Fluid Matrix Research Articles

Real-time Iontophoresis with Tetramethylammonium to Quantify Volume Fraction and Tortuosity of Brain Extracellular Space

This review describes the basic concepts and protocol to perform the real-time iontophoresis (RTI) method, the gold-standard to explore and quantify the extracellular space (ECS) of the living brain. The ECS surrounds all brain cells and contains both interstitial fluid and extracellular matrix. The transport of many substances required for brain activity, including neurotransmitters, hormones, and nutrients, occurs by diffusion through the ECS. Changes in the volume and geometry of this space occur during normal brain processes, like sleep, and pathological conditions, like ischemia. However, the structure and regulation of brain ECS, particularly in diseased states, remains largely unexplored. The RTI method measures two physical parameters of living brain: volume fraction and tortuosity. Volume fraction is the proportion of tissue volume occupied by ECS. Tortuosity is a measure of the relative hindrance a substance encounters when diffusing through a brain region as compared to a medium with no obstructions. In RTI, an inert molecule is pulsed from a source microelectrode into the brain ECS. As molecules diffuse away from this source, the changing concentration of the ion is measured over time using an ion-selective microelectrode positioned roughly 100 µm away. From the resulting diffusion curve, both volume fraction and tortuosity can be calculated. This technique has been used in brain slices from multiple species (including humans) and in vivo to study acute and chronic changes to ECS. Unlike other methods, RTI can be used to examine both reversible and irreversible changes to the brain ECS in real time.

Real-time Iontophoresis with Tetramethylammonium to Quantify Volume Fraction and Tortuosity of Brain Extracellular Space

This review describes the basic concepts and protocol to perform the real-time iontophoresis (RTI) method, the gold-standard to explore and quantify the extracellular space (ECS) of the living brain. The ECS surrounds all brain cells and contains both interstitial fluid and extracellular matrix. The transport of many substances required for brain activity, including neurotransmitters, hormones, and nutrients, occurs by diffusion through the ECS. Changes in the volume and geometry of this space occur during normal brain processes, like sleep, and pathological conditions, like ischemia. However, the structure and regulation of brain ECS, particularly in diseased states, remains largely unexplored. The RTI method measures two physical parameters of living brain: volume fraction and tortuosity. Volume fraction is the proportion of tissue volume occupied by ECS. Tortuosity is a measure of the relative hindrance a substance encounters when diffusing through a brain region as compared to a medium with no obstructions. In RTI, an inert molecule is pulsed from a source microelectrode into the brain ECS. As molecules diffuse away from this source, the changing concentration of the ion is measured over time using an ion-selective microelectrode positioned roughly 100 µm away. From the resulting diffusion curve, both volume fraction and tortuosity can be calculated. This technique has been used in brain slices from multiple species (including humans) and in vivo to study acute and chronic changes to ECS. Unlike other methods, RTI can be used to examine both reversible and irreversible changes to the brain ECS in real time.

Mechanical characterization of compressible chromatographic particles

During operation of packed-bed chromatography columns, the mechanical properties of the porous chromatographic particles determine the overall macroscopic compression behavior. The porous particles are biphasic materials consisting of a solid matrix and interstitial fluid. Mechanical characterization of selected arrays of two types of polymeric chromatographic particles made of agarose and methacrylate with a mean particle diameter of 60μm and 83μm, respectively, was carried out by applying a high-resolution micromanipulation technique. The effect of compression speed and displacement level was investigated. Both particle types showed pronounced time-dependent compression behavior and force relaxation. Long-time compression load relaxation experiments revealed that two different time-dependent mechanisms were involved. It was shown that the characteristic force relaxation times describing either mechanism differed by a factor of 13–31. Short-time quasistatic compression experiments were excellently described by a Maxwell-type standard linear solid model in which the force relaxation time matched the shorter relaxation time. It was assumed, that force relaxation occurring at short time is ascribed to poroelastic material behavior and at longer times to viscoelastic material behavior. This enabled the determination of fundamental particle properties, i.e. instantaneous and relaxed particle shear and Young's moduli, Poisson's ratio, and coefficient of restitution.

Cerebrospinal fluid matrix metalloproteinase 9 levels, blood-brain barrier permeability, and treatment outcome in tuberculous meningitis

ObjectivesTuberculous meningitis is characterized by elevated levels of matrix metalloproteinase 9 (MMP9) in the cerebrospinal fluid (CSF). However, it is unclear whether elevated MMP9 levels are associated with poor treatment outcome. We tested the hypothesis that pretreatment MMP9 levels in the CSF would be higher in tuberculous meningitis patients experiencing a poor treatment outcome.MethodsWe prospectively assessed the treatment outcome in a consecutive sample of human immunodeficiency virus-negative patients with tuberculous meningitis. We defined good outcome as survival without severe neurological disability (modified Rankin scale scores 0–2). We estimated levels of MMP9 and its tissue inhibitor (TIMP1) on pretreatment CSF samples. We used albumin index to assess blood-brain barrier permeability.ResultsWe studied 40 patients (23 males [58%]) with tuberculous meningitis. Sixteen patients (40%) had stage 3 disease. On follow-up, 18 (45%) patients had a poor treatment outcome—15 patients died and 3 had severe neurological disability. Pretreatment MMP9 levels were not associated with treatment outcome (median [interquartile range], 254 [115–389] vs. 192 [60–383] ng/mL in good vs. poor outcome groups; P = 0.693). MMP9 levels did not correlate with the albumin index (Spearman’s rho = 0.142; P = 0.381). However, MMP9 levels significantly correlated with CSF glucose levels (rho = −0.419; P = 0.007) and admission Glasgow coma scale score (rho = 0.324; P = 0.032). Likewise, TIMP1 levels also did not differ by treatment outcome (1239 [889–1511] vs. 1522 [934–1949] ng/mL; P = 0.201). MMP9/TIMP1 ratio that reflects net proteolytic activity was also not different between the two groups (0.191 [0.107–0.250] vs. 0.163 [0.067–0.34]; P = 0.625).ConclusionOur findings do not support the hypothesis that pretreatment levels of MMP9 would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. Further, MMP9 levels in the CSF did not correlate with blood-brain barrier permeability in patients with tuberculous meningitis.

An energy stable algorithm for a quasi-incompressible hydrodynamic phase-field model of viscous fluid mixtures with variable densities and viscosities

A quasi-incompressible hydrodynamic phase field model for flows of fluid mixtures of two incompressible viscous fluids of distinct densities and viscosities is derived by using the generalized Onsager principle, which warrants the variational structure, the mass conservation and energy dissipation law. We recast the model in an equivalent form and discretize the equivalent system in space firstly to arrive at a time-dependent ordinary differential and algebraic equation (DAE) system, which preserves the mass conservation and energy dissipation law at the semi-discrete level. Then, we develop a temporal discretization scheme for the DAE system, where the mass conservation and the energy dissipation law are once again preserved at the fully discretized level. We prove that the fully discretized algorithm is unconditionally energy stable. Several numerical examples, including drop dynamics of viscous fluid drops immersed in another viscous fluid matrix and mixing dynamics of binary polymeric solutions, are presented to show the convergence property as well as the accuracy and efficiency of the new scheme.

The combined exposure to intra-amniotic inflammation and neonatal respiratory distress syndrome increases the risk of intraventricular hemorrhage in preterm neonates.

To evaluate the impact of combined exposure to intra-amniotic inflammation and neonatal respiratory distress syndrome (RDS) on the development of intraventricular hemorrhage (IVH) in preterm neonates. This retrospective cohort study includes 207 consecutive preterm births (24.0-33.0 weeks of gestation). Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. According to McMenamin's classification, IVH was defined as grade II or higher when detected by neurosonography within the first weeks of life. (1) IVH was diagnosed in 6.8% (14/207) of neonates in the study population; (2) IVH was frequent among newborns exposed to intra-amniotic inflammation when followed by postnatal RDS [33% (6/18)]. The frequency of IVH was 7% (8/115) among neonates exposed to either of these conditions - intra-amniotic inflammation or RDS - and 0% (0/64) among those who were not exposed to these conditions; and (3) Neonates exposed to intra-amniotic inflammation and postnatal RDS had a significantly higher risk of IVH than those with only intra-amniotic inflammation [odds ratio (OR) 4.6, 95% confidence interval (CI) 1.1-19.3] and those with RDS alone (OR 5.6, 95% CI 1.0-30.9), after adjusting for gestational age. The combined exposure to intra-amniotic inflammation and postnatal RDS markedly increased the risk of IVH in preterm neonates.

Tangential fluid flow within 3D narrow fissures: Conservative velocity fields on associated triangulations and transport processes

For a fissured medium with uncertainty in the knowledge of fractures' geometry, a conservative tangential flow field is constructed, which is consistent with the physics of stationary fluid flow in porous media and an interpolated geometry of the cracks. The flow field permits computing preferential fluid flow directions of the medium, rates of mechanical energy dissipations, and a stochastic matrix modeling stream lines and fluid mass transportation, for the analysis of solute/contaminant mass advection‐diffusion as well as drainage times.

Deformation and breakup of a confined droplet in shear flows with power-law rheology

In this paper, a multiple-relaxation-time color-gradient lattice Boltzmann model is used to simulate the deformation and breakup of a confined droplet in a simple shear flow with power-law rheology. This model is demonstrated to be accurate in simulating power-law fluids with a broad range of power-law indices. Through a preliminary study, we find that the non-Newtonian rheology of the matrix fluid has a more significant effect on the droplet deformation than that of the droplet. Compared to the Newtonian case, the non-Newtonian rheology is found to strengthen the droplet deformation in the shear-thickening matrix fluid but weaken the deformation in the shear-thinning matrix fluid. The extent of droplet deformation increases with increasing power-law index, and the rate of increase is more rapid near the smallest and largest indices considered than for intermediate values. We then systematically investigate the influence of the capillary number, geometrical confinement, and viscosity ratio on the deformation of a Newtonian droplet in power-law matrix fluids. The non-Newtonian effect on droplet deformation increases with increasing the capillary number or the wall confinement. In all the matrix fluids considered, the viscosity ratio noticeably affects the droplet deformation only when the capillary number is not less than 0.15, and the maximum deformation occurs at the viscosity ratio of unity for a constant capillary number. Finally, the critical capillary number, above which the droplet breakup occurs, is investigated for various confinement ratios in three different power-law matrix fluids. As the confinement ratio increases, the critical capillary number exhibits an overall increasing trend in the shear-thinning matrix fluid and an overall decreasing trend in the shear-thickening matrix fluid, both distinct from that in Newtonian case where the critical capillary number first decreases and then increases. The mode of droplet breakup is found to depend on the confinement ratio and the power-law index of the matrix fluid, and a high confinement ratio or a low power-law index favors the ternary breakup. The present study can provide useful suggestions and guidance for precise control of droplet behavior in microfluidic applications where non-Newtonian rheology is often encountered.

Mind the Line Tension: New Criteria for Nanodomains in Biological Membranes

The compositionally diverse lipid bilayer that forms the two-dimensional fluid matrix of the cell plasma membrane is not simply a passive boundary but has functionality associated with cholesterol-related heterogeneity (1). A key question is whether this heterogeneity leads to the coexistence of liquid-ordered (Lo) and liquid-disordered (Ld) regions on the nanometer scale (2–4). At the moment, there is little experimental evidence of stable Lo domains (i.e., lipid rafts) in live cells (2,5). The work by Usery et al.

S100A6 - focus on recent developments.

The Ca2+-binding protein, S100A6, belongs to the S100 family. Binding of Ca2+ induces a conformational change, which causes an increase in the overall S100A6 hydrophobicity and allows it to interact with many targets. S100A6 is expressed in different normal tissues and in many tumors. Up to now it has been shown that S100A6 is involved in cell proliferation, cytoskeletal dynamics and tumorigenesis, and that it might have some extracellular functions. In this review, we summarize novel discoveries concerning S100A6 targets, its involvement in cellular signaling pathways, and presence in stem/progenitor cells, extracellular matrix and body fluids of diseased patients.

Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation

Recent studies on clinical chorioamnionitis at term suggest that some patients with this diagnosis have neither intraamniotic infection nor intraamniotic inflammation. A false-positive diagnosis of clinical chorioamnionitis in preterm gestation may lead to unwarranted preterm delivery. We sought to determine the frequency of intraamniotic inflammation and microbiologically proven amniotic fluid infection in patients with preterm clinical chorioamnionitis. Amniocentesis was performed in singleton pregnant women with preterm clinical chorioamnionitis (<36 weeks of gestation). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8 concentration. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture; intraamniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration of >23 ng/mL. Nonparametric and survival techniques were used for analysis. Among patients with preterm clinical chorioamnionitis, 24% (12/50) had neither microbiologic evidence of intraamniotic infection nor intraamniotic inflammation. Microbial invasion of the amniotic cavity was present in 34% (18/53) and intraamniotic inflammation in 76% (38/50) of patients. The most common microorganisms isolated from the amniotic cavity were the Ureaplasma species. Finally, patients without microbial invasion of the amniotic cavity or intraamniotic inflammation had significantly lower rates of adverse outcomes (including lower gestational age at delivery, a shorter amniocentesis-to-delivery interval, acute histologic chorioamnionitis, acute funisitis, and significant neonatal morbidity) than those with microbial invasion of the amniotic cavity and/or intraamniotic inflammation. Among patients with preterm clinical chorioamnionitis, 24% had no evidence of either intraamniotic infection or intraamniotic inflammation, and 66% had negative amniotic fluid cultures, using standard microbiologic techniques. These observations call for a reexamination of the criteria used to diagnose preterm clinical chorioamnionitis.

Droplet Dynamics of Newtonian and Inelastic Non-Newtonian Fluids in Confinement

Microfluidic droplet technology has been developing rapidly. However, precise control of dynamical behaviour of droplets remains a major hurdle for new designs. This study is to understand droplet deformation and breakup under simple shear flow in confined environment as typically found in microfluidic applications. In addition to the Newtonian–Newtonian system, we consider also both a Newtonian droplet in a non-Newtonian matrix fluid and a non-Newtonian droplet in a Newtonian matrix. The lattice Boltzmann method is adopted to systematically investigate droplet deformation and breakup under a broad range of capillary numbers, viscosity ratios of the fluids, and confinement ratios considering shear-thinning and shear-thickening fluids. Confinement is found to enhance deformation, and the maximum deformation occurs at the viscosity ratio of unity. The droplet orients more towards the flow direction with increasing viscosity ratio or confinement ratio. In addition, it is noticed that the wall effect becomes more significant for confinement ratios larger than 0.4. Finally, for the whole range of Newtonian carrier fluids tested, the critical capillary number above which droplet breakup occurs is only slightly affected by the confinement ratio for a viscosity ratio of unity. Upon increasing the confinement ratio, the critical capillary number increases for the viscosity ratios less than unity, but decreases for the viscosity ratios more than unity.

NANOVECTORS FOR TRANSDERMAL ADMINISTRATION: WHERE ARE WE?

The skin is the most important barrier of human body to prevent the absorption of exogenous substances. Its ability to limit the absorption of exogenous substances is exercised by the most superficial layer of the epidermis, the stratum corneum, which consists of about 15-20 layers of corneocytes supported by keratin fibres. The extracellular spaces are filled with a very dense lipid matrix organized in periodic lamellae, whereas the interlamellar spaces are constituted by a more fluid lipid matrix. In addition, where the corneocytes are not perfectly overlapped, pores with a higher water content are created. This complex organization allows only the passive diffusion of small molecules with peculiar chemical-physical properties. In all the other cases, it is necessary to improve the transdermal absorption of drugs using techniques able to alter reversibly the functionality of the stratum corneum, such as chemical skin penetration enhancers, iontophoresis or sonophoresis. In the era of nanotechnology, an intense effort has been made to design nanocarriers able to permeate the skin (e.g., polymeric nanoparticles, metal or solid-lipid, micro- and nanoemulsions, lipid vesicles). Nevertheless, the results are contradictory and there is scepticism in the scientific community about the real benefits of these systems compared to other traditional approaches. In fact, assuming the stratum corneum as a nanoporous membrane with openings of about 20-40 nm, the size of most of the nanocarriers is too big for permitting theoretically the skin penetration and diffusion. However, despite this consideration, on the market there are some medicinal products consisting of lipid vesicles. Starting from the critical analysis of the published information on possible permeation mechanisms of different types of nanocarriers, this review outlines lights and shadows on the (trans-)dermal administration of these drug delivery systems.

The Effects of Body Mass Index on Second-Trimester Amniotic Fluid Cytokine and Matrix Metalloproteinase Levels

Aim: The aim of this study was to determine the effects of obesity on amniotic fluid (AF) inflammatory markers in second-trimester AF, testing the hypothesis that there is a relationship between maternal body mass index (BMI) and fetal inflammatory exposure. Methods: AF was obtained from 84 singleton pregnant women undergoing elective amniocentesis for karyotype analysis at 16-24 weeks of gestation between April 2014 and May 2016. The cell-free AF was used to analyze interleukin (IL)-1β and IL-6, and matrix metalloproteinase (MMP)-1, MMP-6, and MMP-13. Results: IL-1β levels were significantly higher in class II-III obese patients than in class I obese, overweight, and normal weight patients (14.68 ± 1.37 vs. 13.34 ± 1.86 vs. 13.00 ± 2.22 vs. 10.78 ± 1.92, respectively; p < 0.05). IL-6 levels were lowest in the normal weight group and highest in class II-III obese patients. MMP-1, MMP-6, and MMP-13 levels were also significantly higher in class II-III obese patients than in the other groups. Conclusion: This study demonstrated that the fetuses of class II-III obese women are exposed in utero to higher cytokine and MMP levels than fetuses of lean women. Modification of current cutoff levels of intra-amniotic cytokines and MMPs according to the BMI could improve the accuracy of the prenatal diagnosis of intra-amniotic infection and inflammation.

Direct and Rapid Electrochemical Detection of Pseudomonas aeruginosa Quorum Signaling Molecules in Bacterial Cultures and Cystic Fibrosis Sputum Samples through Cationic Surfactant‐Assisted Membrane Disruption

AbstractRapid detection of pathogenic bacteria present in patient samples is of utmost importance for the clinical management of bacterial‐induced diseases. Herein, we describe an efficient and direct electrochemical approach for the detection of 2‐heptyl‐3‐hydroxy‐4‐quinolone (PQS), 2‐heptyl‐4‐hydroxyquinoline (HHQ), and pyocyanin (PYO) as a molecular signature of Pseudomonas aeruginosa (PA), a frequently infecting pathogen with high antibiotic resistance. The cationic surfactant hexadecyltrimethylammonium bromide (CTAB) enhances the effectiveness of an unmodified thin‐film boron‐doped diamond (BDD) electrode for the direct detection of PYO, HHQ, and PQS in bacterial cultures of PAO1 and PA14. Differential pulse voltammetry (DPV) is then used to monitor the production of these microbial metabolites in bacterial cultures of PAO1 over 10 h without any sample pretreatment. A proposed mechanism for the interaction of CTAB with bacteria cells is examined by zeta (ζ) potential measurements. Furthermore, the detection method is successfully extended to a clinical fluid matrix and applied to PA spiked cystic fibrosis (CF) sputum samples.

Responses of MSCs to 3D Scaffold Matrix Mechanical Properties under Oscillatory Perfusion Culture.

Both fluid shear stress and matrix stiffness are implicated in bone metabolism and functional adaptation, but the synergistic action of these mechanical cues on the biological behaviors of mesenchymal stem cells (MSCs) is still not well-known. In the present work, a homemade oscillatory flow device was applied to investigate the effects of matrix stiffness on MSCs survival, distribution, and osteogenic differentiation in three-dimensional (3D) conditions. Furthermore, the flow field and cell growth in this bioreactor were theoretically simulated. The results demonstrated that oscillatory shear stress significantly increased the viability and distribution uniformity of MSCs throughout the scaffold after culture for 3 weeks. Compared to static culture, oscillatory shear stress could promote the collagen secretion, mineral deposits, and osteogenic differentiation of MSCs. The findings obtained from this work indicate that the oscillatory perfusion not only provides a higher survival rate and a more uniform distribution of cells but also facilitates osteogenic differentiation of MSCs. Oscillating perfusion bioreactor culture of MSCs in 3D scaffold with optimal matrix stiffness could offer an easy-to-use but efficient bioreactor for bone tissue engineering.

Numerical investigation on laminar round-jet impinging on a surface at uniform heat flux in a channel partially filled with a porous medium

Horizontal channel partially filled with porous media and a single round jet impinging on the porous medium are numerically investigated. The wall facing the round jet is partially heated at uniform heat flux. A two-dimensional axial symmetric flow in the channel is assumed to evaluate the thermal behavior within the channel. The analysis in the porous medium is accomplished in local thermal equilibrium conditions and under the Brinkman–Forchheimer-extended Darcy law assumption. The problem is solved employing the Ansys-Fluent code. Results are given in terms of stream function and temperature fields of fluid and solid matrix, wall temperature profiles, air velocity and temperature profiles along the transversal section of channel. The Peclet number ranges from 1 to 1000 and Rayleigh number values are 10, 50, 100 and 1000. Reynolds jet number, solid wall distance and wall heat flux effects on thermal and fluid dynamic behaviors are investigated. Results indicate that Nusselt number has the highest value for the channel with a porous medium of thickness equal to the channel gap, whereas it presents very small changes increasing the porous medium length on the heated wall. Correlations among average Nusselt, Peclet and Rayleigh numbers are proposed.

Experimental Investigation of Wave Velocity-Permeability Model for Granite Subjected to Different Temperature Processing

Understanding the change of permeability of rocks before and after heating is of great significance for exploitation of hydrocarbon resources and disposal of nuclear waste. The rock permeability under high temperature cannot be measured with most of the existing methods. In this paper, quality, wave velocity, and permeability of granite specimen from Maluanshan tunnel are measured after high temperature processing. Quality and wave velocity of granite decrease and permeability of granite increases with increasing temperature. Using porosity as the medium, a new wave velocity-permeability model is established with modified wave velocity-porosity formula and Kozeny-Carman formula. Under some given wave velocities and corresponding permeabilities through experiment, the permeabilities at different temperatures and wave velocities can be obtained. By comparing the experimental and the theoretical results, the proposed formulas are verified. In addition, a sensitivity analysis is performed to examine the effect of particle size, wave velocities in rock matrix, and pore fluid on permeability: permeability increases with increasing particle size, wave velocities in rock matrix, and pore fluid; the higher the rock wave velocity, the lower the effect of wave velocities in rock matrix and pore fluid on permeability.

Cerebrospinal Fluid Matrix Metalloproteinase-9 Level in Children with Bacterial Meningitis

Cerebrospinal Fluid Matrix Metalloproteinase-9 Level in Children with Bacterial Meningitis

Glycerol in micellar confinement with tunable rigidity.

We investigate the glassy dynamics of glycerol in the confinement of a microemulsion system, which is stable on cooling down to the glass transition of its components. By changing the composition, we vary the viscosity of the matrix, while keeping the confining geometry intact, as is demonstrated by small angle X-ray scattering. By means of 2H NMR, differential scanning calorimetry, and triplet solvation dynamics we, thus, probe the dynamics of glycerol in confinements of varying rigidity. 2H NMR results show that, at higher temperatures, the dynamics of confined glycerol is unchanged compared to bulk behavior, while the reorientation of glycerol molecules becomes significantly faster than in the bulk in the deeply supercooled regime. However, comparison of different 2H NMR findings with data from calorimetry and solvation dynamics reveals that this acceleration is not due to the changed structural relaxation of glycerol, but rather due to the rotational motion of essentially rigid glycerol droplets or of aggregates of such droplets in a more fluid matrix. Thus, independent of the matrix mobility, the glycerol dynamics remains unchanged except for the smallest droplets, where an increase of Tg and, thus, a slowdown of the structural relaxation is observed even in a fluid matrix.