Number Average Diameter Research Articles

Aqueous-phase synthesis of cationic hydrogel nanoparticles with antibacterial properties

Antibacterial hydrogel nanoparticles are expected to be used in many biomedical applications, such as drug delivery and the development of antibacterial materials. In this study, we developed a synthesis for hydrogel nanoparticles that are dispersible in liquid media and have antibacterial properties. The particles were synthesized by copolymerizing a hydrophilic monomer (2-hydroxyethyl methacrylate), a cationic monomer containing a quaternary ammonium cation (dimethylaminoethyl methacrylate hydrochloride), and a crosslinker (ethylene glycol dimethacrylate) in an aqueous solution with a cationic polymerization initiator (2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride) to form a hydrogel. A hydrophobic monomer (methyl methacrylate) was then added and the polymerization was continued. The number average particle diameter by scanning electron microscopy was 122nm, and the hydrodynamic diameter by dynamic light scattering measurement in water was about 380nm, suggesting swelling of the particles by water. Furthermore, water was able to penetrate the solidified dry powder, confirming the hydrophilic properties of the particles. The zeta potential of the particles was about +40mV, and bovine serum albumin, which generally has a high adsorption to positively charged substances, was adsorbed in large amounts to the particle surface, indicating that the particles had sufficient cationicity. The particles maintained stable dispersions even in liquid media with high ionic strength and containing impurities, which is important for nanoparticles used in medical and hygiene applications. The antibacterial activity of the particles was evaluated by incubation with Klebsiella pneumoniae, a Gram-negative bacterium. Almost no K. pneumoniae remained present in the supernatant after incubation, demonstrating the antibacterial properties of the particles.

Controlled Size Characterization Process for In-Situ TiB2 Particles from Al Matrix Composites Using Nanoparticle Size Analysis.

The wide size range and high tendency to agglomerate of in-situ TiB2 particles in reinforced Al matrix composites introduce great difficulties in their size characterization. In order to use a nanoparticle size analyzer (NSA) to obtain the precise size distribution of TiB2 particles, a controlled size characterization process has been explored. First, the extraction and drying processes for TiB2 particles were optimized. In the extraction process, alternated applications of magnetic stirring and normal ultrasound treatments were proven to accelerate the dissolution of the Al matrix in HCl solution. Furthermore, freeze-drying was found to minimize the agglomeration tendency among TiB2 particles, facilitating the acquisition of pure powders. Such powders were quantitatively made into an initial TiB2 suspension. Second, the chemical and physical dispersion technologies involved in initial TiB2 suspension were put into focus. Chemically, adding PEI (M.W. 10000) at a ratio of mPEI/mTiB2 = 1/30 into the initial suspension can greatly improve the degree of TiB2 dispersion. Physically, the optimum duration for high-energy ultrasound application to achieve TiB2 dispersion was 10 min. Overall, the corresponding underlying dispersion mechanisms were discussed in detail. With the combination of these chemical and physical dispersion specifications for TiB2 suspension, the bimodal size distribution of TiB2 was able to be characterized by NSA for the first time, and its number-average diameter was 111 ± 6 nm, which was reduced by 59.8% over the initial suspension. Indeed, the small-sized and large-sized peaks of the TiB2 particles characterized by NSA mostly match the results obtained from transmission electron microscopy and scanning electron microscopy, respectively.

Effects of Cerium Content on the Nonmetallic Inclusions and Impact Toughness of Transformation‐Induced Plasticity Steel

The effects of Ce treatment on the inclusion evolution and impact toughness of as‐cast transformation‐induced plasticity (TRIP) steel are systematically investigated by scanning electron microscope (SEM) and impact toughness testing. The results reveal that in Fe‐2Mn‐1.5Al‐1Si‐0.2C steel without Ce, the primary inclusions consist of AlN, MnS, and Al2O3. After Ce addition, the inclusions evolve into Ce‐Al‐O, Ce2O2S, CeS, and Ce2O3 inclusions. The evolution of inclusions exhibits an initial reduction in both quantity and size with increasing Ce content, followed by a subsequent increase. In cases of excessive Ce content, there is an observable rise in the overall inclusion count, marked by the emergence of CeAs, CeP, and CeC2 inclusions. The segregation model suggests that P‐containing inclusions predominantly precipitate in the late solidification process, while As‐ and C‐containing inclusions form during the solid phase. When the Ce content reaches 0.0075 wt%, the minimum values of the number density and average diameter are 96.7 mm−2 and 1.6 μm, respectively. Furthermore, the influence of the size, morphology, quantity, and type of inclusions on the impact toughness are analyzed. The highest recorded impact energy is 6.8 J with a Ce content of 0.0075 wt%.

Oxidation of fine aluminum particles: thermally induced transformations in particle shells and kinetics of oxide nucleation.

This paper investigates the process of oxidation of fine aluminum powder, consisting of spherical Al particles of 'metal core/oxide shell' type, when heated in air at temperatures below 550 °C. The highly dispersed aluminum powder 'Alex' used in this work (particle size: 0.05-1.5 μm and number average particle diameter (DN): 0.11 μm) was produced by electric explosion of a thin Al wire in argon with subsequent passivation in an oxygen-containing atmosphere. For the first time, the influence of the particle size on the oxidation process has been identified. During the reaction, individual γ-Al2O3 oxide nuclei grow at the surface of Al particles with diameters less than 300 nm without laterally overlapping to form a protective passivating layer, as typically occurs during the oxidation of micron-sized particles or bulk metal. The localization of γ-Al2O3 nuclei is determined by the regions where peeling of the primary amorphous oxide film from the surface of the metal core of an Al particle occurs due to the thermal decomposition of aluminum hydroxides (T ≈ 350 °C) present within the particle shells. A significant increase in the contributions of the following factors leads to a high oxidation rate: the diffusion within the disordered structure of a particle core and the surface diffusion of cations (Ea = 80.6 ± 5.3 kJ mol-1, 400-450 °C), the surface and grain boundary diffusion of oxygen during the growth of γ-Al2O3 crystallites (Ea = 108.3 ± 11.2 kJ mol-1, 470-500 °C) and the surface and grain boundary transport of anions through an amorphous and underlying nanocrystalline oxide layer with a constant thickness (Ea = 205.1 ± 8.6 kJ mol-1, 520-550 °C). The results obtained make it possible to expand the theoretical understanding of the manifestations of the size effect in solid-phase reactions and take into account its influence in practice.

Charged colloidal SiO2 dispersions in water and chloroform: Synthesis, properties and perspectives in dyes adsorption

The paper proposes a new method for the synthesis of ultradispersed amorphous SiO2 powders in the reverse emulsions stabilized by sodium bis-(2-ethylhexyl) sulfosuccinate (AOT). Colloidal dispersions of the powders were obtained by ultrasonication in water and chloroform. The number average effective hydrodynamic diameter of particles in the sols was 90 and 200 nm, and ζ-potential was − 68 ± 3 and 52 ± 7 mV for water and chloroform, respectively. Accountable for charge formation and transformation are the AOT molecules that were adsorbed on the SiO2 surface during the synthesis in АОТ emulsions. In water, АОТ– ions serve as the potential-determining ones, while Na+ ions act as the counterions that form the diffusion part of the electrical double layer. With a decrease in the solvent polarity, Na+ ions become the potential-determining ones, and АОТ– ions – the counterions. Thus, the АОТ molecules embedded into the hybrid SiO2 @ АОТ particle during the synthesis are a certain switch key of the particle surface potential. The transformation of the surface charge in dependence on polarity of the organic solvent makes it possible to apply the synthesized powders both as the cation- and anion-exchange sorbents for the recovery of dyes from aqueous and non-aqueous media. In terms of fundamental advances, the novelty of our work consists in extending the ion-exchange sorption mechanism of ionic dyes to the media with a low dielectric constant.

Supernucleation Dominates Lignin/Poly(ethylene oxide) Crystallization Kinetics

The effect of lignin nanoparticles (LNPs) on the crystallization kinetics of poly(ethylene oxide) (PEO) is examined. Lignin from spruce and ionic isolation was used to prepare LNPs with a number-averaged diameter of 85 nm (with a relatively large polydispersity) by an ultrasonication method. PEO-based nanocomposites with four different LNP contents (5, 10, 15, and 20 wt %) were prepared and subject to isothermal and nonisothermal crystallization protocols in a series of experiments. Scanning electron microscopy (SEM) images showed well-dispersed LNPs in the crystallized PEO matrix. The incorporation of LNPs exponentially increases nucleation density at moderate loadings, with this trend apparently saturating at higher loadings. However, the spherulitic growth rate decreases monotonically with LNP loading. This is attributed to the substantial PEO/LNP affinity, which impacts chain diffusion and induces supernucleation effect (with efficiencies in the order of 200%), but leads to slower growth rates. The overall crystallization kinetics, measured by the DSC, shows faster nanocomposite crystallization rates relative to the neat PEO at all LNP contents examined. This indicates that the supernucleation effect of LNPs dominates over the decrease in the growth rates, although its influence slightly decreases as the LNP content increases. The strong hydrogen-bonded interactions between the LNPs and the PEO are thus reminiscent of confinement effects found in polymer-grafted NP nanocomposites (e.g., PEO-g-SiO2/PEO) in the brush-controlled regime.

Advanced quantitative analysis of colloidal solution of metal nanoparticles produced by laser ablation in liquids

The diameter of laser synthesized colloidal nanoparticles can be derived from a volume of ablated material and absorbance at surface plasmon resonance wavelength. The origin of such nanoparticles’ diameter is studied in this work. The study is based on Beer-Lambert law where nanoparticle size-distribution and UV-Vis photoabsorbance data are used. Theoretically modeled diameter is verified by independent integral approach proving that simple model derived in our previous work is by most means usable for determination of diameter of laser synthesized nanoparticles in colloidal solution with sizes less than SPR wavelength. Here is also presented the mathematical proof which indicates that in monodisperse limit, under assumption that size-distribution of synthesized nanoparticles can be described by log-normal function, diameter obtained by simple analytical model is in fact mode diameter (most frequent diameter) of size-distribution. Furthermore, it is shown that mode diameter of size-distributions can be obtained from volume average diameter of nanoparticles over experimentally determined diameter distribution as well as from number average diameter of nanoparticles over the same diameter distribution by multiplication of those diameters with shift factors depended only on standard deviation of log-normal distribution. This is verified for size-distributions obtained independently by AFM, TEM and DLS techniques and is proposed to be universal property of log-normal distribution function.

Airborne LTA Nanozeolites Characterization during the Manufacturing Process and External Sources Interaction with the Workplace Background.

Engineered nanoscale amorphous silica nanomaterials are widespread and used in many industrial sectors. Currently, some types of silicon-based nanozeolites (NZs) have been synthesized, showing potential advantages compared to the analogous micro-forms; otherwise, few studies are yet available regarding their potential toxicity. In this respect, the aim of the present work is to investigate the potential exposure to airborne Linde Type A (LTA) NZs on which toxicological effects have been already assessed. Moreover, the contributions to the background related to the main emission sources coming from the outdoor environment (i.e., vehicular traffic and anthropogenic activities) were investigated as possible confounding factors. For this purpose, an LTA NZ production line in an industrial factory has been studied, according to the Organisation for Economic Cooperation and Development (OECD) guidelines on multi-metric approach to investigate airborne nanoparticles at the workplace. The main emission sources of nanoparticulate matter within the working environment have been identified by real-time measurements (particle number concentration, size distribution, average diameter, and lung-deposited surface area). Events due to LTA NZ spillage in the air during the cleaning phases have been chemically and morphologically characterized by ICP-MS and SEM analysis, respectively.

Synthesis of Amphiphilic Copolymers of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether for Co-Delivery of Doxorubicin and Paclitaxel.

Co-delivery of chemotherapeutics in cancer treatment has been proven essential for overcoming multidrug resistance and improving the outcome of therapy. We report the synthesis of amphiphilic copolymers of N-vinyl-2-pyrrolidone and allyl glycidyl ether of various compositions and demonstrate that they can form nanoaggregates capable of simultaneous covalent immobilization of doxorubicin by the epoxy groups in the shell and hydrophobic-driven incorporation of paclitaxel into the core of nanoparticles. The structure of the obtained copolymers was characterized by 13C NMR, IR, and MALDI spectroscopy, as well as adsorption at the water/toluene interface. A linear increase in the number-average molecular weight of amphiphilic copolymers and a decrease in the number-average diameter of macromolecular aggregates with an increase in the ratio N-vinyl-2-pyrrolidone/allyl glycidyl ether were observed. The assembled nanocarriers were characterized by DLS. The reported novel nanocarriers can be of interest for delivery and co-delivery of a wide range of pharmacological preparations and combined therapy for cancer and other deceases.

In-situ TEM investigation of dislocation loop reaction and irradiation hardening in H2+-He+ dual-beam irradiated Mo

• Irradiation can directly cause the formation of 1/2<111> loops and <100> loops. • Irradiation can directly induce 1/2<111>loop to transform into <100> loop. • Two 1/2<111> loops react to form <100> loop without strict size similarity condition. • Yield strength increment caused by irradiation-induced loops is analyzed. • Loop evolution and its relationship with irradiation dose are established. Through in-situ TEM observation during 30 keV H 2 + -He + dual-beam irradiation at 723 K, the reaction and transformation of dislocation loops in pure Mo were investigated, especially for <100> loops. Irradiation could directly cause the formation of 1/2<111> loops and <100> loops, but 1/2<111> loops were dominant. In-situ observation confirmed the formation mechanism of <100> loops, including direct irradiation induced mechanism, 1/2<111> loop direct conversion mechanism, and reaction mechanism of two 1/2<111> loops. Meanwhile, the reaction of two 1/2<111> loops to produce <100> loop should not require the strict size similarity condition. The reaction between 1/2<111> loops could also produce 1/2<111> loop, which was essentially a process in which one loop absorbed another one. The yield strength increment caused by irradiation-induced loops was analyzed, and its saturation value reached 0.48 GPa at 0.06 dpa. Compared with single He + irradiation, the number density and average diameter of loops increased significantly and more serious damage was caused under the synergistic effect of hydrogen and helium. The mechanism based on in-situ experimental observation was discussed in depth. Graphical Abstract .

A Biomonitoring Pilot Study in Workers from a Paints Production Plant Exposed to Pigment-Grade Titanium Dioxide (TiO2).

Among particulate matter composing paints, titanium dioxide (TiO2) forms about 20% of the final suspension. Although TiO2 is broadly used in many applications, TiO2 powders represent an established respiratory hazard for workers with long-term exposure. In 35 workers of a paints production plant (15 exposed and 20 not exposed), we assessed pro-inflammatory cytokines (IL-1β, TNF-α, IL-10, IL-17), surfactant protein D (SP-D) and Krebs von den Lungen-6 glycoprotein (KL-6) in exhaled breath condensate (EBC). In urine samples, we measured 8-isoprostane (Isop) and Malondialdehyde (MDA) as biomarkers of oxidative stress, and Titanium (Ti-U) as a biomarker of exposure. Health status, habits and occupational history were recorded. Airborne respirable dusts and Ti were quantified. Particle number concentration and average diameter (nm) were detected by a NanoTracer™ monitoring device. Ti was measurable in filters collected at the respiratory breathing zone (0.11–0.44 µg/m3 8-h TWA). IL-1β and IL-10 values were significantly higher in exposed workers, whereas SP-D was significantly lower (p < 0.001). KL-6 was significantly higher in workers than in controls (p < 0.01). MDA levels were significantly increased in exposed workers and were positively correlated with Ti-U. Exposure to TiO2 in paint production is associated with the subtle alterations of lung pathobiology. These findings suggest the need for an integrated approach relying on both personal exposure and biomarker assessment to improve the hazard characterisation in occupational settings.

Self-Assembled Nanostructures from Amphiphilic Sucrose-Soyates for Solubilizing Hydrophobic Guest Molecules.

We studied self-assembly and colloidal properties of poly(ethylene glycol) (pEG) conjugated sucrose soyate polyols (PSSP). These molecular platforms were synthesized by covalently connecting PEGs of different molecular weights (Mn) (12 and 16 ethylene oxide units) to epoxidized sucrose soyate (ESS). The synthesized PSSP products showed amphiphilicity, reduced water surface tension, and exhibited critical Aggregation Concentration (CAC) within the range of 0.3-0.4 mg/mL. We observed that PSSP self-assembles in water in the form of nanoparticles without the need of any cosolvents. These nanoparticles exhibited number-average hydrodynamic diameter of 120 ± 8 nm with a polydispersity index (PDI) of <0.3, and negatively charged surfaces. We also found out that PSSP nanoparticles can encapsulate and homogeneously distribute a hydrophobic model compound, such as a phthalocyanine dye, Solvent Blue-70 (BL-70), on a metal surface. Collectively, our studies explored and demonstrated the possibility of molecular diversification of biobased starting materials to form amphiphilic nanoparticles with industrially relevant colloidal and surface properties.

Formation of micro/nanoparticles and microspheres from polyesters by dispersion ring‐opening polymerization

AbstractThe micro/nanoparticles and microspheres of polyesters derived from the heterocyclic monomers of lactide (L,L or D,L), ε‐caprolactone, and glycolide have received significant interest as drug carriers for biomedical applications. This review focuses on the recent advances in the study of polyester‐based micro/nanoparticles and microspheres derived from the dispersion ring‐opening polymerization (ROP) of heterocyclic monomers, and/or self‐assembly of polyester macromolecules, and/or dialysis of polyester solution in water‐miscible organic solvents against water. The dispersion polymerization of heterocyclic monomers in the presence of non‐polar miscible solvents and amphiphilic polymer surfactant leads to the formation of polyester particles with a narrower size distribution. The use of the polymer surfactant is crucial in controlling the diameter, morphology, and stability of the polyester particles formed during the ROP. The polymer surfactant acts as a stabilizer and is bound to the polyester particles strongly and irreversibly to control the size and morphology of polyester microspheres. The properties of polyester particles are varied by controlling the number average diameter and diameter polydispersity index. Hence, in this article, we review different synthetic strategies developed for the formation of polyester based particles with controlled diameter of distribution and the factors influencing its formation such as structure of the polymer surfactant, critical micelle concentration of the surfactant, type of radical initiator/monomer used, reaction parameters, etc. The article also describes methods developed for transforming the polyester microspheres into the water for better biocompatibility and encapsulation of bioactive compounds, drugs, and proteins into the polyester particles and their potential release at the targeted specific site are reviewed.

100 nm単分散粒径標準粒子の開発：微分型電気移動度分析器を用いたポリスチレンラテックス粒子への個数平均径および粒径分布幅の高精度値づけ

100 nm単分散粒径標準粒子の開発：微分型電気移動度分析器を用いたポリスチレンラテックス粒子への個数平均径および粒径分布幅の高精度値づけ

Viscosity, size, structural and interfacial properties of sodium caseinate obtained from A2 milk

Sodium caseinate (NaCN) obtained from A1A2 (regular) and A2 milks were compared for their viscosity, particle size and structure, and their absorption polystyrene particles surfaces. It was found that the viscosity as a function of concentration follows that of hard spheres dispersion, and is well described by the Quemada equation for concentrations up to 10 wt%, yielding a swelling ratio of Q=4.48 ± 0.01 mL/g. Dynamic light scattering measurements showed that the number and intensity average diameters were ∼10 and ∼68 nm, respectively. The difference is likely to be due to the presence of a few large NaCN particles. Small angle X-ray scattering showed that the radius of the particles was approximately ∼7 nm and that the NaCN internal structure was not homogeneous. NaCN formed a ∼10 nm protein layer at the surface of the latex particles with an estimated full surface coverage of 15.6 mg/m2. While these findings are within the values reported in the literature for NaCN solutions, this study showed that there is no obvious difference between the NaCN derived from A1A2 and A2 milks.

Biocompatible polypeptide nanogel: Effect of surfactants on nanogelation in inverse miniemulsion, in vivo biodistribution and blood clearance evaluation

Horseradish peroxidase (HRP)/H2O2-mediated crosslinking of polypeptides in inverse miniemulsion is a promising approach for the development of next-generation biocompatible and biodegradable nanogels. Herein, we present a fundamental investigation of the effects of three surfactants and their different concentrations on the (HRP)/H2O2-mediated nanogelation of poly[N5-(2-hydroxyethyl)-l-glutamine-ran-N5-propargyl-l-glutamine-ran-N5-(6-aminohexyl)-l-glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)-l-glutamine] (PHEG-Tyr) in inverse miniemulsion. The surfactants sorbitan monooleate (SPAN 80), polyoxyethylenesorbitan trioleate (TWEEN 85), and dioctyl sulfosuccinate sodium salt (AOT) were selected and their influence on the nanogel size, size distribution, and morphology was evaluated. The most effective nanogelation stabilization was achieved with 20 wt% nonionic surfactant SPAN 80. The diameter of the hydrogel nanoparticles was 230 nm (dynamic light scattering, DLS) and was confirmed also by nanoparticle tracking analysis (NTA) which showed the diameters ranging from 200 to 300 nm. Microscopy and image analyses showed that the nanogel in the dry state was spherical in shape and had number-average diameter Dn = 26 nm and dispersity Ð = 1.91. In the frozen-hydrated state, the nanogel appeared porous and was larger in size with Dn = 182 nm and Ð = 1.52. Our results indicated that the nanogelation of the polymer precursor required a higher concentration of surfactant than classical inverse miniemulsion polymerization to ensure effective stabilization. The developed polypeptide nanogel was radiolabeled with 125I, and in vivo biodistribution and blood clearance evaluations were performed. We found that the 125I-labeled nanogel was well-biodistributed in the bloodstream, cleared from mouse blood during 48 h by renal and hepatic pathways and did not provoke any sign of toxic effects.

Size measurement of silica nanoparticles by Asymmetric Flow Field-Flow Fractionation coupled to Multi-Angle Light Scattering: A comparison exercise between two metrological institutes

In this work we present a comparison exercise between two metrological institutes for size measurement of silica nanoparticles by Asymmetrical Flow Field-Flow Fractionation (AF4) coupled to static light scattering. The work has been performed in the frame of a French inter-laboratory comparison (ILC) exercise organized by the nanoMetrology Club (CnM). The general aim of this multi-technique comparison was to improve the measurement process for each technique, after establishing a well-defined measurement procedure. The results obtained by two national metrological institutes (NMIs), the LNE (France) and the SMD (Belgium) by AF4-UV-DRI-MALS will be presented and discussed. Three different samples were characterized: the reference material ERM®-FD304, which is a suspension of colloidal silica in aqueous solution and two silica bimodal samples consisting of two populations of SiO2 nanoparticles of unknown size in aqueous solution, with different populations’ ratios. The procedure for the preparation of the sample before the analysis, and main separation parameters have been previously defined between the two institutes and will be described. The principals measured parameters were the weight-average (dge_w), number-average (dge_n) and z-average (dge_z) geometric diameter; the average hydrodynamic diameter (dh); and the diameter obtained by external calibration using polystyrene latex standards (dcal). Results between the two NMIs were comparable and coherent with the expected size values of those obtained by other techniques like Scanning Mobility Particle Sizer (SMPS) and Scanning Electron Microscopy (SEM) also involved in this ILC exercise. Where discrepancies are observed, they leave the results compatible within their uncertainties and underpin the challenges in analysing data and reporting results, making AF4 a powerful tool to compare to other measurement techniques.

Effect of polystyrene and silica compositions on formation of raspberry-like hollow nanoparticles: synthesis strategy and morphological study

Raspberry-like hollow hybrid nanoparticles were facilely prepared via simultaneous miniemulsion sol–gel reaction/free radical polymerization of tetraethyl orthosilicate, 3-methacryloxypropyl trimethoxysilane (MEMO) and styrene (ST). MEMO played an important role in controlling their morphologies from dense silica nanoparticles to raspberry-like and raspberry-like hollow hybrid nanoparticles. The hybrid nanoparticles were obtained from the miniemulsion reaction technique with 2 wt% MEMO with or without ST exhibit raspberry-like hollow nanoparticles. The corresponding number-average diameter of hybrid nanoparticles increased from 112 to 126 nm as the ST concentration increased from 0 to 5 wt%. The (raspberry-like hollow) porous silica particle sizes after calcination are 47, 76, 78 and 85 nm for the runs with 0, 1, 2 and 5 wt% ST, respectively. Moreover, for constant level of MEMO at 2 wt%, the highest specific surface area (800 m2 g–1) was achieved for the runs with the ST concentration = 0–1 wt%. Then, it steadily decreased from ca. 710 to 510 m2 g–1 when the ST concentration increased from 1.5 to 20 wt%. As for constant level of ST at 0.5 wt%, the specific surface area is ca. 626, 797 and 580 m2 g–1 for the runs with 1, 2 and 3 wt% of MEMO, respectively.

Abnormalities of the lymphatic system and impaired fluid clearance in patients with heart failure with preserved ejection fraction

Abstract Background Coronary and skeletal muscle microvascular dysfunction have been proposed as main factors in the pathogenesis of Heart Failure with Preserved Ejection Fraction (HFpEF). However, assessment of systemic arterial function has only been indirect thus far; most importantly, no direct link between systemic microvasculature and congestion, one of the core characteristics of the syndrome, has yet been investigated. Purpose To provide direct functional and anatomical characterisation of the systemic microvasculature and to explore in vivo parameters of capillary fluid extravasation and lymphatic clearance in HFpEF. Methods In 16 patients with HFpEF and 16 age- and sex-matched healthy controls (72±6 and 68±5 years, respectively) we determined peripheral microvascular filtration coefficient (proportional to vascular permeability and area) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation) by venous occlusion plethysmography and collected a skin biopsy for vascular immunohistochemistry and gene expression analysis (TaqMan). Additionally, we measured brachial flow-mediated dilatation (FMD) and assessed by wire myography the vascular function of resistance arteries isolated from gluteal subcutaneous fat biopsies. Results Skin biopsies in patients with HFpEF showed rarefaction of small blood vessels (82±31 vs 112±21 vessels/mm2; p=0.003) and in ex-vivo analysis (n=6/group) we found defective relaxation of peripheral resistance arteries (p&amp;lt;0.001). Accordingly, post-ischaemic hyperaemic response (fold-change vs baseline, 4.6±1.6 vs 6.7±1.7; p=0.002) and FMD (3.9±2.1 vs 5.6±1.5%; p=0.014) were found to be reduced in patients with HFpEF compared to controls. In the skin of patients with HFpEF we also observed a reduced number (85±27 vs 130±60 vessels/mm2; p=0.012) but larger average diameter of lymphatic vessels (42±19 vs 26±9 μm2; p=0.007) compared to control subjects. These changes were paralleled by reduced expression of LYVE1 (p&amp;lt;0.05) and PROX1 (p&amp;lt;0.001), key determinants of lymphatic differentiation and function. Whilst patients with HFpEF had reduced peripheral capillary fluid extravasation compared to controls (microvascular filtration coefficient, leg 33.1±13.3 vs 48.4±15.2, p&amp;lt;0.01; trend for arm 49.9±20.5 vs 66.3±30.1, p=0.09), they had lower lymphatic clearance (isovolumetric pressure: leg 22±4 vs 16±4 mmHg, p&amp;lt;0.005; arm 25±5 vs 17±4 mmHg, p&amp;lt;0.001). Conclusions We provide direct evidence of systemic dysfunction and rarefaction of small blood vessels in patients with HFpEF. Despite a reduced microvascular filtration coefficient, which is in keeping with microvascular rarefaction, the clearance of extravasated fluid in HFpEF is limited by an anatomically and functionally defective lymphatic system. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation Centre of Research Excellence Award

Quantitative characterization of the blockage effect from dispersed phase on wax molecular diffusion in water-in-oil emulsion

Molecular diffusion is the main mechanism of wax deposition, whereas the dispersed water droplets influence the wax diffusivity in water-in-oil (w/o) emulsion by restricting the diffusion path. In the present work, geometric analysis method was used to analyze the blockage effect from dispersed phase on the restricted diffusion path of wax molecules in w/o emulsion, and a correlation was proposed relating the blockage effect with water fraction, dispersed degree and nonuniformity of dispersed phase in real emulsions. Firstly, regarding water droplets as spherical particles with uniform size and arrangement pattern, the average tortuosity of different wax diffusion paths was deduced in two-dimensional (2D) and three-dimensional (3D) ideal conditions. The results showed that the blockage degree was enhanced with the increase in water fraction. Moreover, the droplet size distribution of different w/o emulsions was investigated by microscopic observation and a set of microstructure characterization parameters were summarized in statistics. A 3D microstructure model of real emulsion was established to derive the tortuosity, taking the effect of droplet size distribution into consideration. The blockage effect was enhanced by the increase in the dispersity and polydispersity of water droplets, but this influence was not significant and water fraction was still the main influencing factor. On this basis, a correlation of blockage coefficient with water fraction, number-averaged diameter and polydispersity was proposed and validated using the 1H/19F-NMR test results in literature with the average relative error being 3.17%. This will provide a support to the revealing of wax diffusion mechanism in w/o emulsions and the wax deposition prediction of multiphase flow pipelines.