2max) and continuous exercise (65% V̇O2max). Continuous exercise, but not interval exercise, reduced CD62E + MP concentrations in men and women by 18% immediately after exercise (from 914.5 ± 589.6 to 754.4 ± 390.5 MPs μl -1 ; P interval exercise did not alter CD62E + MPs per se, the concentrations after interval exercise were higher than those observed after continuous exercise (P interval exercise in men or women. Our results suggest that exercise-induced MP alterations are intensity dependent and sex specific and impact MP populations differentially. © 2018 The Authors

Microparticle Flow Sensor

Science.gov (United States)

Morrison, Dennis R.

2005-01-01

The microparticle flow sensor (MFS) is a system for identifying and counting microscopic particles entrained in a flowing liquid. The MFS includes a transparent, optoelectronically instrumented laminar-flow chamber (see figure) and a computer for processing instrument-readout data. The MFS could be used to count microparticles (including micro-organisms) in diverse applications -- for example, production of microcapsules, treatment of wastewater, pumping of industrial chemicals, and identification of ownership of liquid products.

Continuous sheathless microparticle and cell patterning using CL-SSAWs (conductive liquid-based standing surface acoustic waves

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Jeonghun Nam

2017-01-01

Full Text Available We present continuous, sheathless microparticle patterning using conductive liquid (CL-based standing surface acoustic waves (SSAWs. Conventional metal electrodes patterned on a piezoelectric substrate were replaced with electrode channels filled with a CL. The device performance was evaluated with 5-μm fluorescent polystyrene particles at different flow rate and via phase shifting. In addition, our device was further applied to continuous concentration of malaria parasites at the sidewalls of the fluidic channel.

Avoiding false positive antigen detection by flow cytometry on blood cell derived microparticles: the importance of an appropriate negative control.

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Emerence Crompot

Full Text Available Microparticles (MPs, also called microvesicles (MVs are plasma membrane-derived fragments with sizes ranging from 0.1 to 1μm. Characterization of these MPs is often performed by flow cytometry but there is no consensus on the appropriate negative control to use that can lead to false positive results.We analyzed MPs from platelets, B-cells, T-cells, NK-cells, monocytes, and chronic lymphocytic leukemia (CLL B-cells. Cells were purified by positive magnetic-separation and cultured for 48h. Cells and MPs were characterized using the following monoclonal antibodies (CD19,20 for B-cells, CD3,8,5,27 for T-cells, CD16,56 for NK-cells, CD14,11c for monocytes, CD41,61 for platelets. Isolated MPs were stained with annexin-V-FITC and gated between 300nm and 900nm. The latex bead technique was then performed for easy detection of MPs. Samples were analyzed by Transmission (TEM and Scanning Electron microscopy (SEM.Annexin-V positive events within a gate of 300-900nm were detected and defined as MPs. Our results confirmed that the characteristic antigens CD41/CD61 were found on platelet-derived-MPs validating our technique. However, for MPs derived from other cell types, we were unable to detect any antigen, although they were clearly expressed on the MP-producing cells in the contrary of several data published in the literature. Using the latex bead technique, we confirmed detection of CD41,61. However, the apparent expression of other antigens (already deemed positive in several studies was determined to be false positive, indicated by negative controls (same labeling was used on MPs from different origins.We observed that mother cell antigens were not always detected on corresponding MPs by direct flow cytometry or latex bead cytometry. Our data highlighted that false positive results could be generated due to antibody aspecificity and that phenotypic characterization of MPs is a difficult field requiring the use of several negative controls.

Microparticles engineered to highly express peroxisome proliferator-activated receptor-γ decreased inflammatory mediator production and increased adhesion of recipient monocytes.

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Julie Sahler

Full Text Available Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particularly during inflammatory provocation. We therefore engineered the composition of megakaryocyte culture-derived microparticles to generate distinct microparticle populations that were given to human monocytes to assay for influences recipient cell function. Herein, we tested the responses of monocytes exposed to either control microparticles or microparticles that contain the anti-inflammatory transcription factor, peroxisome proliferator-activated receptor-γ (PPARγ. In order to normalize relative microparticle abundance from two microparticle populations, we implemented a novel approach that utilizes a Nanodrop Spectrophotometer to assay for microparticle density rather than concentration. We found that when given to peripheral blood mononuclear cells, microparticles were preferentially internalized by CD11b+ cells, and furthermore, microparticle composition had a profound functional impact on recipient monocytes. Specifically, microparticles containing PPARγ reduced activated monocyte production of the proinflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared to activated monocytes exposed to control microparticles. Additionally, treatment with PPARγ microparticles greatly increased monocyte cell adherence. This change in morphology occurred simultaneously with increased production of the key extracellular matrix protein, fibronectin and increased expression of the fibronectin-binding integrin, ITGA5. PPARγ microparticles

Preparation of alginate coated chitosan microparticles for vaccine delivery

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Wei YuQuan

2008-11-01

Full Text Available Abstract Background Absorption of antigens onto chitosan microparticles via electrostatic interaction is a common and relatively mild process suitable for mucosal vaccine. In order to increase the stability of antigens and prevent an immediate desorption of antigens from chitosan carriers in gastrointestinal tract, coating onto BSA loaded chitosan microparticles with sodium alginate was performed by layer-by-layer technology to meet the requirement of mucosal vaccine. Results The prepared alginate coated BSA loaded chitosan microparticles had loading efficiency (LE of 60% and loading capacity (LC of 6% with mean diameter of about 1 μm. When the weight ratio of alginate/chitosan microparticles was greater than 2, the stable system could be obtained. The rapid charge inversion of BSA loaded chitosan microparticles (from +27 mv to -27.8 mv was observed during the coating procedure which indicated the presence of alginate layer on the chitosan microparticles surfaces. According to the results obtained by scanning electron microscopy (SEM, the core-shell structure of BSA loaded chitosan microparticles was observed. Meanwhile, in vitro release study indicated that the initial burst release of BSA from alginate coated chitosan microparticles was lower than that observed from uncoated chitosan microparticles (40% in 8 h vs. about 84% in 0.5 h. SDS-polyacrylamide gel electrophoresis (SDS-PAGE assay showed that alginate coating onto chitosan microparticles could effectively protect the BSA from degradation or hydrolysis in acidic condition for at least 2 h. The structural integrity of alginate modified chitosan microparticles incubated in PBS for 24 h was investigated by FTIR. Conclusion The prepared alginate coated chitosan microparticles, with mean diameter of about 1 μm, was suitable for oral mucosal vaccine. Moreover, alginate coating onto the surface of chitosan microparticles could modulate the release behavior of BSA from alginate coated chitosan

Optical and non-optical methods for detection and characterization of microparticles and exosomes

NARCIS (Netherlands)

van der Pol, E.; Hoekstra, A.G.; Sturk, A.; Otto, C.; van Leeuwen, T.G.; Nieuwland, R.

2010-01-01

Microparticles and exosomes are cell-derived microvesicles present in body fluids that play a role in coagulation, inflammation, cellular homeostasis and survival, intercellular communication, and transport. Despite increasing scientific and clinical interest, no standard procedures are available

Whispering Gallery Mode Spectroscopy as a Diagnostic for Dusty Plasmas

International Nuclear Information System (INIS)

Thieme, G.; Basner, R.; Ehlbeck, J.; Roepcke, J.; Maurer, H.; Kersten, H.; Davies, P. B.

2008-01-01

Whispering-gallery-mode spectroscopy is being assessed as a diagnostic method for the characterisation of size and chemical composition of spherical particles levitated in a plasma. With a pulsed laser whispering gallery modes (cavity resonances) are excited in individual microspheres leading to enhanced Raman scattering or fluorescence at characteristic wavelengths. This method can be used to gain specific information from the particle surface and is thus of great interest for the characterisation of layers deposited on microparticles, e.g. in molecular plasmas. We present investigations of different microparticles in air and results from fluorescent particles levitated in an Argon rf plasma.

Innate immune cell-derived microparticles facilitate hepatocarcinoma metastasis by transferring integrin α(M)β₂ to tumor cells.

Science.gov (United States)

Ma, Jingwei; Cai, Wenqian; Zhang, Yi; Huang, Chunmei; Zhang, Huafeng; Liu, Jing; Tang, Ke; Xu, Pingwei; Katirai, Foad; Zhang, Jianmin; He, Wei; Ye, Duyun; Shen, Guan-Xin; Huang, Bo

2013-09-15

Mechanisms by which tumor cells metastasize to distant organs still remain enigmatic. Immune cells have been assumed to be the root of metastasis by their fusing with tumor cells. This fusion theory, although interpreting tumor metastasis analogically and intriguingly, is arguable to date. We show in this study an alternative explanation by immune cell-derived microparticles (MPs). Upon stimulation by PMA or tumor cell-derived supernatants, immune cells released membrane-based MPs, which were taken up by H22 tumor cells, leading to tumor cell migration in vitro and metastasis in vivo. The underlying molecular basis was involved in integrin α(M)β₂ (CD11b/CD18), which could be effectively relayed from stimulated innate immune cells to MPs, then to tumor cells. Blocking either CD11b or CD18 led to significant decreases in MP-mediated tumor cell metastasis. This MP-mediated transfer of immune phenotype to tumor cells might also occur in vivo. These findings suggest that tumor cells may usurp innate immune cell phenotypes via MP pathway for their metastasis, providing new insight into tumor metastatic mechanism.

Sustainability of a public system for plasma collection, contract fractionation and plasma-derived medicinal product manufacturing.

Science.gov (United States)

Grazzini, Giuliano; Ceccarelli, Anna; Calteri, Deanna; Catalano, Liviana; Calizzani, Gabriele; Cicchetti, Americo

2013-09-01

In Italy, the financial reimbursement for labile blood components exchanged between Regions is regulated by national tariffs defined in 1991 and updated in 1993-2003. Over the last five years, the need for establishing standard costs of healthcare services has arisen critically. In this perspective, the present study is aimed at defining both the costs of production of blood components and the related prices, as well as the prices of plasma-derived medicinal products obtained by national plasma, to be used for interregional financial reimbursement. In order to analyse the costs of production of blood components, 12 out 318 blood establishments were selected in 8 Italian Regions. For each step of the production process, driving costs were identified and production costs were. To define the costs of plasma-derived medicinal products obtained by national plasma, industrial costs currently sustained by National Health Service for contract fractionation were taken into account. The production costs of plasma-derived medicinal products obtained from national plasma showed a huge variability among blood establishments, which was much lower after standardization. The new suggested plasma tariffs were quite similar to those currently in force. Comparing the overall costs theoretically sustained by the National Health Service for plasma-derived medicinal products obtained from national plasma to current commercial costs, demonstrates that the national blood system could gain a 10% cost saving if it were able to produce plasma for fractionation within the standard costs defined in this study. Achieving national self-sufficiency through the production of plasma-derived medicinal products from national plasma, is a strategic goal of the National Health Service which must comply not only with quality, safety and availability requirements but also with the increasingly pressing need for economic sustainability.

Cell-derived microparticles after exercise in individuals with G6PD Viangchan.

Science.gov (United States)

Chanda, Makamas; Nantakomol, Duangdao; Suksom, Daroonwan; Palasuwan, Attakorn

2015-07-16

Glucose-6-phospate dehydrogenase (G6PD) deficient cells are sensitive to oxidative damage leading to the formation of microparticles (MPs). Therefore, we examined the concentration of MPs and changes in the antioxidant balance after an acute strenuous exercise (SEx) and moderate-intensity exercise (MEx). Eighteen healthy females (18-24 years) with G6PD normal and eighteen age-matched females with G6PD Viangchan (871G>A) were tested by running on a treadmill at their maximal oxygen uptake for SEx and at 75% of their maximal heart rate for MEx. It was found that SEx triggered the release of total microparticles (TTMPs) above baseline levels and remained significantly higher 45 minutes after the exercise in G6PD normal individuals. However, SEx-induced increase in TTMPs was significantly higher in G6PD Viangchan as compared to G6PD normal. In contrast, MEx did not to alter the release of TTMPs in both G6PD normal and Viangchan. Moreover, TTMPs concentrations were inversely correlated with G6PD activity (r =-0.82, P stress compared with G6PD normal.

Theoretical analysis of ferromagnetic microparticles in streaming liquid under the influence of external magnetic forces

International Nuclear Information System (INIS)

Brandl, Martin; Mayer, Michael; Hartmann, Jens; Posnicek, Thomas; Fabian, Christian; Falkenhagen, Dieter

2010-01-01

The microsphere based detoxification system (MDS) is designed for high specific toxin removal in extracorporeal blood purification using functionalized microparticles. A thin wall hollow fiber membrane filter separates the microparticle-plasma suspension from the bloodstream. For patient safety, it is necessary to have a safety system to detect membrane ruptures that could lead to the release of microparticles into the bloodstream. A non-invasive optical detection system including a magnetic trap is developed to monitor the extracorporeal venous bloodstream for the presence of released microparticles. For detection, fluorescence-labeled ferromagnetic beads are suspended together with adsorbent particles in the MDS circuit. In case of a membrane rupture, the labeled particles would be released into the venous bloodstream and partly captured by the magnetic trap of the detector. A physical model based on fluidic, gravitational and magnetic forces was developed to simulate the motion and sedimentation of ferromagnetic particles in a magnetic trap. In detailed simulation runs, the concentrations of accumulated particles under different applied magnetic fields within the magnetic trap are shown. The simulation results are qualitatively compared with laboratory experiments and show excellent accordance. Additionally, the sensitivity of the particle detection system is proofed in a MDS laboratory experiment by simulation of a membrane rupture.

Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

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Federica Novelli

Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

Apoptotic-cell-derived membrane microparticles and IFN-α induce an inflammatory immune response.

Science.gov (United States)

Niessen, Anna; Heyder, Petra; Krienke, Stefan; Blank, Norbert; Tykocinski, Lars-Oliver; Lorenz, Hanns-Martin; Schiller, Martin

2015-07-15

A dysregulation in the clearance of apoptotic material is considered a major pathogenetic factor for the emergence of autoimmune diseases. Apoptotic-cell-derived membrane microparticles (AdMPs), which are released from the cell surface during apoptosis, have been implicated in the pathogenesis of autoimmunity. Also of importance are cytokines, such as interferon-α (IFN-α), which is known to be a major player in patients with systemic lupus erythematosus (SLE). This study investigates the combined effect of AdMPs and IFN-α on professional phagocytes. In the presence of IFN-α, phagocytosis of AdMPs by human monocytes was significantly increased in a dose-dependent manner. The combination of AdMPs and raised IFN-α concentrations resulted in an increase in the secretion of pro-inflammatory cytokines and an upregulation of surface molecule expression involved in antigen uptake. In addition, macrophage polarisation was shifted towards a more inflammatory type of cell. The synergism between IFN-α and AdMPs seemed to be mediated by an upregulation of phosphorylated STAT1. Our results indicate that IFN-α, together with AdMPs, amplify the initiation and maintenance of inflammation. This mechanism might especially play a crucial role in disorders with a defective clearance of apoptotic material. © 2015. Published by The Company of Biologists Ltd.

Local delivery of cannabinoid-loaded microparticles inhibits tumor growth in a murine xenograft model of glioblastoma multiforme.

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Dolores Hernán Pérez de la Ossa

Full Text Available Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ(9-Tetrahydrocannabinol (THC and Cannabidiol (CBD - the two major ingredients of marijuana - have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.

Characterization of Microparticles after Hepatic Ischemia-Reperfusion Injury

Science.gov (United States)

Freeman, Christopher M.; Quillin, Ralph C.; Wilson, Gregory C.; Nojima, Hiroyuki; Johnson, Bobby L.; Sutton, Jeffrey M.; Schuster, Rebecca M.; Blanchard, John; Edwards, Michael J.; Caldwell, Charles C.; Lentsch, Alex B.

2014-01-01

Background Hepatic ischemia-reperfusion (I/R) is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs) are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins–platelets, neutrophils, and endolethial cells–following hepatic ischemia-reperfusion injury. Methods A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. Results MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. Conclusion This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver. PMID:24879335

Development of an Injectable Calcium Phosphate/Hyaluronic Acid Microparticles System for Platelet Lysate Sustained Delivery Aiming Bone Regeneration.

Science.gov (United States)

Babo, Pedro S; Santo, Vítor E; Gomes, Manuela E; Reis, Rui L

2016-11-01

Despite the biocompatibility and osteoinductive properties of calcium phosphate (CaP) cements their low biodegradability hampers full bone regeneration. Herein the incorporation of CaP cement with hyaluronic acid (HAc) microparticles loaded with platelet lysate (PL) to improve the degradability and biological performance of the cements is proposed. Cement formulations incorporating increasing weight ratios of either empty HAc microparticles or microparticles loaded with PL (10 and 20 wt%) are developed as well as cements directly incorporating PL. The direct incorporation of PL improves the mechanical properties of the plain cement, reaching values similar to native bone. Morphological analysis shows homogeneous particle distribution and high interconnectivity between the HAc microparticles. The cements incorporating PL (with or without the HAc microparticles) present a sustained release of PL proteins for up to 8 d. The sustained release of PL modulates the expression of osteogenic markers in seeded human adipose tissue derived stem cells, thus suggesting the stimulatory role of this hybrid system toward osteogenic commitment and bone regeneration applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel broadband impedance method for detection of cell-derived microparticles.

Science.gov (United States)

Lvovich, Vadim; Srikanthan, Sowmya; Silverstein, Roy L

2010-10-15

A novel label-free method is presented to detect and quantify cell-derived microparticles (MPs) by the electrochemical potential-modulated electrochemical impedance spectroscopy (EIS). MPs are present in elevated concentrations during pathological conditions and play a major role in the establishment and pathogenesis of many diseases. Considering this, accurate detection and quantification of MPs is very important in clinical diagnostics and therapeutics. A combination of bulk solution electrokinetic sorting and interfacial impedance responses allows achieving detection limits as low as several MPs per μL. By fitting resulting EIS spectra with an equivalent electrical circuit, the bulk solution electrokinetic and interfacial impedance responses were characterized. In the bulk solution two major relaxations were prominent-β-relaxation in low MHz region due to the MP capacitive membrane bridging, and α-relaxation at ∼10 kHz due to counter ions diffusion. At low frequencies (10-0.1 Hz) at electrochemical potentials exceeding -100 mV, a facile interfacial Faradaic process of oxidation in MPs coupled with diffusion and non-Faradaic double layer charging dominate, probably due to oxidation of phospholipids and/or proteins on the MP surface and MP lysis. Buffer influence on the MP detection demonstrated that a relatively low conductivity Tyrode's buffer background solution is preferential for the MP electrokinetic separation and characterization. This study also demonstrated that standard laboratory methods such as flow cytometry underestimate MP concentrations, especially those with smaller average sizes, by as much as a factor of 2-40. Copyright © 2010 Elsevier B.V. All rights reserved.

Economical impact of plasma fractionation project in Iran on affordability of plasma-derived medicines.

Science.gov (United States)

Cheraghali, A M; Aboofazeli, R

2009-12-01

In Iran all transfusion services are concentrated under authority of one public and centralized transfusion organization which has created the opportunity of using plasma produced in its blood centers for fractionation. In 2008 voluntary and non remunerated Iranian donors donated 1.8 million units of blood. This indicates a 25/1000 donation index. After responding to the needs for fresh plasma and cryoprecipitate each year about 150000 L of recovered plasma are reserved for fractionation. In an attempt to improve both blood safety profile and availability and affordability of plasma derived medicines, Iran's national transfusion service has entered into a contract fractionation agreement for surplus of plasma produced from donated blood by voluntary non remunerated donors. In order to ensure safety of product produced, Iran has chosen to collaborate with international fractionators based in highly regulated countries. The main objective of this study was to evaluate the impact of contract plasma fractionation on the affordability of the plasma derived medicines in Iran. During 2006-2008, Iran's contract fractionation project was able to produce 46%, 18% and 6% of IVIG, Albumin and FVIII consumed in Iran's market, respectively. In contrary to IVIG and Albumin, due to fairly high consumption of FVIII in Iran, the role of fractionation project in meeting the needs to FVIII was not substantial. However, Iran's experience has shown that contract plasma fractionation, through direct and indirect effects on price of plasma derived medicines, could substantially improve availability and affordability of such products in national health care system.

Optical and non-optical methods for detection and characterization of microparticles and exosomes.

Science.gov (United States)

van der Pol, E; Hoekstra, A G; Sturk, A; Otto, C; van Leeuwen, T G; Nieuwland, R

2010-12-01

Microparticles and exosomes are cell-derived microvesicles present in body fluids that play a role in coagulation, inflammation, cellular homeostasis and survival, intercellular communication, and transport. Despite increasing scientific and clinical interest, no standard procedures are available for the isolation, detection and characterization of microparticles and exosomes, because their size is below the reach of conventional detection methods. Our objective is to give an overview of currently available and potentially applicable methods for optical and non-optical determination of the size, concentration, morphology, biochemical composition and cellular origin of microparticles and exosomes. The working principle of all methods is briefly discussed, as well as their applications and limitations based on the underlying physical parameters of the technique. For most methods, the expected size distribution for a given microvesicle population is determined. The explanations of the physical background and the outcomes of our calculations provide insights into the capabilities of each method and make a comparison possible between the discussed methods. In conclusion, several (combinations of) methods can detect clinically relevant properties of microparticles and exosomes. These methods should be further explored and validated by comparing measurement results so that accurate, reliable and fast solutions come within reach. © 2010 International Society on Thrombosis and Haemostasis.

Investigation of strain-induced magnetization change in ferromagnetic microparticles

International Nuclear Information System (INIS)

Chuklanov, A P; Nurgazizov, N I; Bizyaev, D A; Khanipov, T F; Bukharaev, A A; Yu Petukhov, V; Chirkov, V V; Gumarov, G G

2016-01-01

This work is devoted to investigation of magnetoelastic strain effect on the ferromagnetic microparticles of permalloy. An original method of sample fabrication with compressed microparticles is proposed. Magnetic force microscopy and magneto-optical Kerr experiments were carried out with unstrained and compressed microparticles. The domain walls transformation in compressed microparticles is in good agreement with numerical calculations. Hard axis of magnetization was observed on the compressed sample. (paper)

Micro-particles in ITER: A comprehensive review

International Nuclear Information System (INIS)

Grisolia, C.; Rosanvallon, S.; Sharpe, Ph.; Winter, J.

2009-01-01

In a fusion reactor like ITER, in-vessel materials are subjected to interactions with the plasma. One of the main consequences of these plasma-material interactions is the creation of co-deposited layers. Due to internal stresses, part of these layers can crack leading to micro particle creation. The purpose of the following paper is to review the Tokamak operation processes which lead to erosion and layer creation. Then, the proportion of these layers that is converted into micro-particles will be evaluated in the case of Tore Supra experiments and extrapolated for ITER. It is major importance to measure the ITER mobilizable dusts present in the Vacuum Vessel and compare the measured quantity with the safety limits. When approaching these limits, removal systems must be used in order to control the in-vessel dust inventory. In the second part of the paper, diagnostics and removal system under development will be presented.

Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/ Rho kinase pathways targeted to lipid rafts.

Science.gov (United States)

Burger, Dylan; Montezano, Augusto C; Nishigaki, Nobuhiro; He, Ying; Carter, Anthony; Touyz, Rhian M

2011-08-01

Circulating microparticles are increased in cardiovascular disease and may themselves promote oxidative stress and inflammation. Molecular mechanisms underlying their formation and signaling are unclear. We investigated the role of reactive oxygen species (ROS), Rho kinase, and lipid rafts in microparticle formation and examined their functional significance in endothelial cells (ECs). Microparticle formation from angiotensin II (Ang II)-stimulated ECs and apolipoprotein E(-/-) mice was assessed by annexin V or by CD144 staining and electron microscopy. Ang II promoted microparticle formation and increased EC O(2)(-) generation and Rho kinase activity. Ang II-stimulated effects were inhibited by irbesartan (Ang II receptor type I blocker) and fasudil (Rho kinase inhibitor). Methyl-β-cyclodextrin and nystatin, which disrupt lipid rafts/caveolae, blocked microparticle release. Functional responses, assessed in microparticle-stimulated ECs, revealed increased O(2)(-) production, enhanced vascular cell adhesion molecule/platelet-EC adhesion molecule expression, and augmented macrophage adhesion. Inhibition of epidermal growth factor receptor blocked the prooxidative and proinflammatory effects of microparticles. In vitro observations were confirmed in apolipoprotein E(-/-) mice, which displayed vascular inflammation and high levels of circulating endothelial microparticles, effects that were reduced by apocynin. We demonstrated direct actions of Ang II on endothelial microparticle release, mediated through NADPH oxidase, ROS, and Rho kinase targeted to lipid rafts. Microparticles themselves stimulated endothelial ROS formation and inflammatory responses. Our findings suggest a feedforward system whereby Ang II promotes EC injury through its own endothelial-derived microparticles.

Absolute hypoxic exercise training enhances in vitro thrombin generation by increasing procoagulant platelet-derived microparticles under high shear stress in sedentary men.

Science.gov (United States)

Chen, Yu-Wen; Chen, Yi-Ching; Wang, Jong-Shyan

2013-05-01

HS (high shear) stress associated with artery stenosis facilitates TG (thrombin generation) by increasing the release of procoagulant PDMPs (platelet-derived microparticles). Physical exercise and hypoxia may paradoxically modulate vascular thrombotic risks. The aim of the present study was to investigate how exercise training with/without hypoxia affected TG mediated by PDMPs under physio-pathological shear flows. A total of 75 sedentary males were randomly divided into five groups (n=15 in each group): 21% O2 [NC (normoxic control)] or 15% O2 [HC (hypoxic control)] at rest or were trained at 50% of peak work rate under 21% O2 [NT (normoxic training)] or 15% O2 [HAT (hypoxic-absolute training)], or 50% of HR (heart rate) reserve under 15% O2 [HRT (hypoxic-relative training)] for 30 min/day, 5 days/week for 4 weeks. The PDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. Before the intervention, strenuous exercise markedly increased the PDMP count (14.8%) and TG rate (19.5%) in PDMP-rich plasma at 100 dynes/cm2 of shear stress (Pexercise. Conversely, HAT notably promoted the PDMP count (37.3%) and TG rate (38.9%) induced by HS (Pexercise. We conclude that both HRT and NT depress similarly HS-mediated TG during exercise, but HAT accelerates the prothrombotic response to vigorous exercise. These findings provide new insights into how exercise training under a hypoxic condition influences the risk of thrombosis associated with stenotic arteries.

Preparation and Characterization of Keratin/Alginate Blend Microparticles

Directory of Open Access Journals (Sweden)

Yaowalak Srisuwan

2018-01-01

Full Text Available The water-in-oil (W/O emulsification-diffusion method was used for construction of keratin (Ker, alginate (Alg, and Ker/Alg blend microparticles. The Ker, Alg, and Ker/Alg blend solutions were used as the water phase, while ethyl acetate was used as the oil phase. Firstly, different concentrations of Ker solution was used to find suitable content. 1.6% w/v Ker solution was blended with the same concentration of the Alg solution for further microparticle construction. Results from scanning electron microscope analysis show that the microparticles have different shapes: spherical, bowl-like, porous, and hollow, with several sizes depending on the blend ratio. FTIR and TG analyses indicated that the secondary structure and thermal stability of the microparticles were influenced by the Ker/Alg blend ratio. The interaction between functional groups of keratin and alginate was the main factor for both β-sheet structure and Td,max values of the microparticles. The results suggested that Ker/Alg blend microparticles might be applied in many fields by varying the Ker/Alg ratio.

Acoustic radiation- and streaming-induced microparticle velocities determined by microparticle image velocimetry in an ultrasound symmetry plane

DEFF Research Database (Denmark)

Barnkob, Rune; Augustsson, Per; Laurell, Thomas

2012-01-01

We present microparticle image velocimetry measurements of suspended microparticles of diameters from 0.6 to 10μm undergoing acoustophoresis in an ultrasound symmetry plane in a microchannel. The motion of the smallest particles is dominated by the Stokes drag from the induced acoustic streaming...

Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles.

Science.gov (United States)

Jansen, Felix; Yang, Xiaoyan; Hoelscher, Marion; Cattelan, Arianna; Schmitz, Theresa; Proebsting, Sebastian; Wenzel, Daniela; Vosen, Sarah; Franklin, Bernardo S; Fleischmann, Bernd K; Nickenig, Georg; Werner, Nikos

2013-10-29

Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. We sought to investigate whether endothelial microparticles (EMPs), released from apoptotic endothelial cells (ECs), influence EC repair. Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP-mediated effects on human coronary artery endothelial cell migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMPs derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes mellitus revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients. Endothelial microparticles promote vascular endothelial repair by delivering functional miR-126 into recipient cells. In pathological hyperglycemic conditions, EMP-mediated miR-126-induced EC repair is altered.

Fabrication and characterization of carboxymethyl cellulose novel microparticles for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Gaihre, Bipin [Department of Bioengineering, The University of Toledo, Toledo, OH 43614 (United States); Jayasuriya, Ambalangodage C., E-mail: a.jayasuriya@utoledo.edu [Department of Bioengineering, The University of Toledo, Toledo, OH 43614 (United States); Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH 43614 (United States)

2016-12-01

In this study we developed carboxymethyl cellulose (CMC) microparticles through ionic crosslinking with the aqueous ion complex of zirconium (Zr) and further complexing with chitosan (CS) and determined the physio-chemical and biological properties of these novel microparticles. In order to assess the role of Zr, microparticles were prepared in 5% and 10% (w/v) zirconium tetrachloride solution. Scanning electron microscopy (SEM) with energy dispersive X-ray spectrometer (EDS) results showed that Zr was uniformly distributed on the surface of the microparticles as a result of which uniform groovy surface was obtained. We found that Zr enhances the surface roughness of the microparticles and stability studies showed that it also increases the stability of microparticles in phosphate buffered saline. The crosslinking of anionic CMC with cationic Zr and CS was confirmed by Fourier transform infrared spectroscopy (FTIR) results. The response of murine pre-osteoblasts (OB-6) when cultured with microparticles was investigated. Live/dead cell assay showed that microparticles did not induce any cytotoxic effects as cells were attaching and proliferating on the well plate as well as along the surface of microparticles. In addition, SEM images showed that microparticles support the attachment of cells and they appeared to be directly interacting with the surface of microparticle. Within 10 days of culture most of the top surface of microparticles was covered with a layer of cells indicating that they were proliferating well throughout the surface of microparticles. We observed that Zr enhances the cell attachment and proliferation as more cells were present on microparticles with 10% Zr. These promising results show the potential applications of CMC-Zr microparticles in bone tissue engineering. - Highlights: • Zirconium ions crosslinked carboxymethyl cellulose microparticles were fabricated. • The microparticles were further stabilized by complexation with chitosan. �

Fabrication and characterization of carboxymethyl cellulose novel microparticles for bone tissue engineering

International Nuclear Information System (INIS)

Gaihre, Bipin; Jayasuriya, Ambalangodage C.

2016-01-01

In this study we developed carboxymethyl cellulose (CMC) microparticles through ionic crosslinking with the aqueous ion complex of zirconium (Zr) and further complexing with chitosan (CS) and determined the physio-chemical and biological properties of these novel microparticles. In order to assess the role of Zr, microparticles were prepared in 5% and 10% (w/v) zirconium tetrachloride solution. Scanning electron microscopy (SEM) with energy dispersive X-ray spectrometer (EDS) results showed that Zr was uniformly distributed on the surface of the microparticles as a result of which uniform groovy surface was obtained. We found that Zr enhances the surface roughness of the microparticles and stability studies showed that it also increases the stability of microparticles in phosphate buffered saline. The crosslinking of anionic CMC with cationic Zr and CS was confirmed by Fourier transform infrared spectroscopy (FTIR) results. The response of murine pre-osteoblasts (OB-6) when cultured with microparticles was investigated. Live/dead cell assay showed that microparticles did not induce any cytotoxic effects as cells were attaching and proliferating on the well plate as well as along the surface of microparticles. In addition, SEM images showed that microparticles support the attachment of cells and they appeared to be directly interacting with the surface of microparticle. Within 10 days of culture most of the top surface of microparticles was covered with a layer of cells indicating that they were proliferating well throughout the surface of microparticles. We observed that Zr enhances the cell attachment and proliferation as more cells were present on microparticles with 10% Zr. These promising results show the potential applications of CMC-Zr microparticles in bone tissue engineering. - Highlights: • Zirconium ions crosslinked carboxymethyl cellulose microparticles were fabricated. • The microparticles were further stabilized by complexation with chitosan. �

Postprandial changes in the phospholipid composition of circulating microparticles are not associated with coagulation activation

NARCIS (Netherlands)

Tushuizen, Maarten E.; Diamant, Michaela; Peypers, Erik G.; Hoek, Frans J.; Heine, Robert J.; Sturk, Augueste; Nieuwland, Rienk

2012-01-01

Introduction: Evidence is present that the phospholipid composition of circulating cell-derived microparticles (MP) affects coagulation in vivo, and that postprandial metabolic alterations may be associated with hypercoagulable state. Our objective was to investigate whether postprandial metabolic

Exploring the limits of cooperative phenomena using complex plasmas

International Nuclear Information System (INIS)

Schwabe, M.; Zhdanov, S.; Ivlev, A. V.; Thomas, H. M.; Morfill, G. E.

2011-01-01

With the advancing miniaturization of technological applications, processes on the mesoscale become increasingly important. This is the scale where the individual movement of particles transforms into cooperative behavior-behavior that cannot be explained by investigating the motion of individual particles alone.Complex plasmas are ideally suited to study the limits of cooperative behavior. The time scales of the dynamics of the microparticles embedded in the plasma are such that their movement can be fully resolved, and an investigation on the atomistic (kinetic) level is possible. In addition, complex plasmas can be considered a model system for ordinary fluids: The internal microparticle dynamics is basically undamped and is characterized by the similarity parameters matching those of other fluids. This similarity does not break down even at small scales: For instance, in [2], microparticle droplets comprised of only a few 1000-10000 particles were examined. In these experiments, the Weber number (the ratio of inertia to surface tension forces) matches that of falling water drops. As another example, the onset of a Rayleigh-Taylor instability in a complex plasma can be described by the ordinary dispersion relation, even at scales of only few particle layers. This allows investigating the 'nanoscale' of fluid flows, and, hence, the limits of cooperative behavior.

Correlational approach to study interactions between dust Brownian particles in a plasma

Science.gov (United States)

Lisin, E. A.; Vaulina, O. S.; Petrov, O. F.

2018-01-01

A general approach to the correlational analysis of Brownian motion of strongly coupled particles in open dissipative systems is described. This approach can be applied to the theoretical description of various non-ideal statistically equilibrium systems (including non-Hamiltonian systems), as well as for the analysis of experimental data. In this paper, we consider an application of the correlational approach to the problem of experimental exploring the wake-mediated nonreciprocal interactions in complex plasmas. We derive simple analytic equations, which allows one to calculate the gradients of forces acting on a microparticle due to each of other particles as well as the gradients of external field, knowing only the information on time-averaged correlations of particles displacements and velocities. We show the importance of taking dissipative and random processes into account, without which consideration of a system with a nonreciprocal interparticle interaction as linearly coupled oscillators leads to significant errors in determining the characteristic frequencies in a system. In the examples of numerical simulations, we demonstrate that the proposed original approach could be an effective instrument in exploring the longitudinal wake structure of a microparticle in a plasma. Unlike the previous attempts to study the wake-mediated interactions in complex plasmas, our method does not require any external perturbations and is based on Brownian motion analysis only.

Analysis of the neutral drag force in a dc glow discharge dusty plasma

International Nuclear Information System (INIS)

Thomas, Edward Jr.; Williams, Jeremiah

2005-01-01

In this paper, the authors report on a series of experiments that use carefully applied perturbations to a dust cloud to reproducibly investigate the formation of the microparticle cloud and the formation of dust cloud-plasma interface. Here, one micron diameter alumina microparticles are suspended in an argon dc glow discharge plasma. A perturbing voltage pulse is applied to the cathode, causing a momentary disruption in the confinement of the dust cloud. After the perturbation, the cloud reforms, typically with a central 'mass' and two 'streams' of particles that are flowing into the cloud from both sides. Through the use of stereoscopic particle image velocimetry (stereo-PIV), the complete three-dimensional velocity of the microparticles can be measured. The particles in the streams are used as test particles to characterize the forces acting upon the microparticles. Analysis of the experimental measurements suggests that the effective neutral drag force may be lower than expected

Preparation of donut-shaped starch microparticles by aqueous-alcoholic treatment.

Science.gov (United States)

Farrag, Yousof; Sabando, Constanza; Rodríguez-Llamazares, Saddys; Bouza, Rebeca; Rojas, Claudio; Barral, Luís

2018-04-25

A simple method for producing donut-shaped starch microparticles by adding ethanol to a heated aqueous slurry of corn starch is presented. The obtained microparticles were analysed by SEM, XRD and DSC. The average size of microparticles was 14.1 ± 0.3 μm with holes of an average size of 4.6 ± 0.2 μm. The crystalline arrangement of the microparticles was of a V-type single helix. The change in crystallinity from A-type of the starch granules to a more open structure, where water molecules could penetrate easier within the microparticles, substantially increased their solubility and swelling power. The microparticles exhibited a higher gelatinization temperature and a lower gelatinization enthalpy than did the starch granules. The donut-shaped microparticles were stable for more than 18 months and can be used as a carrier of an active compound or as a filler in bioplastics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chitosan microparticles for sustaining the topical delivery of minoxidil sulphate.

Science.gov (United States)

Gelfuso, Guilherme Martins; Gratieri, Taís; Simão, Patrícia Sper; de Freitas, Luís Alexandre Pedro; Lopez, Renata Fonseca Vianna

2011-01-01

Given the hypothesis that microparticles can penetrate the skin barrier along the transfollicular route, this work aimed to obtain and characterise chitosan microparticles loaded with minoxidil sulphate (MXS) and to study their ability to sustain the release of the drug, attempting a further application utilising them in a targeted delivery system for the topical treatment of alopecia. Chitosan microparticles, containing different proportions of MXS/polymer, were prepared by spray drying and were characterised by yield, encapsulation efficiency, size and morphology. Microparticles selected for further studies showed high encapsulation efficiency (∼82%), a mean diameter of 3.0 µm and a spherical morphology without porosities. When suspended in an ethanol/water solution, chitosan microparticles underwent instantaneous swelling, increasing their mean diameter by 90%. Release studies revealed that the chitosan microparticles were able to sustain about three times the release rate of MXS. This feature, combined with suitable size, confers to these microparticles the potential to target and improve topical therapy of alopecia with minoxidil.

Enhanced bioavailability and anthelmintic efficacy of mebendazole in redispersible microparticles with low-substituted hydroxypropylcellulose

Directory of Open Access Journals (Sweden)

Torre-Iglesias PM

2014-09-01

Full Text Available Paloma Marina de la Torre-Iglesias,1,2 Juan José García-Rodriguez,3 Guillermo Torrado,4 Susana Torrado,1,2 Santiago Torrado-Santiago,1,5 Francisco Bolás-Fernández3 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Madrid, Spain; 2Institute of Industrial Pharmacy, Complutense University, Madrid, Spain; 3Department of Parasitology, Faculty of Pharmacy, Complutense University, Madrid, Spain; 4Department of Pharmaceutical Technology, Faculty of Pharmacy, Alcala University, Alcala de Henares (Madrid, Spain; 5Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD, Madrid, Spain Background: Mebendazole (MBZ is an extremely insoluble and therefore poorly absorbed drug and the variable clinical results may correlate with blood concentrations. The necessity of a prolonged high dose treatment of this drug increases the risk of adverse effects. Methods: In the present study we prepared redispersible microparticles (RDM containing MBZ, an oral, poorly water-soluble drug, in different proportions of low-substituted hydroxypropylcellulose (L-HPC. We investigated the microparticulate structures that emerge spontaneously upon dispersion of an RDM in aqueous medium and elucidated their influence on dissolution, and also on their oral bioavailability and therapeutic efficiency using a murine model of infection with the nematode parasite Trichinella spiralis.Results: Elevated percentages of dissolved drug were obtained with RDM at 1:2.5 and 1:5 ratios of MBZ: L-HPC. Thermal analysis showed an amorphization of MBZ in the RDM by the absence of a clear MBZ melting peak in formulations. The rapid dissolution behavior could be due to the decreased drug crystallinity, the fast dissolution time of carriers as L-HPC, together with its superior dispersibility and excellent wetting properties. RDM-1:2.5 and RDM-1:5 resulted in increased maximum plasma concentration and area(s under the curve (AUC0

Profile analysis of microparticles

International Nuclear Information System (INIS)

Konarski, P.; Iwanejko, I.; Mierzejewska, A.

2001-01-01

Depth resolved analyses of several types of microparticles are presented. Particles for secondary ion mass spectrometry (SIMS) depth profile analysis were collected in the working environment of glass plant, steelworks and welding station using eight-stage cascade impactor with particle size range of 0.3 μm to 15 μm. Ion beam sputtering and sample rotation technique allowed to describe morphology i.e. the elemental structure of collected sub-micrometer particles. Also model particles Iriodin 221 (Merck) were depth profiled. The core-shell structure is found for all types of investigated particles. Steelworks particles consist mainly of iron and manganese cores. At the shells of these microparticles: lead, chlorine and fluorine are found. The particles collected in the glass-works consist mainly of lead-zirconium glass cores covered by carbon and copper. Stainless-steel welding particles compose of iron, manganese and chromium cores covered by a shell rich in carbon, chlorine and fluorine. Sample rotation technique applied in SIMS appears to be an effective tool for environmental microparticle morphology studies

Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation.

Science.gov (United States)

Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D

2016-01-01

Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

pH-Sensitive Microparticles with Matrix-Dispersed Active Agent

Science.gov (United States)

Li, Wenyan (Inventor); Buhrow, Jerry W. (Inventor); Jolley, Scott T. (Inventor); Calle, Luz M. (Inventor)

2014-01-01

Methods to produce pH-sensitive microparticles that have an active agent dispersed in a polymer matrix have certain advantages over microcapsules with an active agent encapsulated in an interior compartment/core inside of a polymer wall. The current invention relates to pH-sensitive microparticles that have a corrosion-detecting or corrosion-inhibiting active agent or active agents dispersed within a polymer matrix of the microparticles. The pH-sensitive microparticles can be used in various coating compositions on metal objects for corrosion detecting and/or inhibiting.

Use of protein containing magnetic microparticles in radioassays

International Nuclear Information System (INIS)

Ithakissios, D.S.; Kubiatowicz, D.O.

1977-01-01

We describe a radioassay method that involves the use of magnetic protein microparticles composed of a water-insoluble protein matrix containing magnetically responsive material. We define two different types of particles according to the mechanism of action: The substrate is sorbed nonspecifically by the protein matrix of the particle or by a second substance such as charcoal or ion-exchange resin incorporated within the protein matrix of the particle. These particles are useful for separating free from bound substrate. Examples of these are albumin magnetic microparticles for use in a total thyroxine radioassay and triiodothyronine uptake test, or albumin magnetic microparticles containing charcoal for use in a vitamin B 12 radioassay. The substrate is sorbed specifically by a binding protein incorporated within the matrix of the particles. The binding protein can include antibodies or other specific nonimmune proteins. Particles of this type are useful in solid-phase radioassays. These particles are exemplified by albumin magnetic microparticles containing sockeye salmon serum, used in a solid-phase B 12 radioassay. We discuss the methods for the preparation of both types of magnetic microparticles and their use in radioassays. We describe a unique inexpensive magnetic separation rack, which provides simple, fast, and reproducible separation of the magnetic microparticles from their suspending medium during the assay

Circulating Microparticles in Patients with Benign and Malignant Ovarian Tumors

NARCIS (Netherlands)

Rank, A.; Liebhardt, S.; Zwirner, J.; Burges, A.; Nieuwland, R.; Toth, B.

2012-01-01

Background: Microparticles are known to be increased in various malignancies. In this prospective study, microparticle levels were evaluated in patients with benign and malignant ovarian lesions. Patients and Methods: Microparticles from platelets/megakaryocytes, activated platelets and endothelial

Plasma Membrane-Located Purine Nucleotide Transport Proteins Are Key Components for Host Exploitation by Microsporidian Intracellular Parasites

Science.gov (United States)

Heinz, Eva; Hacker, Christian; Dean, Paul; Mifsud, John; Goldberg, Alina V.; Williams, Tom A.; Nakjang, Sirintra; Gregory, Alison; Hirt, Robert P.; Lucocq, John M.; Kunji, Edmund R. S.; Embley, T. Martin

2014-01-01

Microsporidia are obligate intracellular parasites of most animal groups including humans, but despite their significant economic and medical importance there are major gaps in our understanding of how they exploit infected host cells. We have investigated the evolution, cellular locations and substrate specificities of a family of nucleotide transport (NTT) proteins from Trachipleistophora hominis, a microsporidian isolated from an HIV/AIDS patient. Transport proteins are critical to microsporidian success because they compensate for the dramatic loss of metabolic pathways that is a hallmark of the group. Our data demonstrate that the use of plasma membrane-located nucleotide transport proteins (NTT) is a key strategy adopted by microsporidians to exploit host cells. Acquisition of an ancestral transporter gene at the base of the microsporidian radiation was followed by lineage-specific events of gene duplication, which in the case of T. hominis has generated four paralogous NTT transporters. All four T. hominis NTT proteins are located predominantly to the plasma membrane of replicating intracellular cells where they can mediate transport at the host-parasite interface. In contrast to published data for Encephalitozoon cuniculi, we found no evidence for the location for any of the T. hominis NTT transporters to its minimal mitochondria (mitosomes), consistent with lineage-specific differences in transporter and mitosome evolution. All of the T. hominis NTTs transported radiolabelled purine nucleotides (ATP, ADP, GTP and GDP) when expressed in Escherichia coli, but did not transport radiolabelled pyrimidine nucleotides. Genome analysis suggests that imported purine nucleotides could be used by T. hominis to make all of the critical purine-based building-blocks for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis. PMID:25474405

Plasma membrane-located purine nucleotide transport proteins are key components for host exploitation by microsporidian intracellular parasites.

Directory of Open Access Journals (Sweden)

Eva Heinz

2014-12-01

Full Text Available Microsporidia are obligate intracellular parasites of most animal groups including humans, but despite their significant economic and medical importance there are major gaps in our understanding of how they exploit infected host cells. We have investigated the evolution, cellular locations and substrate specificities of a family of nucleotide transport (NTT proteins from Trachipleistophora hominis, a microsporidian isolated from an HIV/AIDS patient. Transport proteins are critical to microsporidian success because they compensate for the dramatic loss of metabolic pathways that is a hallmark of the group. Our data demonstrate that the use of plasma membrane-located nucleotide transport proteins (NTT is a key strategy adopted by microsporidians to exploit host cells. Acquisition of an ancestral transporter gene at the base of the microsporidian radiation was followed by lineage-specific events of gene duplication, which in the case of T. hominis has generated four paralogous NTT transporters. All four T. hominis NTT proteins are located predominantly to the plasma membrane of replicating intracellular cells where they can mediate transport at the host-parasite interface. In contrast to published data for Encephalitozoon cuniculi, we found no evidence for the location for any of the T. hominis NTT transporters to its minimal mitochondria (mitosomes, consistent with lineage-specific differences in transporter and mitosome evolution. All of the T. hominis NTTs transported radiolabelled purine nucleotides (ATP, ADP, GTP and GDP when expressed in Escherichia coli, but did not transport radiolabelled pyrimidine nucleotides. Genome analysis suggests that imported purine nucleotides could be used by T. hominis to make all of the critical purine-based building-blocks for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis.

Reconfigurable engineered motile semiconductor microparticles.

Science.gov (United States)

Ohiri, Ugonna; Shields, C Wyatt; Han, Koohee; Tyler, Talmage; Velev, Orlin D; Jokerst, Nan

2018-05-03

Locally energized particles form the basis for emerging classes of active matter. The design of active particles has led to their controlled locomotion and assembly. The next generation of particles should demonstrate robust control over their active assembly, disassembly, and reconfiguration. Here we introduce a class of semiconductor microparticles that can be comprehensively designed (in size, shape, electric polarizability, and patterned coatings) using standard microfabrication tools. These custom silicon particles draw energy from external electric fields to actively propel, while interacting hydrodynamically, and sequentially assemble and disassemble on demand. We show that a number of electrokinetic effects, such as dielectrophoresis, induced charge electrophoresis, and diode propulsion, can selectively power the microparticle motions and interactions. The ability to achieve on-demand locomotion, tractable fluid flows, synchronized motility, and reversible assembly using engineered silicon microparticles may enable advanced applications that include remotely powered microsensors, artificial muscles, reconfigurable neural networks and computational systems.

Nicotine–magnesium aluminum silicate microparticle surface modified with chitosan for mucosal delivery

Energy Technology Data Exchange (ETDEWEB)

Kanjanakawinkul, Watchara [Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002 (Thailand); Rades, Thomas [School of Pharmacy, University of Otago, Dunedin 9054 (New Zealand); Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen (Denmark); Puttipipatkhachorn, Satit [Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400 (Thailand); Pongjanyakul, Thaned, E-mail: thaned@kku.ac.th [Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002 (Thailand)

2013-04-01

Magnesium aluminum silicate (MAS), a negatively charged clay, and nicotine (NCT), a basic drug, can interact electrostatically to form microparticles. Chitosan (CS) was used for the surface modification of the microparticles, and a lyophilization method was used to preserve the original particle morphology. The microparticles were characterized in terms of their physicochemical properties, NCT content, mucoadhesive properties, and release and permeation across porcine esophageal mucosa. The results showed that the microparticles formed via electrostatic interaction between MAS and protonated NCT had an irregular shape and that their NCT content increased with increasing NCT ratios in the microparticle preparation solution. High molecular weight CS (800 kDa) adsorbed to the microparticle surface and induced a positive surface charge. CS molecules intercalated into the MAS silicate layers and decreased the crystallinity of the microparticles, leading to an increase in the release rate and diffusion coefficient of NCT from the microparticles. Moreover, the microparticle surface modified with CS was found to have higher NCT permeation fluxes and mucoadhesive properties, which indicated the significant role of CS for NCT mucosal delivery. However, the enhancement of NCT permeation and of mucoadhesive properties depended on the molecular weight and concentration of CS. These findings suggest that NCT-MAS microparticle surface modified with CS represents a promising mucosal delivery system for NCT. Highlights: ► Nicotine–magnesium aluminum silicate microparticles were prepared using electrostatic interaction. ► Lyophilization was used for drying and maintaining an original morphology of the microparticles. ► Chitosan (CS) was used for surface modification of the microparticles at acidic pH. ► Surface modification using CS caused an increase in release and permeation of nicotine. ► Microparticle surface-modified with CS presented better mucoadhesive properties.

Nicotine–magnesium aluminum silicate microparticle surface modified with chitosan for mucosal delivery

International Nuclear Information System (INIS)

Kanjanakawinkul, Watchara; Rades, Thomas; Puttipipatkhachorn, Satit; Pongjanyakul, Thaned

2013-01-01

Magnesium aluminum silicate (MAS), a negatively charged clay, and nicotine (NCT), a basic drug, can interact electrostatically to form microparticles. Chitosan (CS) was used for the surface modification of the microparticles, and a lyophilization method was used to preserve the original particle morphology. The microparticles were characterized in terms of their physicochemical properties, NCT content, mucoadhesive properties, and release and permeation across porcine esophageal mucosa. The results showed that the microparticles formed via electrostatic interaction between MAS and protonated NCT had an irregular shape and that their NCT content increased with increasing NCT ratios in the microparticle preparation solution. High molecular weight CS (800 kDa) adsorbed to the microparticle surface and induced a positive surface charge. CS molecules intercalated into the MAS silicate layers and decreased the crystallinity of the microparticles, leading to an increase in the release rate and diffusion coefficient of NCT from the microparticles. Moreover, the microparticle surface modified with CS was found to have higher NCT permeation fluxes and mucoadhesive properties, which indicated the significant role of CS for NCT mucosal delivery. However, the enhancement of NCT permeation and of mucoadhesive properties depended on the molecular weight and concentration of CS. These findings suggest that NCT-MAS microparticle surface modified with CS represents a promising mucosal delivery system for NCT. Highlights: ► Nicotine–magnesium aluminum silicate microparticles were prepared using electrostatic interaction. ► Lyophilization was used for drying and maintaining an original morphology of the microparticles. ► Chitosan (CS) was used for surface modification of the microparticles at acidic pH. ► Surface modification using CS caused an increase in release and permeation of nicotine. ► Microparticle surface-modified with CS presented better mucoadhesive properties

Preparation and characterisation of ethylcellulose microparticles containing propolis

Directory of Open Access Journals (Sweden)

G. B. AVANçO

2009-02-01

Full Text Available

Ethylcellulose microparticles containing propolis ethanolic extract (PE were prepared by the emulsification and solvent evaporation method. Three ratios of ethylcellulose to PE dry residue value (DR were tested (1:0.25, 1:4 and 1:10. Moreover, polysorbate 80 was used as emulsifier in the external phase (1.0 or 1.5% w/w. Regular particle morphology without amorphous and/or sticking characteristics was achieved only when an ethylcellulose:DR ratio of 1:0.25 and 1.0% polysorbate 80 were used. Microparticles had a mean diameter of 85.83 µm. The entrapment efficiency for propolis of the microparticles was 62.99 ± 0.52%. These ethylcellulose microparticles containing propolis would be useful for developing propolis aqueous dosage forms without the strong and unpleasant taste, aromatic odour and high ethanol concentration of PE. Keywords: Brazilian propolis; ethylcellulose; emulsification and solvent evaporation; microparticle characterisation; optimisation.

IGF-1 release kinetics from chitosan microparticles fabricated using environmentally benign conditions

Energy Technology Data Exchange (ETDEWEB)

Mantripragada, Venkata P. [Biomedical Engineering Program, The University of Toledo, Toledo, OH 43614-5807 (United States); Jayasuriya, Ambalangodage C., E-mail: a.jayasuriya@utoledo.edu [Biomedical Engineering Program, The University of Toledo, Toledo, OH 43614-5807 (United States); Department of Orthopaedic Surgery, The University of Toledo, Toledo, OH 43614-5807 (United States)

2014-09-01

The main objective of this study is to maximize growth factor encapsulation efficiency into microparticles. The novelty of this study is to maximize the encapsulated growth factors into microparticles by minimizing the use of organic solvents and using relatively low temperatures. The microparticles were fabricated using chitosan biopolymer as a base polymer and cross-linked with tripolyphosphate (TPP). Insulin like-growth factor-1 (IGF-1) was encapsulated into microparticles to study release kinetics and bioactivity. In order to authenticate the harms of using organic solvents like hexane and acetone during microparticle preparation, IGF-1 encapsulated microparticles prepared by the emulsification and coacervation methods were compared. The microparticles fabricated by emulsification method have shown a significant decrease (p < 0.05) in IGF-1 encapsulation efficiency, and cumulative release during the two-week period. The biocompatibility of chitosan microparticles and the bioactivity of the released IGF-1 were determined in vitro by live/dead viability assay. The mineralization data observed with von Kossa assay, was supported by mRNA expression levels of osterix and runx2, which are transcription factors necessary for osteoblasts differentiation. Real time RT-PCR data showed an increased expression of runx2 and a decreased expression of osterix over time, indicating differentiating osteoblasts. Chitosan microparticles prepared in optimum environmental conditions are a promising controlled delivery system for cells to attach, proliferate, differentiate and mineralize, thereby acting as a suitable bone repairing material. - Highlights: • Coacervation chitosan microparticles were biocompatible and biodegradable. • IGF-1 encapsulation efficiency increased with coacervation chitosan microparticles. • Coacervation chitosan microparticles support osteoblast attachment and differentiation. • Coacervation chitosan microparticles support osteoblast mineralization.

IGF-1 release kinetics from chitosan microparticles fabricated using environmentally benign conditions

International Nuclear Information System (INIS)

Mantripragada, Venkata P.; Jayasuriya, Ambalangodage C.

2014-01-01

The main objective of this study is to maximize growth factor encapsulation efficiency into microparticles. The novelty of this study is to maximize the encapsulated growth factors into microparticles by minimizing the use of organic solvents and using relatively low temperatures. The microparticles were fabricated using chitosan biopolymer as a base polymer and cross-linked with tripolyphosphate (TPP). Insulin like-growth factor-1 (IGF-1) was encapsulated into microparticles to study release kinetics and bioactivity. In order to authenticate the harms of using organic solvents like hexane and acetone during microparticle preparation, IGF-1 encapsulated microparticles prepared by the emulsification and coacervation methods were compared. The microparticles fabricated by emulsification method have shown a significant decrease (p < 0.05) in IGF-1 encapsulation efficiency, and cumulative release during the two-week period. The biocompatibility of chitosan microparticles and the bioactivity of the released IGF-1 were determined in vitro by live/dead viability assay. The mineralization data observed with von Kossa assay, was supported by mRNA expression levels of osterix and runx2, which are transcription factors necessary for osteoblasts differentiation. Real time RT-PCR data showed an increased expression of runx2 and a decreased expression of osterix over time, indicating differentiating osteoblasts. Chitosan microparticles prepared in optimum environmental conditions are a promising controlled delivery system for cells to attach, proliferate, differentiate and mineralize, thereby acting as a suitable bone repairing material. - Highlights: • Coacervation chitosan microparticles were biocompatible and biodegradable. • IGF-1 encapsulation efficiency increased with coacervation chitosan microparticles. • Coacervation chitosan microparticles support osteoblast attachment and differentiation. • Coacervation chitosan microparticles support osteoblast mineralization

Plasma Distribution in Mercury's Magnetosphere Derived from MESSENGER Magnetometer and Fast Imaging Plasma Spectrometer Observations

Science.gov (United States)

Korth, Haje; Anderson, Brian J.; Gershman, Daniel J.; Raines, Jim M.; Slavin, James A.; Zurbuchen, Thomas H.; Solomon, Sean C.; McNutt, Ralph L.

2014-01-01

We assess the statistical spatial distribution of plasma in Mercury's magnetosphere from observations of magnetic pressure deficits and plasma characteristics by the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft. The statistical distributions of proton flux and pressure were derived from 10months of Fast Imaging Plasma Spectrometer (FIPS) observations obtained during the orbital phase of the MESSENGER mission. The Magnetometer-derived pressure distributions compare favorably with those deduced from the FIPS observations at locations where depressions in the magnetic field associated with the presence of enhanced plasma pressures are discernible in the Magnetometer data. The magnitudes of the magnetic pressure deficit and the plasma pressure agree on average, although the two measures of plasma pressure may deviate for individual events by as much as a factor of approximately 3. The FIPS distributions provide better statistics in regions where the plasma is more tenuous and reveal an enhanced plasma population near the magnetopause flanks resulting from direct entry of magnetosheath plasma into the low-latitude boundary layer of the magnetosphere. The plasma observations also exhibit a pronounced north-south asymmetry on the nightside, with markedly lower fluxes at low altitudes in the northern hemisphere than at higher altitudes in the south on the same field line. This asymmetry is consistent with particle loss to the southern hemisphere surface during bounce motion in Mercury's offset dipole magnetic field.

Antifungal Effect of a Dental Tissue Conditioner Containing Nystatin-Loaded Alginate Microparticles.

Science.gov (United States)

Kim, Hyun-Jin; Son, Jun Sik; Kwon, Tae-Yub

2018-02-01

In this in vitro study, nystatin-alginate microparticles were successfully fabricated to control the release of nystatin from a commercial dental tissue conditioner. These nystatin-alginate microparticles were spherical and had a slightly rough surface. The microparticles incorporated into the tissue conditioner were distributed homogeneously throughout the tissue conditioner matrix. The incorporation of the microparticles did not deteriorate the mechanical properties of the original material. The agar diffusion test results showed that the tissue conditioner containing the microparticles had a good antifungal effect against Candida albicans. The nystatin-alginate microparticles efficiently controlled the release of nystatin from the tissue conditioner matrix over the experimental period of 14 days. Moreover, the nystatin-alginate microparticles incorporated in the tissue conditioner showed effective antifungal function even at lower concentrations of nystatin. The current study suggests that the tissue conditioner containing the nystatin-alginate microparticle carrier system has potential as an effective antifungal material.

Development of Alginate/Chitosan Microparticles for Dust Mite ...

African Journals Online (AJOL)

Erah

surface of chitosan microparticles [4]. .... The reverse-phase high performance liquid .... The surface charge of alginate ... negative charge was as a result of the alginate on the microparticle surface. ... electrostatic interaction of the positively-.

In vitro release kinetics of Tolmetin from tabletted Eudragit microparticles.

Science.gov (United States)

Pignatello, R; Consoli, P; Puglisi, G

2000-01-01

In a previous paper the preparation has been described, by three different techniques, of microparticles made of Eudragit RS 100 and RL 100 containing a NSAI agent, Tolmetin. Freely flowing microparticles failed to affect significantly the in vitro drug release, which displayed a similar dissolution profile after micro-encapsulation to the free drug powder. Microparticles were then converted into tablets and the effect of compression on drug delivery, as well as that of the presence of co-additives, was studied in the present work. Furthermore, microparticles were also prepared by adding MgO to the polymer matrix, to reduce the sensitivity of the drug to pH changes during its dissolution. Similarly, magnesium stearate was also used for microparticle formation as a droplet stabilizer, in order to reduce particle size and hinder rapid drug release. A mathematical evaluation, by using two semi-empirical equations, was applied to evaluate the influence of dissolution and diffusion phenomena upon drug release from microparticle tablets.

Evaluating conditions for the formation of chitosan/gelatin microparticles

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Marcia C. Silva

2009-06-01

Full Text Available Chitosan/gelatin microparticles were prepared by complex coacervation. Three chitosan (CH samples, with different acetylation degrees and intrinsic viscosities, were used together with commercial gelatin (G samples. Microparticles formation was investigated at various CH/G ratios, within the pH range of 3.5 to 6.0. Reactions were carried out at 40 and 60 ºC, for 2, 4, and 6 hours. Turbidity measurements performed at 633 nm were used to monitor the process. The resulting curves revealed maximum values, which were correlated to the glucosamine content of CH samples. After isolation, yields were determined, and the microparticles were characterized by infrared spectroscopy (FTIR and thermogravimetry (TGA. Both techniques evidenced the formation of coacervate microparticles. The highest yields in microparticles were determined for the system comprising the CH sample with the lowest degree of acetylation and intrinsic viscosity, and the gelatin sample with the lowest bloom strength.

SU-8 micropatterning for microfluidic droplet and microparticle focusing

International Nuclear Information System (INIS)

Debuisson, Damien; Senez, Vincent; Arscott, Steve

2011-01-01

We demonstrate micropatterned surfaces consisting of concentric circles and spirals which can focus an evaporating sessile droplet to a specific location on a surface. We also study the micropattern geometry to focus microparticles contained within the droplet. The micropatterned surfaces are fabricated using the photoresist SU-8. Our process enables the modification of the surface wetting via the formation of smooth trench-like defects in the SU-8 which define the micropatterns; the geometry of these micropatterns determines the droplet/microparticle focusing. It is clearly shown that the introduction of small gaps into the micropatterns promotes microparticle centring due to the modification of the depinning angle of the droplet. We also show that the use of spiral micropatterns promotes microparticle centring. Finally, microparticle focusing can be enhanced by modification of surface wetting via the addition of a thin fluorocarbon hydrophobic layer onto the SU-8

Vitamin B12 and iron in the plasma of hamster infected with the intestinal parasite Prohemistomum vivax

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Nemat M. El-Kewaisny

2012-03-01

The results showed no significant change in the level of vitamin B12, whereas, a significant decrease was observed in the level of iron (P < 0.01 in the plasma of the infected animals compared with the control group. This result suggested that a malabsorption condition occurred probably due to complex interactions between host and the used parasite (trematode.

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters.

Science.gov (United States)

György, Bence; Módos, Károly; Pállinger, Eva; Pálóczi, Krisztina; Pásztói, Mária; Misják, Petra; Deli, Mária A; Sipos, Aron; Szalai, Anikó; Voszka, István; Polgár, Anna; Tóth, Kálmán; Csete, Mária; Nagy, György; Gay, Steffen; Falus, András; Kittel, Agnes; Buzás, Edit I

2011-01-27

Numerous diseases, recently reported to associate with elevated microvesicle/microparticle (MP) counts, have also long been known to be characterized by accelerated immune complex (IC) formation. The goal of this study was to investigate the potential overlap between parameters of protein complexes (eg, ICs or avidin-biotin complexes) and MPs, which might perturb detection and/or isolation of MPs. In this work, after comprehensive characterization of MPs by electron microscopy, atomic force microscopy, dynamic light-scattering analysis, and flow cytometry, for the first time, we drive attention to the fact that protein complexes, especially insoluble ICs, overlap in biophysical properties (size, light scattering, and sedimentation) with MPs. This, in turn, affects MP quantification by flow cytometry and purification by differential centrifugation, especially in diseases in which IC formation is common, including not only autoimmune diseases, but also hematologic disorders, infections, and cancer. These data may necessitate reevaluation of certain published data on patient-derived MPs and contribute to correct the clinical laboratory assessment of the presence and biologic functions of MPs in health and disease.

Strategy for the hemocompatibility testing of microparticles.

Science.gov (United States)

Braune, S; Basu, S; Kratz, K; Johansson, J Bäckemo; Reinthaler, M; Lendlein, A; Jung, F

2016-01-01

Polymer-based microparticles are applied as non-thrombogenic or thrombogenic materials in a wide variety of intra- or extra-corporeal medical devices. As demanded by the regulatory agencies, the hemocompatibility of these blood contacting biomaterials has to be evaluated in vitro to ensure that the particle systems appropriately fulfill the envisioned function without causing undesired events such as thrombosis or inflammation. Currently described in vitro assays for hemocompatibility testing of particles comprise tests with different single cell types (e.g. erythrocytes or leukocytes), varying concentrations/dilutions of the used blood cells or whole blood, which are not standardized.Here, we report about an in vitro dynamic test system for studying the hemocompatibility of polymeric microparticles utilizing fresh human whole blood from apparently healthy subjects, collected and processed under standardized conditions. Spherical poly(ether imide) microparticles with an average diameter of 140±30 μm were utilized as model systems. Reported as candidate materials for the removal of uremic toxins, these microparticles are anticipated to facilitate optimal flow conditions in a dialyzer with minimal backflow and blood cell damage. Pristine (PEI) and potassium hydroxide (PEI-KOH) functionalized microparticles exhibited similarly nanoporous surfaces (PEI: ØExternal pore = 90±60 nm; PEI-KOH ØExternal pore = 150±130 nm) but varying water wettabilities (PEI: θadv = 112±10° PEI-KOH θadv = 60±2°). The nanoporosity of the microparticle surfaces allows the exchange of toxic solutes from blood towards the interconnective pores in the particle core, while an immigration of the substantially larger blood cells is inhibited.Sterilized PEI microparticles were incorporated -air-free -in a syringe-based test system and exposed to whole blood for 60 minutes under gentle agitation. Thereafter, thrombi formation on the particles surfaces were analyzed

Evaluating tamsulosin hydrochloride-released microparticles prepared using single-step matrix coating.

Science.gov (United States)

Maeda, Atsushi; Shinoda, Tatsuki; Ito, Naoki; Baba, Keizo; Oku, Naoto; Mizumoto, Takao

2011-04-15

The objective of the present study was to determine the optimum composition for sustained-release of tamsulosin hydrochloride from microparticles intended for orally disintegrating tablets. Microparticles were prepared from an aqueous ethylcellulose dispersion (Aquacoa®), and an aqueous copolymer based on ethyl acrylate and methyl methacrylate dispersion (Eudragit®) NE30D), with microcrystalline cellulose as core particles with a fluidized bed coating process. Prepared microparticles were about 200 μm diameter and spherical. The microparticles were evaluated for in vitro drug release and in vivo absorption to assess bioequivalence in a commercial product, Harnal® pellets. The optimum ratio of Aquacoat® and Eudragit® NE30D in the matrix was 9:1. We observed similar drug release profiles in microparticles and Harnal® pellets. Higuchi model analysis of the in vitro drug release from microparticles was linear up to 80% release, typical of Fickian diffusion sustained-release profile. The in vivo absorption properties from microparticles were comparable to Harnal® pellets, and there was a linear relationship between in vitro drug release and in vivo drug release. In conclusion, this development produces microparticles in single-step coating, that provided a sustained-release of tamsulosin hydrochloride comparable to Harnal® pellets. Copyright © 2011 Elsevier B.V. All rights reserved.

Method validation for preparing serum and plasma samples from human blood for downstream proteomic, metabolomic, and circulating nucleic acid-based applications.

Science.gov (United States)

Ammerlaan, Wim; Trezzi, Jean-Pierre; Lescuyer, Pierre; Mathay, Conny; Hiller, Karsten; Betsou, Fay

2014-08-01

Formal method validation for biospecimen processing in the context of accreditation in laboratories and biobanks is lacking. Serum and plasma processing protocols were validated for fitness-for-purpose in terms of key downstream endpoints, and this article demonstrates methodology for biospecimen processing method validation. Serum and plasma preparation from human blood was optimized for centrifugation conditions with respect to microparticle counts. Optimal protocols were validated for methodology and reproducibility in terms of acceptance criteria based on microparticle counts, DNA and hemoglobin concentration, and metabolomic and proteomic profiles. These parameters were also used to evaluate robustness for centrifugation temperature (4°C versus room temperature [RT]), deceleration (low, medium, high) and blood stability (after a 2-hour delay). Optimal protocols were 10-min centrifugation for serum and 20-min for plasma at 2000 g, medium brake, RT. Methodology and reproducibility acceptance criteria were met for both protocols except for reproducibility of plasma metabolomics. Overall, neither protocol was robust for centrifugation at 4°C versus RT. RT gave higher microparticles and free DNA yields in serum, and fewer microparticles with less hemolysis in plasma. Overall, both protocols were robust for fast, medium, and low deceleration, with a medium brake considered optimal. Pre-centrifugation stability after a 2-hour delay was seen at both temperatures for hemoglobin concentration and proteomics, but not for microparticle counts. We validated serum and plasma collection methods suitable for downstream protein, metabolite, or free nucleic acid-based applications. Temperature and pre-centrifugation delay can influence analytic results, and laboratories and biobanks should systematically record these conditions in the scope of accreditation.

Graft Product for Autologous Peripheral Blood Stem Cell Transplantation Enhances Thrombin Generation and Expresses Procoagulant Microparticles and Tissue Factor.

Science.gov (United States)

Sidibe, Fatoumata; Spanoudaki, Anastasia; Vanneaux, Valerie; Mbemba, Elisabeth; Larghero, Jerome; Van Dreden, Patrick; Lotz, Jean-Pierre; Elalamy, Ismail; Larsen, Annette K; Gerotziafas, Grigoris T

2018-05-01

The beneficial effect of autologous peripheral blood stem cell transplantation (APBSCT) may be compromised by acute vascular complications related to hypercoagulability. We studied the impact of graft product on thrombin generation of normal plasma and the expression of tissue factor (TF) and procoagulant platelet-derived procoagulant microparticles (Pd-MPs) in samples of graft products. Graft products from 10 patients eligible for APBSCT were mixed with platelet-poor plasma (PPP) or platelet-rich plasma (PRP) from healthy volunteers and assessed for in vitro thrombin generation. In control experiments, thrombin generation was assessed in (1) PPP and PRP without any exogenous TF and/or procoagulant phospholipids, (2) PPP with the addition of TF (5 pM) and procoagulant phospholipids (4 μM), (3) in PRP with the addition of TF (5 pM). Graft products were assessed with Western blot assay for TF expression, with a specific clotting assay for TF activity and with flow cytometry assay for Pd-MPs. The graft product enhanced thrombin generation and its procoagulant activity was related to the presence of Pd-MPs and TF. The concentration of Pd-MPs in the graft product was characterized by a significant interindividual variability. The present study reveals the need for a thorough quality control of the graft products regarding their procoagulant potential.

Regulation of the Incorporation of Tissue Factor into Microparticles by Serine Phosphorylation of the Cytoplasmic Domain of Tissue Factor*

Science.gov (United States)

Collier, Mary E. W.; Ettelaie, Camille

2011-01-01

The mechanisms that regulate the incorporation and release of tissue factors (TFs) into cell-derived microparticles are as yet unidentified. In this study, we have explored the regulation of TF release into microparticles by the phosphorylation of serine residues within the cytoplasmic domain of TF. Wild-type and mutant forms of TF, containing alanine and aspartate substitutions at Ser253 and Ser258, were overexpressed in coronary artery and dermal microvascular endothelial cells and microparticle release stimulated with PAR2 agonist peptide (PAR2-AP). The release of TF antigen and activity was then monitored. In addition, the phosphorylation state of the two serine residues within the released microparticles and the cells was monitored for 150 min. The release of wild-type TF as procoagulant microparticles peaked at 90 min and declined thereafter in both cell types. The TF within these microparticles was phosphorylated at Ser253 but not at Ser258. Aspartate substitution of Ser253 resulted in rapid release of TF antigen but not activity, whereas TF release was reduced and delayed by alanine substitution of Ser253 or aspartate substitution of Ser258. Alanine substitution of Ser258 prolonged the release of TF following PAR2-AP activation. The release of TF was concurrent with phosphorylation of Ser253 and was followed by dephosphorylation at 120 min and phosphorylation of Ser258. We propose a sequential mechanism in which the phosphorylation of Ser253 through PAR2 activation results in the incorporation of TF into microparticles, simultaneously inducing Ser258 phosphorylation. Phosphorylation of Ser258 in turn promotes the dephosphorylation of Ser253 and suppresses the release of TF. PMID:21310953

Corrosive and cytotoxic properties of compact specimens and microparticles of Ni-Cr dental alloy.

Science.gov (United States)

Ristic, Ljubisa; Vucevic, Dragana; Radovic, Ljubica; Djordjevic, Snezana; Nikacevic, Milutin; Colic, Miodrag

2014-04-01

Nickel-chromium (Ni-Cr) dental alloys have been widely used in prosthodontic practice, but there is a permanent concern about their biocompatibility due to the release of metal ions. This is especially important when Ni-Cr metal microparticles are incorporated into gingival tissue during prosthodontic procedures. Therefore, the aim of this study was to examine and compare the corrosion and cytotoxic properties of compact specimens and microparticles of Ni-Cr dental alloy. Ni-Cr alloy, Remanium CSe bars (4 mm diameter), were made by the standard casting method and then cut into 0.5-mm-thick disks. Metal particles were obtained by scraping the bars using a diamond instrument for crown preparation. The microstructure was observed by an optical microscope. Quantitative determination and morphological and dimensional characterization of metal particles were carried out by a scanning electron microscope and Leica Application Suite software for image analysis. Corrosion was studied by conditioning the alloy specimens in the RPMI 1640 medium, containing 10% fetal calf serum in an incubator with 5% CO2 for 72 hours at 37°C. Inductively coupled plasma-optical emission spectrometry was used to assess metal ion release. The cytotoxity of conditioning medium (CM) was investigated on L929 cells using an MTT test. One-way ANOVA was used for statistical analysis. After casting, the microstructure of the Remanium CSe compact specimen composed of Ni, Cr, Mo, Si, Fe, Al, and Co had a typical dendritic structure. Alloy microparticles had an irregular shape with a wide size range: from less than 1 μm to more than 100 μm. The release of metal ions, especially Ni and Mo from microparticles, was significantly higher, compared to the compact alloy specimen. The CM prepared from compact alloy was not cytotoxic at any tested dilutions, whereas CM from alloy microparticles showed dose-dependent cytotoxicity (90% CM and 45% CM versus control; p alloy. This could affect health on long

Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.

Science.gov (United States)

Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia

2014-10-15

Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system. Copyright © 2014 Elsevier B.V. All rights reserved.

Blood parasites, total plasma protein and packed cell volume of small wild mammals trapped in three mountain ranges of the Atlantic Forest in Southeastern Brazil

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MAML. Silva

Full Text Available A study of blood parasites in small wild non-flying mammals was undertaken in three areas of the Atlantic Forest in Southeastern Brazil: Serra de Itatiaia, RJ, Serra da Bocaina, SP and Serra da Fartura, SP, from June 1999 to May 2001. A total of 450 animals (15 species were captured in traps and it was observed in 15.5% of the blood smears the presence of Haemobartonella sp. and Babesia sp. in red blood cells. There was no statistically significant difference between parasited and non-parasited specimens regarding total plasma protein, packed cell volume and body weight, which strongly suggests that these specimens might be parasite reservoirs.

Magnetic filtered plasma deposition and implantation technique

CERN Document Server

Zhang Hui Xing; Wu Xian Ying

2002-01-01

A high dense metal plasma can be produced by using cathodic vacuum arc discharge technique. The microparticles emitted from the cathode in the metal plasma can be removed when the metal plasma passes through the magnetic filter. It is a new technique for making high quality, fine and close thin films which have very widespread applications. The authors describe the applications of cathodic vacuum arc technique, and then a filtered plasma deposition and ion implantation system as well as its applications

Myeloid-derived suppressor cell functionality and interaction with Leishmania major parasites differ in C57BL/6 and BALB/c mice.

Science.gov (United States)

Schmid, Maximilian; Zimara, Nicole; Wege, Anja Kathrin; Ritter, Uwe

2014-11-01

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of CD11b+ cells. According to the surface molecules Ly6G and Ly6C (where Ly6G and Ly6C are lymphocyte antigen 6, locus G and C, respectively), MDSCs are further divided into monocytic (Mo-MDSCs, CD11b+ /Ly6C(high) /Ly6G-) and polymorphonucleated suppressor cells (PMN-MDSCs, CD11b+ /Ly6C(int) /Ly6G+). Most published manuscripts focus on the suppressive role of MDSCs in cancer, whereas their impact on adaptive immunity against obligatory intracellular parasites is not well understood. Furthermore, it is not clear how the genetic background of mice influences MDSC functionality. Therefore, we implemented an experimental model of leishmaniasis, and analyzed MDSC maturation and the impact of MDSCs on the parasite-specific T-cell responses in resistant C57BL/6 and susceptible BALB/c mice. This experimental setup demonstrated the impaired ability of BALB/c mice to produce Mo-MDSCs when compared with C57BL/6 mice. This phenotype is detectable after subcutaneous infection with parasites and is specifically represented by a reduced accumulation of Mo-MDSCs at the site of infection in BALB/c mice. Moreover, infected C57BL/6-derived MDSCs were able to suppress Leishmania-specific CD4+ -cell proliferation, whereas BALB/c-derived MDSCs harboring parasites lost this suppressive function. In conclusion, we demonstrate that (i) genetic background defines MDSC differentiation; and (ii) Leishmania major parasites are able to modulate the suppressive effect of MDSCs in a strain-dependent manner. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Liposomes self-assembled from electrosprayed composite microparticles

International Nuclear Information System (INIS)

Yu Dengguang; Yang Junhe; Wang Xia; Tian Feng

2012-01-01

Composite microparticles, consisting of polyvinylpyrrolidone (PVP), naproxen (NAP) and lecithin (PC), have been successfully prepared using an electrospraying process and exploited as templates to manipulate molecular self-assembly for the synthesis of liposomes in situ. Field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM) observations demonstrate that the microparticles have an average diameter of 960 ± 140 nm and a homogeneous structure. X-ray diffraction (XRD) patterns, differential scanning calorimetry (DSC) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) results verify that the building blocks NAP and PC are scattered in the polymer matrix in a molecular way owing to the very fast drying of the electrospraying process and the favorable secondary interactions among the components. FESEM, scanning probe microscope (SPM) and TEM observations demonstrate that the liposomes can be achieved through molecular self-assembly in situ when the microparticles contact water thanks to ‘like prefers like’ and by means of the confinement effect of the microparticles. The liposomes have an encapsulation rate of 91.3%, and 80.7% of the drug in the liposomes can be freed into the dissolution medium in a sustained way and by a diffusion mechanism over a period of 24 h. The developed strategy not only provides a new, facile, and effective method to assemble and organize molecules of multiple components into liposomes with electrosprayed microparticles as templates, but also opens a new avenue for nanofabrication in a step-by-step and controllable way. (paper)

Influence of microparticle size on cavitation noise during ultrasonic vibration

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H. Ge

2015-09-01

Full Text Available The cavitation noise in the ultrasonic vibration system was found to be influenced by the size of microparticles added in water. The SiO2 microparticles with the diameter smaller than 100 μm reduced the cavitation noise, and the reason was attributed to the constrained oscillation of the cavitation bubbles, which were stabilized by the microparticles.

Peritoneum from Trypanosoma cruzi-infected mice is a homing site of Syndecan-1 neg plasma cells which mainly provide non-parasite-specific antibodies.

Science.gov (United States)

Merino, Maria C; Montes, Carolina L; Acosta-Rodriguez, Eva V; Bermejo, Daniela A; Amezcua-Vesely, Maria C; Gruppi, Adriana

2010-05-01

Humoral immunity during experimental Chagas disease has been considered a double-edge sword, critical to control Trypanosoma cruzi spreading but also associated to tissue damage. Peritoneal B-1 cells have been linked to the pathogenesis of Chagas disease; however, they may also help to control the infection by providing a fast wave of antibodies. In the present work, we determined that peritoneal B-cell response to T. cruzi is characterized by a marked reduction of CD19(+) B cells due to plasma cell differentiation rather than to cell death. Both peritoneal B-2 and B-1 cells decrease after parasite infection, but with different kinetics. Thus, the reduction in B-2 cell number can be detected from day 4 postinfection while the number of B-1 cells decreases only after 15 days of infection. Differentiation of peritoneal B-1 and B-2 cells into IgM-secreting cells was triggered by parasites but not by cytokines produced by peritoneal cells. Electron microscopy studies showed that peritoneum of infected mice lodges plasma cells with typical morphology as well as atypical plasma cells named 'Mott-like cells' containing high number of cytoplasmatic Ig(+) granules. The plasma cells induced during the infection showed a phenotype that may allow their persistence in peritoneum and they may contribute to the high levels of antibodies exhibited at the chronic phase of infection. We also showed that the peritoneal B-cell response is scarcely specific for the invading pathogen and rather constitute an important source of non-parasite-specific IgM and IgG in the infected host.

Functionalized Raspberry-Like Microparticles obtained by Assembly of Nanoparticles during Electrospraying

International Nuclear Information System (INIS)

Cho, Eun Chul; Jeong, Unyong; Hwang, Yoon Kyun

2014-01-01

The present study suggests a novel method to produce raspberry-like microparticles containing diverse functional materials inside. The raspberry-like microparticles were produced from a random assembly of uniformly-sized poly(methyl methacrylate) (PMMA) nanoparticles via electrospraying. The solution containing the PMMA nanoparticles were supplied through the inner nozzle and compressed air was emitted through the outer nozzle. The air supply helped fast evaporation of acetone, so it enabled copious amount of microparticles as dry powder. The microparticles were highly porous both on the surface and interiors, hence various materials with a function of UV-blocking (TiO 2 nanoparticles and methoxyphenyl triazine) or anti-aging (ethyl(4-(2,3-dihydro-1H-indene-5-carboxyamido) benzoate)) were loaded in large amount (17 wt % versus PMMA). The surface and interior structures of the microparticles were dependent on the characteristics of functional materials. The results clearly suggest that the process to prepare the raspberry-like microparticles can be an excellent approach to generate functional microstructures

Interval and continuous exercise regimens suppress neutrophil-derived microparticle formation and neutrophil-promoted thrombin generation under hypoxic stress.

Science.gov (United States)

Chen, Yi-Ching; Ho, Ching-Wen; Tsai, Hsing-Hua; Wang, Jong-Shyan

2015-04-01

Acute hypoxic exposure increases vascular thrombotic risk. The release of procoagulant-rich microparticles from neutrophils accelerates the pathogenesis of inflammatory thrombosis. The present study explicates the manner in which interval and continuous exercise regimens affect neutrophil-derived microparticle (NDMP) formation and neutrophil/NDMP-mediated thrombin generation (TG) under hypoxic condition. A total of 60 sedentary males were randomized to perform either aerobic interval training [AIT; 3-min intervals at 40% and 80% V̇O2max (maximal O2 consumption)] or moderate continuous training (MCT; sustained 60% V̇O2max) for 30 min/day, 5 days/week for 5 weeks, or to a control (CTL) group who did not receive any form of training. At rest and immediately after hypoxic exercise test (HE, 100 W under 12% O2 for 30 min), the NDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. Before the intervention, HE (i) elevated coagulant factor VIII/fibrinogen concentrations and shortened activated partial thromboplastin time (aPTT), (ii) increased total and tissue factor (TF)-rich/phosphatidylserine (PS)-exposed NDMP counts and (iii) enhanced the peak height and rate of TG promoted by neutrophils/NDMPs. Following the 5-week intervention, AIT exhibited higher enhancement of V̇O2max than did MCT. Notably, both MCT and AIT attenuated the extents of HE-induced coagulant factor VIII/fibrinogen elevations and aPTT shortening. Furthermore, the two exercise regimens significantly decreased TF-rich/PS-exposed NDMP formation and depressed neutrophil/NDMP-mediated dynamic TG at rest and following HE. Hence, we conclude that AIT is superior to MCT for enhancing aerobic capacity. Moreover, either AIT or MCT effectively ameliorates neutrophil/NDMP-promoted TG by down-regulating expression of procoagulant factors during HE, which may reduce thrombotic risk evoked by hypoxia. Moreover, either AIT or MCT effectively ameliorates neutrophil

Magnetic tagging of cell-derived microparticles: new prospects for imaging and manipulation of these mediators of biological information.

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Vats, Nidhi; Wilhelm, Claire; Rautou, Pierre-Emmanuel; Poirier-Quinot, Marie; Péchoux, Christine; Devue, Cécile; Boulanger, Chantal M; Gazeau, Florence

2010-07-01

Submicron membrane fragments termed microparticles (MPs), which are released by apoptotic or activated cells, are newly considered as vectors of biological information and actors of pathology development. We propose the tagging of MPs with magnetic nanoparticles as a new approach allowing imaging, manipulation and targeting of cell-derived MPs. MPs generated in vitro from human endothelial cells or isolated from atherosclerotic plaques were labeled using citrate-coated 8 nm iron-oxide nanoparticles. MPs were tagged with magnetic nanoparticles on their surface and detected as Annexin-V positive by flow cytometry. Labeled MPs could be mobilized, isolated and manipulated at a distance in a magnetic field gradient. Magnetic mobility of labeled MPs was quantified by micromagnetophoresis. Interactions of labeled MPs with endothelial cells could be triggered and modulated by magnetic guidance. Nanoparticles served as tracers at different scales: at the subcellular level by electron microscopy, at the cellular level by histology and at the macroscopic level by MRI. Magnetic labeling of biogenic MPs opens new prospects for noninvasive monitoring and distal manipulations of these biological effectors.

Photochemical half-cells using mixture films of fullerene-ethylenediamine adduct microparticles and polythiophene

International Nuclear Information System (INIS)

Akiyama, Tsuyoshi; Oku, Takeo; Matsumura, Satoshi; Matsuoka, Ken-ichi; Yamada, Sunao

2013-01-01

In this study, C 60 fullerene–ethylenediamine adduct microparticles were prepared. Mixture films of these microparticles and polythiophene were fabricated on indium–tin-oxide transparent electrodes by spin-coating. Incorporation of C 60 –ethylenediamine microparticles was verified by scanning electron microscopy (SEM) measurements. The coverage values of these microparticles were approximately 3–17%, which were calculated from SEM images of modified electrodes. Fluorescence spectra of modified electrodes indicated that the emission intensity of polythiophene in these mixture films was apparently quenched by these C 60 –ethylenediamine microparticles as compared with a polythiophene film without these microparticles. In the presence of methylviologen, these modified electrodes generated stable photocurrent. The photoexciting species was polythiophene, which was verified by profiles of photocurrent action spectra. The C 60 –ethylenediamine microparticles substantially enhanced the photocurrent signals generated by the polythiophene-modified electrode.

Bimodal Nanoparticle Size Distributions Produced by Laser Ablation of Microparticles in Aerosols

International Nuclear Information System (INIS)

Nichols, William T.; Malyavanatham, Gokul; Henneke, Dale E.; O'Brien, Daniel T.; Becker, Michael F.; Keto, John W.

2002-01-01

Silver nanoparticles were produced by laser ablation of a continuously flowing aerosol of microparticles in nitrogen at varying laser fluences. Transmission electron micrographs were analyzed to determine the effect of laser fluence on the nanoparticle size distribution. These distributions exhibited bimodality with a large number of particles in a mode at small sizes (3-6-nm) and a second, less populated mode at larger sizes (11-16-nm). Both modes shifted to larger sizes with increasing laser fluence, with the small size mode shifting by 35% and the larger size mode by 25% over a fluence range of 0.3-4.2-J/cm 2 . Size histograms for each mode were found to be well represented by log-normal distributions. The distribution of mass displayed a striking shift from the large to the small size mode with increasing laser fluence. These results are discussed in terms of a model of nanoparticle formation from two distinct laser-solid interactions. Initially, laser vaporization of material from the surface leads to condensation of nanoparticles in the ambient gas. Material evaporation occurs until the plasma breakdown threshold of the microparticles is reached, generating a shock wave that propagates through the remaining material. Rapid condensation of the vapor in the low-pressure region occurs behind the traveling shock wave. Measurement of particle size distributions versus gas pressure in the ablation region, as well as, versus microparticle feedstock size confirmed the assignment of the larger size mode to surface-vaporization and the smaller size mode to shock-formed nanoparticles

Field Effect Microparticle Generation for Cell Microencapsulation.

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Hsu, Brend Ray-Sea; Fu, Shin-Huei

2017-01-01

The diameter and sphericity of alginate-poly-L-lysine-alginate microcapsules, determined by the size and the shape of calcium alginate microspheres, affect their in vivo durability and biocompatibility and the results of transplantation. The commonly used air-jet spray method generates microspheres with a wider variation in diameter, larger sphere morphology, and evenly distributed encapsulated cells. In order to overcome these drawbacks, we designed a field effect microparticle generator to create a stable electric field to prepare microparticles with a smaller diameter and more uniform morphology. Using this electric field microparticle generator the encapsulated cells will be located at the periphery of the microspheres, and thus the supply of oxygen and nutrients for the encapsulated cells will be improved compared with the centrally located encapsulated cells in the air-jet spray method.

Simultaneous capture and sequential detection of two malarial biomarkers on magnetic microparticles.

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Markwalter, Christine F; Ricks, Keersten M; Bitting, Anna L; Mudenda, Lwiindi; Wright, David W

2016-12-01

We have developed a rapid magnetic microparticle-based detection strategy for malarial biomarkers Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein II (PfHRPII). In this assay, magnetic particles functionalized with antibodies specific for pLDH and PfHRPII as well as detection antibodies with distinct enzymes for each biomarker are added to parasitized lysed blood samples. Sandwich complexes for pLDH and PfHRPII form on the surface of the magnetic beads, which are washed and sequentially re-suspended in detection enzyme substrate for each antigen. The developed simultaneous capture and sequential detection (SCSD) assay detects both biomarkers in samples as low as 2.0parasites/µl, an order of magnitude below commercially available ELISA kits, has a total incubation time of 35min, and was found to be reproducible between users over time. This assay provides a simple and efficient alternative to traditional 96-well plate ELISAs, which take 5-8h to complete and are limited to one analyte. Further, the modularity of the magnetic bead-based SCSD ELISA format could serve as a platform for application to other diseases for which multi-biomarker detection is advantageous. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Identification of second harmonic optical effects from vaccine coated gold microparticles

International Nuclear Information System (INIS)

Jumah, N A; Ameer-Beg, S M; White, N S; Prasad, K V R; Bellhouse, B J

2004-01-01

This study investigates the optical effects observed from uncoated and protein vaccine coated gold microparticles while imaging with two-photon excitation in the Mie scattering regime. When observed with time correlated single photon counting fluorescence lifetime microscopy, the emission from the gold microparticles appeared as an intense instrument-limited temporal response. The intensity of the emission showed a second-order dependence on the laser power and frequency doubling of the emitted light was observed for fundamental light between 890 and 970 nm. The optical effect was attributed to two-photon induced second harmonic generation. The vaccine coated gold microparticles had a much weaker second harmonic signal than the uncoated gold microparticles. Chemical analysis of the surface of the gold microparticles revealed that the vaccine coating decreases the surface charge thereby diminishing the observed second harmonic signal. These optical properties can be exploited to identify both the location of the protein vaccine coating as well as the gold microparticles in vitro and potentially to investigate the vaccine delivery kinetics in vivo

Microparticles and exosomes: impact on normal and complicated pregnancy

NARCIS (Netherlands)

Toth, Bettina; Lok, Christianne A. R.; Böing, Anita; Diamant, Michaela; van der Post, Joris A. M.; Friese, Klaus; Nieuwland, Rienk

2007-01-01

Eukaryotic cells release vesicles into their environment by membrane shedding (ectosomes or microparticles) and secretion (exosomes). Microparticles and exosomes occur commonly in vitro and in vivo. The occurrence, composition and function(s) of these vesicles change during disease (progression).

Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

Science.gov (United States)

Selheim, F; Holmsen, H; Vassbotn, F S

1999-08-15

We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

Detection of microparticles from human red blood cells by multiparametric flow cytometry

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Grisendi, Giulia; Finetti, Elena; Manganaro, Daniele; Cordova, Nicoletta; Montagnani, Giuliano; Spano, Carlotta; Prapa, Malvina; Guarneri, Valentina; Otsuru, Satoru; Horwitz, Edwin M.; Mari, Giorgio; Dominici, Massimo

2015-01-01

Background During storage, red blood cells (RBC) undergo chemical and biochemical changes referred to as “storage lesions”. These events determine the loss of RBC integrity, resulting in lysis and release of microparticles. There is growing evidence of the clinical importance of microparticles and their role in blood transfusion-related side effects and pathogen transmission. Flow cytometry is currently one of the most common techniques used to quantify and characterise microparticles. Here we propose multiparametric staining to monitor and quantify the dynamic release of microparticles by stored human RBC. Material and methods RBC units (n=10) were stored under blood bank conditions for up to 42 days. Samples were tested at different time points to detect microparticles and determine the haemolysis rate (HR%). Microparticles were identified by flow cytometry combining carboxyfluorescein diacetate succinimidyl ester (CFSE) dye, annexin V and anti-glycophorin A antibody. Results We demonstrated that CFSE can be successfully used to label closed vesicles with an intact membrane. The combination of CFSE and glycophorin A antibody was effective for monitoring and quantifying the dynamic release of microparticles from RBC during storage. Double staining with CFSE/glycophorin A was a more precise approach, increasing vesicle detection up to 4.7-fold vs the use of glycophorin A/annexin V alone. Moreover, at all the time points tested, we found a robust correlation (R=0.625; p=0.0001) between HR% and number of microparticles detected. Discussion Multiparametric staining, based on a combination of CFSE, glycophorin A antibody and annexin V, was able to detect, characterise and monitor the release of microparticles from RBC units during storage, providing a sensitive approach to labelling and identifying microparticles for transfusion medicine and, more broadly, for cell-based therapies. PMID:25369588

Mechanism-based design of parasite-targeted artemisinin derivatives: synthesis and antimalarial activity of new diamine containing analogues.

Science.gov (United States)

Hindley, Stephen; Ward, Stephen A; Storr, Richard C; Searle, Natalie L; Bray, Patrick G; Park, B Kevin; Davies, Jill; O'Neill, Paul M

2002-02-28

The potent antimalarial activity of chloroquine against chloroquine-sensitive strains can be attributed, in part, to its high accumulation in the acidic environment of the heme-rich parasite food vacuole. A key component of this intraparasitic chloroquine accumulation mechanism is a weak base "ion-trapping" effect whereupon the basic drug is concentrated in the acidic food vacuole in its membrane-impermeable diprotonated form. By the incorporation of amino functionality into target artemisinin analogues, we hoped to prepare a new series of analogues that, by virtue of increased accumulation into the ferrous-rich vacuole, would display enhanced antimalarial potency. The initial part of the project focused on the preparation of piperazine-linked analogues (series 1 (7-16)). Antimalarial evaluation of these derivatives demonstrated potent activity versus both chloroquine-sensitive and chloroquine-resistant parasites. On the basis of these observations, we then set about preparing a series of C-10 carba-linked amino derivatives. Optimization of the key synthetic step using a newly developed coupling protocol provided a key intermediate, allyldeoxoartemisinin (17) in 90% yield. Further elaboration, in three steps, provided nine target C-10 carba analogues (series 2 (21-29)) in good overall yields. Antimalarial assessment demonstrated that these compounds were 4-fold more potent than artemisinin and about twice as active as artemether in vitro versus chloroquine-resistant parasites. On the basis of the products obtained from biomimetic Fe(II) degradation of the C-10 carba analogue (23), we propose that these analogues may have a mode of action subtly different from that of the parent drug artemisinin (series 1 (7-16)) and other C-10 ether derivatives such as artemether. Preliminary in vivo testing by the WHO demonstrated that four of these compounds are active orally at doses of less than 10 mg/kg. Since these analogues are available as water-soluble salts and cannot

Flow rate calibration to determine cell-derived microparticles and homogeneity of blood components.

Science.gov (United States)

Noulsri, Egarit; Lerdwana, Surada; Kittisares, Kulvara; Palasuwan, Attakorn; Palasuwan, Duangdao

2017-08-01

Cell-derived microparticles (MPs) are currently of great interest to screening transfusion donors and blood components. However, the current approach to counting MPs is not affordable for routine laboratory use due to its high cost. The current study aimed to investigate the potential use of flow-rate calibration for counting MPs in whole blood, packed red blood cells (PRBCs), and platelet concentrates (PCs). The accuracy of flow-rate calibration was investigated by comparing the platelet counts of an automated counter and a flow-rate calibrator. The concentration of MPs and their origins in whole blood (n=100), PRBCs (n=100), and PCs (n=92) were determined using a FACSCalibur. The MPs' fold-changes were calculated to assess the homogeneity of the blood components. Comparing the platelet counts conducted by automated counting and flow-rate calibration showed an r 2 of 0.6 (y=0.69x+97,620). The CVs of the within-run and between-run variations of flow-rate calibration were 8.2% and 12.1%, respectively. The Bland-Altman plot showed a mean bias of -31,142platelets/μl. MP enumeration revealed both the difference in MP levels and their origins in whole blood, PRBCs, and PCs. Screening the blood components demonstrated high heterogeneity of the MP levels in PCs when compared to whole blood and PRBCs. The results of the present study suggest the accuracy and precision of flow-rate calibration for enumerating MPs. This flow-rate approach is affordable for assessing the homogeneity of MPs in blood components in routine laboratory practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction.

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Choi, Hoon Young; Lee, Hyun Gyu; Kim, Beom Seok; Ahn, Sun Hee; Jung, Ara; Lee, Mirae; Lee, Jung Eun; Kim, Hyung Jong; Ha, Sung Kyu; Park, Hyeong Cheon

2015-03-11

Microparticles (MPs) derived from kidney-derived mesenchymal stem cells (KMSCs) have recently been reported to ameliorate rarefaction of peritubular capillaries (PTC) in ischemic kidneys via delivery of proangiogenic effectors. This study aimed to investigate whether KMSC-derived MPs show anti-fibrotic effects by ameliorating endothelial-to-mesenchymal transition (EndoMT) in human umbilical vein endothelial cells (HUVEC) in vitro and by preserving PTC in kidneys with unilateral ureteral obstruction (UUO) in vivo. MPs isolated from the supernatants of KMSC were co-cultured with HUVEC to assess their in vitro biologic effects on endothelial cells. Mice were treated with MPs via the tail vein after UUO injury to assess their anti-fibrotic and PTC sparing effects. Renal tubulointerstitial damage and inflammatory cell infiltration were examined with Masson's trichrome, F4/80 and α-smooth muscle actin (α-SMA) staining and PTC rarefaction index was determined by CD31 staining. KMSC-derived MPs significantly ameliorated EndoMT and improved in vitro proliferation of TGF-β1 treated HUVEC. In vivo administration of KMSC-derived MPs significantly inhibited EndoMT of PTC endothelial cells and improved PTC rarefaction in UUO kidneys. Furthermore, administration of KMSC-derived MPs inhibited inflammatory cell infiltration as well as tubulointerstitial fibrosis in UUO mice as demonstrated by decreased F4/80 and α-SMA-positive cells and Masson's trichrome staining, respectively. Our results suggest that KMSC-derived MPs ameliorate PTC rarefaction via inhibition of EndoMT and protect against progression of renal damage by inhibiting tubulointerstitial fibrosis.

Novel hierarchical microparticles super-assembled from nanoparticles with the induction of casein micelles

Energy Technology Data Exchange (ETDEWEB)

Xiong, Xiaopeng, E-mail: xpxiong@xmu.edu.cn; Duan, Jiangjiang; Wang, Yong; Yu, Zhaoju [Xiamen University, Department of Materials Science and Engineering, College of Materials (China)

2013-08-15

We have demonstrated a solution-based synthesis of novel waxberry-like hierarchical ZnO microparticles in the presence casein micelles under mild conditions. The microstructures of the sub-micrometer-sized hierarchical microparticles were characterized, and the synthesis conditions were optimized. The formation mechanism of the hierarchical microparticle was analyzed through control experiments. The hierarchical ZnO microparticles are found to be super-assemblies of 30-70 nm ZnO nanoparticles, which are thought to be based on casein micelle induction followed by Ostwald ripening. In the same manner, copper-based hierarchical microparticles with a similar morphology have also been successfully synthesized. By controlling the synthetic time or temperature, solid or hollow microparticles can be fabricated. The narrowly distributed ZnO microparticles have a high specific surface area, exhibiting great potential application in fields such as photocatalytic and energy conversion. Our findings may meanwhile open a new bottom-up strategy in order to construct structurally sophisticated nanomaterials.

Novel hierarchical microparticles super-assembled from nanoparticles with the induction of casein micelles

Science.gov (United States)

Xiong, Xiaopeng; Duan, Jiangjiang; Wang, Yong; Yu, Zhaoju

2013-08-01

We have demonstrated a solution-based synthesis of novel waxberry-like hierarchical ZnO microparticles in the presence casein micelles under mild conditions. The microstructures of the sub-micrometer-sized hierarchical microparticles were characterized, and the synthesis conditions were optimized. The formation mechanism of the hierarchical microparticle was analyzed through control experiments. The hierarchical ZnO microparticles are found to be super-assemblies of 30-70 nm ZnO nanoparticles, which are thought to be based on casein micelle induction followed by Ostwald ripening. In the same manner, copper-based hierarchical microparticles with a similar morphology have also been successfully synthesized. By controlling the synthetic time or temperature, solid or hollow microparticles can be fabricated. The narrowly distributed ZnO microparticles have a high specific surface area, exhibiting great potential application in fields such as photocatalytic and energy conversion. Our findings may meanwhile open a new bottom-up strategy in order to construct structurally sophisticated nanomaterials.

Novel hierarchical microparticles super-assembled from nanoparticles with the induction of casein micelles

International Nuclear Information System (INIS)

Xiong, Xiaopeng; Duan, Jiangjiang; Wang, Yong; Yu, Zhaoju

2013-01-01

We have demonstrated a solution-based synthesis of novel waxberry-like hierarchical ZnO microparticles in the presence casein micelles under mild conditions. The microstructures of the sub-micrometer-sized hierarchical microparticles were characterized, and the synthesis conditions were optimized. The formation mechanism of the hierarchical microparticle was analyzed through control experiments. The hierarchical ZnO microparticles are found to be super-assemblies of 30–70 nm ZnO nanoparticles, which are thought to be based on casein micelle induction followed by Ostwald ripening. In the same manner, copper-based hierarchical microparticles with a similar morphology have also been successfully synthesized. By controlling the synthetic time or temperature, solid or hollow microparticles can be fabricated. The narrowly distributed ZnO microparticles have a high specific surface area, exhibiting great potential application in fields such as photocatalytic and energy conversion. Our findings may meanwhile open a new bottom-up strategy in order to construct structurally sophisticated nanomaterials

Obtain and characterization of chitosan / propranolol microparticles by spray drying

International Nuclear Information System (INIS)

Nascimento, Ednaldo G. do; Silva Junior, Arnobio A. da; Santos, Katia S.C.R. dos

2015-01-01

The study investigated the application of chitosan microparticles as carriers into hard gelatin capsule containing propranolol, evaluating the variability of the molecular weight and the chitosan particles by spray drying. The formulations were characterized by average weight, dosing unit dose uniformity and dissolution profile according to the pharmacopoeia. While the microparticles were characterized by Fourier transformed infrared spectroscopy, scanning electron microscopy and X-ray diffraction. The results showed that chitosan microparticles obtained without the drug and then physically mixed with propranolol promoted a modified release 85% of the drug after 5 hours. While, chitosan microparticles sprayed with propranolol released only 55% at 5 hours is presented both as a modified release system. Samples of dried chitosan showed up amorphous and homogeneous and spherical morphology. (author)

The value of microparticles in detecting acute rejection episodes after liver transplantation.

Science.gov (United States)

Morgul, Mehmet Haluk; Splith, Katrin; Leonhardt, Christoph; Raschzok, Nathanael; Reutzel-Selke, Anja; Schmuck, Rosa Bianca; Andreou, Andreas; Atanasov, Georgi; Benzing, Christian; Krenzien, Felix; Hau, Hans-Michael; Felgendreff, Philipp; Klunk, Sergej; Pratschke, Johann; Sauer, Igor Maximillian; Schmelzle, Moritz

2018-02-01

Non-invasive markers for diagnosis of acute rejection (AR) following liver transplantation have not been developed, yet. We analyzed the correlation of plasma microparticle levels (MP) with AR. MP (CD4, CD8, CD25, CD31, MHC) of 11 AR patients and 11 controls were analyzed within the first week after transplantation. CD4, CD8 and CD31 positive MP were higher in the AR, whereas overall MP count, CD25 and MHCI positive MP proportions did not differ between both groups. MP dynamics within the first period of transplantation could help to clarify on-going mechanisms of immunomodulation.

Effects of microparticle size and Fc density on macrophage phagocytosis.

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Patricia Pacheco

Full Text Available Controlled induction of phagocytosis in macrophages offers the ability to therapeutically regulate the immune system as well as improve delivery of chemicals or biologicals for immune processing. Maximizing particle uptake by macrophages through Fc receptor-mediated phagocytosis could lead to new delivery mechanisms in drug or vaccine development. Fc ligand density and particle size were examined independently and in combination in order to optimize and tune the phagocytosis of opsonized microparticles. We show the internalization efficiency of small polystyrene particles (0.5 µm to 2 µm is significantly affected by changes in Fc ligand density, while particles greater than 2 µm show little correlation between internalization and Fc density. We found that while macrophages can efficiently phagocytose a large number of smaller particles, the total volume of phagocytosed particles is maximized through the non-specific uptake of larger microparticles. Therefore, larger microparticles may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles can deliver bio-active substances to a greater percentage of the macrophage population. This study is the first to treat as independent variables the physical and biological properties of Fc density and microparticle size that initiate macrophage phagocytosis. Defining the physical and biological parameters that affect phagocytosis efficiency will lead to improved methods of microparticle delivery to macrophages.

Exocrine cell-derived microparticles in response to lipopolysaccharide promote endocrine dysfunction in cystic fibrosis.

Science.gov (United States)

Constantinescu, Andrei Alexandru; Gleizes, Céline; Alhosin, Mahmoud; Yala, Elhassan; Zobairi, Fatiha; Leclercq, Alexandre; Stoian, Gheorghe; Mitrea, Ioan Liviu; Prévost, Gilles; Toti, Florence; Kessler, Laurence

2014-03-01

Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas alteration followed by endocrine dysfunction at a later stage. Microparticles (MPs) are plasma membrane fragments shed from stimulated or damaged cells that act as cellular effectors. Our aim was to identify a new form of interaction between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the context of recurrent infection in CF. MPs from either human exocrine CFTRΔF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1) cells were collected after treatment by LPS from Pseudomonas aeruginosa and applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane integration in target cells was established by confocal microscopy and flow cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin secretion were measured after 18 h. MP-mediated NF-κB activation was measured in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by Western blot. In endocrine normal cells, CFTR inhibition was achieved using Inhibitor-172. Compared to PANC-1, MPs from CFPAC-1 significantly reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF-κB activation by increasing the level of IκB phosphorylation. Moreover, the inhibition of NF-κB activation using specific inhibitors was associated with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN-m5F cells promoted apoptosis and decreased insulin secretion. During recurrent infections associated with CF, exocrine MPs may contribute to endocrine cell dysfunction via NF-κB pathways. Membrane CFTR dysfunction is associated with decreased insulin secretion. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

Quantitative proteome analysis of plasma microparticles for the characterization of HCV-induced hepatic cirrhosis and hepatocellular carcinoma.

Science.gov (United States)

Taleb, Raghda Saad Zaghloul; Moez, Pacint; Younan, Doreen; Eisenacher, Martin; Tenbusch, Matthias; Sitek, Barbara; Bracht, Thilo

2017-12-01

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. Cirrhosis induced by hepatitis-C virus (HCV) infection is the most critical risk factor for HCC. However, the mechanism of HCV-induced carcinogenesis is not fully understood. Plasma microparticles (PMP) contribute to numerous physiological and pathological processes and contain proteins whose composition correlates to the respective pathophysiological conditions. We analyzed PMP from 22 HCV-induced cirrhosis patients, 16 HCV-positive HCC patients with underlying cirrhosis and 18 healthy controls. PMP were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS. We identified 840 protein groups and quantified 507 proteins. 159 proteins were found differentially abundant between the three experimental groups. PMP in both disease entities displayed remarkable differences in the proteome composition compared to healthy controls. Conversely, the proteome difference between both diseases was minimal. GO analysis revealed that PMP isolated from both diseases were significantly enriched in proteins involved in complement activation, while endopeptidase activity was downregulated exclusively in HCC patients. This study reports for the first time a quantitative proteome analysis for PMP from patients with HCV-induced cirrhosis and HCC. Data are available via ProteomeXchange with identifier PXD005777. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microparticles from kidney-derived mesenchymal stem cells act as carriers of proangiogenic signals and contribute to recovery from acute kidney injury.

Directory of Open Access Journals (Sweden)

Hoon Young Choi

Full Text Available We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188, bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.

p38α phosphorylates serine 258 within the cytoplasmic domain of tissue factor and prevents its incorporation into cell-derived microparticles.

Science.gov (United States)

Ettelaie, Camille; Elkeeb, Azza M; Maraveyas, Anthony; Collier, Mary Elizabeth W

2013-03-01

We previously showed that the phosphorylation of Ser253 within the cytoplasmic domain of human tissue factor (TF) initiates the incorporation and release of this protein into cell-derived microparticles. Furthermore, subsequent phosphorylation of Ser258 terminates this process. However, the identity of the kinase responsible for the phosphorylation of Ser258 and mode of action of this enzyme remain unknown. In this study, p38α was identified as the proline-directed kinase capable of phosphorylating Ser258 specifically, and without any detectable activity towards Ser253. Furthermore, using synthetic peptides, it was shown that the Km for the reaction decreased by approximately 10 fold on substitution of Ser253 with phospho-Ser253. Either inhibition of p38 using SB202190 or knockdown of p38α expression in coronary artery endothelial cells overexpressing wild-type TF, resulted in decreased phosphorylation of Ser258, following activation of cells with PAR2-agonist peptide (PAR2-AP). In agreement with our previous data, inhibition of phosphorylation of this residue maintained the release of TF. Activation of PAR2 in cells transfected to overexpress TF, resulted in two separate peaks of p38 activity at approximately 40 and 120 min post-activation. Furthermore, overexpression of Ala253-substituted TF enhanced the second p38 activation peak. However, the second peak was absent in cells devoid of TF or in cells overexpressing the Asp253-substituted TF. Our data clearly identifies p38α as a kinase capable of phosphorylating Ser258 within the cytoplasmic domain of TF. Moreover, it appears that the presence of TF within the cells regulates the late activation of p38 and consequently the termination of TF release into microparticles. Copyright © 2012 Elsevier B.V. All rights reserved.

Monocyte-Derived Signals Activate Human Natural Killer Cells in Response to Leishmania Parasites

Science.gov (United States)

Messlinger, Helena; Sebald, Heidi; Heger, Lukas; Dudziak, Diana; Bogdan, Christian; Schleicher, Ulrike

2018-01-01

Activated natural killer (NK) cells release interferon (IFN)-γ, which is crucial for the control of intracellular pathogens such as Leishmania. In contrast to experimental murine leishmaniasis, the human NK cell response to Leishmania is still poorly characterized. Here, we investigated the interaction of human blood NK cells with promastigotes of different Leishmania species (Leishmania major, Leishmania mexicana, Leishmania infantum, and Leishmania donovani). When peripheral blood mononuclear cells or purified NK cells and monocytes (all derived from healthy blood donors from Germany without a history of leishmaniasis) were exposed to promastigotes, NK cells showed increased surface expression of the activation marker CD69. The extent of this effect varied depending on the Leishmania species; differences between dermotropic and viscerotropic L. infantum strains were not observed. Upregulation of CD69 required direct contact between monocytes and Leishmania and was partly inhibitable by anti-interleukin (IL)-18. Unexpectedly, IL-18 was undetectable in most of the supernatants (SNs) of monocyte/parasite cocultures. Confocal fluorescence microscopy of non-permeabilized cells revealed that Leishmania-infected monocytes trans-presented IL-18 to NK cells. Native, but not heat-treated SNs of monocyte/Leishmania cocultures also induced CD69 on NK cells, indicating the involvement of a soluble heat-labile factor other than IL-18. A role for the NK cell-activating cytokines IL-1β, IL-2, IL-12, IL-15, IL-21, and IFN-α/β was excluded. The increase of CD69 was not paralleled by NK cell IFN-γ production or enhanced cytotoxicity. However, prior exposure of NK cells to Leishmania parasites synergistically increased their IFN-γ release in response to IL-12, which was dependent on endogenous IL-18. CD1c+ dendritic cells were identified as possible source of Leishmania-induced IL-12. Finally, we observed that direct contact between Leishmania and NK cells reduced the

Monocyte-Derived Signals Activate Human Natural Killer Cells in Response to Leishmania Parasites

Directory of Open Access Journals (Sweden)

Helena Messlinger

2018-01-01

Full Text Available Activated natural killer (NK cells release interferon (IFN-γ, which is crucial for the control of intracellular pathogens such as Leishmania. In contrast to experimental murine leishmaniasis, the human NK cell response to Leishmania is still poorly characterized. Here, we investigated the interaction of human blood NK cells with promastigotes of different Leishmania species (Leishmania major, Leishmania mexicana, Leishmania infantum, and Leishmania donovani. When peripheral blood mononuclear cells or purified NK cells and monocytes (all derived from healthy blood donors from Germany without a history of leishmaniasis were exposed to promastigotes, NK cells showed increased surface expression of the activation marker CD69. The extent of this effect varied depending on the Leishmania species; differences between dermotropic and viscerotropic L. infantum strains were not observed. Upregulation of CD69 required direct contact between monocytes and Leishmania and was partly inhibitable by anti-interleukin (IL-18. Unexpectedly, IL-18 was undetectable in most of the supernatants (SNs of monocyte/parasite cocultures. Confocal fluorescence microscopy of non-permeabilized cells revealed that Leishmania-infected monocytes trans-presented IL-18 to NK cells. Native, but not heat-treated SNs of monocyte/Leishmania cocultures also induced CD69 on NK cells, indicating the involvement of a soluble heat-labile factor other than IL-18. A role for the NK cell-activating cytokines IL-1β, IL-2, IL-12, IL-15, IL-21, and IFN-α/β was excluded. The increase of CD69 was not paralleled by NK cell IFN-γ production or enhanced cytotoxicity. However, prior exposure of NK cells to Leishmania parasites synergistically increased their IFN-γ release in response to IL-12, which was dependent on endogenous IL-18. CD1c+ dendritic cells were identified as possible source of Leishmania-induced IL-12. Finally, we observed that direct contact between Leishmania and NK cells

Preparation and evaluation of microparticles from thiolated polymers via air jet milling.

Science.gov (United States)

Hoyer, Herbert; Schlocker, Wolfgang; Krum, Kafedjiiski; Bernkop-Schnürch, Andreas

2008-06-01

Microparticles were formulated by incorporation of the model protein horseradish peroxidase in (thiolated) chitosan and (thiolated) poly(acrylic acid) via co-precipitation. Dried protein/polymer complexes were ground with an air jet mill and resulting particles were evaluated regarding size distribution, shape, zeta potential, drug load, protein activity, release pattern, swelling behaviour and cytotoxicity. The mean particle size distribution was 0.5-12 microm. Non-porous microparticles with a smooth surface were prepared. Microparticles from (thiolated) chitosan had a positive charge whereas microparticles from (thiolated) poly(acrylic acid) were negatively charged. The maximum protein load for microparticles based on chitosan, chitosan-glutathione (Ch-GSH), poly(acrylic acid) (PAA) and for poly(acrylic acid)-glutathione (PAA-GSH) was 7+/-1%, 11+/-2%, 4+/-0.2% and 7+/-2%, respectively. The release profile of all microparticles followed a first order release kinetic. Chitosan (0.5mg), Ch-GSH, PAA and PAA-GSH particles showed a 31.4-, 13.8-, 54.2- and a 42.2-fold increase in weight, respectively. No significant cytotoxicity could be found. Thiolated microparticles prepared by jet milling technique were shown to be stable and to have controlled drug release characteristics. After further optimizations the preparation method described here might be a useful tool for the production of protein loaded drug delivery systems.

Fabrication of chitosan microparticles loaded in chitosan and poly

Indian Academy of Sciences (India)

In recent decades, the use of microparticle-mediated drug delivery is widely applied in the field of biomedicalapplication. Here, we report the new dressing material with ciprofloxacin-loaded chitosan microparticle (CMP) impregnatedin chitosan (CH) and poly(vinyl alcohol) (PVA) scaffold for effective delivery of drug in a ...

Physicochemical characteristics of uranium microparticles collected at nuclear fuel cycle plants

International Nuclear Information System (INIS)

Kaurov, G.; Stebelkov, V.; Kolesnikov, O.; Frolov, D.

2001-01-01

Any industrial process is accompanied by appearance of some quantity of microparticles of processed matter in the environment in immediate proximity to the manufacturing object. These particles can be transferred in atmosphere and can be collected at some distances from the plant. The determination of characteristics of industrial dust microparticles at nuclear fuel cycle plants (form, size, structure of surface, elemental composition, isotopic composition, presence of fission products, presence of activation products) in conjunction with the ability to connect these characteristics with certain nuclear manufacturing processes can become the main technical method of detecting of undeclared nuclear activity. Systematization of the experimental data on morphology, elemental and isotopic composition of uranium microparticles, collected at nuclear fuel cycle plants, is given. The purpose of this work is to establish the relationship between morphological characteristics of uranium dust microparticles and types of nuclear manufacture and to define the reference attributes of the most informative microparticles

Facile fabrication of siloxane @ poly (methylacrylic acid) core-shell microparticles with different functional groups

Energy Technology Data Exchange (ETDEWEB)

Zhao, Zheng-Bai; Tai, Li; Zhang, Da-Ming; Jiang, Yong, E-mail: yj@seu.edu.cn [Southeast University, School of Chemistry and Chemical Engineering (China)

2017-02-15

Siloxane @ poly (methylacrylic acid) core-shell microparticles with functional groups were prepared by a facile hydrolysis-condensation method in this work. Three different silane coupling agents 3-methacryloxypropyltrimethoxysilane (MPS), 3-triethoxysilylpropylamine (APTES), and 3-glycidoxypropyltrimethoxysilane (GPTMS) were added along with tetraethoxysilane (TEOS) into the polymethylacrylic acid (PMAA) microparticle ethanol dispersion to form the Si@PMAA core-shell microparticles with different functional groups. The core-shell structure and the surface special functional groups of the resulting microparticles were measured by transmission electron microscopy and FTIR. The sizes of these core-shell microparticles were about 350–400 nm. The corresponding preparation conditions and mechanism were discussed in detail. This hydrolysis-condensation method also could be used to functionalize other microparticles which contain active groups on the surface. Meanwhile, the Si@PMAA core-shell microparticles with carbon-carbon double bonds and amino groups have further been applied to prepare hydrophobic coatings.

Facile fabrication of siloxane @ poly (methylacrylic acid) core-shell microparticles with different functional groups

International Nuclear Information System (INIS)

Zhao, Zheng-Bai; Tai, Li; Zhang, Da-Ming; Jiang, Yong

2017-01-01

Siloxane @ poly (methylacrylic acid) core-shell microparticles with functional groups were prepared by a facile hydrolysis-condensation method in this work. Three different silane coupling agents 3-methacryloxypropyltrimethoxysilane (MPS), 3-triethoxysilylpropylamine (APTES), and 3-glycidoxypropyltrimethoxysilane (GPTMS) were added along with tetraethoxysilane (TEOS) into the polymethylacrylic acid (PMAA) microparticle ethanol dispersion to form the Si@PMAA core-shell microparticles with different functional groups. The core-shell structure and the surface special functional groups of the resulting microparticles were measured by transmission electron microscopy and FTIR. The sizes of these core-shell microparticles were about 350–400 nm. The corresponding preparation conditions and mechanism were discussed in detail. This hydrolysis-condensation method also could be used to functionalize other microparticles which contain active groups on the surface. Meanwhile, the Si@PMAA core-shell microparticles with carbon-carbon double bonds and amino groups have further been applied to prepare hydrophobic coatings.

Controlled electrosprayed formation of non-spherical microparticles

Science.gov (United States)

Jeyhani, Morteza; Mak, Sze Yi; Sammut, Stephen; Shum, Ho Cheung; Hwang, Dae Kun; Tsai, Scott S. H.

2017-11-01

Fabrication of biocompatible microparticles, such as alginate particles, with the possibility of controlling the particles' morphology in a high-throughput manner, is essential for pharmaceutical and cosmetic industries. Even though the shape of alginate particles has been shown to be an important parameter in controlling drug delivery, there are very limited manufacturing methods to produce non-spherical alginate microparticles in a high-throughput fashion. Here, we present a system that generates non-spherical biocompatible alginate microparticles with a tunable size and shape, and at high-throughput, using an electrospray technique. Alginate solution, which is a highly biocompatible material, is flown through a needle using a constant flow rate syringe pump. The alginate phase is connected to a high-voltage power supply to charge it positively. There is a metallic ring underneath the needle that is charged negatively. The applied voltage creates an electric field that forces the dispensing droplets to pass through the metallic ring toward the collection bath. During this migration, droplets break up to smaller droplets to dissipate their energy. When the droplets reach the calcium chloride bath, polymerization happens and solidifies the droplets. We study the effects of changing the distance from the needle to the bath, and the concentration of calcium chloride in the bath, to control the size and the shape of the resulting microparticles.

Restructuring of microparticles in nuclear ceramic materials. Part III. Form distribution

International Nuclear Information System (INIS)

Lameiras, F.S.

1991-01-01

According to the present model, the modification of the microparticle form, tending to an equiaxial one, is a way to decrease the interface energy of a microparticle set. If the microparticles are dispersed, these ones tend to the spherical form. If they form aggregates (grains), the interface energy is stored in the grain boundaries, triple lines and quadruple points. A mean topological structure combining two kinds of nearly equiaxed polyhedra is proposed for aggregates of microparticles in order to minimize the surface of the grain boundaries, the length of the triple lines and the number of the quadruple points. As the restructuring evolutes, the average grain form tends to take the one of this polyhedra structure. (author)

Stimuli sensitive polymethacrylic acid microparticles (PMAA)--oral insulin delivery.

Science.gov (United States)

Victor, Sunita Prem; Sharma, Chandra P

2002-10-01

This study investigated polymethacrylic acid (PMAA) microparticles for controlled release of Insulin in oral administration. The microparticles were characterised by scanning electron microscopy (SEM) for morphological studies. The swelling behaviour and drug release profile in various pH media were studied. The % swelling of gels was found to be inversely related to the amount of crosslinker added. Inclusion complex of betaCD and Insulin was studied using polyacrylamide gel electrophoresis (PAGE). Optimum complexation was obtained in the ratio 100 mg betaCD: 200 IU Insulin. The release pattern of Insulin from Insulin-betaCD complex encapsulated PMAA microparticles showed release of Insulin for more than seven hours.

Resveratrol-loaded poly(ε-caprolactone) microparticles: preparation and characterization

International Nuclear Information System (INIS)

Mendes, Jessica B.E.; Mainardes, Rubiana M.; Farago, Paulo V.; Michel, Milton D.; Zawadzki, Sonia F.

2011-01-01

Resveratrol-loaded poly(ε-caprolactone) (PCL) microparticles were obtained by simple emulsion/solvent evaporation method. Three drug-loaded formulations were prepared with the aim of investigating the influence of composition on the encapsulation efficiency. Morphological and spectroscopic methods were performed for these materials. The microparticles revealed residual moisture close to 1.5% and encapsulation efficiency above 80%. Spherical shape and smooth surface were observed by SEM. No pores were either verified. Resveratrol-loaded microparticles showed an average particle size of around 50 μm. X-ray diffraction analysis demonstrated that the microencapsulation reduced the drug crystallinity. The FTIR results suggest that no chemical bond was formed between polymer and drug. (author)

In vitro assessment of biopolymer-modified porous silicon microparticles for wound healing applications.

Science.gov (United States)

Mori, Michela; Almeida, Patrick V; Cola, Michela; Anselmi, Giulia; Mäkilä, Ermei; Correia, Alexandra; Salonen, Jarno; Hirvonen, Jouni; Caramella, Carla; Santos, Hélder A

2014-11-01

The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Breaking the mold: transcription factors in the anucleate platelet and platelet-derived microparticles

Directory of Open Access Journals (Sweden)

Katie L Lannan

2015-02-01

Full Text Available Platelets are small anucleate blood cells derived from megakaryocytes. In addition to their pivotal roles in hemostasis, platelets are the smallest, yet most abundant, immune cell and regulate inflammation, immunity, and disease progression. Although platelets lack DNA, and thus no functional transcriptional activities, they are nonetheless rich sources of RNAs, possess an intact spliceosome, and are thus capable of synthesizing proteins. Previously, it was thought that platelet RNAs and translational machinery were remnants from the megakaryocyte. We now know that the initial description of platelets as cellular fragments is an antiquated notion, as mounting evidence suggests otherwise. Therefore, it is reasonable to hypothesize that platelet transcription factors are not vestigial remnants from megakaryoctes, but have important, if only partly understood functions. Proteins play multiple cellular roles to minimize energy expenditure for maximum cellular function; thus, the same can be expected for transcription factors. In fact, numerous transcription factors have non-genomic roles, both in platelets and in nucleated cells. Our lab and others have discovered the presence and nongenomic roles of transcription factors in platelets, such as the nuclear factor kappa β (NFκB family of proteins and peroxisome proliferator activated receptor gamma (PPARγ. In addition to numerous roles in regulating platelet activation, functional transcription factors can be transferred to vascular and immune cells through platelet microparticles. This method of transcellular delivery of key immune molecules may be a vital mechanism by which platelet transcription factors regulate inflammation and immunity. At the very least, platelets are an ideal model cell to dissect out the nongenomic roles of transcription factors in nucleated cells. There is abundant evidence to suggest that transcription factors in platelets play key roles in regulating inflammatory and

Protein encapsulation via porous CaCO3 microparticles templating.

Science.gov (United States)

Volodkin, Dmitry V; Larionova, Natalia I; Sukhorukov, Gleb B

2004-01-01

Porous microparticles of calcium carbonate with an average diameter of 4.75 microm were prepared and used for protein encapsulation in polymer-filled microcapsules by means of electrostatic layer-by-layer assembly (ELbL). Loading of macromolecules in porous CaCO3 particles is affected by their molecular weight due to diffusion-limited permeation inside the particles and also by the affinity to the carbonate surface. Adsorption of various proteins and dextran was examined as a function of pH and was found to be dependent both on the charge of the microparticles and macromolecules. The electrostatic effect was shown to govern this interaction. This paper discusses the factors which can influence the adsorption capacity of proteins. A new way of protein encapsulation in polyelectrolyte microcapsules is proposed exploiting the porous, biocompatible, and decomposable microparticles from CaCO3. It consists of protein adsorption in the pores of the microparticles followed by ELbL of oppositely charged polyelectrolytes and further core dissolution. This resulted in formation of polyelectrolyte-filled capsules with protein incorporated in interpenetrating polyelectrolyte network. The properties of CaCO3 microparticles and capsules prepared were characterized by scanning electron microscopy, microelectrophoresis, and confocal laser scanning microscopy. Lactalbumin was encapsulated by means of the proposed technique yielding a content of 0.6 pg protein per microcapsule. Horseradish peroxidase saves 37% of activity after encapsulation. However, the thermostability of the enzyme was improved by encapsulation. The results demonstrate that porous CaCO3 microparticles can be applied as microtemplates for encapsulation of proteins into polyelectrolyte capsules at neutral pH as an optimal medium for a variety of bioactive material, which can also be encapsulated by the proposed method. Microcapsules filled with encapsulated material may find applications in the field of

Preparation of TPP-crosslinked chitosan microparticles by spray drying for the controlled delivery of progesterone intended for estrus synchronization in cattle.

Science.gov (United States)

Helbling, Ignacio M; Busatto, Carlos A; Fioramonti, Silvana A; Pesoa, Juan I; Santiago, Liliana; Estenoz, Diana A; Luna, Julio A

2018-02-20

Planned reproduction in cattle involves regulation of estrous cycle and the use of artificial insemination. Cycle control includes the administration of exogenous progesterone during 5-8 days in a controlled manner allowing females to synchronize their ovulation. Several progesterone delivery systems are commercially available but they have several drawbacks. The aim of the present contribution was to evaluate chitosan microparticles entrapping progesterone as an alternative system. Microparticles were prepared by spray drying. The effect of formulation parameters and experimental conditions on particle features and delivery was studied. A mathematical model to predict progesterone plasma concentration in animals was developed and validated with experimental data. Microparticle size was not affected by formulation parameters but sphericity enhances as Tween 80 content increases and it impairs as TPP content rises. Z potential decreases as phosphate content rises. Particles remain stable in acidic solution but the addition of surfactant is required to stabilize dispersions in neutral medium. Encapsulation efficiencies was 69-75%. In vitro delivery studies showed burst and diffusion-controlled phases, being progesterone released faster at low pH. In addition, delivery extend in cows was affected mainly by particle size and hormone initial content, while the amount injected altered plasma concentration. Theoretical predictions with excellent accuracy were obtained. The mathematical model developed can help to find proper particle features to reach specific delivery rates in the animals. This not only save time, money and effort but also minimized experimentation with animals which is desired from an ethical point of view.

Biosensing utilizing the motion of magnetic microparticles in a microfluidic system

KAUST Repository

Giouroudi, Ioanna

2010-10-23

The study for the design of a compact and inexpensive biosensing device, which can be operated either by primary care personnel or by patients as opposed to skilled operators, is presented. The main parts of the proposed device are a microfluidic channel, permanent magnets and functionalized magnetic microparticles. The innovative aspect of the proposed biosensing method is that it utilizes the volumetric increase of magnetic microparticles when analyte binds to their surface. Their velocity decreases drastically when they are accelerated by an externally applied magnetic force within a microfluidic channel. This effect is utilized to detect the presence of analyte e.g. microbes. Analytical calculations showed that a decrease in velocity of approximately 23% can be achieved due to the volumetric change of a magnetic microparticle of View the MathML source1μm diameter when HIV virions of approximately View the MathML source0,135μm are bound to its surface and by keeping its magnetic properties the same. Preliminary experiments were carried out utilizing superparamagnetic microparticles coated with streptavidin and polystyrene microparticles coated with biotin.

Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery.

Science.gov (United States)

Sajeesh, S; Vauthier, C; Gueutin, C; Ponchel, G; Sharma, Chandra P

2010-08-01

In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles

Directory of Open Access Journals (Sweden)

Rita E. Serda

2011-01-01

Full Text Available Mass transport of drug delivery vehicles is guided by particle properties, such as size, shape, composition, and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two-dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light variable chain, fibrinogen, and complement component 1 compared to their anionic counterparts. Anionic microparticles were found to accumulate in equal abundance in murine liver and spleen, whereas cationic microparticles showed preferential accumulation in the spleen. Immunohistochemistry supported macrophage uptake of both anionic and cationic microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution.

Force field inside the void in complex plasmas under microgravity conditions

International Nuclear Information System (INIS)

Kretschmer, M.; Khrapak, S.A.; Zhdanov, S.K.; Thomas, H.M.; Morfill, G.E.; Fortov, V.E.; Lipaev, A.M.; Molotkov, V.I.; Ivanov, A.I.; Turin, M.V.

2005-01-01

Observations of complex plasmas under microgravity conditions onboard the International Space Station performed with the Plasma-Kristall experiment-Nefedov facility are reported. A weak instability of the boundary between the central void (region free of microparticles) and the microparticle cloud is observed at low gas pressures. The instability leads to periodic injections of a relatively small number of particles into the void region (by analogy this effect is called the 'trampoline effect'). The trajectories of injected particles are analyzed providing information on the force field inside the void. The experimental results are compared with theory which assumes that the most important forces inside the void are the electric and the ion drag forces. Good agreement is found clearly indicating that under conditions investigated the void formation is caused by the ion drag force

Circulating Endothelial-Derived Activated Microparticle: A Useful Biomarker for Predicting One-Year Mortality in Patients with Advanced Non-Small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Chin-Chou Wang

2014-01-01

Full Text Available Background. This study tested the hypothesis that circulating microparticles (MPs are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer (ES-NSCLC. Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1 platelet-derived activated MPs (PDAc-MPs, (2 platelet-derived apoptotic MPs (PDAp-MPs, (3 endothelial-derived activated MPs (EDAc-MPs, and (4 endothelial-derived apoptotic MPs (EDAp-MPs, were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1 (n=56 (one-year survivors and patients who survived less than one year were categorized into group 2 (n=51 (one-year nonsurvivors. Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (all P<0.05. Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1 (P=0.006. Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (all P<0.035. Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.

Robust and Optimal Control of Magnetic Microparticles inside Fluidic Channels with Time-Varying Flow Rates

Directory of Open Access Journals (Sweden)

Islam S.M. Khalil

2016-06-01

Full Text Available Targeted therapy using magnetic microparticles and nanoparticles has the potential to mitigate the negative side-effects associated with conventional medical treatment. Major technological challenges still need to be addressed in order to translate these particles into in vivo applications. For example, magnetic particles need to be navigated controllably in vessels against flowing streams of body fluid. This paper describes the motion control of paramagnetic microparticles in the flowing streams of fluidic channels with time-varying flow rates (maximum flow is 35 ml.hr−1. This control is designed using a magnetic-based proportional-derivative (PD control system to compensate for the time-varying flow inside the channels (with width and depth of 2 mm and 1.5 mm, respectively. First, we achieve point-to-point motion control against and along flow rates of 4 ml.hr−1, 6 ml.hr−1, 17 ml.hr−1, and 35 ml.hr−1. The average speeds of single microparticle (with average diameter of 100 μm against flow rates of 6 ml.hr−1 and 30 ml.hr−1 are calculated to be 45 μm.s−1 and 15 μm.s−1, respectively. Second, we implement PD control with disturbance estimation and compensation. This control decreases the steady-state error by 50%, 70%, 73%, and 78% at flow rates of 4 ml.hr−1, 6 ml.hr−1, 17 ml.hr−1, and 35 ml.hr−1, respectively. Finally, we consider the problem of finding the optimal path (minimal kinetic energy between two points using calculus of variation, against the mentioned flow rates. Not only do we find that an optimal path between two collinear points with the direction of maximum flow (middle of the fluidic channel decreases the rise time of the microparticles, but we also decrease the input current that is supplied to the electromagnetic coils by minimizing the kinetic energy of the microparticles, compared to a PD control with disturbance compensation.

Droplet-based microfluidic method for synthesis of microparticles

CSIR Research Space (South Africa)

Mbanjwa, MB

2012-10-01

Full Text Available Droplet-based microfluidics has, in recent years, received increased attention as an important tool for performing numerous methods in modern day chemistry and biology such as the synthesis of hydrogel microparticles. Hydrogels have been used in many..., in recent years, received increased attention as an important tool for performing numerous methods in modern day chemistry and biology, such as synthesis of hydrogel microparticles. CONCLUSION AND OUTLOOK The droplet-based microfluidic method offers...

Microparticles containing guaraná extract obtained by spray-drying technique: development and characterization

Directory of Open Access Journals (Sweden)

Traudi Klein

Full Text Available AbstractGuaraná (Paullinia cupana Kunth, Sapindaceae is well known for its dietary and pharmaceutical potential, and the semipurified extract of guaraná shows antidepressant and panicolytic effects. However, the low solubility, bioavailability and stability of the semipurified extract limit its use as a component of pharmaceutical agents. Delivery of the semipurified extract in a microparticle form could help to optimize its stability. In this study, microparticles containing semipurified extract of guaraná were obtained by the spray-drying technique, using a combination of maltodextrin and gum arabic. The raw materials and microparticles produced were characterized by particle size analysis, differential scanning calorimetry, thermogravimetric analysis, and scanning electron microscopy. The drug content and antioxidant capacity were also evaluated. In vitrodissolution tests using flow cell dissolution apparatus, were carried out to investigate the influence of formulation parameters on the release of semipurified extract of guaraná from the microparticles. The spray-drying technique and the processing conditions selected gave satisfactory encapsulation efficiency (80–110% and product yield (55–60%. The mean diameter of microparticles was around 4.5 µm. The DPPH radical scavenging capacity demonstrated that microparticles can protect the semipurified extract of guaraná from the effect of high temperatures during the process maintained the antioxidant capacity. Differential scanning calorimetry results indicated an interaction between semipurified extract of guaraná and gum arabic: maltodextrin in the microparticles, and thermogravimetric analysis indicate that the profile curves of the microparticles are similar to the adjuvants used in drying, probably due to the higher proportion of adjuvants compared to semipurified extract of guaraná. In vitro dissolution tests demonstrate that all formulations complete dissolution within 60 min

Fabrication of starch-based microparticles by an emulsification-crosslinking method

Science.gov (United States)

Starch-based microparticles (MPs) fabricated by a water-in-water (w/w) emulsification-crosslinking method could be used as a controlled-release delivery vehicle for food bioactives. Due to the processing route without the use of toxic organic solvents, it is expected that these microparticles can be...

Ethanol oxidation on a nichrome-supported spherical platinum microparticle electrocatalyst prepared by electrodeposition

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhen-Hui; Li, Jing; Dong, Xiaoya; Wang, Dong; Chen, Tiwei; Qiao, Haiyan; Huang, Aiping [College of Chemistry and Environmental Science, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, Jianshe Road, Xinxiang 453007 (China)

2008-11-15

A novel electrode was rapidly prepared by depositing microparticle platinum onto a nichrome substrate in dilute chloroplatinic acid solution by cyclic voltammetry. The SEM results revealed that the deposits were composed of spherical Pt microparticles. Cyclic voltammetry and chronoamperometry were used for the characterization of the electrodes. Results of the electrochemical measurements showed that the spherical Pt microparticle electrodes retained the properties of metal platinum, increased the catalytic activity and promoted the electrocatalytic oxidation of ethanol. Moreover, the deposited Pt microparticles improved the electrochemical properties of the support material and reduced the dosage of noble metal platinum remarkably. The cost could be reduced dramatically by decreasing the contents of platinum. The spherical Pt microparticles deposited on the nichrome supports are likely a potential electrocatalyst for ethanol electrooxidation. (author)

Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release

Energy Technology Data Exchange (ETDEWEB)

Hao, Shilei; Wang, Yazhou; Wang, Bochu, E-mail: wangbc2000@126.com; Deng, Jia; Zhu, Liancai; Cao, Yang

2014-06-01

In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. - Highlights: • The porous PLGA microparticles were successfully prepared by the electrospray deposition method at one step. • The porous microparticles had high loading capacity and low density. • The microparticle showed a sustained release in the simulated gastric liquid. • The microparticles showed a slight cytotoxicity in vitro.

Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release

International Nuclear Information System (INIS)

Hao, Shilei; Wang, Yazhou; Wang, Bochu; Deng, Jia; Zhu, Liancai; Cao, Yang

2014-01-01

In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. - Highlights: • The porous PLGA microparticles were successfully prepared by the electrospray deposition method at one step. • The porous microparticles had high loading capacity and low density. • The microparticle showed a sustained release in the simulated gastric liquid. • The microparticles showed a slight cytotoxicity in vitro

Preparation and chemical stability of iron-nitride-coated iron microparticles

International Nuclear Information System (INIS)

Luo Xin; Liu Shixiong

2007-01-01

Iron-nitride-coated iron microparticles were prepared by nitridation of the surface of iron microparticles with ammonia gas at a temperature of 510 deg. C. The phases, composition, morphology, magnetic properties, and chemical stability of the particles were studied. The phases were α-Fe, ε-Fe 3 N, and γ-Fe 4 N. The composition varied from the core to the surface, with 99.8 wt% Fe in the core, and 93.8 wt% Fe and 6 wt% N in the iron-nitride coating. The thickness of the iron-nitride coating was about 0.28 μm. The chemical stability of the microparticles was greatly improved, especially the corrosion resistance in corrosive aqueous media. The saturation magnetization and the coercive force were 17.1x10 3 and 68 kA/m, respectively. It can be concluded that iron-nitride-coated iron microparticles will be very useful in many fields, such as water-based magnetorheological fluids and polishing fluids

Cytokine Secreting Microparticles Engineer the Fate and the Effector Functions of T-Cells.

Science.gov (United States)

Majedi, Fatemeh S; Hasani-Sadrabadi, Mohammad Mahdi; Kidani, Yoko; Thauland, Timothy J; Moshaverinia, Alireza; Butte, Manish J; Bensinger, Steven J; Bouchard, Louis-S

2018-02-01

T-cell immunotherapy is a promising approach for cancer, infection, and autoimmune diseases. However, significant challenges hamper its therapeutic potential, including insufficient activation, delivery, and clonal expansion of T-cells into the tumor environment. To facilitate T-cell activation and differentiation in vitro, core-shell microparticles are developed for sustained delivery of cytokines. These particles are enriched by heparin to enable a steady release of interleukin-2 (IL-2), the major T-cell growth factor, over 10+ d. The controlled delivery of cytokines is used to steer lineage specification of cultured T-cells. This approach enables differentiation of T-cells into central memory and effector memory subsets. It is shown that the sustained release of stromal cell-derived factor 1α could accelerate T-cell migration. It is demonstrated that CD4+ T-cells could be induced to high concentrations of regulatory T-cells through controlled release of IL-2 and transforming growth factor beta. It is found that CD8+ T-cells that received IL-2 from microparticles are more likely to gain effector functions as compared with traditional administration of IL-2. Culture of T-cells within 3D scaffolds that contain IL-2-secreting microparticles enhances proliferation as compared with traditional, 2D approaches. This yield a new method to control the fate of T-cells and ultimately to new strategies for immune therapy. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microparticles in a RF plasma under hyper gravity conditions

NARCIS (Netherlands)

Beckers, J.; Stoffels, W.W.; Ockenga, T.; Wolter, M.; Kersten, H.

2009-01-01

Summary form only given: For diagnostic purposes micrometer-sized particles can be used as floating electrostatic probes. Once injected into a complex rf plasma, these particles will become negatively charged and can be trapped in the plasma sheath due to an equilibrium of several forces working on

Experimental demonstration of plasma-drag acceleration of a dust cloud to hypervelocities.

Science.gov (United States)

Ticoş, C M; Wang, Zhehui; Wurden, G A; Kline, J L; Montgomery, D S; Dorf, L A; Shukla, P K

2008-04-18

Simultaneous acceleration of hundreds of dust particles to hypervelocities by collimated plasma flows ejected from a coaxial gun is demonstrated. Graphite and diamond grains with radii between 5 and 30 microm, and flying at speeds up to 3.7 km/s, have been recorded with a high-speed camera. The observations agree well with a model for plasma-drag acceleration of microparticles much larger than the plasma screening length.

Polyelectrolyte microparticles for enhancing anode performance in an air–cathode μ-Liter microbial fuel cell

International Nuclear Information System (INIS)

Chen, Yan-Yu; Wang, Hsiang-Yu

2015-01-01

Highlights: • Microparticles with high consistency and surface area per volume are fabricated. • P(DADMAC) microparticles facilitate microorganism accumulation and charge transfer. • Microbes in microparticles are capable of proliferation and electricity generation. • Microparticles increase limiting current/power output to more than 200% of biofilm. • Microparticles decrease the anode charge-transfer resistance to 44% of biofilm. - Abstract: Microbial fuel cell (MFC) is considered an environmentally friendly energy source because it generates electrical power by digesting organic substrates in the wastewater. However, it is still challenging for MFC to become an economically affordable and highly efficient energy source due to its relatively low power output and coulombic efficiency. The aim of this study is to increase the performance of anode by using polyelectrolyte microparticles to facilitate the accumulation of microorganisms and the collection of electrons. The polyelectrolyte microparticle is subjected to microscopy, cyclic voltammetry, electrochemical impedance spectroscopy and continuous electricity generation in an air–cathode μ-Liter MFC (μMFC) to validate its biocompatibility, ability in retaining redox species, reduced electron transfer resistance, and sustained energy generation. During the 168-hour operation, microorganisms proliferate inside the microparticle and generate around 250% power output and 200% limiting current of those from microorganism biofilm. The polyelectrolyte microparticle also decreased charge-transfer resistance of anode electrode in air–cathode μMFC by 56% compared with biofilm.

Inactivation of Zika virus by solvent/detergent treatment of human plasma and other plasma-derived products and pasteurization of human serum albumin.

Science.gov (United States)

Kühnel, Denis; Müller, Sebastian; Pichotta, Alexander; Radomski, Kai Uwe; Volk, Andreas; Schmidt, Torben

2017-03-01

In 2016 the World Health Organization declared the mosquito-borne Zika virus (ZIKV) a "public health emergency of international concern." ZIKV is a blood-borne pathogen, which therefore causes concerns regarding the safety of human plasma-derived products due to potential contamination of the blood supply. This study investigated the effectiveness of viral inactivation steps used during the routine manufacturing of various plasma-derived products to reduce ZIKV infectivity. Human plasma and intermediates from the production of various plasma-derived products were spiked with ZIKV and subjected to virus inactivation using the identical techniques (either solvent/detergent [S/D] treatment or pasteurization) and conditions used for the actual production of the respective products. Samples were taken and the viral loads measured before and after inactivation. After S/D treatment of spiked intermediates of the plasma-derived products Octaplas(LG), Octagam, and Octanate, the viral loads were below the limit of detection in all cases. The mean log reduction factor (LRF) was at least 6.78 log for Octaplas(LG), at least 7.00 log for Octagam, and at least 6.18 log for Octanate after 60, 240, and 480 minutes of S/D treatment, respectively. For 25% human serum albumin (HSA), the mean LRF for ZIKV was at least 7.48 log after pasteurization at 60°C for 120 minutes. These results demonstrate that the commonly used virus inactivation processes utilized during the production of human plasma and plasma-derived products, namely, S/D treatment or pasteurization, are effective for inactivation of ZIKV. © 2016 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Proliferation-promoting effect of platelet-rich plasma on human adipose-derived stem cells and human dermal fibroblasts.

Science.gov (United States)

Kakudo, Natsuko; Minakata, Tatsuya; Mitsui, Toshihito; Kushida, Satoshi; Notodihardjo, Frederik Zefanya; Kusumoto, Kenji

2008-11-01

This study evaluated changes in platelet-derived growth factor (PDGF)-AB and transforming growth factor (TGF)-beta1 release from platelets by platelet-rich plasma activation, and the proliferation potential of activated platelet-rich plasma and platelet-poor plasma on human adipose-derived stem cells and human dermal fibroblasts. Platelet-rich plasma was prepared using a double-spin method, with the number of platelets counted in each preparation stage. Platelet-rich and platelet-poor plasma were activated with autologous thrombin and calcium chloride, and levels of platelet-released PDGF-AB and TGF-beta1 were determined by enzyme-linked immunosorbent assay. Cells were cultured for 1, 4, or 7 days in serum-free Dulbecco's Modified Eagle Medium supplemented with 5% whole blood plasma, nonactivated platelet-rich plasma, nonactivated platelet-poor plasma, activated platelet-rich plasma, or activated platelet-poor plasma. In parallel, these cells were cultured for 1, 4, or 7 days in serum-free Dulbecco's Modified Eagle Medium supplemented with 1%, 5%, 10%, or 20% activated platelet-rich plasma. The cultured human adipose-derived stem cells and human dermal fibroblasts were assayed for proliferation. Platelet-rich plasma contained approximately 7.9 times as many platelets as whole blood, and its activation was associated with the release of large amounts of PDGF-AB and TGF-beta1. Adding activated platelet-rich or platelet-poor plasma significantly promoted the proliferation of human adipose-derived stem cells and human dermal fibroblasts. Adding 5% activated platelet-rich plasma to the medium maximally promoted cell proliferation, but activated platelet-rich plasma at 20% did not promote it. Platelet-rich plasma can enhance the proliferation of human adipose-derived stem cells and human dermal fibroblasts. These results support clinical platelet-rich plasma application for cell-based, soft-tissue engineering and wound healing.

Incorporation of essential oil in alginate microparticles by multiple emulsion/ionic gelation process.

Science.gov (United States)

Hosseini, Seyede Marzieh; Hosseini, Hedayat; Mohammadifar, Mohammad Amin; Mortazavian, Amir Mohammad; Mohammadi, Abdorreza; Khosravi-Darani, Kianoosh; Shojaee-Aliabadi, Saeedeh; Dehghan, Solmaz; Khaksar, Ramin

2013-11-01

In this study, an o/w/o multiple emulsion/ionic gelation method was developed for production of alginate microparticles loaded with Satureja hortensis essential oil (SEO). It was found that the essential oil concentration has significant influence on encapsulation efficiency (EE), loading capacity (LC) and size of microparticles. The values of EE, LC and particle mean diameter were about 52-66%, 20-26%, and 47-117 μm, respectively, when the initial SEO content was 1-3% (v/v) .The essential oil-loaded microparticles were porous, as displayed by scanning electron micrograph. The presence of SEO in alginate microparticles was confirmed by Fourier transform-infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analyses. SEO-loaded microparticles showed good antioxidant (with DPPH radical scavenging activity of 40.7-73.5%) and antibacterial properties; this effect was greatly improved when the concentration of SEO was 3% (v/v). S. aureus was found to be the most sensitive bacterium to SEO and showed a highest inhibition zone of 304.37 mm(2) in the microparticles incorporated with 3% (v/v) SEO. In vitro release studies showed an initial burst release and followed by a slow release. In addition, the release of SEO from the microparticles followed Fickian diffusion with acceptable release. Copyright © 2013 Elsevier B.V. All rights reserved.

SIMS depth profile analysis of environmental microparticles

International Nuclear Information System (INIS)

Konarski, P.

2000-01-01

Environmental and technological research demands chemical characterization of aerosol particles so minute in size, that conventional methods for bulk analyses are simply not applicable. In this work novel application of secondary ion mass spectrometry (SIMS) for characterization of microparticles suspended in atmosphere of the working environment of glass plant Thomson Polkolor, Piaseczno and steelworks Huta Sendzimira, Cracow is presented. The new technique based on sample rotation in depth profile analysis of sub-micrometer particulate material was performed on SAJW-02 analyser equipped with Balzers 16 mm quadrupole spectrometer and sample rotation manipulator using 5 keV Ar + and O 2 + ion beams. The results were compared with the standard method used on ims-3f Cameca analyser 12 keV O 2 + ion beam. Grain size distributions of aerosol microparticles were estimated using eight-stage cascade impactor with particle size range of 0.2 μm to 15 μm. Elemental concentration and crystalline structure of the collected dust particles were performed using spark source mass spectrometry and X-ray diffraction methods. SIMS depth profile analysis shows that sub-micrometer particles do not have uniform morphology, The core-shell structure has been observed for particles collected in both factories. Presented models show that the steelworks particles consists mainly of iron and manganese cores. At the shells of these microparticles :lead, chlorine and fluorine are found. The cores of glass plant submicrometer particles consists mainly of lead-zirconium glass covered by a shell containing carbon and copper. Sample rotation technique applied SIMS appears to be an effective tool for environmental microparticle morphology studies. (author)

Assessing the biodegradability of microparticles disposed down the drain.

Science.gov (United States)

McDonough, Kathleen; Itrich, Nina; Casteel, Kenneth; Menzies, Jennifer; Williams, Tom; Krivos, Kady; Price, Jason

2017-05-01

Microparticles made from naturally occurring materials or biodegradable plastics such as poly(3-hydroxy butyrate)-co-(3-hydroxy valerate), PHBV, are being evaluated as alternatives to microplastics in personal care product applications but limited data is available on their ultimate biodegradability (mineralization) in down the drain environmental compartments. An OECD 301B Ready Biodegradation Test was used to quantify ultimate biodegradability of microparticles made of PHBV foam, jojoba wax, beeswax, rice bran wax, stearyl stearate, blueberry seeds and walnut shells. PHBV polymer was ready biodegradable reaching 65.4 ± 4.1% evolved CO 2 in 5 d and 90.5 ± 3.1% evolved CO 2 in 80 d. PHBV foam microparticles (125-500 μm) were mineralized extensively with >66% CO 2 evolution in 28 d and >82% CO 2 evolution in 80 d. PHBV foam microparticles were mineralized at a similar rate and extent as microparticles made of jojoba wax, beeswax, rice bran wax, and stearyl stearate which reached 84.8  ± 4.8, 84.9  ± 2.2, 82.7  ± 4.7, and 86.4 ± 3.2% CO 2 evolution respectively in 80 d. Blueberry seeds and walnut shells mineralized more slowly only reaching 39.3  ± 6.9 and 5.1 ± 2.8% CO 2 evolution in 80 d respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Concentration of nanoparticles and/or microparticles in flow conditions by dielectrophoresis

DEFF Research Database (Denmark)

2017-01-01

A device for concentration of nanoparticles and/or microparticles in liquid flow conditions by dielectrophoresis is disclosed in this invention.......A device for concentration of nanoparticles and/or microparticles in liquid flow conditions by dielectrophoresis is disclosed in this invention....

Increased circulating cell-derived microparticle count is associated with recurrent implantation failure after IVF and embryo transfer.

Science.gov (United States)

Martínez-Zamora, M Angeles; Tàssies, Dolors; Reverter, Juan Carlos; Creus, Montserrat; Casals, Gemma; Cívico, Salvadora; Carmona, Francisco; Balasch, Juan

2016-08-01

Cell-derived microparticles (cMPs) are small membrane vesicles that are released from many different cell types in response to cellular activation or apoptosis. Elevated cMP counts have been found in almost all thrombotic diseases and pregnancy wastage, such as recurrent spontaneous abortion and in a number of conditions associated with inflammation, cellular activation and angiogenesis. cMP count was investigated in patients experiencing unexplained recurrent implantation failure (RIF). The study group was composed of 30 women diagnosed with RIF (RIF group). The first control group (IVF group) (n = 30) comprised patients undergoing a first successful IVF cycle. The second control group (FER group) included 30 healthy women who had at least one child born at term and no history of infertility or obstetric complications. cMP count was significantly higher in the RIF group compared with the IVF and FER groups (P < 0.05 and P < 0.01, respectively) (RIF group: 15.8 ± 6.2 nM phosphatidylserine equivalent [PS eq]; IVF group: 10.9 ± 5.3 nM PS eq; FER group: 9.6 ± 4.0 nM PS eq). No statistical difference was found in cMP count between the IVF and FER groups. Increased cMP count is, therefore, associated with RIF after IVF and embryo transfer. Copyright © 2016. Published by Elsevier Ltd.

Novel injectable gellan gum hydrogel composites incorporating Zn- and Sr-enriched bioactive glass microparticles: High-resolution X-ray microcomputed tomography, antibacterial and in vitro testing.

Science.gov (United States)

Douglas, Timothy E L; Dziadek, Michal; Gorodzha, Svetlana; Lišková, Jana; Brackman, Gilles; Vanhoorne, Valérie; Vervaet, Chris; Balcaen, Lieve; Del Rosario Florez Garcia, Maria; Boccaccini, Aldo R; Weinhardt, Venera; Baumbach, Tilo; Vanhaecke, Frank; Coenye, Tom; Bačáková, Lucie; Surmeneva, Maria A; Surmenev, Roman A; Cholewa-Kowalska, Katarzyna; Skirtach, Andre G

2018-06-01

Mineralization of hydrogel biomaterials is desirable to improve their suitability as materials for bone regeneration. In this study, gellan gum (GG) hydrogels were formed by simple mixing of GG solution with bioactive glass microparticles of 45S5 composition, leading to hydrogel formation by ion release from the amorphous bioactive glass microparticles. This resulted in novel injectable, self-gelling composites of GG hydrogels containing 20% bioactive glass. Gelation occurred within 20 min. Composites containing the standard 45S5 bioactive glass preparation were markedly less stiff. X-ray microcomputed tomography proved to be a highly sensitive technique capable of detecting microparticles of diameter approximately 8 μm, that is, individual microparticles, and accurately visualizing the size distribution of bioactive glass microparticles and their aggregates, and their distribution in GG hydrogels. The widely used melt-derived 45S5 preparation served as a standard and was compared with a calcium-rich, sol-gel derived preparation (A2), as well as A2 enriched with zinc (A2Zn5) and strontium (A2Sr5). A2, A2Zn, and A2Sr bioactive glass particles were more homogeneously dispersed in GG hydrogels than 45S5. Composites containing all four bioactive glass preparations exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus. Composites containing A2Zn5 and A2Sr5 bioactive glasses supported the adhesion and growth of osteoblast-like cells and were considerably more cytocompatible than 45S5. All composites underwent mineralization with calcium-deficient hydroxyapatite upon incubation in simulated body fluid. The extent of mineralization appeared to be greatest for composites containing A2Zn5 and 45S5. The results underline the importance of the choice of bioactive glass when preparing injectable, self-gelling composites. Copyright © 2018 John Wiley & Sons, Ltd.

Physiologic Impact of Circulating RBC Microparticles upon Blood-Vascular Interactions

Directory of Open Access Journals (Sweden)

Ahmed S. Said

2018-01-01

Full Text Available Here, we review current data elucidating the role of red blood cell derived microparticles (RMPs in normal vascular physiology and disease progression. Microparticles (MPs are submicron-size, membrane-encapsulated vesicles derived from various parent cell types. MPs are produced in response to numerous stimuli that promote a sequence of cytoskeletal and membrane phospholipid changes and resulting MP genesis. MPs were originally considered as potential biomarkers for multiple disease processes and more recently are recognized to have pleiotropic biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in initiating apoptosis. RMPs, specifically, form normally during RBC maturation in response to injury during circulation, and are copiously produced during processing and storage for transfusion. Notably, several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs markedly from that of intact RBCs and the nature/composition of RMP components are affected by the specific circumstances of RMP genesis. Described RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion as well as influence upon vasoregulation via influence upon nitric oxide (NO bioavailability. Of particular relevance, RMPs scavenge NO more avidly than do intact RBCs; this physiology has been proposed to contribute to the impaired oxygen delivery homeostasis that may be observed following transfusion. In summary, RMPs are submicron particles released from RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in normal and patho-physiology and in transfusion recipients is an area of continued investigation.

Salbutamol sulphate-ethylcellulose microparticles: formulation and in-vitro evaluation with emphasis on mathematical approaches

Directory of Open Access Journals (Sweden)

G Murtaza

2009-10-01

Full Text Available "n "nBackground and the purpose of the study: This study reports the laboratory optimization for the preparation of salbutamol sulphate-ethylcellulose microparticles by a non-solvent addition coacervation technique through adjustment of the ratio of salbutamol sulphate to ethylcellulose. The variation of drug release between the microparticles and tabletted microparticles was also investigated. "nMethods: In vitro release profiles of developed microparticles and tabletted microparticles were studied using USP XXIV dissolution apparatus I and II, respectively, in 450 ml double distilled water at 50 rpm maintained at 37°C. "nResults: White microparticles with no definite shape having good entrapment efficiency (96.68 to 97.83% and production yield (97.48 ± 1.21 to 98.35 ± 1.08% were obtained. In this investigation, initial burst effect was observed in the drug release behavior. The rate of drug release from microparticles decreased as the concentration of polyisobutylene was increased from 6% to 12% during microencapsulation. The release pattern of tabletted microparticles was affected significantly (p < 0.05 by the addition of hydroxy propyl methyl cellulose (HPMC as excepient and insignificantly (p > 0.05 by the type of dissolution media and stirring speed. Tabletted microparticles showed good stability and reproducibility. Ethylcellulose was found to be compatible with salbutamol sulphate. The drug release from all formulations was best fit to Higuchi's equation and the mechanism of drug release was anomalous diffusion from all formulations. "nConclusion: The results of this study suggest that by using ethylcellulose it is possible to design a single-unit, sustained-release oral dosage form of salbutamol sulphate for indication of twice a day.

Characterization of Chlorhexidine-Loaded Calcium-Hydroxide Microparticles as a Potential Dental Pulp-Capping Material

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Balasankar M. Priyadarshini

2017-06-01

Full Text Available This study explores the delivery of novel calcium hydroxide [Ca(OH2] microparticles loaded with chlorhexidine (CHX for potential dental therapeutic and preventive applications. Herein, we introduce a new approach for drug-delivery to deep dentin-surfaces in the form of drug-loaded microparticles. Unloaded Ca(OH2 [Ca(OH2/Blank] and CHX-loaded/Ca(OH2 microparticles were fabricated by aqueous chemical-precipitation technique. The synthesized-microparticles were characterized in vitro for determination of surface-morphology, crystalline-features and thermal-properties examined by energy-dispersive X-ray scanning and transmission electron-microscopy (EDX-SEM/TEM, Fourier-transform infrared-spectroscopy (FTIR, X-ray diffraction (XRD, thermogravimetric analysis (TGA and differential scanning-calorimetry (DSC. Time-related pH changes, initial antibacterial/biofilm-abilities and cytotoxicity of CHX-loaded/Ca(OH2 microparticles were evaluated. Microparticles were delivered to dentin-surfaces with subsequent SEM examination of treated dentin-substrates. The in vitro and ex vivo CHX-release profiles were characterized. Ca(OH2/Blank were hexagonal-shaped with highest z-average diameter whereas CHX-inclusion evidenced micro-metric spheres with distinguishable surface “rounded deposits” and a negative-shift in diameter. CHX:Ca(OH2/50 mg exhibited maximum encapsulation-efficiency with good antibacterial and cytocompatible properties. SEM examination revealed an intact layer of microparticles on exposed dentin-surfaces with retention of spherical shape and smooth texture. Microparticles loaded on dentin-surfaces showed prolonged release of CHX indicating substantial retention on dentin-substrates. This study validated the inherent-applicability of this novel drug-delivery approach to dentin-surfaces using micro-metric CHX-loaded/Ca(OH2 microparticles.

Preparation and Characterization of Keratin/Alginate Blend Microparticles

OpenAIRE

Srisuwan, Yaowalak; Srihanam, Prasong

2018-01-01

The water-in-oil (W/O) emulsification-diffusion method was used for construction of keratin (Ker), alginate (Alg), and Ker/Alg blend microparticles. The Ker, Alg, and Ker/Alg blend solutions were used as the water phase, while ethyl acetate was used as the oil phase. Firstly, different concentrations of Ker solution was used to find suitable content. 1.6% w/v Ker solution was blended with the same concentration of the Alg solution for further microparticle construction. Results from scanning ...

Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering

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Sudhir H. Ranganath

2016-06-01

Full Text Available Mesenchymal stromal cells (MSCs are promising therapeutic candidates given their potent immunomodulatory and anti-inflammatory secretome. However, controlling the MSC secretome post-transplantation is considered a major challenge that hinders their clinical efficacy. To address this, we used a microparticle-based engineering approach to non-genetically modulate pro-inflammatory pathways in human MSCs (hMSCs under simulated inflammatory conditions. Here we show that microparticles loaded with TPCA-1, a small-molecule NF-κB inhibitor, when delivered to hMSCs can attenuate secretion of pro-inflammatory factors for at least 6 days in vitro. Conditioned medium (CM derived from TPCA-1-loaded hMSCs also showed reduced ability to attract human monocytes and prevented differentiation of human cardiac fibroblasts to myofibroblasts, compared with CM from untreated or TPCA-1-preconditioned hMSCs. Thus, we provide a broadly applicable bioengineering solution to facilitate intracellular sustained release of agents that modulate signaling. We propose that this approach could be harnessed to improve control over MSC secretome post-transplantation, especially to prevent adverse remodeling post-myocardial infarction.

Moldless PEGDA-Based Optoelectrofluidic Platform for Microparticle Selection

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Shih-Mo Yang

2011-01-01

Full Text Available This paper reports on an optoelectrofluidic platform which consists of the organic photoconductive material, titanium oxide phthalocyanine (TiOPc, and the photocrosslinkable polymer, poly (ethylene glycol diacrylate (PEGDA. TiOPc simplifies the fabrication process of the optoelectronic chip due to requiring only a single spin-coating step. PEGDA is applied to embed the moldless PEGDA-based microchannel between the top ITO glass and the bottom TiOPc substrate. A real-time control interface via a touch panel screen is utilized to select the target 15 μm polystyrene particles. When the microparticles flow to an illuminating light bar, which is oblique to the microfluidic flow path, the lateral driving force diverts the microparticles. Two light patterns, the switching oblique light bar and the optoelectronic ladder phenomenon, are designed to demonstrate the features. This work integrating the new material design, TiOPc and PEGDA, and the ability of mobile microparticle manipulation demonstrates the potential of optoelectronic approach.

Micro-particle filter made in SU-8 for biomedical applications

DEFF Research Database (Denmark)

Noeth, Nadine-Nicole; Keller, Stephan Urs; Fetz, Stefanie

2009-01-01

We have integrated a micro-particle filter in a polymer cantilever to filter micro-particles from a fluid while simultaneously measuring the amount of filtered particles. In a 3,8 mum thick SU-8 cantilever a filter was integrated with pore sizes between 3 and 30 mum. The chip was inserted in a mi...

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles.

Science.gov (United States)

Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

2017-04-11

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly( γ -glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca 2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates.

Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles

Science.gov (United States)

Serda, Rita E.; Blanco, Elvin; Mack, Aaron; Stafford, Susan J.; Amra, Sarah; Li, Qingpo; van de Ven, Anne L.; Tanaka, Takemi; Torchilin, Vladimir P.; Wiktorowicz, John E.; Ferrari, Mauro

2014-01-01

Mass transport of drug delivery vehicles is guided by particle properties, such as shape, composition and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light chain variable region, fibrinogen, and complement component 1 compared to their anionic counterparts. The anionic-surface favored equal accumulation of microparticles in the liver and spleen, while cationic-surfaces favored preferential accumulation in the spleen. Immunohistochemistry supported macrophage internalization of both anionic and cationic silicon microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution. PMID:21303614

A Stability-Indicating HPLC-DAD Method for Determination of Ferulic Acid into Microparticles: Development, Validation, Forced Degradation, and Encapsulation Efficiency

Directory of Open Access Journals (Sweden)

Jessica Mendes Nadal

2015-01-01

Full Text Available A simple stability-indicating HPLC-DAD method was validated for the determination of ferulic acid (FA in polymeric microparticles. Chromatographic conditions consisted of a RP C18 column (250 mm × 4.60 mm, 5 μm, 110 Å using a mixture of methanol and water pH 3.0 (48 : 52 v/v as mobile phase at a flow rate of 1.0 mL/min with UV detection at 320 nm. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of quantification, limit of detection, accuracy, precision, and robustness provided suitable results regarding all parameters investigated. The calibration curve was linear in the concentration range of 10.0–70.0 μg/mL with a correlation coefficient >0.999. Precision (intraday and interday was demonstrated by a relative standard deviation lower than 2.0%. Accuracy was assessed by the recovery test of FA from polymeric microparticles (99.02% to 100.73%. Specificity showed no interference from the components of polymeric microparticles or from the degradation products derived from acidic, basic, and photolytic conditions. In conclusion, the method is suitable to be applied to assay FA as bulk drug and into polymeric microparticles and can be used for studying its stability and degradation kinetics.

Characterization of microparticles prepared by emulsion method from pectin and protein

Science.gov (United States)

In this study, pectin was extracted from apple peel and formulated into microparticles in combination with zein, an edible food protein. The physical, chemical, and structural properties of the resultant pectin structures were evaluated. The resultant microparticles were also examined in vitro for c...

Population-specific plasma proteomes of marine and freshwater three-spined sticklebacks (Gasterosteus aculeatus).

Science.gov (United States)

Kültz, Dietmar; Li, Johnathon; Zhang, Xuezhen; Villarreal, Fernando; Pham, Tuan; Paguio, Darlene

2015-12-01

Molecular phenotypes that distinguish resident marine (Bodega Harbor) from landlocked freshwater (FW, Lake Solano) three-spined sticklebacks were revealed by label-free quantitative proteomics. Secreted plasma proteins involved in lipid transport, blood coagulation, proteolysis, plasminogen-activating cascades, extracellular stimulus responses, and immunity are most abundant in this species. Globulins and albumins are much less abundant than in mammalian plasma. Unbiased quantitative proteome profiling identified 45 highly population-specific plasma proteins. Population-specific abundance differences were validated by targeted proteomics based on data-independent acquisition. Gene ontology enrichment analyses and known functions of population-specific plasma proteins indicate enrichment of processes controlling cell adhesion, tissue remodeling, proteolytic processing, and defense signaling in marine sticklebacks. Moreover, fetuin B and leukocyte cell derived chemotaxin 2 are much more abundant in marine fish. These proteins promote bone morphogenesis and likely contribute to population-specific body armor differences. Plasma proteins enriched in FW fish promote translation, heme biosynthesis, and lipid transport, suggesting a greater presence of plasma microparticles. Many prominent population-specific plasma proteins (e.g. apoptosis-associated speck-like protein containing a CARD) lack any homolog of known function or adequate functional characterization. Their functional characterization and the identification of population-specific environmental contexts and selective pressures that cause plasma proteome diversification are future directions emerging from this study. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selective microrobot control using a thermally responsive microclamper for microparticle manipulation

International Nuclear Information System (INIS)

Go, Gwangjun; Choi, Hyunchul; Ko, Seong Young; Park, Jong-Oh; Park, Sukho; Jeong, Semi

2016-01-01

Microparticle manipulation using a microrobot in an enclosed environment, such as a lab-on-a-chip, has been actively studied because an electromagnetic actuated microrobot can have accurate motility and wireless controllability. In most studies on electromagnetic actuated microrobots, only a single microrobot has been used to manipulate cells or microparticles. However, the use of a single microrobot can pose several limitations when performing multiple roles in microparticle manipulation. To overcome the limitations associated with using a single microrobot, we propose a new method for the control of multiple microrobots. Multiple microrobots can be controlled independently by an electromagnetic actuation system and multiple microclampers combined with microheaters. To select a specific microrobot among multiple microrobots, we propose a microclamper composed of a clamper structure using thermally responsive hydrogel and a microheater for controlling the microclamper. A fundamental test of the proposed microparticle manipulation system is performed by selecting a specific microrobot among multiple microrobots. Through the independent locomotion of multiple microrobots with U- and V-shaped tips, heterogeneous microparticle manipulation is demonstrated in the creation of a two-dimensional structure. In the future, our proposed multiple-microrobot system can be applied to tasks that are difficult to perform using a single microrobot, such as cell manipulation, cargo delivery, tissue assembly, and cloning. (paper)

Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions

OpenAIRE

Roca, Elisa; Lacroix, Romaric; Judicone, Coralie; Laroumagne, Sophie; Robert, St?phane; Cointe, Sylvie; Muller, Alexandre; Kaspi, Elise; Roll, Patrice; Brisson, Alain R.; Tantucci, Claudio; Astoul, Philippe; Dignat-George, Fran?oise

2015-01-01

Pleural biomarkers allowing to mini-invasively discriminate benign from malignant pleural effusions are needed. Among potential candidates, microparticles (MPs) are extracellular vesicles that vectorize antigen derived from the parent cell. We hypothesized that tumor-derived MPs could be present in the pleural liquid and help to identify patients with malignant pleural effusions. Using highly sensitive flow cytometry and cryo-electron microscopy, we showed that large amounts of MPs from hemat...

Circulating microparticles: square the circle

Science.gov (United States)

2013-01-01

Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

Targeting microparticle biogenesis: a novel approach to the circumvention of cancer multidrug resistance.

Science.gov (United States)

Roseblade, Ariane; Luk, Frederick; Ung, Alison; Bebawy, Mary

2015-01-01

Microparticles (MPs) are released from most eukaryotic cells after the vesiculation of the plasma membrane and serve as vectors of long and short-range signaling. MPs derived from multidrug resistant (MDR) cancer cells carry molecular components of the donor cell such as nucleic acids and proteins, and can alter the activity of drug-sensitive recipient cells through the transfer of their cargo. Given the substantial role of MPs in the acquisition and dissemination of MDR, we propose that the inhibition of MP release provides a novel therapeutic approach. This study characterises the effect of a panel of molecules known to act on MP-biosynthetic pathways. We demonstrate a differential effect by these molecules on MP inhibition that appear dependent on the release of intracellular calcium stores following activation with the calcium ionophore A23187. Calpain inhibitor, PD-150606; a selective inhibitor of Rho-associated, coiled-coil containing protein kinase (ROCK), Y-27632; and the vitamin B5 derivative pantethine, inhibited MP release only upon prior activation with A23187. Calpain inhibitor II showed significant inhibition in the absence of cell activation, whereas the vitamin B5 derivatives cystamine dihydrochloride and cysteamine hydrochloride showed no effect on MP inhibition under either condition. In contrast the classical pharmacological inhibitor of MDR, the calcium channel blocker Verapamil, showed an increase in MP formation on resting cells. These results suggest a potential role for calcium in the mechanism of action for PD-150606, Y-27632 and pantethine. These molecules, together with calpain inhibitor II have shown promise as modulators of MP release and warrant consideration as potential candidates for the development of an alternative therapeutic strategy for the prevention of MP-mediated MDR in cancer.

The Emerging Roles of Microparticles in Diabetic Nephropathy.

Science.gov (United States)

Lu, Chen Chen; Ma, Kun Ling; Ruan, Xiong Zhong; Liu, Bi Cheng

2017-01-01

Microparticles (MPs) are a type of extracellular vesicles (EVs) shed from the outward budding of plasma membranes during cell apoptosis and/or activation. These microsized particles then release specific contents (e.g., lipids, proteins, microRNAs) which are active participants in a wide range of both physiological and pathological processes at the molecular level, e.g., coagulation and angiogenesis, inflammation, immune responses. Research limitations, such as confusing nomenclature and overlapping classification, have impeded our comprehension of these tiny molecules. Diabetic nephropathy (DN) is currently the greatest contributor to end-stage renal diseases (ESRD) worldwide, and its public health impact will continue to grow due to the persistent increase in the prevalence of diabetes mellitus (DM). MPs have recently been considered as potentially involved in DN onset and progression, and this review juxtaposes some of the research updates about the possible mechanisms from several relevant aspects and insights into the therapeutic perspectives of MPs in clinical management and pharmacological treatment of DN patients.

Procedure for radiotracer labelling of carbon microparticles

International Nuclear Information System (INIS)

Kallay, Z.; Soltes, L.; Novak, I.; Trnovec, T.; Berek, D.

1988-01-01

A method is suggested for the labelling of carbon microparticles with radioisotopes. A carbon precursor is selected from the group of polymers including phenol-formaldehyde bitumens, polyvinyl chloride, polyvinylidene chloride, polyacrylonitrile, urea-formaldehyde or epoxy bitumens, and polysaccharides. A monodisperse fraction of the porous precursor is saturated with a solution of a salt of the radioisotope, and the carrier solvent is removed by evaporation at 360-420 K. The impregnated precursor is subsequently pyrolyzed at 870-1000 K. This method can find application in the preparation of radiactively labelled microparticles used for examining changes in the function of the cardiovascular system in experimental medicine, pharmacology, physiology and endocrinology. (P.A.)

Inevitability of Genetic Parasites

Science.gov (United States)

Iranzo, Jaime; Puigbò, Pere; Lobkovsky, Alexander E.; Wolf, Yuri I.

2016-01-01

Abstract Almost all cellular life forms are hosts to diverse genetic parasites with various levels of autonomy including plasmids, transposons and viruses. Theoretical modeling of the evolution of primordial replicators indicates that parasites (cheaters) necessarily evolve in such systems and can be kept at bay primarily via compartmentalization. Given the (near) ubiquity, abundance and diversity of genetic parasites, the question becomes pertinent: are such parasites intrinsic to life? At least in prokaryotes, the persistence of parasites is linked to the rate of horizontal gene transfer (HGT). We mathematically derive the threshold value of the minimal transfer rate required for selfish element persistence, depending on the element duplication and loss rates as well as the cost to the host. Estimation of the characteristic gene duplication, loss and transfer rates for transposons, plasmids and virus-related elements in multiple groups of diverse bacteria and archaea indicates that most of these rates are compatible with the long term persistence of parasites. Notably, a small but non-zero rate of HGT is also required for the persistence of non-parasitic genes. We hypothesize that cells cannot tune their horizontal transfer rates to be below the threshold required for parasite persistence without experiencing highly detrimental side-effects. As a lower boundary to the minimum DNA transfer rate that a cell can withstand, we consider the process of genome degradation and mutational meltdown of populations through Muller’s ratchet. A numerical assessment of this hypothesis suggests that microbial populations cannot purge parasites while escaping Muller’s ratchet. Thus, genetic parasites appear to be virtually inevitable in cellular organisms. PMID:27503291

Circulating endothelial cells and procoagulant microparticles in patients with glioblastoma: prognostic value.

Directory of Open Access Journals (Sweden)

Gaspar Reynés

Full Text Available AIM: Circulating endothelial cells and microparticles are prognostic factors in cancer. However, their prognostic and predictive value in patients with glioblastoma is unclear. The objective of this study was to investigate the potential prognostic value of circulating endothelial cells and microparticles in patients with newly diagnosed glioblastoma treated with standard radiotherapy and concomitant temozolomide. In addition, we have analyzed the methylation status of the MGMT promoter. METHODS: Peripheral blood samples were obtained before and at the end of the concomitant treatment. Blood samples from healthy volunteers were also obtained as controls. Endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Microparticles were quantified by flow cytometry. Microparticle-mediated procoagulant activity was measured by endogen thrombin generation and by phospholipid-dependent clotting time. Methylation status of MGMT promoter was determined by multiplex ligation-dependent probe amplification. RESULTS: Pretreatment levels of circulating endothelial cells and microparticles were higher in patients than in controls (p<0.001. After treatment, levels of microparticles and thrombin generation decreased, and phospholipid-dependent clotting time increased significantly. A high pretreatment endothelial cell count, corresponding to the 99(th percentile in controls, was associated with poor overall survival. MGMT promoter methylation was present in 27% of tumor samples and was associated to a higher overall survival (66 weeks vs 30 weeks, p<0.004. CONCLUSION: Levels of circulating endothelial cells may have prognostic value in patients with glioblastoma.

Preparation of Antheraea pernyi Silk Fibroin Microparticles through a Facile Electrospinning Method

Directory of Open Access Journals (Sweden)

Xiufang Li

2016-01-01

Full Text Available The goal of this study was to fabricate Antheraea pernyi silk fibroin (ASF microparticles using electrospinning under mild processing conditions. To improve processability of the ASF solution, poly(ethylene oxide (PEO was used to regulate viscosity of ASF solution for electrospinning. It was found that the blend of ASF with PEO could form a bead-on-string structure with well spherical particles. Furthermore, aqueous ethanol and ultrasonic treatments could disrupt the nanofibrillar string structure between particles and ultimately produced water-insoluble ASF particles with submicron scale. Cell viability studies indicated that the ASF microparticles were nontoxic to EA926 cells. Moreover, fluorescent images based on FITC labeling showed that the ASF microparticles were easily uptaken by the cells. Aqueous-based electrospinning provides a potentially useful option for the fabrication of ASF microparticles based on this unique fibrous protein.

Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

Science.gov (United States)

Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

2014-06-05

The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Modelling of plasma-antenna coupling and non-linear radio frequency wave-plasma-wall interactions in the magnetized plasma device under ion cyclotron range of frequencies

International Nuclear Information System (INIS)

Lu, LingFeng

2016-01-01

Ion Cyclotron Resonant Heating (ICRH) by waves in 30-80 MHz range is currently used in magnetic fusion plasmas. Excited by phased arrays of current straps at the plasma periphery, these waves exist under two polarizations. The Fast Wave tunnels through the tenuous plasma edge and propagates to its center where it is absorbed. The parasitically emitted Slow Wave only exists close to the launchers. How much power can be coupled to the center with 1 A current on the straps? How do the emitted radiofrequency (RF) near and far fields interact parasitically with the edge plasma via RF sheath rectification at plasma-wall interfaces? To address these two issues simultaneously, in realistic geometry over the size of ICRH antennas, this thesis upgraded and tested the Self-consistent Sheaths and Waves for ICH (SSWICH) code. SSWICH couples self-consistently RF wave propagation and Direct Current (DC) plasma biasing via non-linear RF and DC sheath boundary conditions (SBCs) at plasma/wall interfaces. Its upgrade is full wave and was implemented in two dimensions (toroidal/radial). New SBCs coupling the two polarizations were derived and implemented along shaped walls tilted with respect to the confinement magnetic field. Using this new tool in the absence of SBCs, we studied the impact of a density decaying continuously inside the antenna box and across the Lower Hybrid (LH) resonance. Up to the memory limits of our workstation, the RF fields below the LH resonance changed with the grid size. However the coupled power spectrum hardly evolved and was only weakly affected by the density inside the box. In presence of SBCs, SSWICH-FW simulations have identified the role of the fast wave on RF sheath excitation and reproduced some key experimental observations. SSWICH-FW was finally adapted to conduct the first electromagnetic and RF-sheath 2D simulations of the cylindrical magnetized plasma device ALINE. (author) [fr

Properties of iopamidol-incorporated poly(vinyl alcohol) microparticle as an X-ray imaging flow tracer.

Science.gov (United States)

Ahn, Sungsook; Jung, Sung Yong; Lee, Jin Pyung; Lee, Sang Joon

2011-02-10

We have recently reported on poly(vinyl alcohol) microparticles containing X-ray contrast agent, iopamidol, designed as a flow tracer working in synchrotron X-ray imaging ( Biosens. Bioelectron. 2010 , 25 , 1571 ). Although iopamidol is physically encapsulated in the microparticles, it displays a great contrast enhancement and stable feasibility in in vitro human blood pool. Nonetheless, a direct relation between the absolute amount of incorporated iopamidol and the enhancement in imaging efficiency was not observed. In this study, physical properties of the designed microparticle are systematically investigated experimentally with theoretical interpretation to correlate an enhancement in X-ray imaging efficiency. The compositional ratio of X-ray contrast agent in polymeric microparticle is controlled as 1/1 and 10/1 [contrast agent/polymer microparticle (w/w)] with changed degree of cross-linkings. Flory-Huggins interaction parameter (χ), retractive force (τ) and degree of swelling of the designed polymeric microparticles are investigated. In addition, the hydrodynamic size (D(H)) and ζ-potential are evaluated in terms of environment responsiveness. The physical properties of the designed flow tracer microparticles under a given condition are observed to be strongly related with the X-ray absorption efficiency, which are also supported by the Beer-Lambert-Bouguer law. The designed microparticles are almost nontoxic with a reasonable concentration and time period, enough to be utilized as a flow tracer in various biomedical applications. This study would contribute to the basic understanding on the physical property connected with the imaging efficiency of contrast agents.

A study on arrangement characteristics of microparticles in sedimentation on flat and round substrates

Science.gov (United States)

Yeo, Eunju; Son, Minhee; Kim, Kwanoh; Kim, Jeong Hwan; Yoo, Yeong-Eun; Choi, Doo-Sun; Kim, Jungchul; Yoon, Seok Ho; Yoon, Jae Sung

2017-12-01

Recent advances of microfabrication techniques have enabled diverse structures and devices on the microscale. This fabrication method using microparticles is one of the most promising technologies because it can provide a cost effective process for large areas. So, many researchers are studying modulation and manipulation of the microparticles in solution to obtain a proper arrangement. However, the microparticles are in sedimentation status during the process in many cases, which makes it difficult to control their arrangement. In this study, droplets containing microparticles were placed on a substrate with minimal force and we investigated the arrangement of these microparticles after evaporation of the liquid. Experiments have been performed with upward and downward substrates to change the direction of gravity. The geometry of substrates was also changed, which were flat or round. The results show that the arrangement depends on the size of particles and gravity and geometry of the substrate. The arrangement also depends on the movement of the contact line of the droplets, which may recede or be pinned during evaporation. This study is expected to provide a method of the fabrication process for microparticles which may not be easily manipulated due to sedimentation.

Plasma uric acid levels correlate with inflammation and disease severity in Malian children with Plasmodium falciparum malaria.

Directory of Open Access Journals (Sweden)

Tatiana M Lopera-Mesa

Full Text Available Plasmodium falciparum elicits host inflammatory responses that cause the symptoms and severe manifestations of malaria. One proposed mechanism involves formation of immunostimulatory uric acid (UA precipitates, which are released from sequestered schizonts into microvessels. Another involves hypoxanthine and xanthine, which accumulate in parasitized red blood cells (RBCs and may be converted by plasma xanthine oxidase to UA at schizont rupture. These two forms of 'parasite-derived' UA stimulate immune cells to produce inflammatory cytokines in vitro.We measured plasma levels of soluble UA and inflammatory cytokines and chemokines (IL-6, IL-10, sTNFRII, MCP-1, IL-8, TNFα, IP-10, IFNγ, GM-CSF, IL-1β in 470 Malian children presenting with uncomplicated malaria (UM, non-cerebral severe malaria (NCSM or cerebral malaria (CM. UA levels were elevated in children with NCSM (median 5.74 mg/dl, 1.21-fold increase, 95% CI 1.09-1.35, n = 23, p = 0.0007 and CM (median 5.69 mg/dl, 1.19-fold increase, 95% CI 0.97-1.41, n = 9, p = 0.0890 compared to those with UM (median 4.60 mg/dl, n = 438. In children with UM, parasite density and plasma creatinine levels correlated with UA levels. These UA levels correlated with the levels of seven cytokines [IL-6 (r = 0.259, p<0.00001, IL-10 (r = 0.242, p<0.00001, sTNFRII (r = 0.221, p<0.00001, MCP-1 (r = 0.220, p<0.00001, IL-8 (r = 0.147, p = 0.002, TNFα (r = 0.132, p = 0.006 and IP-10 (r = 0.120, p = 0.012]. In 39 children, UA levels were 1.49-fold (95% CI 1.34-1.65; p<0.0001 higher during their malaria episode [geometric mean titer (GMT 4.67 mg/dl] than when they were previously healthy and aparasitemic (GMT 3.14 mg/dl.Elevated UA levels may contribute to the pathogenesis of P. falciparum malaria by activating immune cells to produce inflammatory cytokines. While this study cannot identify the cause of elevated UA levels, their association with parasite density and creatinine levels suggest that parasite-derived UA

Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

Science.gov (United States)

Ma, Ruihua; Ji, Tiantian; Chen, Degao; Dong, Wenqian; Zhang, Huafeng; Yin, Xiaonan; Ma, Jingwei; Liang, Xiaoyu; Zhang, Yi; Shen, Guanxin; Qin, Xiaofeng; Huang, Bo

2016-04-01

Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

On the origin of microparticles: From “platelet dust” to mediators of intercellular communication

Science.gov (United States)

Hargett, Leslie A.; Bauer, Natalie N.

2013-01-01

Microparticles are submicron vesicles shed from a variety of cells. Peter Wolf first identified microparticles in the midst of ongoing blood coagulation research in 1967 as a product of platelets. He termed them platelet dust. Although initially thought to be useless cellular trash, decades of research focused on the tiny vesicles have defined their roles as participators in coagulation, cellular signaling, vascular injury, and homeostasis. The purpose of this review is to highlight the science leading up to the discovery of microparticles, feature discoveries made by key contributors to the field of microparticle research, and discuss their positive and negative impact on the pulmonary circulation. PMID:24015332

Intra-laser-cavity microparticle sensing with a dual-wavelength distributed-feedback laser

NARCIS (Netherlands)

Bernhardi, Edward H.; van der Werf, Kees O; Hollink, Anton J F; Wörhoff, Kerstin; de Ridder, René M; Subramaniam, Vinod; Pollnau, Markus

An integrated intra-laser-cavity microparticle sensor based on a dual-wavelength distributed-feedback channel waveguide laser in ytterbium-doped amorphous aluminum oxide on a silicon substrate is demonstrated. Real-time detection and accurate size measurement of single micro-particles with diameters

Nicotine-magnesium aluminum silicate microparticle surface modified with chitosan for mucosal delivery

DEFF Research Database (Denmark)

Kanjanakawinkul, Watchara; Rades, Thomas; Puttipipatkhachorn, Satit

2013-01-01

Magnesium aluminum silicate (MAS), a negatively charged clay, and nicotine (NCT), a basic drug, can interact electrostatically to form microparticles. Chitosan (CS) was used for the surface modification of the microparticles, and a lyophilization method was used to preserve the original particle...

On-chip microparticle detection and sizing using a dual-wavelength waveguide laser

NARCIS (Netherlands)

Bernhardi, Edward; van der Werf, Kees; Hollink, Anton; Worhoff, Kerstin; de Ridder, R.M.; Subramaniam, Vinod; Pollnau, Markus

An integrated intra-laser-cavity microparticle sensor based on a dual-phase-shift, dual-wavelength distributed-feedback channel waveguide laser in ytterbium-doped aluminium oxide is presented. Single micro-particles with diameters ranging between 1 μm and 20 μm are detected.

Properties of gelatin-based films incorporated with chitosan-coated microparticles charged with rutin.

Science.gov (United States)

Dammak, Ilyes; Bittante, Ana Mônica Quinta Barbosa; Lourenço, Rodrigo Vinicius; do Amaral Sobral, Paulo José

2017-08-01

The aim of this study was development an active film based on gelatin incorporated with antioxidant, rutin carried into microparticles. The complexation between oppositely charged lecithin and chitosan was applied to prepare the chitosan-coated microparticles. The generated microparticles had an average size of 520±4nm and a span of 0.3 were formulated by a rotor-stator homogenize at the homogenization speed 10,000rpm. Composite films were prepared by incorporating chitosan-coated microparticles, at various concentrations (0.05, 0.1, 0.5, or 1% (based on the weight of the gelatin powder)) in the gelatin-based films. For the prepared films, the results showed that obtained physicochemical, water vapor barrier, and mechanical were compared with native gelatin film with a slight decrease for chitosan concentration higher than 0.5%. The microstructure studies done by scanning electron microscopes, revealed different micropores embedded with oil resulting from the incorporation of the microparticles into the gelatin matrix. Moreover, the calorimetric results were comparable to those of gelatin control film with T g value 45°C and increased crystallinity percentage with increasing incorporation of microparticles. This original concept of composite biodegradable films may thus be a good alternative to incorporate liposoluble active compounds to design an active packaging with good properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Luminescence investigation of Yb3+/Er3+ codoped single LiYF4 microparticle

International Nuclear Information System (INIS)

Gao, Wei; Zheng, Hairong; He, Enjie; Lu, Ying; Gao, Fangqi

2014-01-01

Tetragonal phase LiYF 4 :Yb 3+ /Er 3+ microparticles are synthesized via facile hydrothermal method. Single LiYF 4 microparticle is excited with IR laser at 980 nm in a confocal setup, and strong green and weak red emissions are observed. It is found that single LiYF 4 :Yb 3+ /Er 3+ microparticle with sub-structure presents stronger upconversion luminescence emission and smaller intensity ratio of red to green emission than that from LiYF 4 :Yb 3+ /Er 3+ microparticle with no sub-structure. The possible mechanism, the influence of particle size and the existence of EDTA on the upconversion luminescence emission are investigated. The current study suggests that the luminescence observation with single micropaticle can effectively avoid the influence of environment and neighbor particles, which is important for investigating the luminescence properties of micro- or nano-crystals and for extending their application. - Highlights: • Single LiYF 4 microparticle is excited with IR laser at 980 nm in a confocal setup, and strong green and weak red emissions are observed. • Single LiYF 4 microparticle with different morphology exhibits different fluorescence emission intensity and intensity ratio of red to green emission. • The possible mechanism, the influence of particle size and the existence of EDTA on the upconversion emission are investigated

Functionalised alginate flow seeding microparticles for use in Particle Image Velocimetry (PIV).

Science.gov (United States)

Varela, Sylvana; Balagué, Isaac; Sancho, Irene; Ertürk, Nihal; Ferrando, Montserrat; Vernet, Anton

2016-01-01

Alginate microparticles as flow seeding fulfil all the requirements that are recommended for the velocity measurements in Particle Image Velocimetry (PIV). These spherical microparticles offer the advantage of being environmentally friendly, having excellent seeding properties and they can be produced via a very simple process. In the present study, the performances of alginate microparticles functionalised with a fluorescent dye, Rhodamine B (RhB), for PIV have been studied. The efficacy of fluorescence is appreciated in a number of PIV applications since it can boost the signal-to-noise ratio. Alginate microparticles functionalised with RhB have high emission efficiency, desirable match with fluid density and controlled size. The study of the particles behaviour in strong acid and basic solutions and ammonia is also included. This type of particles can be used for measurements with PIV and Planar Laser Induced Fluorescence (PLIF) simultaneously, including acid-base reactions.

Characterization of spray dried bioadhesive metformin microparticles for oromucosal administration

DEFF Research Database (Denmark)

Sander, Camilla; Madsen, Katrine Dragsbæk; Hyrup, Birgitte

2013-01-01

delivery systems are considered a promising approach as they facilitate a close contact between the drug and the oral mucosa. In this study, bioadhesive chitosan-based microparticles of metformin hydrochloride were prepared by spray drying aqueous dispersions with different chitosan:metformin ratios...... be prepared and analyzed using the ex vivo retention model. We observed an increase in metformin retention on porcine mucosa with increasing chitosan:metformin ratios, while no effect of increasing the chitosan molecular weight was found. Rheological characterization of feeds for spray drying was performed...... and chitosan grades with increasing molecular weights. A recently developed ex vivo flow retention model with porcine buccal mucosa was used to evaluate the bioadhesive properties of spray dried microparticles. An important outcome of this study was that microparticles with the desired metformin content could...

Preparation and Evaluation of Poly (ε-caprolactone Nanoparticles-in-Microparticles by W/O/W Emulsion Method

Directory of Open Access Journals (Sweden)

Mitra Jelvehgari

2010-06-01

Full Text Available Objective(sTheophylline, a xanthenes derivative, is still widely used as an effective bronchodilator in the management of asthmatic patients. It is used both as a prophylactic drug and to prevent acute exacerbations of asthma. The aim of study was to formulate and evaluate effect of the microencapsulation of theophylline loaded nanoparticles on the reduction of burst release.Materials and MethodsMicroparticles (simple and composite and nanoparticles were prepared by using water-in-oil-in-water (W1/O/W2 double-emulsion solvent diffusion/evaporation method, taking different ratios of drug/polymer. Solvent systems consist of ethyl acetate and dichloromethane for microspheres and nanospheres, respectively. In the current study formulations were characterized by loading efficiency, yield, particle size, zeta potential, X-ray diffraction (XRD and differential scanning calorimetry (DSC.ResultsIn microparticles, the best drug to polymer ratio was 0.8:1 (F3. F3 formulation had minimum burst effect (37.81%, high loading efficiency (95.88%. In nanoparticles, F4 formulation (0.4:1 drug/polymer ratio showed high production yield (40.8%, loading efficiency (99.05%, low particle size (756 nm and minimum burst effect compared with other nanoparticle formulations. The drug loaded composite microspheres (F9 showed minimum burst effect, acceptable release and mean particle size 17.696 µm. The XRD and DSC showed stable character of theophylline in the drug loaded microspheres. The drug release was found to be diffusion and erosion controlled.ConclusionThe burst was significantly lower with composite microparticles and may be explained by lower diffusion of the drug from double polymeric wall formed by the nanoparticles matrix followed by another diffusion step through the microparticle polymeric wall.

Increased CD39 Nucleotidase Activity on Microparticles from Patients with Idiopathic Pulmonary Arterial Hypertension

Science.gov (United States)

Visovatti, Scott H.; Hyman, Matthew C.; Bouis, Diane; Neubig, Richard; McLaughlin, Vallerie V.; Pinsky, David J.

2012-01-01

Background Idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease characterized by increased pulmonary vascular resistance, smooth muscle and endothelial cell proliferation, perivascular inflammatory infiltrates, and in situ thrombosis. Circulating intravascular ATP, ADP, AMP and adenosine activate purinergic cell signaling pathways and appear to induce many of the same pathologic processes that underlie IPAH. Extracellular dephosphorylation of ATP to ADP and AMP occurs primarily via CD39 (ENTPD1), an ectonucleotidase found on the surface of leukocytes, platelets, and endothelial cells [1]. Microparticles are micron-sized phospholipid vesicles formed from the membranes of platelets and endothelial cells. Objectives: Studies here examine whether CD39 is an important microparticle surface nucleotidase, and whether patients with IPAH have altered microparticle-bound CD39 activity that may contribute to the pathophysiology of the disease. Methodology/ Principal Findings Kinetic parameters, inhibitor blocking experiments, and immunogold labeling with electron microscopy support the role of CD39 as a major nucleotidase on the surface of microparticles. Comparison of microparticle surface CD39 expression and nucleotidase activity in 10 patients with advanced IPAH and 10 healthy controls using flow cytometry and thin layer chromatograph demonstrate the following: 1) circulating platelet (CD39+CD31+CD42b+) and endothelial (CD39+CD31+CD42b−) microparticle subpopulations in patients with IPAH show increased CD39 expression; 2) microparticle ATPase and ADPase activity in patients with IPAH is increased. Conclusions/ Significance We demonstrate for the first time increased CD39 expression and function on circulating microparticles in patients with IPAH. Further research is needed to elucidate whether these findings identify an important trigger for the development of the disease, or reflect a physiologic response to IPAH. PMID:22792409

Effect of cracks in coating on gas release from a fuel microparticle

International Nuclear Information System (INIS)

Bondarenko, A.G.; Gudkov, A.N.; Tselishchev, Yu.V.

1988-01-01

Effect of cracks in protective coating on gas release from a fuel microparticle is investigated in a general form. A fuel microparticle comprizing a kern, a buffer layer and an external protective coating is considered. The pressure of radioactive inert gases in the microparticle buffer layer is evaluated within the 1000-1800 K temperature range on the base of diffusion-defect-trap transport theory. It is shown that the process of radionuclide adsorption interaction with the coating material leads to a more abrupt than by exponent, weakening of mass transfer coefficient. In this case for long-living isotopes the effect of adsorption processes manifests weaker than for short-living ones. Mass transfer coefficient for the crack system depends sufficiently on the total pressure of gas mixture under the coating while for a single cracks such dependence is not observed. A conclusion is drawn that the obtained ratios can be applied for evaluating the character of fuel microparticle protective coating destruction (single non-intersecting cracks or a crack system) using the data on various nuclide release. These ratios can be also applied for the choice of the coating thichness under which gaseous fission product release from the fuel microparticle in case of its protective coating failure does not exceed the acceptable limits

Effect of Formulation and Process Parameters on Chitosan Microparticles Prepared by an Emulsion Crosslinking Technique.

Science.gov (United States)

Rodriguez, Lidia B; Avalos, Abraham; Chiaia, Nicholas; Nadarajah, Arunan

2017-05-01

There are many studies about the synthesis of chitosan microparticles; however, most of them have very low production rate, have wide size distribution, are difficult to reproduce, and use harsh crosslinking agents. Uniform microparticles are necessary to obtain repeatable drug release behavior. The main focus of this investigation was to study the effect of the process and formulation parameters during the preparation of chitosan microparticles in order to produce particles with narrow size distribution. The technique evaluated during this study was emulsion crosslinking technique. Chitosan is a biocompatible and biodegradable material but lacks good mechanical properties; for that reason, chitosan was ionically crosslinked with sodium tripolyphosphate (TPP) at three different ratios (32, 64, and 100%). The model drug used was acetylsalicylic acid (ASA). During the preparation of the microparticles, chitosan was first mixed with ASA and then dispersed in oil containing an emulsifier. The evaporation of the solvents hardened the hydrophilic droplets forming microparticles with spherical shape. The process and formulation parameters were varied, and the microparticles were characterized by their morphology, particle size, drug loading efficiency, and drug release behavior. The higher drug loading efficiency was achieved by using 32% mass ratio of TPP to chitosan. The average microparticle size was 18.7 μm. The optimum formulation conditions to prepare uniform spherical microparticles were determined and represented by a region in a triangular phase diagram. The drug release analyses were evaluated in phosphate buffer solution at pH 7.4 and were mainly completed at 24 h.

The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles.

Directory of Open Access Journals (Sweden)

Bing Xu

2017-08-01

Full Text Available Microparticles (MPs are cell-cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17 creates transverse-tubule (t-tubule membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold-generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus. We explored the possibility that cBIN1-microfolds are externally released from cardiomyocytes. Using electron microscopy imaging with immunogold labeling, we found in mouse plasma that cBIN1 exists in membrane vesicles about 200 nm in size, which is consistent with the size of MPs. In mice with cardiac-specific heterozygous Bin1 deletion, flow cytometry identified 47% less cBIN1-MPs in plasma, supporting cardiac origin. Cardiac release was also evidenced by the detection of cBIN1-MPs in medium bathing a pure population of isolated adult mouse cardiomyocytes. In human plasma, osmotic shock increased cBIN1 detection by enzyme-linked immunosorbent assay (ELISA, and cBIN1 level decreased in humans with heart failure, a condition with reduced cardiac muscle cBIN1, both of which support cBIN1 release in MPs from human hearts. Exploring putative mechanisms of MP release, we found that the membrane fission complex endosomal sorting complexes required for transport (ESCRT-III subunit charged multivesicular body protein 4B (CHMP4B colocalizes and coimmunoprecipitates with cBIN1, an interaction enhanced by actin stabilization. In HeLa cells with cBIN1 overexpression, knockdown of CHMP4B reduced the release of cBIN1-MPs. Using truncation mutants, we identified that the N-terminal BAR (N-BAR domain in cBIN1 is required for CHMP4B binding and MP release. This study links the BAR protein superfamily

The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles.

Science.gov (United States)

Xu, Bing; Fu, Ying; Liu, Yan; Agvanian, Sosse; Wirka, Robert C; Baum, Rachel; Zhou, Kang; Shaw, Robin M; Hong, TingTing

2017-08-01

Microparticles (MPs) are cell-cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold-generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus. We explored the possibility that cBIN1-microfolds are externally released from cardiomyocytes. Using electron microscopy imaging with immunogold labeling, we found in mouse plasma that cBIN1 exists in membrane vesicles about 200 nm in size, which is consistent with the size of MPs. In mice with cardiac-specific heterozygous Bin1 deletion, flow cytometry identified 47% less cBIN1-MPs in plasma, supporting cardiac origin. Cardiac release was also evidenced by the detection of cBIN1-MPs in medium bathing a pure population of isolated adult mouse cardiomyocytes. In human plasma, osmotic shock increased cBIN1 detection by enzyme-linked immunosorbent assay (ELISA), and cBIN1 level decreased in humans with heart failure, a condition with reduced cardiac muscle cBIN1, both of which support cBIN1 release in MPs from human hearts. Exploring putative mechanisms of MP release, we found that the membrane fission complex endosomal sorting complexes required for transport (ESCRT)-III subunit charged multivesicular body protein 4B (CHMP4B) colocalizes and coimmunoprecipitates with cBIN1, an interaction enhanced by actin stabilization. In HeLa cells with cBIN1 overexpression, knockdown of CHMP4B reduced the release of cBIN1-MPs. Using truncation mutants, we identified that the N-terminal BAR (N-BAR) domain in cBIN1 is required for CHMP4B binding and MP release. This study links the BAR protein superfamily to the ESCRT

Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease.

Science.gov (United States)

Ma, Qiu-Lan; Teng, Edmond; Zuo, Xiaohong; Jones, Mychica; Teter, Bruce; Zhao, Evan Y; Zhu, Cansheng; Bilousova, Tina; Gylys, Karen H; Apostolova, Liana G; LaDu, Mary Jo; Hossain, Mir Ahamed; Frautschy, Sally A; Cole, Gregory M

2018-06-01

Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking. We evaluated neuronal pentraxin 1 (NP1), a potential CNS-derived plasma biomarker of excitatory synaptic pathology. NP1 is preferentially expressed in brain and involved in glutamate receptor internalization. NP1 is secreted presynaptically induced by Aβ oligomers, and implicated in excitatory synaptic and mitochondrial deficits. Levels of NP1 and its fragments were increased in a correlated fashion in both brain and plasma of 7-8 month-old E4FAD mice relative to E3FAD mice. NP1 was also found in exosome preparations and reduced by dietary DHA supplementation. Plasma NP1 was higher in E4FAD+ (APOE4 +/+ /FAD +/- ) relative to E4FAD- (non-carrier; APOE4 +/+ /FAD -/- ) mice, suggesting NP1 is modulated by Aβ expression. Finally, relative to normal elderly, plasma NP1 was also elevated in patients with mild cognitive impairment (MCI) and elevated further in the subset who progressed to early-stage AD. In those patients, there was a trend towards increased NP1 levels in APOE4 carriers relative to non-carriers. These findings indicate that NP1 may represent a potential synapse-derived plasma biomarker relevant to early alterations in excitatory synapses in MCI and early-stage AD. Copyright © 2018. Published by Elsevier Inc.

The strigolactone germination stimulants of the plant-parasitic Striga and Orobanche spp. are derived from the carotenoid pathway.

Science.gov (United States)

Matusova, Radoslava; Rani, Kumkum; Verstappen, Francel W A; Franssen, Maurice C R; Beale, Michael H; Bouwmeester, Harro J

2005-10-01

The seeds of parasitic plants of the genera Striga and Orobanche will only germinate after induction by a chemical signal exuded from the roots of their host. Up to now, several of these germination stimulants have been isolated and identified in the root exudates of a series of host plants of both Orobanche and Striga spp. In most cases, the compounds were shown to be isoprenoid and belong to one chemical class, collectively called the strigolactones, and suggested by many authors to be sesquiterpene lactones. However, this classification was never proven; hence, the biosynthetic pathways of the germination stimulants are unknown. We have used carotenoid mutants of maize (Zea mays) and inhibitors of isoprenoid pathways on maize, cowpea (Vigna unguiculata), and sorghum (Sorghum bicolor) and assessed the effects on the root exudate-induced germination of Striga hermonthica and Orobanche crenata. Here, we show that for these three host and two parasitic plant species, the strigolactone germination stimulants are derived from the carotenoid pathway. Furthermore, we hypothesize how the germination stimulants are formed. We also discuss this finding as an explanation for some phenomena that have been observed for the host-parasitic plant interaction, such as the effect of mycorrhiza on S. hermonthica infestation.

Hierarchical assembly of viral nanotemplates with encoded microparticles via nucleic acid hybridization.

Science.gov (United States)

Tan, Wui Siew; Lewis, Christina L; Horelik, Nicholas E; Pregibon, Daniel C; Doyle, Patrick S; Yi, Hyunmin

2008-11-04

We demonstrate hierarchical assembly of tobacco mosaic virus (TMV)-based nanotemplates with hydrogel-based encoded microparticles via nucleic acid hybridization. TMV nanotemplates possess a highly defined structure and a genetically engineered high density thiol functionality. The encoded microparticles are produced in a high throughput microfluidic device via stop-flow lithography (SFL) and consist of spatially discrete regions containing encoded identity information, an internal control, and capture DNAs. For the hybridization-based assembly, partially disassembled TMVs were programmed with linker DNAs that contain sequences complementary to both the virus 5' end and a selected capture DNA. Fluorescence microscopy, atomic force microscopy (AFM), and confocal microscopy results clearly indicate facile assembly of TMV nanotemplates onto microparticles with high spatial and sequence selectivity. We anticipate that our hybridization-based assembly strategy could be employed to create multifunctional viral-synthetic hybrid materials in a rapid and high-throughput manner. Additionally, we believe that these viral-synthetic hybrid microparticles may find broad applications in high capacity, multiplexed target sensing.

Use of prebiotic carbohydrate as wall material on lime essential oil microparticles.

Science.gov (United States)

Campelo, Pedro Henrique; Figueiredo, Jayne de Abreu; Domingues, Rosana Zacarias; Fernandes, Regiane Victória de Barros; Botrel, Diego Alvarenga; Borges, Soraia Vilela

2017-09-01

The aim of this work was to study the use of different prebiotic biopolymers in lime essential oil microencapsulation. Whey protein isolate, inulin and oligofructose biopolymers were used. The addition of prebiotic biopolymers reduced emulsion viscosity, although it produced larger droplet sizes (0.31-0.32 µm). Moisture values (2.94-3.13 g/100 g dry solids) and water activity (0.152-0.185) were satisfactory, being within the appropriate range for powdered food quality. Total oil content, limonene retention values and antioxidant activity of the microparticles containing essential oil decreased in the presence of the carbohydrates. The addition of prebiotic biopolymers reduced the microparticle thermal stability. X-ray diffraction confirmed the amorphous characteristic of the microparticles and the interaction of the essential oil with the wall material. The presence of prebiotic biopolymers can be a good alternative for lime essential oil microparticles, mainly using fibre that has a functional food appeal and can improve consumer health.

The Young's Modulus, Fracture Stress, and Fracture Strain of Gellan Hydrogels Filled with Whey Protein Microparticles.

Science.gov (United States)

Lam, Cherry Wing Yu; Ikeda, Shinya

2017-05-01

Texture modifying abilities of whey protein microparticles are expected to be dependent on pH during heat-induced aggregation of whey protein in the microparticulation process. Therefore, whey protein microparticles were prepared at either pH 5.5 or 6.8 and their effects on small and large deformation properties of gellan gels containing whey protein microparticles as fillers were investigated. The majority of whey protein microparticles had diameters around 2 μm. Atomic force microscopy images showed that whey protein microparticles prepared at pH 6.8 partially collapsed and flatted by air-drying, while those prepared at pH 5.5 did not. The Young's modulus of filled gels adjusted to pH 5.5 decreased by the addition of whey protein microparticles, while those of filled gels adjusted to pH 6.8 increased with increasing volume fraction of filler particles. These results suggest that filler particles were weakly bonded to gel matrices at pH 5.5 but strongly at pH 6.8. Whey protein microparticles prepared at pH 5.5 showed more enhanced increases in the Young's modulus than those prepared at pH 6.8 at volume fractions between 0.2 and 0.4, indicating that microparticles prepared at pH 5.5 were mechanically stronger. The fracture stress of filled gels showed trends somewhat similar to those of the Young's modulus, while their fracture strains decreased by the addition of whey protein microparticles in all examined conditions, indicating that the primary effect of these filler particles was to enhance the brittleness of filled gels. © 2017 Institute of Food Technologists®.

Microparticles in high-voltage accelerator tubes

International Nuclear Information System (INIS)

Griffith, G.L.; Eastham, D.A.

1979-01-01

Microparticles with radii greater than 2 μm have been observed in a high voltage vacuum accelerator tube. The charge acquired by most of the particles is similar to the contact charging of a conducting sphere on a plane. (author)

Microparticles and Exosomes in Gynecologic Neoplasias

NARCIS (Netherlands)

Nieuwland, Rienk; van der Post, Joris A. M.; Lok Gemma, Christianne A. R.; Kenter, G.; Sturk, Augueste

2010-01-01

This review presents an overview of the functions of microparticles and exosomes in gynecologic neoplasias. Growing evidence suggests that vesicles released from cancer cells in gynecologic malignancies contribute to the hypercoagulable state of these patients and contribute to tumor progression by

Imaging efficiency of an X-ray contrast agent-incorporated polymeric microparticle.

Science.gov (United States)

Ahn, Sungsook; Jung, Sung Yong; Lee, Jin Pyung; Lee, Sang Joon

2011-01-01

Biocompatible polymeric encapsulants have been widely used as a delivery vehicle for a variety of drugs and imaging agents. In this study, X-ray contrast agent (iopamidol) is encapsulated into a polymeric microparticle (polyvinyl alcohol) as a particulate flow tracer in synchrotron X-ray imaging system. The physical properties of the designed microparticles are investigated and correlated with enhancement in the imaging efficiency by experimental observation and theoretical interpretation. The X-ray absorption ability of the designed microparticle is assessed by Beer-Lambert-Bouguer law. Particle size, either in dried state or in solvent, primarily dominates the X-ray absorption ability under the given condition, thus affecting imaging efficiency of the designed X-ray contrast flow tracers. Copyright © 2011 John Wiley & Sons, Ltd.

Effect of cigarette smoke on monocyte procoagulant activity: Focus on platelet-derived brain-derived neurotrophic factor (BDNF).

Science.gov (United States)

Amadio, Patrizia; Baldassarre, Damiano; Sandrini, Leonardo; Weksler, Babette B; Tremoli, Elena; Barbieri, Silvia S

2017-01-01

Cigarette smoke (CS) activates platelets, promotes vascular dysfunction, and enhances Tissue Factor (TF) expression in blood monocytes favoring pro-thrombotic states. Brain-derived neurotrophic factor (BDNF), a member of the family of neurotrophins involved in survival, growth, and maturation of neurons, is released by activated platelets (APLTs) and plays a role in the cardiovascular system. The effect of CS on circulating levels of BDNF is controversial and the function of circulating BDNF in atherothrombosis is not fully understood. Here, we have shown that human platelets, treated with an aqueous extract of CS (CSE), released BDNF in a dose-dependent manner. In addition, incubation of human monocytes with BDNF or with the supernatant of platelets activated with CSE increased TF activity by a Tropomyosin receptor kinase B (TrkB)-dependent mechanism. Finally, comparing serum and plasma samples of 12 male never smokers (NS) and 29 male active smokers (AS) we observed a significant increase in microparticle-associated TF activity (MP-TF) as well as BDNF in AS, while in serum, BDNF behaved oppositely. Taken together these findings suggest that platelet-derived BDNF is involved in the regulation of TF activity and that CS plays a role in this pathway by favoring a pro-atherothrombotic state.

A Comparison of Aerosolization and Homogenization Techniques for Production of Alginate Microparticles for Delivery of Corticosteroids to the Colon.

Science.gov (United States)

Samak, Yassmin O; El Massik, Magda; Coombes, Allan G A

2017-01-01

Alginate microparticles incorporating hydrocortisone hemisuccinate were produced by aerosolization and homogenization methods to investigate their potential for colonic drug delivery. Microparticle stabilization was achieved by CaCl 2 crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by diffusion into blank microparticles or by direct encapsulation. Homogenization method produced smaller microparticles (45-50 μm), compared to aerosolization (65-90 μm). High drug loadings (40% wt/wt) were obtained for diffusion-loaded aerosolized microparticles. Aerosolized microparticles suppressed drug release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) prior to drug release in simulated colonic fluid (SCF) to a higher extent than homogenized microparticles. Microparticles prepared using aerosolization or homogenization (1 M CaCl 2 , diffusion loaded) released 5% and 17% of drug content after 2 h in SGF and 4 h in SIF, respectively, and 75% after 12 h in SCF. Thus, aerosolization and homogenization techniques show potential for producing alginate microparticles for colonic drug delivery in the treatment of inflammatory bowel disease. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Cancer cells cause vascular endothelial cell (vEC) retraction via 12(S)HETE secretion; the possible role of cancer cell derived microparticle.

Science.gov (United States)

Uchide, Keiji; Sakon, Masato; Ariyoshi, Hideo; Nakamori, Syouji; Tokunaga, Masaru; Monden, Morito

2007-02-01

Cancer cell mediated vascular endothelial cell (vEC) retraction plays a pivotal role in cancer metastasis. The aim of this study is to clarify the biochemical character of vEC retraction factor derived from human breast cancer cell line, MCF-7. In order to estimate vEC retracting activity, transwell chamber assay system was employed. We first tested the effects of trypsin digestion as well as lipid extraction of culture medium (CM). Trypsin digestion of CM resulted in approximately 40% loss of vEC retracting activity and lipid extraction of CM by Brigh and Dyer methods recovered approximately 60% of vEC retracting activity, suggesting that approximately 60% of vEC retracting activity in MCF-7 derived CM is due to lipid. Although Nordihydroguaiaretic acid (NDGA), the specific lipoxygenase inhibitor, suppressed vEC retracting activity in CM, Acetyl salicylic acid (ASA), a specific cyclooxygenase inhibitor, did not affect the activity, suggesting that lipid exerting vEC retracting activity in CM belongs to lipoxygenase mediated arachidonate metabolites. Thin layer chromatography clearly demonstrated that Rf value of lipid vEC retracting factor in CM is identical to 12HETE. Authentic 12(S)HETE, but not 12(R)HETE, showed vEC retracting activity. After the ultracentrifugation of CM, most lipid vEC retracting activity was recovered from the pellet fraction, and flow cytometric analysis using specific antibody against 12(S)HETE clearly showed the association of 12(S)HETE with small particle in CM. These findings suggested the principal involvement of 12(S)HETE in cancer cell derived microparticles in cancer cell mediated vEC retraction.

Preparation of bovine serum albumin hollow microparticles by the water-in-oil emulsion solvent diffusion technique for drug delivery applications

International Nuclear Information System (INIS)

Baimark, Y.; Srisa-Ard, M.; Srihaman, P.

2012-01-01

Biodegradable bovine serum albumin (BSA) hollow microparticles have been prepared by a single step and rapid water-in-oil emulsion solvent diffusion method without any emulsifiers and templates. Aqueous BSA solution and ethyl acetate were used as water and oil phases, respectively. BSA solution was cross-linked with polyethylene glycol diglycidyl ether (PEGDE) before microparticle formation. Methylene blue (MB) was used as a water-soluble model drug to entrap in the microparticle matrix. The non-cross-linked and cross-linked BSA microparticles contained empty core structure with outer smooth surface. Inner surface and matrix of hollow microparticles consisted void structure. Drug loading did not affect the microparticle morphology. Cumulative drug released from microparticles was decreased steadily as decreasing of MB ratio and increasing of PEGDE ratio. The BSA hollow microparticles may have potential application in controlled release drug delivery application. (author)

On-chip microparticle detection and sizing using a dual-wavelength waveguide laser

NARCIS (Netherlands)

Bernhardi, Edward H.; van der Werf, Kees O; Hollink, Anton J F; Worhoff, Kerstin; De Ridder, Rene M.; Subramaniam, Vinod; Pollnau, Markus

2013-01-01

An integrated intra-laser-cavity microparticle sensor based on a dual-phase-shift, dual-wavelength distributed-feedback channel waveguide laser in Al2O3:Yb3+ is presented. Real-time detection and accurate size measurement of single microparticles with diameters ranging between 1 μm and 20 μm are

Microparticle-initiated losses in magnetically insulated transmission lines

International Nuclear Information System (INIS)

Gray, E.W.; Stinnett, R.W.

1986-01-01

The author's discuss the effects of high and hypervelocity microparticles in magnetically-insulated transmission lines (MITLs) and how they may be a possible source for ion production near the anode in early stages of the voltage pulse, and current carriers during and after the power pulse, resulting in power flow losses. Early losses in the voltage pulse, due to microparticles, are estimated to be approximately 0.3 mA/cm/sup 2/. Blistering of the electrode surface, thought to be due to H/sup -/ bombardment, was also observed and appears to be consistent with losses due to negative ions previously reported by one of the authors

Biomimetic Molecular Signaling using DNA Walkers on Microparticles.

Science.gov (United States)

Damase, Tulsi Ram; Spencer, Adam; Samuel, Bamidele; Allen, Peter B

2017-06-22

We report the release of catalytic DNA walkers from hydrogel microparticles and the detection of those walkers by substrate-coated microparticles. This might be considered a synthetic biology analog of molecular signal release and reception. One type of particles was coated with components of a DNA one-step strand displacement (OSD) reaction to release the walker. A second type of particle was coated with substrate (or "track") for the molecular walker. We distinguish these particle types using fluorescence barcoding: we synthesized and distinguished multiple particle types with multicolor fluorescence microscopy and automated image analysis software. This represents a step toward amplified, multiplex, and microscopically localized detection based on DNA nanotechnology.

Sustained release of milrinone delivered via microparticles in a rodent model of myocardial infarction.

Science.gov (United States)

Al Kindi, Hamood; Paul, Arghya; You, Zhipeng; Nepotchatykh, Oleg; Schwertani, Adel; Prakash, Satya; Shum-Tim, Dominique

2014-11-01

The aim of the present study was to construct a new drug delivery system for milrinone using microparticles. This novel technology enhances drug bioavailability and decreases toxicity, with future implications for the treatment of end-stage heart failure. Polylactic-co-glycolic acid microparticles (PLGA-MPs) loaded with milrinone were prepared using a double emulsion-solvent evaporation technique. In vitro release kinetics was evaluated at physiologic conditions. A total of 24 female Lewis rats underwent left coronary artery ligation. One week after ligation, all rats were randomized to 1 of 3 groups (n=8 per group). Group I received an intravenous injection of PLGA-MPs alone; group II, a bolus intravenous injection of milrinone; and group III an intravenous injection of milrinone-PLGA-MPs. All injections were administrated slowly by way of the tail vein over 10 minutes. Transthoracic echocardiography, noninvasive heart rate monitoring, and blood pressure measurements were performed at different predetermined intervals before and for 24 hours after the injection. All rats survived for 24 hours and were then killed by euthanasia. Serum plasma was taken for cytokine assays and determination of milrinone levels using high-performance liquid chromatography. Group III had a significantly greater left ventricular ejection fraction at 90 minutes and 3, 6, and 12 hours after treatment compared with the other groups. The milrinone plasma level was significantly greater in group III than in the other groups (group I, 0 ng/mL; group II, 1.7±2.4 ng/mL; group III, 9.1±2.2 ng/mL; Pmilrinone. We propose a new strategy for future drug delivery in patients with end-stage heart failure. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections

International Nuclear Information System (INIS)

Flores, Claudia; Degoutin, Stephanie; Chai, Feng; Raoul, Gwenael; Hornez, Jean-Chritophe; Martel, Bernard; Siepmann, Juergen; Ferri, Joel; Blanchemain, Nicolas

2016-01-01

Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60 μm, allowing for incorporation inside the macropores (100 μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25–30 days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions. - Highlights: • The optimization of microparticle preparation parameters allows to obtain a size compatible with the bone substitute porosity • PDL% has a direct impact on the burst effect, a control release of gentamicin was obtained • The incorporation of microparticles into the macroporosity

Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections

Energy Technology Data Exchange (ETDEWEB)

Flores, Claudia [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Degoutin, Stephanie [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Chai, Feng [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Raoul, Gwenael [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Hornez, Jean-Chritophe [Laboratoire des Matériaux Céramiques et Procédés Associés (LMCPA), Université de Valenciennes, 59300 Valenciennes (France); Martel, Bernard [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Siepmann, Juergen [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Ferri, Joel [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Blanchemain, Nicolas, E-mail: nicolas.blanchemain@univ-lille2.fr [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France)

2016-07-01

Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60 μm, allowing for incorporation inside the macropores (100 μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25–30 days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions. - Highlights: • The optimization of microparticle preparation parameters allows to obtain a size compatible with the bone substitute porosity • PDL% has a direct impact on the burst effect, a control release of gentamicin was obtained • The incorporation of microparticles into the

The Electrical Properties of Plasma-Deposited Thin Films Derived from Pelargonium graveolens

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Ahmed Al-Jumaili

2017-10-01

Full Text Available Inherently volatile at atmospheric pressure and room temperature, plant-derived precursors present an interesting human-health-friendly precursor for the chemical vapour deposition of thin films. The electrical properties of films derived from Pelargonium graveolens (geranium were investigated in metal–insulator–metal (MIM structures. Thin polymer-like films were deposited using plasma-enhanced synthesis under various plasma input power. The J–V characteristics of thus-fabricated MIM were then studied in order to determine the direct current (DC conduction mechanism of the plasma polymer layers. It was found that the capacitance of the plasma-deposited films decreases at low frequencies (C ≈ 10−11 and remains at a relatively constant value (C ≈ 10−10 at high frequencies. These films also have a low dielectric constant across a wide range of frequencies that decreases as the input RF power increases. The conductivity was determined to be around 10−16–10−17 Ω−1 m−1, which is typical for insulating materials. The Richardson–Schottky mechanism might dominate charge transport in the higher field region for geranium thin films.

Polyamide Microparticles Containing Vitamin C by Interfacial Polymerization: An Approach by Design of Experimentation

Directory of Open Access Journals (Sweden)

Lionel Ripoll

2016-11-01

Full Text Available Vitamin C is widely use in cosmetics and pharmaceutics products for its active properties. However ascorbic acid shows unfavourable chemical instability such as oxidation leading to formulation problems. Therefore, carriers, such as micro- and nanoparticles, have been widely investigated as delivery systems for vitamin C to improve its beneficial effects in skin treatment. However, none of the previous studies have been able to produce microparticles with a high encapsulation entrapment of vitamin C. The aim of the present study is to use an experimental design to optimize the synthesis of polyamide microparticles for the delivery of ascorbic acid. The effect of four formulation parameters on microparticles properties (size and morphology, encapsulation efficiency and yield, release kinetics were investigated using a surface response design. Finally, we were able to obtain stable microparticles containing more than 65% of vitamin C. This result confirms the effectiveness of using design of experiments for the optimisation of microparticle formulation and supports the proposal of using them as candidate for the delivery of vitamin C in skin treatment.

Food plant derived disease tolerance and resistance in a natural butterfly-plant-parasite interactions.

Science.gov (United States)

Sternberg, Eleanore D; Lefèvre, Thierry; Li, James; de Castillejo, Carlos Lopez Fernandez; Li, Hui; Hunter, Mark D; de Roode, Jacobus C

2012-11-01

Organisms can protect themselves against parasite-induced fitness costs through resistance or tolerance. Resistance includes mechanisms that prevent infection or limit parasite growth while tolerance alleviates the fitness costs from parasitism without limiting infection. Although tolerance and resistance affect host-parasite coevolution in fundamentally different ways, tolerance has often been ignored in animal-parasite systems. Where it has been studied, tolerance has been assumed to be a genetic mechanism, unaffected by the host environment. Here we studied the effects of host ecology on tolerance and resistance to infection by rearing monarch butterflies on 12 different species of milkweed food plants and infecting them with a naturally occurring protozoan parasite. Our results show that monarch butterflies experience different levels of tolerance to parasitism depending on the species of milkweed that they feed on, with some species providing over twofold greater tolerance than other milkweed species. Resistance was also affected by milkweed species, but there was no relationship between milkweed-conferred resistance and tolerance. Chemical analysis suggests that infected monarchs obtain highest fitness when reared on milkweeds with an intermediate concentration, diversity, and polarity of toxic secondary plant chemicals known as cardenolides. Our results demonstrate that environmental factors-such as interacting species in ecological food webs-are important drivers of disease tolerance. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

[Cellular microparticles, potential useful biomarkers in the identification of cerebrovascular accidents].

Science.gov (United States)

Anglés-Cano, Eduardo; Vivien, Denis

2009-10-01

The clinical utility of biomarkers depends on their ability to identify high-risk individuals in order to establish preventive, diagnostic or therapeutic measures. Currently, no practical, rapid and sensitive test is available for the diagnosis of acute ischemic stroke. A number of soluble molecules have been identified that are merely associated to these cerebrovascular accidents. Despite this association not a single molecule has the characteristics of a true biomarker directly involved in the pathophysiology of ischemic stroke-none of them is organ-specific and may therefore be elevated in the context of medical comorbidities. When explored as a combination of biomarkers, e.g. matrix metalloproteinase 9, brain natriuretic protein, D-dimer, protein S100B, the question still remains whether serial biomarker analysis provides additional prognostic information. Even S100B, a glial activation protein, has a low specificity for acute ischemic stroke because it may originate from extracranial sources. Current knowledge from the field of cell-derived microparticles suggests that these membrane fragments may represent reliable biomarkers as they are cell-specific and are released early in the pathophysiological cascade of a disease. These microparticles can be found not only in the cerebrospinal fluid but also in tears and circulating blood in case of blood-brain barrier dysfunction. They represent a new challenge in stroke diagnosis and management.

Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.

Science.gov (United States)

Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca; Zhang, Hongbo; Mäkilä, Ermei M; Kauppila, Jussi; Sarmento, Bruno; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

2014-08-01

Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (P(app)) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane. Copyright © 2014 Elsevier Ltd. All rights reserved.

Second derivative Langmuir probe diagnostics of gas discharge plasma at intermediate pressures (review article)

International Nuclear Information System (INIS)

Popov, Tsv K; Dimitrova, M; Dias, F M; Tsaneva, V N; Stelmashenko, N A; Blamire, M G; Barber, Z H

2006-01-01

The second-derivative Langmuir probe method for precise determination of the plasma potential, the electron energy distribution function (respectively the electron temperature,) and the electron density of gas discharge plasma at intermediate pressures (100-1000 Pa) is reviewed. Results of applying the procedure proposed to different kinds of gas discharges are presented. Factors affecting the accuracy of the plasma characteristics evaluated are discussed

Detection of microparticles in dynamic processes

International Nuclear Information System (INIS)

Ten, K A; Pruuel, E R; Kashkarov, A O; Rubtsov, I A; Shechtman, L I; Zhulanov, V V; Tolochko, B P; Rykovanov, G N; Muzyrya, A K; Smirnov, E B; Stolbikov, M Yu; Prosvirnin, K M

2016-01-01

When a metal plate is subjected to a strong shock impact, its free surface emits a flow of particles of different sizes (shock-wave “dusting”). Traditionally, the process of dusting is investigated by the methods of pulsed x-ray or piezoelectric sensor or via an optical technique. The particle size ranges from a few microns to hundreds of microns. The flow is assumed to include also finer particles, which cannot be detected with the existing methods yet. On the accelerator complex VEPP-3-VEPP-4 at the BINP there are two experiment stations for research on fast processes, including explosion ones. The stations enable measurement of both passed radiation (absorption) and small-angle x-ray scattering on synchrotron radiation (SR). Radiation is detected with a precision high-speed detector DIMEX. The detector has an internal memory of 32 frames, which enables recording of the dynamics of the process (shooting of movies) with intervals of 250 ns to 2 μ s. Flows of nano- and microparticles from free surfaces of various materials (copper and tin) have been examined. Microparticle flows were emitted from grooves of 50-200 μ s in size and joints (gaps) between metal parts. With the soft x-ray spectrum of SR one can explore the dynamics of a single microjet of micron size. The dynamics of density distribution along micro jets were determined. Under a shock wave (∼ 60 GPa) acting on tin disks, flows of microparticles from a smooth surface were recorded. (paper)

Quasi-static motion of microparticles at the depinning contact line of an evaporating droplet on PDMS surface

Science.gov (United States)

Yu, Ying-Song; Xia, Xue-Lian; Zheng, Xu; Huang, Xianfu; Zhou, Jin-Zhi

2017-09-01

In this paper, evaporation of sessile water droplets containing fluorescent polystyrene (PS) microparticles on polydimethylsiloxane (PDMS) surfaces with different curing ratios was studied experimentally using laser confocal microscopy. At the beginning, there were some microparticles located at the contact line and some microparticles moved towards the line. Due to contact angle hysteresis, at first both the contact line and the microparticles were pinned. With the depinning contact line, the microparticles moved together spontaneously. Using the software ImageJ, the location of contact lines at different time were acquired and the circle centers and radii of the contact lines were obtained via the least square method. Then the average distance of two neighbor contact lines at a certain time interval was obtained to characterize the motion of the contact line. Fitting the distance-time curve at the depinning contact line stage with polynomials and differentiating the polynomials with time, we obtained the velocity and acceleration of both the contact line and the microparticles located at the line. The velocity and the maximum acceleration were, respectively, of the orders of 1 μm/s and 20-200 nm/s2, indicating that the motion of the microparticles located at the depinning contact line was quasi-static. Finally, we presented a theoretical model to describe the quasi-static process, which may help in understanding both self-pinning and depinning of microparticles.

Application of stereoscopic particle image velocimetry to studies of transport in a dusty (complex) plasma

International Nuclear Information System (INIS)

Thomas, Edward Jr.; Williams, Jeremiah D.; Silver, Jennifer

2004-01-01

Over the past 5 years, two-dimensional particle image velocimetry (PIV) techniques [E. Thomas, Jr., Phys. Plasmas 6, 2672 (1999)] have been used to obtain detailed measurements of microparticle transport in dusty plasmas. This Letter reports on an extension of these techniques to a three-dimensional velocity vector measurement approach using stereoscopic PIV. Initial measurements using the stereoscopic PIV diagnostic are presented

Parasitic helminths: a pharmacopeia of anti-inflammatory molecules.

Science.gov (United States)

Johnston, M J G; MacDonald, J A; McKay, D M

2009-02-01

Infection with parasitic helminths takes a heavy toll on the health and well-being of humans and their domestic livestock, concomitantly resulting in major economic losses. Analyses have consistently revealed bioactive molecules in extracts of helminths or in their excretory/secretory products that modulate the immune response of the host. It is our view that parasitic helminths are an untapped source of immunomodulatory substances that, in pure form, could become new drugs (or models for drug design) to treat disease. Here, we illustrate the range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules. There are many examples of the partial characterization of helminth-derived immunomodulatory molecules, but these have not yet translated into new drugs, reflecting the difficulty of isolating and fully characterizing proteins, glycoproteins and lipid-based molecules from small amounts of parasite material. However, this should not deter the investigator, since analytical techniques are now being used to accrue considerable structural information on parasite-derived molecules, even when only minute quantities of tissue are available. With the introduction of methodologies to purify and structurally-characterize molecules from small amounts of tissue and the application of high throughput immunological assays, one would predict that an assessment of parasitic helminths will yield a variety of novel drug candidates in the coming years.

Functionalized diatom silica microparticles for removal of mercury ions

International Nuclear Information System (INIS)

Yu Yang; Addai-Mensah, Jonas; Losic, Dusan

2012-01-01

Diatom silica microparticles were chemically modified with self-assembled monolayers of 3-mercaptopropyl-trimethoxysilane (MPTMS), 3-aminopropyl-trimethoxysilane (APTES) and n-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (AEAPTMS), and their application for the adsorption of mercury ions (Hg(II)) is demonstrated. Fourier transform infrared spectroscopy and x-ray photoelectron spectroscopy analyses revealed that the functional groups (–SH or –NH 2 ) were successfully grafted onto the diatom silica surface. The kinetics and efficiency of Hg(II) adsorption were markedly improved by the chemical functionalization of diatom microparticles. The relationship among the type of functional groups, pH and adsorption efficiency of mercury ions was established. The Hg(II) adsorption reached equilibrium within 60 min with maximum adsorption capacities of 185.2, 131.7 and 169.5 mg g -1 for particles functionalized with MPTMS, APTES and AEAPTMS, respectively. The adsorption behavior followed a pseudo-second-order reaction model and Langmuirian isotherm. These results show that mercapto- or amino-functionalized diatom microparticles are promising natural, cost-effective and environmentally benign adsorbents suitable for the removal of mercury ions from aqueous solutions.

Dynamic transformation of self-assembled structures using anisotropic magnetized hydrogel microparticles

Science.gov (United States)

Yoshida, Satoru; Takinoue, Masahiro; Iwase, Eiji; Onoe, Hiroaki

2016-08-01

This paper describes a system through which the self-assembly of anisotropic hydrogel microparticles is achieved, which also enables dynamic transformation of the assembled structures. Using a centrifuge-based microfluidic device, anisotropic hydrogel microparticles encapsulating superparamagnetic materials on one side are fabricated, which respond to a magnetic field. We successfully achieve dynamic assembly using these hydrogel microparticles and realize three different self-assembled structures (single and double pearl chain structures, and close-packed structures), which can be transformed to other structures dynamically via tuning of the precessional magnetic field. We believe that the developed system has potential application as an effective platform for a dynamic cell manipulation and cultivation system, in biomimetic autonomous microrobot organization, and that it can facilitate further understanding of the self-organization and complex systems observed in nature.

Development of thiolated poly(acrylic acid) microparticles for the nasal administration of exenatide.

Science.gov (United States)

Millotti, Gioconda; Vetter, Anja; Leithner, Katharina; Sarti, Federica; Shahnaz Bano, Gul; Augustijns, Patrick; Bernkop-Schnürch, Andreas

2014-12-01

The purpose of this study was to develop a microparticulate formulation for nasal delivery of exenatide utilizing a thiolated polymer. Poly(acrylic acid)-cysteine (PAA-cys) and unmodified PAA microparticles loaded with exenatide were prepared via coprecipitation of the drug and the polymer followed by micronization. Particle size, drug load and release of incorporated exenatide were evaluated. Permeation enhancing properties of the formulations were investigated on excised porcine respiratory mucosa. The viability of the mucosa was investigated by histological studies. Furthermore, ciliary beat frequency (CBF) studies were performed. Microparticles displayed a mean size of 70-80 µm. Drug encapsulation was ∼80% for both thiolated and non-thiolated microparticles. Exenatide was released from both thiolated and non-thiolated particles in comparison to exenatide in buffer only within 40 min. As compared to exenatide dissolved in buffer only, non-thiolated and thiolated microparticles resulted in a 2.6- and 4.7-fold uptake, respectively. Histological studies performed before and after permeation studies showed that the mucosa is not damaged during permeation studies. CBF studies showed that the formulations were cilio-friendly. Based on these results, poly(acrylic acid)-cysteine-based microparticles seem to be a promising approach starting point for the nasal delivery of exenatide.

Controlled release of beta-estradiol from PLAGA microparticles: the effect of organic phase solvent on encapsulation and release.

Science.gov (United States)

Birnbaum, D T; Kosmala, J D; Henthorn, D B; Brannon-Peppas, L

2000-04-03

To determine the effect of the organic solvent used during microparticle preparation on the in vitro release of beta-estradiol, a number of formulations were evaluated in terms of size, shape and drug delivery performance. Biodegradable microparticles of poly(lactide-co-glycolide) were prepared containing beta-estradiol that utilized dichloromethane, ethyl acetate or a mixture of dichloromethane and methanol as the organic phase solvent during the particle preparation. The drug delivery behavior from the microparticles was studied and comparisons were made of their physical properties for different formulations. The varying solubilities of beta-estradiol and poly(lactide-co-glycolide) in the solvents studied resulted in biodegradable microparticles with very different physical characteristics. Microparticles prepared from solid suspensions of beta-estradiol using dichloromethane as the organic phase solvent were similar in appearance to microparticles prepared without drug. Microparticles prepared from dichloromethane/methanol solutions appeared transparent to translucent depending on the initial amount of drug used in the formulation. Microparticles prepared using ethyl acetate appeared to have the most homogeneous encapsulation of beta-estradiol, appearing as solid white spheres regardless of initial drug content. Studies showed that microparticles prepared from either ethyl acetate or a mixture of dichloromethane and methanol gave a more constant release profile of beta-estradiol than particles prepared using dichloromethane alone. For all formulations, an initial burst of release increased with increasing drug loading, regardless of the organic solvent used.

Aerosol-Assisted Fast Formulating Uniform Pharmaceutical Polymer Microparticles with Variable Properties toward pH-Sensitive Controlled Drug Release

Directory of Open Access Journals (Sweden)

Hong Lei

2016-05-01

Full Text Available Microencapsulation is highly attractive for oral drug delivery. Microparticles are a common form of drug carrier for this purpose. There is still a high demand on efficient methods to fabricate microparticles with uniform sizes and well-controlled particle properties. In this paper, uniform hydroxypropyl methylcellulose phthalate (HPMCP-based pharmaceutical microparticles loaded with either hydrophobic or hydrophilic model drugs have been directly formulated by using a unique aerosol technique, i.e., the microfluidic spray drying technology. A series of microparticles of controllable particle sizes, shapes, and structures are fabricated by tuning the solvent composition and drying temperature. It is found that a more volatile solvent and a higher drying temperature can result in fast evaporation rates to form microparticles of larger lateral size, more irregular shape, and denser matrix. The nature of the model drugs also plays an important role in determining particle properties. The drug release behaviors of the pharmaceutical microparticles are dependent on their structural properties and the nature of a specific drug, as well as sensitive to the pH value of the release medium. Most importantly, drugs in the microparticles obtained by using a more volatile solvent or a higher drying temperature can be well protected from degradation in harsh simulated gastric fluids due to the dense structures of the microparticles, while they can be fast-released in simulated intestinal fluids through particle dissolution. These pharmaceutical microparticles are potentially useful for site-specific (enteric delivery of orally-administered drugs.

Development of Suppositories Containing Flutamide-Loaded Alginate-Tamarind Microparticles for Rectal Administration: In Vitro and in Vivo Studies.

Science.gov (United States)

Patil, Bharati Shivajirao; Mahajan, Hitendra Shaligram; Surana, Sanjay Javerilal

2015-01-01

In the present work the absorption of flutamide from suppositories containing hydrophilic tamarind alginate microparticles after rectal administration in rats was investigated with the purpose of enhancing bioavailability and to avoid hepatic toxicity. Microparticles were developed by ionic gelation method and optimized using one factorial design of response surface methodology. The optimized batch of microparticles had tamarind gum-sodium alginate (1 : 3) ratio and showed entrapment efficiency 94.969% and mucoadhesion strength 94.646% with desirability of 0.961. Suppositories loaded with microparticles were developed by fusion method using poloxamer 407 and poloxamer 188 in combination as suppository base. Kinetic analysis of the release data of microparticle-loaded suppositories showed time-independent release of drug. Higher values of 'n' (>0.89) represent Super Case II-type drug release. The pharmacokinetics of flutamide from flutamide tamarind alginate microparticle-loaded suppository were compared with oral suspension. Cmax of microparticle-loaded suppository was significantly larger than that of oral suspension (1.711 and 0.859 µg/mL, respectively).

Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique

Science.gov (United States)

Tobar-Grande, Blanca; Godoy, Ricardo; Bustos, Paulina; von Plessing, Carlos; Fattal, Elias; Tsapis, Nicolas; Olave, Claudia; Gómez-Gaete, Carolina

2013-01-01

In this work, microparticles were prepared by spray-drying using albumin, chondroitin sulfate, and hyaluronic acid as excipients to create a controlled-release methylprednisolone system for use in inflammatory disorders such as arthritis. Scanning electron microscopy demonstrated that these microparticles were almost spherical, with development of surface wrinkling as the methylprednisolone load in the formulation was increased. The methylprednisolone load also had a direct influence on the mean diameter and zeta potential of the microparticles. Interactions between formulation excipients and the active drug were evaluated by x-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis, showing limited amounts of methylprednisolone in a crystalline state in the loaded microparticles. The encapsulation efficiency of methylprednisolone was approximately 89% in all formulations. The rate of methylprednisolone release from the microparticles depended on the initial drug load in the formulation. In vitro cytotoxic evaluation using THP-1 cells showed that none of the formulations prepared triggered an inflammatory response on release of interleukin-1β, nor did they affect cellular viability, except for the 9.1% methylprednisolone formulation, which was the maximum test concentration used. The microparticles developed in this study have characteristics amenable to a therapeutic role in inflammatory pathology, such as arthritis. PMID:23737670

Microparticle Analysis in Disorders of Hemostasis and Thrombosis

Science.gov (United States)

Mooberry, Micah J.; Key, Nigel S.

2015-01-01

Microparticles (MPs) are submicron vesicles released from the plasma membrane of eukaryotic cells in response to activation or apoptosis. MPs are known to be involved in numerous biologic processes, including inflammation, the immune response, cancer metastasis, and angiogenesis. Their earliest recognized and most widely accepted role, however, is the ability to promote and support the process of blood coagulation. Consequently, there is ongoing interest in studying MPs in disorders of hemostasis and thrombosis. Both phosphatidylserine (PS) exposure and the presence of tissue factor (TF) in the MP membrane may account for their procoagulant properties, and elevated numbers of MPs in plasma have been reported in numerous prothrombotic conditions. To date, however, there are few data on true causality linking MPs to the genesis of thrombosis. A variety of methodologies have been employed to characterize and quantify MPs, although detection is challenging due to their submicron size. Flow cytometry (FCM) remains the most frequently utilized strategy for MP detection; however, it is associated with significant technological limitations. Additionally, pre-analytical and analytical variables can influence the detection of MPs by FCM, rendering data interpretation difficult. Lack of methodologic standardization in MP analysis by FCM confounds the issue further, although efforts are currently underway to address this limitation. Moving forward, it will be important to address these technical challenges as a scientific community if we are to better understand the role that MPs play in disorders of hemostasis and thrombosis. PMID:25704723

Generation of reactive oxygen species from porous silicon microparticles in cell culture medium.

Science.gov (United States)

Low, Suet Peng; Williams, Keryn A; Canham, Leigh T; Voelcker, Nicolas H

2010-06-01

Nanostructured (porous) silicon is a promising biodegradable biomaterial, which is being intensively researched as a tissue engineering scaffold and drug-delivery vehicle. Here, we tested the biocompatibility of non-treated and thermally-oxidized porous silicon particles using an indirect cell viability assay. Initial direct cell culture on porous silicon determined that human lens epithelial cells only poorly adhered to non-treated porous silicon. Using an indirect cell culture assay, we found that non-treated microparticles caused complete cell death, indicating that these particles generated a toxic product in cell culture medium. In contrast, thermally-oxidized microparticles did not reduce cell viability significantly. We found evidence for the generation of reactive oxygen species (ROS) by means of the fluorescent probe 2',7'-dichlorofluorescin. Our results suggest that non-treated porous silicon microparticles produced ROS, which interacted with the components of the cell culture medium, leading to the formation of cytotoxic species. Oxidation of porous silicon microparticles not only mitigated, but also abolished the toxic effects.

Self-organized internal architectures of chiral micro-particles

International Nuclear Information System (INIS)

Provenzano, Clementina; Mazzulla, Alfredo; Desiderio, Giovanni; Pagliusi, Pasquale; De Santo, Maria P.; Cipparrone, Gabriella; Perrotta, Ida

2014-01-01

The internal architecture of polymeric self-assembled chiral micro-particles is studied by exploring the effect of the chirality, of the particle sizes, and of the interface/surface properties in the ordering of the helicoidal planes. The experimental investigations, performed by means of different microscopy techniques, show that the polymeric beads, resulting from light induced polymerization of cholesteric liquid crystal droplets, preserve both the spherical shape and the internal self-organized structures. The method used to create the micro-particles with controlled internal chiral architectures presents great flexibility providing several advantages connected to the acquired optical and photonics capabilities and allowing to envisage novel strategies for the development of chiral colloidal systems and materials

Smart swelling biopolymer microparticles by a microfluidic approach: synthesis, in situ encapsulation and controlled release.

Science.gov (United States)

Fang, Aiping; Cathala, Bernard

2011-01-01

This paper reports a microfluidic synthesis of biopolymer microparticles aiming at smart swelling. Monodisperse aqueous emulsion droplets comprising biopolymer and its cross-linking agent were formed in mineral oil and solidified in the winding microfluidic channels by in situ chaotic mixing, which resulted in internal chemical gelation for hydrogels. The achievement of pectin microparticles from in situ mixing pectin with its cross-linking agent, calcium ions, successfully demonstrates the reliability of this microfluidic synthesis approach. In order to achieve hydrogels with smart swelling, the following parameters and their impacts on the swelling behaviour, stability and morphology of microparticles were investigated: (1) the type of biopolymers (alginate or mixture of alginate and carboxymethylcellulose, A-CMC); (2) rapid mixing; (3) concentration and type of cross-linking agent. Superabsorbent microparticles were obtained from A-CMC mixture by using ferric chloride as an additional external cross-linking agent. The in situ encapsulation of a model protein, bovine serum albumin (BSA), was also carried out. As a potential protein drug-delivery system, the BSA release behaviours of the biopolymer particles were studied in simulated gastric and intestinal fluids. Compared with alginate and A-CMC microparticles cross-linked with calcium ions, A-CMC microparticles cross-linked with both calcium and ferric ions demonstrate a significantly delayed release. The controllable release profile, the facile encapsulation as well as their biocompatibility, biodegradability, mucoadhesiveness render this microfluidic approach promising in achieving biopolymer microparticles as protein drug carrier for site-specific release. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of poly(lactide-co-glycolide) molecular weight on the release of dexamethasone sodium phosphate from microparticles.

Science.gov (United States)

Jaraswekin, Saowanee; Prakongpan, Sompol; Bodmeier, Roland

2007-03-01

The objective of this study was to investigate the effect of poly(lactide-co-glycolide) (PLGA) molecular weight (Resomer RG 502H, RG 503H, and RG 504H) on the release behavior of dexamethasone sodium phosphate-loaded microparticles. The microparticles were prepared by three modifications of the solvent evaporation method (O/W-cosolvent, O/W-dispersion, and W/O/W-methods). The encapsulation efficiency of microparticles prepared by the cosolvent- and W/O/W-methods increased from approximately 50% to >90% upon addition of NaCl to the external aqueous phase, while the dispersion method resulted in lower encapsulation efficiencies. The release of dexamethasone sodium phosphate from PLGA microparticles (>50 microm) was biphasic. The initial burst release correlated well with the porosity of the microparticles, both of which increased with increasing polymer molecular weight (RG 504H > 503H > 502H). The burst was also dependent on the method of preparation and was in the order of dispersion method > WOW method > consolvent method. In contrast to the higher molecular weight PLGA microparticles, the release from RG 502H microparticles prepared by cosolvent method was not affected by volume of organic solvent (1.5-3.0 ml) and drug loading (4-13%). An initial burst of approximately 10% followed by a 5-week sustained release phase was obtained. Microparticles with a size <50 microm released in a triphasic manner; an initial burst was followed by a slow release phase and then by a second burst.

The Strigolactone Germination Stimulants of the Plant-Parasitic Striga and Orobanche spp. Are Derived from the Carotenoid Pathway1

Science.gov (United States)

Matusova, Radoslava; Rani, Kumkum; Verstappen, Francel W.A.; Franssen, Maurice C.R.; Beale, Michael H.; Bouwmeester, Harro J.

2005-01-01

The seeds of parasitic plants of the genera Striga and Orobanche will only germinate after induction by a chemical signal exuded from the roots of their host. Up to now, several of these germination stimulants have been isolated and identified in the root exudates of a series of host plants of both Orobanche and Striga spp. In most cases, the compounds were shown to be isoprenoid and belong to one chemical class, collectively called the strigolactones, and suggested by many authors to be sesquiterpene lactones. However, this classification was never proven; hence, the biosynthetic pathways of the germination stimulants are unknown. We have used carotenoid mutants of maize (Zea mays) and inhibitors of isoprenoid pathways on maize, cowpea (Vigna unguiculata), and sorghum (Sorghum bicolor) and assessed the effects on the root exudate-induced germination of Striga hermonthica and Orobanche crenata. Here, we show that for these three host and two parasitic plant species, the strigolactone germination stimulants are derived from the carotenoid pathway. Furthermore, we hypothesize how the germination stimulants are formed. We also discuss this finding as an explanation for some phenomena that have been observed for the host-parasitic plant interaction, such as the effect of mycorrhiza on S. hermonthica infestation. PMID:16183851

Study of Formulation Variables Influencing Polymeric Microparticles by Experimental Design

Directory of Open Access Journals (Sweden)

Jitendra B. Naik

2014-04-01

Full Text Available The objective of this study was to prepare diclofenac sodium loaded microparticles by single emulsion [oil-in-water (o/w] solvent evaporation method. The 22 experimental design methodology was used to evaluate the effect of two formulation variables on microspheres properties using the Design-Expert® software and evaluated for their particle size, morphology, and encapsulation efficiency and in vitro drug release. The graphical and mathematical analysis of the design showed that the independent variables were a significant effect on the encapsulation efficiency and drug release of microparticles. The low magnitudes of error and significant values of R2 prove the high prognostic ability of the design. The microspheres showed high encapsulation efficiency with an increase in the amount of polymer and decrease in the amount of PVA in the formulation. The particles were found to be spherical with smooth surface. Prolonged drug release and enhancement of encapsulation efficiency of polymeric microparticles can be successfully obtained with an application of experimental design technique.

Magnetic-Responsive Microparticles that Switch Shape at 37 °C

Directory of Open Access Journals (Sweden)

Koichiro Uto

2017-11-01

Full Text Available Shape-memory polymers have seen tremendous research efforts driven by the need for better drug carries and biomedical devices. In contrast to these advancements, fabrication of shape-memory particles which actuate at body temperature remains scarce. We developed a shape-memory microparticle system with dynamically tunable shapes under physiological temperature. Temperature-responsive poly(ε-caprolactone (PCL microparticles were successfully prepared by an in situ oil-in-water (o/w emulsion polymerization technique using linear telechelic and tetra-branched PCL macromonomers. By optimizing the mixing ratios of branched PCL macromonomers, the crystal-amorphous transition temperature was adjusted to the biological relevant temperature. The particles with a disk-like temporal shape were achieved by compression. The shape recovery from the disk to spherical shape was also realized at 37 °C. We also incorporated magnetic nanoparticles within the PCL microparticles, which can be remote-controllable by a magnet, in such a way that they can be actuated and manipulated in a controlled way.

Furosemide Loaded Silica-Lipid Hybrid Microparticles: Formulation Development, in vitro and ex vivo Evaluation.

Science.gov (United States)

Sambaraj, Swapna; Ammula, Divya; Nagabandi, Vijaykumar

2015-09-01

The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. In vitro dissolution studies conducted under simulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silica-lipid hybrid microparticles. It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs.

Diving with microparticles in acoustic fields

DEFF Research Database (Denmark)

2012-01-01

Sound can move particles. A good example of this phenomenon is the Chladni plate, in which an acoustic wave is induced in a metallic plate and particles migrate to the nodes of the acoustic wave. For several years, acoustophoresis has been used to manipulate microparticles in microscopic scales...

Chemical characterization of microparticles by laser ablation in an ion trap mass spectrometer

International Nuclear Information System (INIS)

Dale, J.M.; Whitten, W.B.; Ramsey, J.M.

1991-01-01

We are developing a new technique for the chemical characterization of microparticles based upon the use of electrodynamic traps. The electrodynamic trap has achieved widespread use in the mass spectrometry community in the form of the ion trap mass spectrometer or quadrupole ion trap. Small macroscopic particles can be confined or leviated within the electrode structure of a three-dimensional quadrupole electrodynamic trap in the same way as fundamental charges or molecular ions by using a combination of ac and dc potentials. Our concept is to use the same electrode structure to perform both microparticle levitation and ion trapping/mass analysis. The microparticle will first be trapped and spatially stabilized within the trap for characterization by optical probes, i.e., absorption, fluorescence, or Raman spectroscopy. After the particle has been optically characterized, it is further characterized using mass spectrometry. Ions are generated from the particle surface using laser ablation or desorption. The characteristics of the applied voltages are changed to trap the ions formed by the laser with the ions subsequently mass analyzed. The work described in this paper focuses on the ability to perform laser desorption experiments on microparticles contained within the ion trap. Laser desorption has previously been demonstrated in ion trap devices by applying the sample to a probe which is inserted so as to place the sample at the surface of the ring electrode. Our technique requires the placement of a microparticle in the center of the trap. Our initial experiments have been performed on falling microparticles rather than levitated particles to eliminate voltage switching requirements when changing from particle to ion trapping modes

Synchronous ultrasonic Doppler imaging of magnetic microparticles in biological tissues

Energy Technology Data Exchange (ETDEWEB)

Pyshnyi, Michael Ph. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Kuznetsov, Oleg A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation)], E-mail: kuznetsov_oa@yahoo.com; Pyshnaya, Svetlana V.; Nechitailo, Galina S.; Kuznetsov, Anatoly A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation)

2009-05-15

We considered applicability of acoustic imaging technology for the detection of magnetic microparticles and nanoparticles inside soft biological tissues. Such particles are widely used for magnetically targeted drug delivery and magnetic hyperthermia. We developed a new method of ultrasonic synchronous tissue Doppler imaging with magnetic modulation for in vitro and in vivo detection and visualization of magnetic ultradisperse objects in soft tissues. Prototype hardware with appropriate software was produced and the method was successfully tested on magnetic microparticles injected into an excised pig liver.

Synchronous ultrasonic Doppler imaging of magnetic microparticles in biological tissues

International Nuclear Information System (INIS)

Pyshnyi, Michael Ph.; Kuznetsov, Oleg A.; Pyshnaya, Svetlana V.; Nechitailo, Galina S.; Kuznetsov, Anatoly A.

2009-01-01

We considered applicability of acoustic imaging technology for the detection of magnetic microparticles and nanoparticles inside soft biological tissues. Such particles are widely used for magnetically targeted drug delivery and magnetic hyperthermia. We developed a new method of ultrasonic synchronous tissue Doppler imaging with magnetic modulation for in vitro and in vivo detection and visualization of magnetic ultradisperse objects in soft tissues. Prototype hardware with appropriate software was produced and the method was successfully tested on magnetic microparticles injected into an excised pig liver.

Design and characterization of core-shell mPEG-PLGA composite microparticles for development of cell-scaffold constructs

DEFF Research Database (Denmark)

Wen, Yanhong; Gallego, Monica Ramos; Nielsen, Lene Feldskov

2013-01-01

/DS or Alg/CS/DS particles in the mPEG-PLGA microparticles were significantly dependent on the operating conditions, including the flow rate ratio (Qout/Qin) and the viscosity of the polymer solutions (Vout, Vin) between the outer and the inner feeding channels. The core-shell composite microparticles.......e. more sustainable cell growth was induced by the DS released from the core-shell composite microparticles comprising Alg/CS/DS particles. After seeding fibroblasts onto the composite microparticles, excellent cell adhesion was observed, and a successful assembly of the cell-scaffold constructs...... was induced within 7 days. Therefore, the present study demonstrates a novel strategy for fabrication of core-shell composite microparticles comprising additional particulate drug carriers in the core, which provides controlled delivery of DS and favorable cell biocompatibility; an approach to potentially...

Free microparticles-An inducing mechanism of pre-firing in high pressure gas switches for fast linear transformer drivers.

Science.gov (United States)

Li, Xiaoang; Pei, Zhehao; Wu, Zhicheng; Zhang, Yuzhao; Liu, Xuandong; Li, Yongdong; Zhang, Qiaogen

2018-03-01

Microparticle initiated pre-firing of high pressure gas switches for fast linear transformer drivers (FLTDs) is experimentally and theoretically verified. First, a dual-electrode gas switch equipped with poly-methyl methacrylate baffles is used to capture and collect the microparticles. By analyzing the electrode surfaces and the collecting baffles by a laser scanning confocal microscope, microparticles ranging in size from tens of micrometers to over 100 μm are observed under the typical working conditions of FLTDs. The charging and movement of free microparticles in switch cavity are studied, and the strong DC electric field drives the microparticles to bounce off the electrode. Three different modes of free microparticle motion appear to be responsible for switch pre-firing. (i) Microparticles adhere to the electrode surface and act as a fixed protrusion which distorts the local electric field and initiates the breakdown in the gap. (ii) One particle escapes toward the opposite electrode and causes a near-electrode microdischarge, inducing the breakdown of the residual gap. (iii) Multiple moving microparticles are occasionally in cascade, leading to pre-firing. Finally, as experimental verification, repetitive discharges at ±90 kV are conducted in a three-electrode field-distortion gas switch, with two 8 mm gaps and pressurized with nitrogen. An ultrasonic probe is employed to monitor the bounce signals. In pre-firing incidents, the bounce is detected shortly before the collapse of the voltage waveform, which demonstrates that free microparticles contribute significantly to the mechanism that induces pre-firing in FLTD gas switches.

Review Article: Fabricated Microparticles: An Innovative Method to Minimize the Side Effects of NSAIDs in Arthritis.

Science.gov (United States)

Abadi, Shaivad Shabee Hulhasan; Moin, Afrasim; Veerabhadrappa, Gangadharappa Hosahalli

2016-01-01

Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs. A trend in NSAID development has been to improve therapeutic efficacy while reducing the severity of GI side effects by altering dosage through modified release to optimize drug delivery. One such approach is the use of fabricated microparticles such as microcapsules and microspheres as carriers of drugs. Microparticles provide delivery of macromolecules and micromolecules via different routes and effectively control the release profile of such drugs. Microcapsules and microspheres are compatible with most natural and synthetic polymers and can be used for several routes of administration, including parenteral, oral, nasal, intra-ocular, topical, and the like. Because of greater stability and multiple manufacturing techniques, microspheres and microcapsules are preferred as drug carriers over other colloidal drug delivery systems. Microparticles provide effective protection of the encapsulated agent against degradation by enzymatic activities, controlled and confined delivery of drugs from a few hours to months, and ingenious administration compared to alternative forms of controlled-release parenteral dosages, such as macro-sized implants. This comprehensive overview of fabricated microparticles describes microencapsulation technologies to produce microparticles for targeted therapy of arthritis and other

Improved positioning and detectability of microparticles in droplet microfluidics using two-dimensional acoustophoresis

DEFF Research Database (Denmark)

Ohlin, M.; Fornell, A.; Bruus, Henrik

2017-01-01

, by using acoustic actuation, (99.8 ± 0.4)% of all encapsulated microparticles can be detected compared to only (79.0 ± 5.1)% for unactuated operation. In our experiments we observed a strong ordering of the microparticles in distinct patterns within the droplet when using 2D acoustophoresis; to explain...

Formulation and Evaluation of Organogels Containing Hyaluronan Microparticles for Topical Delivery of Caffeine.

Science.gov (United States)

Simsolo, Erol Eli; Eroğlu, İpek; Tanrıverdi, Sakine Tuncay; Özer, Özgen

2018-04-01

Cellulite is a dermal disorder including the extracellular matrix, the lymphatic and microcirculatory systems and the adipose tissue. Caffeine is used as the active moiety depending its preventive effect on localization of fat in the cellular structure. Hyaluronic acid (hyaluronan-HA) is a natural constituent of skin that generates formation and poliferation of new cells having a remarkable moisturizing ability. The aim of this study is to formulate HA microparticles loaded with caffeine via spray-drying method. Resulting microparticle formulations (33.97 ± 0.3 μm, span < 2, 88.56 ± 0.42% encapsulation efficiency) were distributed in lecithin organogels to maintain the proper viscosity for topical application. Following the characterization and cell culture studies, in vitro drug release and ex vivo permeation studies were performed. The accumulated amount of caffeine was twice higher than the aqueous solution for the microparticle-loaded organogels at 24 h (8262,673 μg/cm 2 versus 4676,691 μg/cm 2 ). It was related to the sustained behaviour of caffeine release from the microparticles. As a result, lecithin organogel containing HA-encapsulated microparticles could be considered as suitable candidate formulations for efficient topical drug delivery system of caffeine. In addition to that, synergistic effect of this combination appears as a promising approach for long-acting treatment of cellulite.

Investigation of Water Absorption and Diffusion in Microparticles Containing Xylitol to Provide a Cooling Effect by Thermal Analysis

Science.gov (United States)

Salaün, F.; Bedek, G.; Devaux, E.; Dupont, D.; Deranton, D.

2009-08-01

Polyurethane microparticles containing xylitol as a sweat sensor system were prepared by interfacial polymerization. The structural and thermal properties of the resultant microparticles were studied. The surface morphology and chemical structure of microparticles were investigated using an optical microscope (OM) and a Fourier-transform infrared spectroscope (FTIR), respectively. The thermal properties of samples were investigated by thermogravimetric analysis (TGA) and by differential scanning calorimetry (DSC). Thus, two types of microparticles were synthesized by varying the percentage of monomers introduced. The obtained morphology is directly related to the synthesis conditions. DSC analysis indicated that the mass content of crystalline xylitol was up to 63.8 %, which resulted in a high enthalpy of dilution of 127.7 J · g-1. Furthermore, the water release rate monitored by TGA analysis was found to be faster from the microparticles than from raw xylitol. Thus, the microparticles could be applied for thermal energy storage and moisture sensor enhancement.

Preparation of Starch/Gelatin Blend Microparticles by a Water-in-Oil Emulsion Method for Controlled Release Drug Delivery.

Science.gov (United States)

Phromsopha, Theeraphol; Baimark, Yodthong

2014-01-01

Information on the preparation and properties of starch/gelatin blend microparticles with and without crosslinking for drug delivery is presented. The blend microparticles were prepared by the water-in-oil emulsion solvent diffusion method. Glutaraldehyde and methylene blue were used as the crosslinker and the water-soluble drug model, respectively. The blend microparticles were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and UV-Vis spectroscopy. The functional groups of the starch and gelatin blend matrices were determined from the FTIR spectra. Blend microparticles with a nearly spherical shape and internal porous structure were observed from SEM images. The average particle size of the gelatin microparticles depended on the crosslinker ratio but not on the starch/gelatin blend ratio. The in vitro drug release content significantly decreased as the crosslinker ratio increased and the starch blend ratio decreased. The results demonstrated that the starch/gelatin blend microparticles should be a useful controlled release delivery carrier for water-soluble drugs.

SERS-Fluorescence Dual-Mode pH-Sensing Method Based on Janus Microparticles.

Science.gov (United States)

Yue, Shuai; Sun, Xiaoting; Wang, Ning; Wang, Yaning; Wang, Yue; Xu, Zhangrun; Chen, Mingli; Wang, Jianhua

2017-11-15

A surface-enhanced Raman scattering (SERS)-fluorescence dual-mode pH-sensing method based on Janus microgels was developed, which combined the advantages of high specificity offered by SERS and fast imaging afforded by fluorescence. Dual-mode probes, pH-dependent 4-mercaptobenzoic acid, and carbon dots were individually encapsulated in the independent hemispheres of Janus microparticles fabricated via a centrifugal microfluidic chip. On the basis of the obvious volumetric change of hydrogels in different pHs, the Janus microparticles were successfully applied for sensitive and reliable pH measurement from 1.0 to 8.0, and the two hemispheres showed no obvious interference. The proposed method addressed the limitation that sole use of the SERS-based pH sensing usually failed in strong acidic media. The gastric juice pH and extracellular pH change were measured separately in vitro using the Janus microparticles, which confirmed the validity of microgels for pH sensing. The microparticles exhibited good stability, reversibility, biocompatibility, and ideal semipermeability for avoiding protein contamination, and they have the potential to be implantable sensors to continuously monitor pH in vivo.

Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

International Nuclear Information System (INIS)

Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto; Borsato, Débora Maria; Almeida, Martinha Antunes; Barboza, Fernanda Malaquias; Zawadzki, Sônia Faria; Kanunfre, Carla Cristine; Farago, Paulo Vitor; Zanin, Sandra Maria Warumby

2016-01-01

This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3 μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. - Highlights: • Ferulic acid-loaded Eudragit® L100 microparticles with high drug-loading were obtained. • Spray-dried Eudragit® L100 microparticles containing ferulic acid showed improved in vitro cytoprotective effect. • Ferulic acid spray-dried microparticles had potential as in vitro anti-inflammatory and immunomodulatory. • In vivo studies demonstrated an enhanced antiplatelet effect for ferulic acid-loaded Eudragit® L100 microparticles.

Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

Energy Technology Data Exchange (ETDEWEB)

Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil); Borsato, Débora Maria [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Almeida, Martinha Antunes [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Barboza, Fernanda Malaquias [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zawadzki, Sônia Faria [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Kanunfre, Carla Cristine [Postgraduate Program in Biomedical Science, Department of General Biology, State University of Ponta Grossa (Brazil); Farago, Paulo Vitor, E-mail: pvfarago@gmail.com [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zanin, Sandra Maria Warumby [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil)

2016-07-01

This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3 μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. - Highlights: • Ferulic acid-loaded Eudragit® L100 microparticles with high drug-loading were obtained. • Spray-dried Eudragit® L100 microparticles containing ferulic acid showed improved in vitro cytoprotective effect. • Ferulic acid spray-dried microparticles had potential as in vitro anti-inflammatory and immunomodulatory. • In vivo studies demonstrated an enhanced antiplatelet effect for ferulic acid-loaded Eudragit® L100 microparticles.

Simulation of kinetic processes in the nuclear-excited helium non-ideal dusty plasma

International Nuclear Information System (INIS)

Budnik, A.P.; Kosarev, V.A.; Rykov, V.A.; Fortov, V.E.; Vladimirov, V.I.; Deputatova, L.V.

2009-01-01

The paper is devoted to the studying of kinetic processes in the nuclear-excited plasma of the helium gas with the fine uranium (or its chemical compounds) particles admixture. A new theoretical model for the mathematical simulation of the kinetic processes in dusty plasma of helium gas was developed. The main goal of this investigation is to determine possibilities of a creation of non-ideal dusty plasma, containing nano- and micro-particles, and excited by fission fragments (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

On-line solid phase extraction using ion-pair microparticles combined with ICP-OES for the simultaneous preconcentration and determination of uranium and thorium

Energy Technology Data Exchange (ETDEWEB)

Yousefi, Seyed Reza; Zolfonoun, Ehsan [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). NFCRS

2016-07-01

In this work, after on-line and in-situ solid phase extraction technique was used for the extraction and preconcentration of uranium and thorium from aqueous samples prior to inductively coupled plasma optical emission spectrometry (ICP-OES) determination. In this method, sodium hexafluorophosphate (as an ion-pairing agent) was added to the sample solution containing the cationic surfactant (dodecyltrimethylammonium bromide) and the complexing agent (dibenzoylmethane). A cloudy solution was formed as a result of formation of an ion pair between surfactant and hexafluorophosphate. The solid microparticles were passed through a microcolumn filter and the adsorbed microparticles were subsequently eluted with acid, which was directly introduced into the ICP-OES nebulizer. The main variables affecting the pre-concentration and determination steps of uranium and thorium were studied and optimized. Under the optimum conditions, the enhancement factors of 97 and 95 and the detection limits of 0.52 and 0.21 μg L{sup -1} were obtained for uranium and thorium, respectively.

In-SITU Raman Spectroscopy of Single Microparticle Li-Intercalation Electrodes

Science.gov (United States)

Dokko, Kaoru; Shi, Qing-Fang; Stefan, Ionel C.; Scherson, Daniel A.

2003-01-01

Modifications in the vibrational properties of a single microparticle of LiMn2O4 induced by extraction and subsequent injection of Li(+) into the lattice have been monitored in situ via simultaneous acquisition of Raman scattering spectra and cyclic voltammetry data in 1M LiC1O4 solutions in ethylene carbonate (EC):diethyl carbonate (DEC) mixtures (1:1 by volume). Statistical analyses of the spectra in the range 15 < SOD < 45%, where SOD represents the state of discharge (in percent) of the nominally fully charged material, i.e. lambda-MnO2, were found to be consistent with the coexistence of two distinct phases of lithiated metal oxide in agreement with information derived from in situ X-ray diffraction (XRD) measurements involving more conventional battery-type electrodes.

Multipole electrodynamic ion trap geometries for microparticle confinement under standard ambient temperature and pressure conditions

Energy Technology Data Exchange (ETDEWEB)

Mihalcea, Bogdan M., E-mail: bogdan.mihalcea@inflpr.ro; Vişan, Gina T.; Ganciu, Mihai [National Institute for Laser, Plasma and Radiation Physics (INFLPR), Atomiştilor Str. Nr. 409, 077125 Măgurele, Ilfov (Romania); Giurgiu, Liviu C. [University of Bucharest, Faculty of Physics, Atomistilor Str. Nr. 405, 077125 Măgurele (Romania); Stan, Cristina [Department of Physics, Politehnica University, 313 Splaiul Independenţei, RO-060042 Bucharest (Romania); Filinov, Vladimir; Lapitsky, Dmitry, E-mail: dmitrucho@yandex.ru; Deputatova, Lidiya; Syrovatka, Roman [Joint Institute for High Temperatures, Russian Academy of Sciences, Izhorskaya Str. 13, Bd. 2, 125412 Moscow (Russian Federation)

2016-03-21

Trapping of microparticles and aerosols is of great interest for physics and chemistry. We report microparticle trapping in case of multipole linear Paul trap geometries, operating under standard ambient temperature and pressure conditions. An 8- and 12-electrode linear trap geometries have been designed and tested with an aim to achieve trapping for larger number of particles and to study microparticle dynamical stability in electrodynamic fields. We report emergence of planar and volume ordered structures of microparticles, depending on the a.c. trapping frequency and particle specific charge ratio. The electric potential within the trap is mapped using the electrolytic tank method. Particle dynamics is simulated using a stochastic Langevin equation. We emphasize extended regions of stable trapping with respect to quadrupole traps, as well as good agreement between experiment and numerical simulations.

Multipole electrodynamic ion trap geometries for microparticle confinement under standard ambient temperature and pressure conditions

International Nuclear Information System (INIS)

Mihalcea, Bogdan M.; Vişan, Gina T.; Ganciu, Mihai; Giurgiu, Liviu C.; Stan, Cristina; Filinov, Vladimir; Lapitsky, Dmitry; Deputatova, Lidiya; Syrovatka, Roman

2016-01-01

Trapping of microparticles and aerosols is of great interest for physics and chemistry. We report microparticle trapping in case of multipole linear Paul trap geometries, operating under standard ambient temperature and pressure conditions. An 8- and 12-electrode linear trap geometries have been designed and tested with an aim to achieve trapping for larger number of particles and to study microparticle dynamical stability in electrodynamic fields. We report emergence of planar and volume ordered structures of microparticles, depending on the a.c. trapping frequency and particle specific charge ratio. The electric potential within the trap is mapped using the electrolytic tank method. Particle dynamics is simulated using a stochastic Langevin equation. We emphasize extended regions of stable trapping with respect to quadrupole traps, as well as good agreement between experiment and numerical simulations.

Mechanisms of CNS invasion and damage by parasites.

Science.gov (United States)

Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina

2013-01-01

Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

Science.gov (United States)

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

The absolute counting of red cell-derived microparticles with red cell bead by flow rate based assay.

Science.gov (United States)

Nantakomol, Duangdao; Imwong, Malika; Soontarawirat, Ingfar; Kotjanya, Duangporn; Khakhai, Chulalak; Ohashi, Jun; Nuchnoi, Pornlada

2009-05-01

Activation of red blood cell is associated with the formation of red cell-derived microparticles (RMPs). Analysis of circulating RMPs is becoming more refined and clinically useful. A quantitative Trucount tube method is the conventional method uses for quantitating RMPs. In this study, we validated a quantitative method called "flow rate based assay using red cell bead (FCB)" to measure circulating RMPs in the peripheral blood of healthy subjects. Citrated blood samples collected from 30 cases of healthy subjects were determined the RMPs count by using double labeling of annexin V-FITC and anti-glycophorin A-PE. The absolute RMPs numbers were measured by FCB, and the results were compared with the Trucount or with flow rate based calibration (FR). Statistical correlation and agreement were analyzed using linear regression and Bland-Altman analysis. There was no significant difference in the absolute number of RMPs quantitated by FCB when compared with those two reference methods including the Trucount tube and FR method. The absolute RMPs count obtained from FCB method was highly correlated with those obtained from Trucount tube (r(2) = 0.98, mean bias 4 cell/microl, limit of agreement [LOA] -20.3 to 28.3 cell/microl), and FR method (r(2) = 1, mean bias 10.3 cell/microl, and LOA -5.5 to 26.2 cell/microl). This study demonstrates that FCB is suitable and more affordable for RMPs quantitation in the clinical samples. This method is a low cost and interchangeable to latex bead-based method for generating the absolute counts in the resource-limited areas. (c) 2008 Clinical Cytometry Society.

Microparticles of Aloe vera/vitamin E/chitosan: microscopic, a nuclear imaging and an in vivo test analysis for burn treatment.

Science.gov (United States)

Pereira, Gabriela Garrastazu; Santos-Oliveira, Ralph; Albernaz, Martha S; Canema, Daniel; Weismüller, Gilberto; Barros, Eduardo Bede; Magalhães, Luciana; Lima-Ribeiro, Maria Helena Madruga; Pohlmann, Adriana Raffin; Guterres, Silvia S

2014-02-01

The use of drug-loaded nanoparticles and microparticles has been increasing, especially for cosmetic and drug delivery purposes. In this work, a new microparticle formulation was developed for use in the healing process of skin burns in a composition of Aloe vera/vitamin E/chitosan. In order to observe the morphological properties, Raman and atomic force microscopy evaluation were performed. The biodistribution studies were analyzed by using a nuclear methodology, labeling the microparticles with Technetium-99m and in vivo test was procedure to analyzed the cicatrization process. The results of AFM analysis show the formation and the adherence property of the microparticles. Raman analyses show the distribution of each component in the microparticle. The nuclear method used shows that the biodistribution of the microparticles remained in the skin. The in vivo cicatrization test showed that the poloxamer gel containing the microparticles make a better cicatrization in relation to the other formulations tested. Copyright © 2013 Elsevier B.V. All rights reserved.

Negative interference by rheumatoid factor in alpha-fetoprotein chemiluminescent microparticle immunoassay.

Science.gov (United States)

Wang, Hui; Bi, Xiaohui; Xu, Lei; Li, Yirong

2017-01-01

Background Rheumatoid factor causes positive interference in multiple immunoassays. Recently, negative interference has also been found in immunoassays in the presence of rheumatoid factor. The chemiluminescent microparticle immunoassay is widely used to determine serum alpha-fetoprotein. However, it is not clear whether the presence of rheumatoid factor in the serum causes interference in the chemiluminescent microparticle immunoassay of alpha-fetoprotein. Methods Serum alpha-fetoprotein was determined using the ARCHITECT alpha-fetoprotein assay. The estimation of alpha-fetoprotein recovery was carried out in samples prepared by diluting high-concentration alpha-fetoprotein serum with rheumatoid factor-positive or rheumatoid factor-negative serum. Paramagnetic microparticles coated with hepatitis B surface antigen-anti-HBs complexes were used to remove rheumatoid factor from the serum. Results The average recovery of alpha-fetoprotein was 88.4% and 93.8% in the rheumatoid factor-positive and rheumatoid factor-negative serum samples, respectively. The recovery of alpha-fetoprotein was significantly lower in the rheumatoid factor-positive serum samples than in the rheumatoid factor-negative serum samples. In two of five rheumatoid factor-positive samples, a large difference was found (9.8%) between the average alpha-fetoprotein recoveries in the serially diluted and initial recoveries. Fourteen rheumatoid factor-positive serum samples were pretreated with hepatitis B surface antigen-anti-HBs complex-coated paramagnetic microparticles. The alpha-fetoprotein concentrations measured in the pretreated samples increased significantly. Conclusions It was concluded that the alpha-fetoprotein chemiluminescent microparticle immunoassay is susceptible to interference by rheumatoid factor, leading to significantly lower results. Eliminating the incidence of negative interference from rheumatoid factor should be an important goal for immunoassay providers. In the meantime

Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

Energy Technology Data Exchange (ETDEWEB)

Xu, Jiajun; Yang, Ming [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Kosterin, Paul [Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Salzberg, Brian M. [Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Milovanova, Tatyana N.; Bhopale, Veena M. [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Thom, Stephen R., E-mail: sthom@smail.umaryland.edu [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

2013-12-01

We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

Use of the spray chilling method to deliver hydrophobic components: physical characterization of microparticles

Directory of Open Access Journals (Sweden)

Izabela Dutra Alvim

2013-02-01

Full Text Available Food industry has been developing products to meet the demands of increasing number of consumers who are concerned with their health and who seek food products that satisfy their needs. Therefore, the development of processed foods that contain functional components has become important for this industry. Microencapsulation can be used to reduce the effects of processing on functional components and preserve their bioactivity. The present study investigated the production of lipid microparticles containing phytosterols by spray chilling. The matrices comprised mixtures of stearic acid and hydrogenated vegetable fat, and the ratio of the matrix components to phytosterols was defined by an experimental design using the mean diameters of the microparticles as the response variable. The melting point of the matrices ranged from 44.5 and 53.4 ºC. The process yield was melting point dependent; the particles that exhibited lower melting point had greater losses than those with higher melting point. The microparticles' mean diameters ranged from 13.8 and 32.2 µm and were influenced by the amount of phytosterols and stearic acid. The microparticles exhibited spherical shape and typical polydispersity of atomized products. From a technological and practical (handling, yield, and agglomeration points of view, lipid microparticles with higher melting point proved promising as phytosterol carriers.

Mode-based microparticle conveyor belt in air-filled hollow-core photonic crystal fiber.

Science.gov (United States)

Schmidt, Oliver A; Euser, Tijmen G; Russell, Philip St J

2013-12-02

We show how microparticles can be moved over long distances and precisely positioned in a low-loss air-filled hollow-core photonic crystal fiber using a coherent superposition of two co-propagating spatial modes, balanced by a backward-propagating fundamental mode. This creates a series of trapping positions spaced by half the beat-length between the forward-propagating modes (typically a fraction of a millimeter). The system allows a trapped microparticle to be moved along the fiber by continuously tuning the relative phase between the two forward-propagating modes. This mode-based optical conveyor belt combines long-range transport of microparticles with a positional accuracy of 1 µm. The technique also has potential uses in waveguide-based optofluidic systems.

Study of conditions of production and characterization of noble metal micro-particles suspensions

International Nuclear Information System (INIS)

Malabre, Catherine

1983-01-01

As the production and identification of metal micro-particle suspensions are some aspects of issues related to nuclear fuel reprocessing, this research thesis reports the use of ruthenium, molybdenum, niobium, palladium and rhodium (fission metals) to generate such micro-particles. They are produced by erosion of two electrodes between which occurs an electric arc discharge in aqueous media. Different analytic methods are developed to determine the characteristics of so-produced colloidal solutions. A granulometry study is performed by transmission electronic microscopy, light quasi-elastic scattering, and turbidimetry associated to centrifugation. This has lead to the production of steady micro-particle suspensions which have been used in a first set of industrial trials [fr

Intestinal parasites : associations with intestinal and systemic inflammation

NARCIS (Netherlands)

Zavala, Gerardo A; García, Olga P; Camacho, Mariela; Ronquillo, Dolores; Campos-Ponce, Maiza; Doak, Colleen; Polman, Katja; Rosado, Jorge L

2018-01-01

AIMS: Evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. METHODS AND RESULTS: Plasma concentrations of CRP, leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and

Herbal carrier-based floating microparticles of diltiazem ...

African Journals Online (AJOL)

Purpose: To formulate and characterize a gastroretentive floating drug delivery system for diltiazem hydrochloride using psyllium husk and sodium alginate as natural herbal carriers to improve the therapeutic effect of the drug in cardiac patients. Methods: Floating microparticles containing diltiazem hydrochloride were ...

Sublingual injection of microparticles containing glycolipid ligands for NKT cells and subunit vaccines induces antibody responses in oral cavity.

Science.gov (United States)

DeLyria, Elizabeth S; Zhou, Dapeng; Lee, Jun Soo; Singh, Shailbala; Song, Wei; Li, Fenge; Sun, Qing; Lu, Hongzhou; Wu, Jinhui; Qiao, Qian; Hu, Yiqiao; Zhang, Guodong; Li, Chun; Sastry, K Jagannadha; Shen, Haifa

2015-03-20

Natural Killer T (NKT) cells are a unique type of innate immune cells which exert paradoxical roles in animal models through producing either Th1 or Th2 cytokines and activating dendritic cells. Alpha-galactosylceramide (αGalCer), a synthetic antigen for NKT cells, was found to be safe and immune stimulatory in cancer and hepatitis patients. We recently developed microparticle-formulated αGalCer, which is selectively presented by dendritic cells and macrophages, but not B cells, and thus can avoid the anergy of NKT cells. In this study, we have examined the immunogenicity of microparticles containing αGalCer and protein vaccine components through sublingual injection in mice. The results showed that sublingual injection of microparticles containing αGalCer and ovalbumin triggered IgG responses in serum (titer >1:100,000), which persisted for more than 3months. Microparticles containing ovalbumin alone also induced comparable level of IgG responses. However, immunoglobulin subclass analysis showed that sublingually injected microparticles containing αGalCer and ovalbumin induced 20 fold higher Th1 biased antibody (IgG2c) than microparticles containing OVA alone (1:20,000 as compared to 1:1000 titer). Sublingual injection of microparticles containing αGalCer and ovalbumin induced secretion of both IgG (titer >1:1000) and IgA (titer=1:80) in saliva secretion, while microparticles containing ovalbumin alone only induced secretion of IgG in saliva. Our results suggest that sublingual injection of microparticles and their subsequent trafficking to draining lymph nodes may induce adaptive immune responses in mucosal compartments. Ongoing studies are focused on the mechanism of antigen presentation and lymphocyte biology in the oral cavity, as well as the toxicity and efficacy of these candidate microparticles for future applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Injectable hydrogel functionalised with thrombocyte-rich solution and microparticles for accelerated cartilage regeneration].

Science.gov (United States)

Rampichová, M; Buzgo, M; Křížková, B; Prosecká, E; Pouzar, M; Štrajtová, L

2013-01-01

Articular cartilage defects arise due to injury or osteochondral disease such as osteonecrosis or osteochondritis dissecans. In adult patients cartilage has minimal ability to repair itself and the lesions develop into degenerative arthritis. Overcoming the low regenerative capacity of the cartilage cells and the Hayflick limit poses a challenge for the therapy of osteochondral defects. Composite scaffolds with appropriate biomechanical properties combined with a suitable blend of proliferation and differentiation factors could be a solution. The aim of this in vitro study was to develop a novel functionalised hydrogel with an integrated drug delivery system stimulating articular cartilage regeneration. Injectable collagen/ hyaluronic acid/fibrin composite hydrogel was mixed with nanofibre-based microparticles. These were loaded with ascorbic acid and dexamethasone. In addition, the effect of thrombocyte-rich solution (TRS) was studied. The gels seeded with mesenchymal stem cells (MSCs) were cultivated for 14 days. The viability, proliferation and morphology of the cells were evaluated using molecular and microscopic methods. Scaffold degradation was also assessed. The cultivation study showed that MSCs remained viable in all experimental groups, which indicated good biocompatibility of the gel. However, the number of cells in the groups enriched with microparticles was lower than in the other groups. On the other hand, confocal microscopy showed higher cell viability and rounded morphology of the cells, which can be associated with chodrogenic differentiation. The scaffolds containing microparticles showed significantly higher stability during the 14-day experiment. Our results suggest that the addition of microparticles to the scaffold improved cell differentiation into the chondrogenic lineage, resulting in a lower proliferation rate. Cell viability was better in the groups enriched with microparticles that served as an efficient drug delivery system. In

The conserved clag multigene family of malaria parasites: essential roles in host-pathogen interaction.

Science.gov (United States)

Gupta, Ankit; Thiruvengadam, Girija; Desai, Sanjay A

2015-01-01

The clag multigene family is strictly conserved in malaria parasites, but absent from neighboring genera of protozoan parasites. Early research pointed to roles in merozoite invasion and infected cell cytoadherence, but more recent studies have implicated channel-mediated uptake of ions and nutrients from host plasma. Here, we review the current understanding of this gene family, which appears to be central to host-parasite interactions and an important therapeutic target. Published by Elsevier Ltd.

Preparation of gold microparticles using halide ions in bulk block copolymer phases via photoreduction

International Nuclear Information System (INIS)

Cha, Sang-Ho; Kim, Ki-Hyun; Lee, Won-Ki; Lee, Jong-Chan

2009-01-01

Gold microparticles were prepared from the gold salt in the solid bulk phase of a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer via a photoreduction process in the presence of halide ions. The shapes and sizes of the gold microparticles were found to be dependent on the types and amount of halide ions as well as the types of cations used due to the combined effects of the adsorption power and oxidative dissolution ability of the additives on gold surfaces. Gold nanorods were obtained when poly(ethylene oxide) was used instead of the block copolymer. This suggests that the poly(propylene oxide) (PPO) parts in the block copolymer are essential for the formation of gold microparticles, even though the degree of the direct interaction between the PPO blocks and gold salt is not significant. - Graphical abstract: Gold microparticles were successfully prepared using halide ions as additives in the polymeric bulk phase via photoreduction with the glow lamp irradiation.

The influence of mannitol on morphology and disintegration of spray-dried nano-embedded microparticles.

Science.gov (United States)

Torge, Afra; Grützmacher, Philipp; Mücklich, Frank; Schneider, Marc

2017-06-15

Nano-embedded microparticles represent a promising approach to deliver nanoparticles to the lungs. Microparticles with an appropriate aerodynamic diameter enable an application by dry powder inhaler and the transport of nanoparticles into the airways. By disintegration after deposition, nanoparticles can be released to exhibit their advantages such as a sustained drug release and delivery of the drug across the mucus barrier. The use of an appropriate matrix excipient to embed the nanoparticles is essential for the necessary disintegration and release of nanoparticles. In this context we investigated the influence of mannitol on the morphology, aerodynamic properties and disintegration behavior of nano-embedded microparticles. PLGA nanoparticles and mannitol were spray dried each as sole component and in combination in three different ratios. An influence of the mannitol content on the morphology was observed. Pure mannitol microparticles were solid and spherical, while the addition of nanoparticles resulted in raisin-shaped hollow particles. The different morphologies can be explained by diffusion processes of the compounds described by the Péclet-number. All powders showed suitable aerodynamic properties. By dispersion of the powders in simulated lung fluid, initial nanoparticle sizes could be recovered for samples containing mannitol. The fraction of redispersed nanoparticles was increased with increasing mannitol content. To evaluate the disintegration under conditions with higher comparability to the in vivo situation, spray-dried powders were exposed to >90% relative humidity. The disintegration behavior was monitored by analyzing roughness values by white light interferometry and supporting SEM imaging. The exposure to high relative humidity was shown to be sufficient for disintegration of the microparticles containing mannitol, releasing morphologically unchanged nanoparticles. With increasing mannitol content, the disintegration occurred faster and to a

Facile moldless fabrication of disk-shaped and reed blood cell-like microparticles using photopolymerization of tripropylene glycol diacrylate

International Nuclear Information System (INIS)

Choi, Jongchul; Won, June; Song, Simon

2014-01-01

A facile method for the moldless fabrication of 2- or 3-dimensional microparticles is proposed by using a photopolymerization technique. Using only a monomer solution of tripropylene glycol diacrylate, a film mask and standard UV lithography equipment, we were able to fabricate microparticles of various shapes, such as disks, dimpled disks similar in shape to red blood cells, and slender gourd shapes, unlike previous moldless fabrication techniques requiring expensive and/or sophisticated equipment. The simple method could produce more than one million particles in a single batch, indicating that it can be applied to the mass production of polymer microparticles. Analyses of scanning electron micrographs and optical micrographs of the microparticles indicated that their size distribution was highly monodisperse. Detailed fabrication processes and statistics on the microparticle sizes are given in this paper. (technical note)

Genetics of simple and complex host-parasite interactions

International Nuclear Information System (INIS)

Sidhu, G.S.; Webster, J.M.

1977-01-01

In nature a host plant can be viewed as a miniature replica of an ecological system where true and incidental parasites share the same habitat. Consequently, they influence each other's presence directly by interspecific interaction, and indirectly by inducing changes in the host's physiology and so form disease complexes. Since all physiological phenomena have their counterpart in the respective genetic systems of interacting organisms, valuable genetic information can be derived from the analysis of complex parasitic systems. Disease complexes may be classified according to the nature of interaction between various parasites on the same host. One parasite may nullify the host's resistance to another (e.g. Tomato - Meloidogyne incognita + Fusarium oxysporum lycopersici system). Conversely, a parasite may invoke resistance in the host against another parasite (e.g. Tomato - Fusarium oxysporum lycopersici + Verticillium albo atrum system). From the study of simple parasitic systems we know that resistance versus susceptibility against a single parasite is normally monogenically controlled. However, when more than one parasite interacts to invoke or nullify each other's responses on the same host plant, the genetic results suggest epistatic ratios. Nevertheless, epistatic ratios have been obtained also from simple parasitic systems owing to gene interaction. The epistatic ratios obtained from complex and simple parasitic systems are contrasted and compared. It is suggested that epistatic ratios obtained from simple parasitic systems may, in fact, be artifacts resulting from complex parasitic associations that often occur in nature. Polygenic inheritance and the longevity of a cultivar is also discussed briefly in relation to complex parasitic associations. Induced mutations can play a significant role in the study of complex parasitic associations, and thus can be very useful in controlling plant diseases

Cantilever-based micro-particle filter with simultaneous single particle detection

DEFF Research Database (Denmark)

Noeth, Nadine-Nicole; Keller, Stephan Sylvest; Boisen, Anja

2011-01-01

Currently, separation of whole blood samples on lab-on-a-chip systems is achieved via filters followed by analysis of the filtered matter such as counting of blood cells. Here, a micro-chip based on cantilever technology is developed, which enables simultaneous filtration and counting of micro-particles...... from a liquid. A hole-array is integrated into a micro-cantilever, which is inserted into a microfluidic channel perpendicular to the flow. A metal pad at the apex of the cantilever enables an optical read-out of the deflection of the cantilever. When a micro-particle is too large to pass a hole...

Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum-infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A

DEFF Research Database (Denmark)

Ricke, C H; Staalsoe, T; Koram, K

2000-01-01

-associated malaria (PAM) in endemic areas is concentrated in the first few pregnancies, indicating that protective immunity to PAM is a function of parity. The placenta is often heavily infected in PAM, and placental parasites show a striking preference for chondroitin sulfate A (CSA) as an adhesion receptor. Plasma...

The effect of vehicles on spray drying of rifampicin inhalable microparticles: In vitro and in vivo evaluation

Directory of Open Access Journals (Sweden)

2008-08-01

Full Text Available Backgrond and the purpose of the study: The aim of this study was to evaluate the effect of solvents used in the spray drying and the aerodynamic properties of the rifampicin microparticles and pulmonary absorption of the microparticles. Methods: Different mixtures of dichloromethane and water were used as solvents for spray drying of rifampicin microparticles. The water to dichloromethane ratios were 25:75, 50:50, 75:25, 80:20, 90:10 and 100:0.   The solutions were dried at inlet temperature of 70 °C. The powder properties of the samples were examined by laser diffraction, scanning electron microscopy (SEM, helium densitometer and infrared spectroscopy (IR. The aerosolization performance of these formulations was investigated using an Andersen cascade impactor. Pulmonary absorptions of formulations were examined by the in situ pulmonary absorption described by Enna and Schanker method. The plasma concentration time profiles of rifampicin were constructed 8 hours following the intravenous and the intrapulmonary administrations. The pharmacokinetics parameters, Cmax, Tmax, t1/2, AUC, mean residence time (MRT, Ka and Ke were determined for each formulations. Results and major conclusions: The Tmax values for the samples decreased by increase in the amount of water in the initial feed. The Tmax values for the spray dried samples from the different mixtures of   dichloromethane and water were 60(min and 30(min respectively. The solvent mixture as the spray drying vehicle played an important role in the in vitro and in vivo lung deposition. The type of spray drying vehicle showed significant effect on the aerodynamic behavior and pharmacokinetic parameters of the particles. The pulmonary absorption of drug revealed the possibility of achieving the minimal inhibitory concentration (MIC of the antibiotics. The spray drying vehicle only affected absorption patterns of the formulations and it did not have any effect on the elimination rat of

Ant parasite queens revert to mating singly

DEFF Research Database (Denmark)

Sumner, Seirian; Hughes, William Owen Hamar; Pedersen, Jes Søe

2004-01-01

quantified and they tend to be similar in related species. Here we compare the mating strategies of the leaf-cutting ant Acromyrmex echinatior and its recently derived social parasite Acromyrmex insinuator, which is also its closest relative 2 (see Fig. 1 ). We find that although the host queens mate with up......A parasitic ant has abandoned the multiple mating habit of the queens of its related host. Multiple mating (polyandry) is widespread among animal groups, particularly insects 1 . But the factors that maintain it and underlie its evolution are hard to verify because benefits and costs are not easily...... to a dozen different males, the social parasite mates only singly. This rapid and surprising reversion to single mating in a socially parasitic ant indicates that the costs of polyandry are probably specific to a free-living lifestyle....

Luminescence investigation of Yb{sup 3+}/Er{sup 3+} codoped single LiYF{sub 4} microparticle

Energy Technology Data Exchange (ETDEWEB)

Gao, Wei; Zheng, Hairong, E-mail: hrzheng@snnu.edu.cn; He, Enjie; Lu, Ying; Gao, Fangqi

2014-08-01

Tetragonal phase LiYF{sub 4}:Yb{sup 3+}/Er{sup 3+} microparticles are synthesized via facile hydrothermal method. Single LiYF{sub 4} microparticle is excited with IR laser at 980 nm in a confocal setup, and strong green and weak red emissions are observed. It is found that single LiYF{sub 4}:Yb{sup 3+}/Er{sup 3+} microparticle with sub-structure presents stronger upconversion luminescence emission and smaller intensity ratio of red to green emission than that from LiYF{sub 4}:Yb{sup 3+}/Er{sup 3+} microparticle with no sub-structure. The possible mechanism, the influence of particle size and the existence of EDTA on the upconversion luminescence emission are investigated. The current study suggests that the luminescence observation with single micropaticle can effectively avoid the influence of environment and neighbor particles, which is important for investigating the luminescence properties of micro- or nano-crystals and for extending their application. - Highlights: • Single LiYF{sub 4} microparticle is excited with IR laser at 980 nm in a confocal setup, and strong green and weak red emissions are observed. • Single LiYF{sub 4} microparticle with different morphology exhibits different fluorescence emission intensity and intensity ratio of red to green emission. • The possible mechanism, the influence of particle size and the existence of EDTA on the upconversion emission are investigated.

Heparin induced alterations in clearance and distribution of blood-borne microparticles following operative trauma.

Science.gov (United States)

Saba, T M; Antikatzides, T G

1979-04-01

The influence of systemic heparin administration on the vascular clearance and tissue distribution of blood-borne microparticles was evaluated in normal rats and rats after operation (laparotomy plus intestinal manipulation) utilizing an (131)I- colloid which is phagocytized by the reticuloendothelial system (RES). Intravenous heparin administration (100 USP/100g body weight) into normal animals three minutes prior to colloid injection (50 mg/lOOg) induced a significant increase in pulmonary localization of the microparticles as compared to nonheparinized control rats, while hepatic and splenic uptake were decreased. Surgical trauma decreased hepatic RE uptake and increased pulmonary localization of the microparticles when injected systemically at 60 minutes postsurgery. Heparin administration 60 minutes after surgery and three minutes prior to colloid injection, magnified the increased pulmonary localization response with an associated further depression of the RES. The ability of heparin to alter both RE clearance function and lung localization of microparticles was dose dependent and a function of the interval between heparin administration and systemic particulate infusion. Thus, low dose heparin administration was capable of stimulating RE activity while heparin in doses of excess of 50 USP units/lOOg body weight decreased RE function. These findings suggest that the functional state of the hepatic RE system can be greatly affected in a dose-dependent manner by systemic heparin administration which may influence distribution of blood-borne microparticles.

Encapsulation and release of the hypnotic agent zolpidem from biodegradable polymer microparticles containing hydroxypropyl-beta-cyclodextrin.

Science.gov (United States)

Trapani, Giuseppe; Lopedota, Angela; Boghetich, Giancarlo; Latrofa, Andrea; Franco, Massimo; Sanna, Enrico; Liso, Gaetano

2003-12-11

The goal of this study was to design a prolonged release system of the hypnotic agent zolpidem (ZP) useful for the treatment of insomnia. In this work, ZP alone or in the presence of HP-beta-CD was encapsulated in microparticles constituted by poly(DL-lactide) (PDLLA) and poly(DL-lactide-co-glycolide) (PLGA) and the drug release from these systems was evaluated. ZP alone-loaded microparticles were prepared by the classical O/W emulsion-solvent evaporation method. Conversely, ZP/HP-beta-CD containing microparticles were prepared by the W/O/W emulsion-solvent evaporation method following two different procedures (i.e. A and B). Following procedure A, the previously produced ZP/HP-beta-CD solid complex was added to the water phase of primary emulsion. In the procedure B, HP-beta-CD was added to the aqueous phase and ZP to the organic phase. The resulting microparticles were characterized about morphology, size, encapsulation efficiency and release rates. FT-IR, X-ray, and DSC results suggest the drug is in an essentially amorphous state within the microparticles. The release profiles of ZP from microparticles were in general biphasic, being characterized by an initial burst effect and a subsequent slow ZP release. It resulted that co-encapsulating ZP with or without HP-beta-CD in PDLLA and PLGA the drug release from the corresponding microparticles was protracted. Moreover, in a preliminary pharmacological screening, the ataxic activity in rats was investigated and it was found that intragastric administration of the ZP/HP-beta-CD/PLGA microparticles prepared according to procedure B produced the same ataxic induction time as the one induced by the currently used formulation Stilnox. Interestingly moreover, there was a longer ataxic lasting and a lower intensity of ataxia produced by the ZP/HP-beta-CD/PLGA-B-formulation already after 60 min following the administration. However, a need for further pharmacokinetic and pharmacodynamic studies resulted to fully evaluate

Thulium-170-labeled microparticles for local radiotherapy: preliminary studies.

Science.gov (United States)

Polyak, Andras; Das, Tapas; Chakraborty, Sudipta; Kiraly, Reka; Dabasi, Gabriella; Joba, Robert Peter; Jakab, Csaba; Thuroczy, Julianna; Postenyi, Zita; Haasz, Veronika; Janoki, Gergely; Janoki, Gyozo A; Pillai, Maroor R A; Balogh, Lajos

2014-10-01

The present article describes the preparation, characterization, and biological evaluation of Thulium-170 ((170)Tm) [T1/2 = 128.4 days; Eβmax = 968 keV; Eγ = 84 keV (3.26%)] labeled tin oxide microparticles for its possible use in radiation synovectomy (RSV) of medium-sized joints. (170)Tm was produced by irradiation of natural thulium oxide target. 170Tm-labeled microparticles were synthesized with high yield and radionuclidic purity (> 99%) along with excellent in vitro stability by following a simple process. Particle sizes and morphology of the radiolabeled particles were examined by light microscope, dynamic light scattering, and transmission electron microscope and found to be of stable spherical morphology within the range of 1.4-3.2 μm. The preparation was injected into the knee joints of healthy Beagle dogs intraarticularly for biological studies. Serial whole-body and regional images were taken by single-photon-emission computed tomography (SPECT) and SPECT-CT cameras up to 9 months postadministration, which showed very low leakage (compound did not show any possible radiotoxicological effect. These preliminary studies showed that 170Tm-labeled microparticles could be a promising nontoxic and effective radiopharmaceutical for RSV applications or later local antitumor therapy.

Microassembly using a Cluster of Paramagnetic Microparticles

NARCIS (Netherlands)

Khalil, I.S.M.; Brink, F.V; Sardan Sukas, Ö.; Misra, Sarthak

2013-01-01

We use a cluster of paramagnetic microparticles to carry out a wireless two-dimensional microassembly operation. A magnetic-based manipulation system is used to control the motion of the cluster under the influence of the applied magnetic fields. Wireless motion control of the cluster is implemented

Host-Parasite Interactions from the Inside: Plant Reproductive Ontogeny Drives Specialization in Parasitic Insects.

Directory of Open Access Journals (Sweden)

Thomas Boivin

Full Text Available Host plant interactions are likely key drivers of evolutionary processes involved in the diversification of phytophagous insects. Granivory has received substantial attention for its crucial role in shaping the interaction between plants and their seed parasites, but fine-scale mechanisms explaining the role of host plant reproductive biology on specialization of seed parasites remain poorly described. In a comparative approach using plant histological techniques, we tested the hypotheses that different seed parasite species synchronize their life cycles to specific stages in seed development, and that the stage they target depends on major differences in seed development programs. In a pinaceous system, seed storage products are initiated before ovule fertilization and the wasps target the ovule's nucellus during megagametogenesis, a stage at which larvae may benefit from the by-products derived from both secreting cells and dying nucellar cells. In a cupressaceous system, oviposition activity peaks later, during embryogenesis, and the wasps target the ovule's megagametophyte where larvae may benefit from cell disintegration during embryogenesis. Our cytohistological approach shows for the first time how, despite divergent oviposition targets, different parasite species share a common strategy that consists of first competing for nutrients with developing plant structures, and then consuming these developed structures to complete their development. Our results support the prediction that seed developmental program is an axis for specialization in seed parasites, and that it could be an important parameter in models of their ecological and taxonomic divergence. This study provides the basis for further investigating the possibility of the link between plant ontogeny and pre-dispersal seed parasitism.

Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity.

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Mello, Debora B; Ramos, Isalira P; Mesquita, Fernanda C P; Brasil, Guilherme V; Rocha, Nazareth N; Takiya, Christina M; Lima, Ana Paula C A; Campos de Carvalho, Antonio C; Goldenberg, Regina S; Carvalho, Adriana B

2015-01-01

Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is a complex disease endemic in Central and South America. It has been gathering interest due to increases in non-vectorial forms of transmission, especially in developed countries. The objective of this work was to investigate if adipose tissue-derived mesenchymal stromal cells (ASC) can alter the course of the disease and attenuate pathology in a mouse model of chagasic cardiomyopathy. ASC were injected intraperitoneally at 3 days post-infection (dpi). Tracking by bioluminescence showed that cells remained in the abdominal cavity for up to 9 days after injection and most of them migrated to the abdominal or subcutaneous fat, an early parasite reservoir. ASC injection resulted in a significant reduction in blood parasitemia, which was followed by a decrease in cardiac tissue inflammation, parasitism and fibrosis at 30 dpi. At the same time point, analyses of cytokine release in cells isolated from the heart and exposed to T. cruzi antigens indicated an anti-inflammatory response in ASC-treated animals. In parallel, splenocytes exposed to the same antigens produced a pro-inflammatory response, which is important for the control of parasite replication, in placebo and ASC-treated groups. However, splenocytes from the ASC group released higher levels of IL-10. At 60 dpi, magnetic resonance imaging revealed that right ventricular (RV) dilation was prevented in ASC-treated mice. In conclusion, the injection of ASC early after T. cruzi infection prevents RV remodeling through the modulation of immune responses. Lymphoid organ response to the parasite promoted the control of parasite burden, while the heart, a target organ of Chagas disease, was protected from damage due to an improved control of inflammation in ASC-treated mice.

Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity.

Directory of Open Access Journals (Sweden)

Debora B Mello

Full Text Available Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi, is a complex disease endemic in Central and South America. It has been gathering interest due to increases in non-vectorial forms of transmission, especially in developed countries. The objective of this work was to investigate if adipose tissue-derived mesenchymal stromal cells (ASC can alter the course of the disease and attenuate pathology in a mouse model of chagasic cardiomyopathy.ASC were injected intraperitoneally at 3 days post-infection (dpi. Tracking by bioluminescence showed that cells remained in the abdominal cavity for up to 9 days after injection and most of them migrated to the abdominal or subcutaneous fat, an early parasite reservoir. ASC injection resulted in a significant reduction in blood parasitemia, which was followed by a decrease in cardiac tissue inflammation, parasitism and fibrosis at 30 dpi. At the same time point, analyses of cytokine release in cells isolated from the heart and exposed to T. cruzi antigens indicated an anti-inflammatory response in ASC-treated animals. In parallel, splenocytes exposed to the same antigens produced a pro-inflammatory response, which is important for the control of parasite replication, in placebo and ASC-treated groups. However, splenocytes from the ASC group released higher levels of IL-10. At 60 dpi, magnetic resonance imaging revealed that right ventricular (RV dilation was prevented in ASC-treated mice.In conclusion, the injection of ASC early after T. cruzi infection prevents RV remodeling through the modulation of immune responses. Lymphoid organ response to the parasite promoted the control of parasite burden, while the heart, a target organ of Chagas disease, was protected from damage due to an improved control of inflammation in ASC-treated mice.

Chemical characterization of microparticles by laser ablation in an ion trap mass spectrometer

International Nuclear Information System (INIS)

Dale, J.M.; Whitten, W.B.; Ramsey, J.M.

1991-01-01

We are developing a new technique for the chemical characterization of microparticles based upon the use of electrodynamic traps. The electrodynamic trap has achieved widespread use in the mass spectrometry community in the form of the ion trap mass spectrometer or quadrupole ion trap. Small macroscopic particles can be confined or levitated within the electrode structure of a three-dimensional quadrupole electrodynamic trap in the same way as fundamental charges or molecular ions by using a combination of ac and dc potentials. Our concept is to use the same electrode structure to perform both microparticle levitation and ion trapping/mass analysis. The microparticle will first be trapped and spatially stabilized within the trap for characterization by optical probes, i.e., absorption, fluorescence, or Raman spectroscopy. After the particle has been optically characterized, it is further characterized using mass spectrometry. Ions are generated from the particle surface using laser ablation or desorption. The characteristics of the applied voltages are changed to trap the ions formed by the laser with the ions subsequently mass analyzed. The work described in this paper focuses on the ability to perform laser desorption experiments on microparticles contained within the ion trap

Pharmaceutical microparticle engineering with electrospraying

DEFF Research Database (Denmark)

Bohr, Adam; Wan, Feng; Kristensen, Jakob

2015-01-01

Microparticles of Celecoxib, dispersed in a matrix of poly(lactic-co-glycolic acid) (PLGA), were prepared by electrospraying using different solvent mixtures to investigate the influence upon particle formation and the resulting particle characteristics. Mixtures consisting of a good solvent, ace...... demonstrated by the increasingly higher drug release rates. The results demonstrate the importance of solvent composition in particle preparation and indicate potential for exploiting this dependence to improve pharmaceutical particle design and performance....

Surface-functionalized polymethacrylic acid based hydrogel microparticles for oral drug delivery.

Science.gov (United States)

Sajeesh, S; Bouchemal, K; Sharma, C P; Vauthier, C